A Role of RIP3-Mediated Macrophage Necrosis in Atherosclerosis Development

Directory of Open Access Journals (Sweden)

Juan Lin

2013-01-01

Full Text Available Necrotic death of macrophages has long been known to be present in atherosclerotic lesions but has not been studied. We examined the role of receptor interacting protein (RIP 3, a mediator of necrotic cell death, in atherosclerosis and found that RIP3−/−;Ldlr−/− mice were no different from RIP3+/+;Ldlr−/− mice in early atherosclerosis but had significant reduction in advanced atherosclerotic lesions. Similar results were observed in Apoe−/− background mice. Bone marrow transplantation revealed that loss of RIP3 expression from bone-marrow-derived cells is responsible for the reduced disease progression. While no difference was found in apoptosis between RIP3−/−;Ldlr−/− and RIP3+/+;Ldlr−/− mice, electron microscopy revealed a significant reduction of macrophage primary necrosis in the advanced lesions of RIP3−/− mice. In vitro cellular studies showed that RIP3 deletion had no effect on oxidized low-density lipoprotein (LDL-induced macrophage apoptosis, but prevented macrophage primary necrosis occurring in response to oxidized LDL under caspase inhibition or RIP3 overexpression conditions. RIP3-dependent necrosis is not postapoptotic, and the increased primary necrosis in advanced atherosclerotic lesions most likely resulted from the increase of RIP3 expression. Our data demonstrate that primary necrosis of macrophages is proatherogenic during advanced atherosclerosis development.

Mapping and Mitigating the International Rip Current Health Hazard

Science.gov (United States)

Trimble, S. M.; Houser, C.

2016-12-01

Rip currents are concentrated seaward flows of water originating in the surf zones of beaches. Rips cause hundreds of international drownings each year. Calculating exact numbers is barred by logistical difficulties in obtaining accurate incident reports, but annual rip current fatalities are estimated at 100, 53 and 21 in the United States (US), Costa Rica, and Australia respectively. Notably, Australia's lifeguards rescue 17,600 swimmers from rips each year. This project addresses the geophysical, social, and systematic causes of fatalities in hopes of decreasing the global number of rip-related deaths. We demonstrate a novel method for mapping bathymetry in the surf zone (20m deep or less), specifically within rip channels (topographic low spots in the nearshore that result from feedback amongst waves, substrate, and antecedent bathymetry). We calculate bathymetry using 8-band multispectral imagery from the Digital Globe WorldView2 (WV2) satellite and field measurements of depth, generating maps of the changing nearshore at two embayed, rip-prone beaches: Playa Cocles, Costa Rica, and Bondi Beach, Australia. WV2 has a 1.1 day pass-over rate with 1.84m ground pixel resolution of 8 bands, including `yellow' (585-625 nm) and `coastal blue' (400-450 nm). Methods are tested for consistency amongst dates and locations. Previous research shows drownings result from a combination of the physical environment with personal and group behaviors; for this reason we build on rip-detection by evaluating tourists' and locals' knowledge and understanding of their beach's rip behavior. By combining the geomorphologic maps developed from WV2 with interview data, we evaluate how the physical environment dictates the exposure of certain swimmers. Controls include rip channel location, beach access points, and environmental factors favored by swimmers. The project serves as an evaluation of the landscape's creation of a physical feature that becomes a hazard when vulnerable humans

Red oak and black walnut growth increased with minesoil ripping

International Nuclear Information System (INIS)

Ashby, W.C.

1996-01-01

Red oak, black walnut, and black walnut with autumn olive, a 'nitrogen-fixing' shrub, were planted on graded, compacted cast overburden (topsoil substitute) coal mining minesoil with a dense ground cover consisting chiefly of all fescue grass. Compaction was mitigated by ripping on half the plots. Year 1 establishment of all species was equal or lower on the graded versus graded/ripped plots. After 12 years red oak survival was 9% where unripped versus 61% where ripped. Black walnut survival was respectively 41% and 74%. Red oak 12-year heights were 2.2 m on the graded and 4.5 m on the graded/ripped plots. Black walnut heights averaged 2.6 m and 5.5 m respectively. Diameter breast height similarly was greater with ripping for the oak and walnut. Deer damage was substantially greater on the red oak than on the black walnut trees. Black walnut was interplanted a year later with autumn olive on unripped and ripped graded minesoils. After 12 years survival of black walnut interplanted with autumn olive was 42% where unripped and 85% in two ripped plots. Corresponding heights averaged 3.8 m where graded and 5.7 to 6.4 m where graded/ripped. 16 refs., 1 fig., 4 tabs

CREATING INPUT TABLES FROM WAPDEG FOR RIP

International Nuclear Information System (INIS)

K.G. Mon

1998-01-01

The purpose of this calculation is to create tables for input into RIP ver. 5.18 (Integrated Probabilistic Simulator for Environmental Systems) from WAPDEG ver. 3.06 (Waste Package Degradation) output. This calculation details the creation of the RIP input tables for TSPA-VA REV.00

Homogeneous and isotropic big rips?

CERN Document Server

Giovannini, Massimo

2005-01-01

We investigate the way big rips are approached in a fully inhomogeneous description of the space-time geometry. If the pressure and energy densities are connected by a (supernegative) barotropic index, the spatial gradients and the anisotropic expansion decay as the big rip is approached. This behaviour is contrasted with the usual big-bang singularities. A similar analysis is performed in the case of sudden (quiescent) singularities and it is argued that the spatial gradients may well be non-negligible in the vicinity of pressure singularities.

Rip current monitoring using GPS buoy system

Science.gov (United States)

Song, DongSeob; Kim, InHo; Kang, DongSoo

2014-05-01

The occurrence of rip current in the Haeundae beach, which is one of the most famous beaches in South Korea, has been threatening beach-goers security in summer season annually. Many coastal scientists have been investigating rip currents by using field observations and measurements, laboratory measurements and wave tank experiments, and computer and numerical modeling. Rip current velocity is intermittent and may rapidly increase within minutes due to larger incoming wave groups or nearshore circulation instabilities. It is important to understand that changes in rip current velocity occur in response to changes in incoming wave height and period as well as changes in water level. GPS buoys have been used to acquire sea level change data, atmospheric parameters and other oceanic variables in sea for the purposes of vertical datum determination, tide correction, radar altimeter calibration, ocean environment and marine pollution monitoring. Therefore, we adopted GPS buoy system for an experiment which is to investigate rip current velocity; it is sporadic and may quickly upsurge within minutes due to larger arriving wave groups or nearshore flow uncertainties. In this study, for high accurate positioning of buy equipment, a Satellite Based Argumentation System DGPS data logger was deployed to investigate within floating object, and it can be acquired three-dimensional coordinate or geodetic position of buoy with continuous NMEA-0183 protocol during 24 hours. The wave height measured by in-situ hydrometer in a cross-shore array clearly increased before and after occurrence of rip current, and wave period also was lengthened around an event. These results show that wave height and period correlate reasonably well with long-shore current interaction in the Haeundae beach. Additionally, current meter data and GPS buoy data showed that rip current velocities, about 0.2 m/s, may become dangerously strong under specific conditions. Acknowledgement This research was

Rip current related drowning deaths and rescues in Australia 2004-2011

Science.gov (United States)

Brighton, B.; Sherker, S.; Brander, R.; Thompson, M.; Bradstreet, A.

2013-04-01

Rip currents are a common hazard to beachgoers found on many beaches around the world, but it has proven difficult to accurately quantify the actual number of rip current related drowning deaths in many regions and countries. Consequently, reported estimates of rip current drowning can fluctuate considerably and are often based on anecdotal evidence. This study aims to quantify the incidence of rip current related drowning deaths and rescues in Australia from 2004 to 2011. A retrospective search was undertaken for fatal and non-fatal rip-related drowning incidents from Australia's National Coronial Information System (NCIS), Surf Life Saving Australia's (SLSA, 2005-2011) SurfGuard Incident Report Database (IRD), and Media Monitors for the period 1 July 2004 to 30 June 2011. In this time, rip currents were recorded as a factor in 142 fatalities of a total of 613 coastal drowning deaths (23.2%), an average of 21 per year. Rip currents were related to 44% of all beach-related drowning deaths and were involved in 57.4% of reported major rescues in Australian locations where rips occur. A comparison with international operational statistics over the same time period describes rip-related rescues as 53.7% of the total rescues in the US, 57.9% in the UK and 49.4% in New Zealand. The range 49-58% is much lower than 80-89% traditionally cited. The results reported are likely to underestimate the size of the rip current hazard, because we are limited by the completeness of data on rip-related events; however this is the most comprehensive estimate to date. Beach safety practitioners need improved data collection and standardized definitions across organisations. The collection of drowning data using consistent categories and the routine collection of rip current information will allow for more accurate global comparisons.

Rip currents, mega-cusps, and eroding dunes

Science.gov (United States)

Thornton, E.B.; MacMahan, J.; Sallenger, A.H.

2007-01-01

Dune erosion is shown to occur at the embayment of beach mega-cusps O(200 m alongshore) that are associated with rip currents. The beach is the narrowest at the embayment of the mega-cusps allowing the swash of large storm waves coincident with high tides to reach the toe of the dune, to undercut the dune and to cause dune erosion. Field measurements of dune, beach, and rip current morphology are acquired along an 18 km shoreline in southern Monterey Bay, California. This section of the bay consists of a sandy shoreline backed by extensive dunes, rising to heights exceeding 40 m. There is a large increase in wave height going from small wave heights in the shadow of a headland, to the center of the bay where convergence of waves owing to refraction over the Monterey Bay submarine canyon results in larger wave heights. The large alongshore gradient in wave height results in a concomitant alongshore gradient in morphodynamic scale. The strongly refracted waves and narrow bay aperture result in near normal wave incidence, resulting in well-developed, persistent rip currents along the entire shoreline. The alongshore variations of the cuspate shoreline are found significantly correlated with the alongshore variations in rip spacing at 95% confidence. The alongshore variations of the volume of dune erosion are found significantly correlated with alongshore variations of the cuspate shoreline at 95% confidence. Therefore, it is concluded the mega-cusps are associated with rip currents and that the location of dune erosion is associated with the embayment of the mega-cusp.

Prolactin receptors in Rip-cre cells, but not in AgRP neurones, are involved in energy homeostasis.

Science.gov (United States)

Ladyman, S R; MacLeod, M A; Khant Aung, Z; Knowles, P; Phillipps, H R; Brown, R S E; Grattan, D R

2017-10-01

Among its many functions, prolactin has been implicated in energy homeostasis, particularly during pregnancy and lactation. The arcuate nucleus is a key site in the regulation of energy balance. The present study aimed to examine whether arcuate nucleus neuronal populations involved in energy homeostasis are prolactin responsive and whether they can mediate the effects of prolactin on energy homeostasis. To determine whether Agrp neurones or Rip-Cre neurones are prolactin responsive, transgenic mice expressing the reporter td-tomato in Agrp neurones (td-tomato/Agrp-Cre) or Rip-Cre neurones (td-tomato/Rip-Cre) were treated with prolactin and perfused 45 minutes later. Brains were processed for double-labelled immunohistochemistry for pSTAT5, a marker of prolactin-induced intracellular signalling, and td-tomato. In addition, Agrp-Cre mice and Rip-Cre mice were crossed with mice in which the prolactin receptor gene (Prlr) was flanked with LoxP sites (Prlr lox/lox mice). The Prlr lox/lox construct was designed such that Cre-mediated recombination resulted in deletion of the Prlr and expression of green fluorescent protein (GFP) in its place. In td-tomato/Rip-Cre mice, prolactin-induced pSTAT5 was co-localised with td-tomato, indicating that there is a subpopulation of Rip-Cre neurones in the arcuate nucleus that respond to prolactin. Furthermore, mice with a specific deletion of Prlr in Rip-Cre neurones had lower body weights, increased oxygen consumption, increased running wheel activity and numerous cells in the arcuate nucleus had positive GFP staining indicating deletion of Prlr from Rip-Cre neurones. By contrast, no co-localisation of td-tomato and pSTAT5 was observed in td-tomato/Agrp-Cre mice after prolactin treatment. Moreover, Prlr lox/lox /Agrp-Cre mice had no positive GFP staining in the arcuate nucleus and did not differ in body weight compared to littermate controls. Overall, these results indicate that Rip-Cre neurones in the arcuate nucleus are

RIP2 Is a Critical Regulator for NLRs Signaling and MHC Antigen Presentation but Not for MAPK and PI3K/Akt Pathways.

Science.gov (United States)

Wu, Xiao Man; Chen, Wen Qin; Hu, Yi Wei; Cao, Lu; Nie, Pin; Chang, Ming Xian

2018-01-01

RIP2 is an adaptor protein which is essential for the activation of NF-κB and NOD1- and NOD2-dependent signaling. Although NOD-RIP2 axis conservatively existed in the teleost, the function of RIP2 was only reported in zebrafish, goldfish, and rainbow trout in vitro . Very little is known about the role and mechanisms of piscine NOD-RIP2 axis in vivo . Our previous study showed the protective role of zebrafish NOD1 in larval survival through CD44a-mediated activation of PI3K-Akt signaling. In this study, we examined whether RIP2 was required for larval survival with or without pathogen infection, and determined the signaling pathways modulated by RIP2. Based on our previous report and the present study, our data demonstrated that NOD1-RIP2 axis was important for larval survival in the early ontogenesis. Similar to NOD1, RIP2 deficiency significantly affected immune system processes. The significantly enriched pathways were mainly involved in immune system, such as "Antigen processing and presentation" and "NOD-like receptor signaling pathway" and so on. Furthermore, both transcriptome analysis and qRT-PCR revealed that RIP2 was a critical regulator for expression of NLRs (NOD-like receptors) and those genes involved in MHC antigen presentation. Different from NOD1, the present study showed that NOD1, but not RIP2 deficiency significantly impaired protein levels of MAPK pathways. Although RIP2 deficiency also significantly impaired the expression of CD44a, the downstream signaling of CD44a-Lck-PI3K-Akt pathway remained unchanged. Collectively, our works highlight the similarity and discrepancy of NOD1 and RIP2 in the regulation of immune signaling pathways in the zebrafish early ontogenesis, and confirm the crucial role of RIP2 in NLRs signaling and MHC antigen presentation, but not for MAPK and PI3K/Akt pathways.

Dark energy, wormholes, and the big rip

International Nuclear Information System (INIS)

Faraoni, V.; Israel, W.

2005-01-01

The time evolution of a wormhole in a Friedmann universe approaching the big rip is studied. The wormhole is modeled by a thin spherical shell accreting the superquintessence fluid--two different models are presented. Contrary to recent claims that the wormhole overtakes the expansion of the universe and engulfs it before the big rip is reached, it is found that the wormhole becomes asymptotically comoving with the cosmic fluid and the future evolution of the universe is fully causal

Analysis of Block OMP using Block RIP

OpenAIRE

Wang, Jun; Li, Gang; Zhang, Hao; Wang, Xiqin

2011-01-01

Orthogonal matching pursuit (OMP) is a canonical greedy algorithm for sparse signal reconstruction. When the signal of interest is block sparse, i.e., it has nonzero coefficients occurring in clusters, the block version of OMP algorithm (i.e., Block OMP) outperforms the conventional OMP. In this paper, we demonstrate that a new notion of block restricted isometry property (Block RIP), which is less stringent than standard restricted isometry property (RIP), can be used for a very straightforw...

Multiple roles for nuclear localization signal (NLS, aa 442-472) of receptor interacting protein 3 (RIP3)

International Nuclear Information System (INIS)

Li Mei; Feng Shanshan; Wu Mian

2008-01-01

RIP3, a Ser/Thr kinase of RIP (Receptor Interacting Protein) family, is recruited to the TNFR1 signaling complex through RIP and has been shown to mediate apoptosis induction and NF-κB activation. RIP3 is a nucleocytoplasmic shuttling protein and its unconventional nuclear localization signal (NLS, 442-472 aa) is sufficient to trigger apoptosis in the nucleus. In this study, we demonstrate that this NLS exhibits several other roles besides apoptotic function. Firstly, this NLS was found to be required for both RIP3-induced apoptosis and RIP3-mediated NF-κB activation. Next, similar to RHIM motif (RIP homotypic interaction motif), NLS of RIP3 was found to be involved in RIP3-RIP interaction. Furthermore, this NLS was found to be both sufficient and necessary for RIP3 self-association. Our primary data also showed that RIP3 might form a homodimer within cells, and its apoptotic activity may not be required for this dimerization, rather the intactness of NLS determines RIP3-induced apoptosis, since a point mutation at amino acid residue 452 (Ile to Ala) within NLS greatly reduced its apoptotic ability, despite that RIP3 point mutant RIP3/I452A is able to dimerize with wild type RIP3 or itself

Bohmian quantization of the big rip

International Nuclear Information System (INIS)

Pinto-Neto, Nelson; Pantoja, Diego Moraes

2009-01-01

It is shown in this paper that minisuperspace quantization of homogeneous and isotropic geometries with phantom scalar fields, when examined in the light of the Bohm-de Broglie interpretation of quantum mechanics, does not eliminate, in general, the classical big rip singularity present in the classical model. For some values of the Hamilton-Jacobi separation constant present in a class of quantum state solutions of the Wheeler-De Witt equation, the big rip can be either completely eliminated or may still constitute a future attractor for all expanding solutions. This is contrary to the conclusion presented in [M. P. Dabrowski, C. Kiefer, and B. Sandhofer, Phys. Rev. D 74, 044022 (2006).], using a different interpretation of the wave function, where the big rip singularity is completely eliminated ('smoothed out') through quantization, independently of such a separation constant and for all members of the above mentioned class of solutions. This is an example of the very peculiar situation where different interpretations of the same quantum state of a system are predicting different physical facts, instead of just giving different descriptions of the same observable facts: in fact, there is nothing more observable than the fate of the whole Universe.

RIP2: A novel player in the regulation of keratinocyte proliferation and cutaneous wound repair?

International Nuclear Information System (INIS)

Adams, Stephanie; Valchanova, Ralitsa S.; Munz, Barbara

2010-01-01

We could recently demonstrate an important role of receptor interacting protein 4 (RIP4) in the regulation of keratinocyte differentiation. Now, we analyzed a potential role of the RIP4 homolog RIP2 in keratinocytes. Specifically, we demonstrate here that rip2 expression is induced by scratch-wounding and after the induction of differentiation in these cells. Furthermore, serum growth factors and cytokines can induce rip2, with TNF-α-dependent induction being dependent on p38 MAPK. In addition, we demonstrate that scratch-induced upregulation of rip2 expression is completely blocked by the steroid dexamethasone. Since we also show that RIP2 is an important player in the regulation of keratinocyte proliferation, these data suggest that inhibition of rip2 upregulation after wounding might contribute to the reduced and delayed wound re-epithelialization phenotype seen in glucocorticoid-treated patients.

Computer optimization of cutting yield from multiple ripped boards

Science.gov (United States)

A.R. Stern; K.A. McDonald

1978-01-01

RIPYLD is a computer program that optimizes the cutting yield from multiple-ripped boards. Decisions are based on automatically collected defect information, cutting bill requirements, and sawing variables. The yield of clear cuttings from a board is calculated for every possible permutation of specified rip widths and both the maximum and minimum percent yield...

"I didn't know her, but…": parasocial mourning of mediated deaths on Facebook RIP pages

Science.gov (United States)

Klastrup, Lisbeth

2015-04-01

This article examines the use of six Danish "Rest in Peace" or (RIP) memorial pages. The article focuses on the relation between news media and RIP page use, in relation to general communicative practices on these pages. Based on an analysis of press coverage of the deaths of six young people and a close analysis of 1,015 comments extracted from the RIP pages created to memorialize them, it is shown that their deaths attracted considerable media attention, as did the RIP pages themselves. Comment activity seem to reflect the news stories in the way the commenters refer to the context of death and the emotional distress they experience, but mainly comments on the RIP pages are conventional expressions of sympathy and "RIP" wishes. The article concludes that public RIP pages might be understood as virtual spontaneous shrines, affording an emerging practice of "RIP-ing."

Rip Currents, Mega-Cusps, and Eroding Dunes

OpenAIRE

Thornton, E.B.; MacMahan, J.; Sallenger, A.H.

2006-01-01

Submitted to Marine Geology 1 November 2006 Dune erosion is shown to occur at the embayment of beach mega-cusps O(200m alongshore) that are associated with rip currents. The beach is the narrowest at the embayment of the mega-cusps allowing the swash of large storm waves coincident with high tides to reach the toe of the dune, to undercut the dune and to cause dune erosion. Field measurements of dune, beach, and rip current morphology are acquired along an 18 km shoreline in southern Mont...

Degree of anisotropy as an automated indicator of rip channels in high resolution bathymetric models

Science.gov (United States)

Trimble, S. M.; Houser, C.; Bishop, M. P.

2017-12-01

A rip current is a concentrated seaward flow of water that forms in the surf zone of a beach as a result of alongshore variations in wave breaking. Rips can carry swimmers swiftly into deep water, and they are responsible for hundreds of fatal drownings and thousands of rescues worldwide each year. These currents form regularly alongside hard structures like piers and jetties, and can also form along sandy coasts when there is a three dimensional bar morphology. This latter rip type tends to be variable in strength and location, making them arguably the most dangerous to swimmers and most difficult to identify. These currents form in characteristic rip channels in surf zone bathymetry, in which the primary axis of self-similarity is oriented shore-normal. This paper demonstrates a new method for automating identification of such rip channels in bathymetric digital surface models (DSMs) using bathymetric data collected by various remote sensing methods. Degree of anisotropy is used to detect rip channels and distinguishes between sandbars, rip channels, and other beach features. This has implications for coastal geomorphology theory and safety practices. As technological advances increase access and accuracy of topobathy mapping methods in the surf zone, frequent nearshore bathymetric DSMs could be more easily captured and processed, then analyzed with this method to result in localized, automated, and frequent detection of rip channels. This could ultimately reduce rip-related fatalities worldwide (i) in present mitigation, by identifying the present location of rip channels, (ii) in forecasting, by tracking the channel's evolution through multiple DSMs, and (iii) in rip education by improving local lifeguard knowledge of the rip hazard. Although this paper on applies analysis of degree of anisotropy to the identification of rip channels, this parameter can be applied to multiple facets of barrier island morphological analysis.

History in Fiction:The Case of “Rip Van Winkle”%History in Fiction: The Case of “Rip Van Winkle”

Institute of Scientific and Technical Information of China (English)

Liu Jun

2009-01-01

Washington Irving's "Rip Van Winkle" has been so ritualistically cited and discussed by historians,political scientists and literary scholars that it is no longer just a simple tale but a prominent text in American culture.The tale,as one critic proclaims,"presides over the birth of the American imagination" (Fiedler xx).This essay revisits "Rip Van Winkle" for the sole purpose of considering how this literary text can also stimulate critical thinking on the connection between fiction (or poetry) and history.

Environmental Information System Baden-Wuerttemberg, RIPS 2016. Spatial information and planning system; Umweltinformationssystem Baden-Wuerttemberg. Konzeption RIPS 2016. Raeumliches Informations- und Planungssystem

Energy Technology Data Exchange (ETDEWEB)

Weissenbach, Kurt; Czommer, Olaf; Ellmenreich, Bastian (eds.)

2016-04-21

The Spatial Information and Planning System (RIPS), as the overarching component of the Environmental Information System Baden-Wuerttemberg (UIS BW), implements the environmental and nature conservation-specific geoinformation-related requirements taking into account applicable framework conditions. To this end, RIPS offers tailor-made services on the basis of a standardized and in transnational cooperation developed technical kit for the areas of geodata processing and management as well as the development and provision of software components with geo-functions and geodata services as part of the technical and information procedures. The coordination and steering takes place via project development offices, working groups and committees in close coordination with the departments of environmental and nature conservation administration as well as further cooperation and in coordination with other specialist administrations. Taking into account changed framework conditions and new geo-referenced requirements in UIS BW, the present RIPS concept focuses on future-oriented geofunction and geodata management in the field of environmental and nature conservation management as well as the provision of geo-specialized environmental and nature conservation data for policy makers, administrators and the public on innovative technologies Applications and Services. [German] Das Raeumliche Informations- und Planungssystem (RIPS) setzt als uebergreifende Komponente des Umweltinformationssystems Baden-Wuerttemberg (UIS BW) die umwelt- und naturschutzspezifischen geoinformationsbezogenen Anforderungen unter Beruecksichtigung geltender Rahmenbedingungen um. Hierzu bietet RIPS massgeschneiderte Dienstleistungen auf der Basis eines standardisierten und in laenderuebergreifenden Kooperationen entwickelten technischen Baukastens fuer die Bereiche Geodatenverarbeitung und -management sowie die Entwicklung und Bereitstellung von Softwarekomponenten mit Geofunktionen und Geodatendiensten

Field Observations of Surf Zone-Inner Shelf Exchange on a Rip-Channeled Beach

NARCIS (Netherlands)

Brown, J.A.; MacMahan, J.H.; Reniers, A.J.H.M.; Thornton, E.B.

2015-01-01

Cross-shore exchange between the surf zone and the inner shelf is investigated using Lagrangian and Eulerian field measurements of rip current flows on a rip-channeled beach in Sand City, California. Surface drifters released on the inner shelf during weak wind conditions moved seaward due to rip

A Role of RIP3-Mediated Macrophage Necrosis in Atherosclerosis Development

OpenAIRE

Lin, Juan; Li, Hanjie; Yang, Min; Ren, Junming; Huang, Zhe; Han, Felicia; Huang, Jian; Ma, Jianhui; Zhang, Duanwu; Zhang, Zhirong; Wu, Jianfeng; Huang, Deli; Qiao, Muzhen; Jin, Guanghui; Wu, Qiao

2013-01-01

Necrotic death of macrophages has long been known to be present in atherosclerotic lesions but has not been studied. We examined the role of receptor interacting protein (RIP) 3, a mediator of necrotic cell death, in atherosclerosis and found that RIP3−/−;Ldlr−/− mice were no different from RIP3+/+;Ldlr−/− mice in early atherosclerosis but had significant reduction in advanced atherosclerotic lesions. Similar results were observed in Apoe−/− background mice. Bone marrow transplantation reveal...

Influence of slope and gradation on rip rap stability and degradation mechanisms

International Nuclear Information System (INIS)

Lefebvre, G.; Rohan, K.; Belfahdel, M. B.

1997-01-01

A major investigation was undertaken at the La Grande hydroelectric complex with some 220 dikes and dams to study rip rap stability and repair. Degradation mechanisms were also studied under laboratory conditions to verify the main field study conclusions and to test different repair techniques. The result of both laboratory and field observation was that rip rap gradation has only marginal effect on slope stability and degradation mechanisms. On the other hand, the inclusion of even a small fraction of fine blocks (as little as 10 per cent) into the rip rap was shown to be very detrimental to the stability of steep rip rap but only marginally effective on flat slopes. 15 refs., 8 figs

XIAP Restricts TNF- and RIP3-Dependent Cell Death and Inflammasome Activation

DEFF Research Database (Denmark)

Yabal, Monica; Müller, Nicole; Adler, Heiko

2014-01-01

of XIAP or deletion of its RING domain lead to excessive cell death and IL-1β secretion from dendritic cells triggered by diverse Toll-like receptor stimuli. Aberrant IL-1β secretion is TNF dependent and requires RIP3 but is independent of cIAP1/cIAP2. The observed cell death also requires TNF and RIP3...... but proceeds independently of caspase-1/caspase-11 or caspase-8 function. Loss of XIAP results in aberrantly elevated ubiquitylation of RIP1 outside of TNFR complex I. Virally infected Xiap(-/-) mice present with symptoms reminiscent of XLP-2. Our data show that XIAP controls RIP3-dependent cell death and IL-1...

Phantom cosmology without Big Rip singularity

Energy Technology Data Exchange (ETDEWEB)

Astashenok, Artyom V. [Baltic Federal University of I. Kant, Department of Theoretical Physics, 236041, 14, Nevsky st., Kaliningrad (Russian Federation); Nojiri, Shin' ichi, E-mail: nojiri@phys.nagoya-u.ac.jp [Department of Physics, Nagoya University, Nagoya 464-8602 (Japan); Kobayashi-Maskawa Institute for the Origin of Particles and the Universe, Nagoya University, Nagoya 464-8602 (Japan); Odintsov, Sergei D. [Department of Physics, Nagoya University, Nagoya 464-8602 (Japan); Institucio Catalana de Recerca i Estudis Avancats - ICREA and Institut de Ciencies de l' Espai (IEEC-CSIC), Campus UAB, Facultat de Ciencies, Torre C5-Par-2a pl, E-08193 Bellaterra (Barcelona) (Spain); Tomsk State Pedagogical University, Tomsk (Russian Federation); Yurov, Artyom V. [Baltic Federal University of I. Kant, Department of Theoretical Physics, 236041, 14, Nevsky st., Kaliningrad (Russian Federation)

2012-03-23

We construct phantom energy models with the equation of state parameter w which is less than -1, w<-1, but finite-time future singularity does not occur. Such models can be divided into two classes: (i) energy density increases with time ('phantom energy' without 'Big Rip' singularity) and (ii) energy density tends to constant value with time ('cosmological constant' with asymptotically de Sitter evolution). The disintegration of bound structure is confirmed in Little Rip cosmology. Surprisingly, we find that such disintegration (on example of Sun-Earth system) may occur even in asymptotically de Sitter phantom universe consistent with observational data. We also demonstrate that non-singular phantom models admit wormhole solutions as well as possibility of Big Trip via wormholes.

Drug dealers' rational choices on which customers to rip-off.

Science.gov (United States)

Jacques, Scott; Allen, Andrea; Wright, Richard

2014-03-01

Drug dealers are infamous for overcharging customers and handing over less than owed. One reason rip-offs frequently occur is blackmarket participants have limited access to formal means of dispute resolution and, as such, are attractive prey. Yet drug dealers do not cheat every customer. Though this is implicitly understood in the literature, sparse theoretical attention has been given to which customers are ripped-off and why. To address that lacuna, this paper uses the rationality perspective to analyze qualitative data obtained in interviews with 25 unincarcerated drug sellers operating in disadvantaged neighborhoods of St. Louis, Missouri. We find that dealers typically rip-off six types of customers: persons who are strangers, first-time or irregular customers; do not have sufficient money on hand to make a purchase; are uninformed about going market rates; are deemed unlikely to retaliate; are offensive; or are addicted to drugs. Dealers target these groups due to perceiving them as unlikely to be repeat business; not worth the hassle of doing business with; unlikely to realize they are being ripped-off; in the wrong and thus deserving of payback; and, unwilling to retaliate or take their money elsewhere. Our findings are discussed in relation to their practical implications, including the importance of giving blackmarket participants greater access to law, and how customers may prevent being ripped-off. Copyright © 2013 Elsevier B.V. All rights reserved.

Membrane-bound transcription factors: regulated release by RIP or RUP.

Science.gov (United States)

Hoppe, T; Rape, M; Jentsch, S

2001-06-01

Regulated nuclear transport of transcription factors from cytoplasmic pools is a major route by which eukaryotes control gene expression. Exquisite examples are transcription factors that are kept in a dormant state in the cytosol by membrane anchors; such proteins are released from membranes by proteolytic cleavage, which enables these transcription factors to enter the nucleus. Cleavage can be mediated either by regulated intramembrane proteolysis (RIP) catalysed by specific membrane-bound proteases or by regulated ubiquitin/proteasome-dependent processing (RUP). In both cases processing can be controlled by cues that originate at or in the vicinity of the membrane.

Rip current evidence by hydrodynamic simulations, bathymetric surveys and UAV observation

Directory of Open Access Journals (Sweden)

G. Benassai

2017-09-01

Full Text Available The prediction of the formation, spacing and location of rip currents is a scientific challenge that can be achieved by means of different complementary methods. In this paper the analysis of numerical and experimental data, including RPAS (remotely piloted aircraft systems observations, allowed us to detect the presence of rip currents and rip channels at the mouth of Sele River, in the Gulf of Salerno, southern Italy. The dataset used to analyze these phenomena consisted of two different bathymetric surveys, a detailed sediment analysis and a set of high-resolution wave numerical simulations, completed with Google EarthTM images and RPAS observations. The grain size trend analysis and the numerical simulations allowed us to identify the rip current occurrence, forced by topographically constrained channels incised on the seabed, which were compared with observations.

Alternative mechanism of avoiding the big rip or little rip for a scalar phantom field

International Nuclear Information System (INIS)

Xi Ping; Zhai Xianghua; Li Xinzhou

2012-01-01

Depending on the choice of its potential, the scalar phantom field φ (the equation of state parameter w 2 correction. The singularity is avoidable under all these potentials. Hence, we conclude that the avoidance of big or little rip is hardly dependent on special potential.

On tridimensional rip current modeling

Science.gov (United States)

Marchesiello, Patrick; Benshila, Rachid; Almar, Rafael; Uchiyama, Yusuke; McWilliams, James C.; Shchepetkin, Alexander

2015-12-01

Do lateral shear instabilities of nearshore circulation account for a substantial part of Very Low-Frequency (VLF) variability? If yes, it would promote stirring and mixing of coastal waters and surf-shelf exchanges. Another question is whether tridimensional transient processes are important for instability generation. An innovative modeling system with tridimensional wave-current interactions was designed to investigate transient nearshore currents and interactions between nearshore and innershelf circulations. We present here some validation of rip current modeling for the Aquitanian coast of France, using in-situ and remote video sensing. We then proceed to show the benefits of 3D versus 2D (depth-mean flow) modeling of rip currents and their low-frequency variability. It appears that a large part of VLF motions is due to intrinsic variability of the tridimensional flow. 3D models may thus provide a valuable, only marginally more expensive alternative to conventional 2D approaches that miss the vertical flow structure and its nonlinear interaction with the depth-averaged flow.

Biochemical, structural and molecular dynamics analyses of the potential virulence factor RipA from Yersinia pestis.

Directory of Open Access Journals (Sweden)

Rodrigo Torres

Full Text Available Human diseases are attributed in part to the ability of pathogens to evade the eukaryotic immune systems. A subset of these pathogens has developed mechanisms to survive in human macrophages. Yersinia pestis, the causative agent of the bubonic plague, is a predominately extracellular pathogen with the ability to survive and replicate intracellularly. A previous study has shown that a novel rip (required for intracellular proliferation operon (ripA, ripB and ripC is essential for replication and survival of Y. pestis in postactivated macrophages, by playing a role in lowering macrophage-produced nitric oxide (NO levels. A bioinformatics analysis indicates that the rip operon is conserved among a distally related subset of macrophage-residing pathogens, including Burkholderia and Salmonella species, and suggests that this previously uncharacterized pathway is also required for intracellular survival of these pathogens. The focus of this study is ripA, which encodes for a protein highly homologous to 4-hydroxybutyrate-CoA transferase; however, biochemical analysis suggests that RipA functions as a butyryl-CoA transferase. The 1.9 Å X-ray crystal structure reveals that RipA belongs to the class of Family I CoA transferases and exhibits a unique tetrameric state. Molecular dynamics simulations are consistent with RipA tetramer formation and suggest a possible gating mechanism for CoA binding mediated by Val227. Together, our structural characterization and molecular dynamic simulations offer insights into acyl-CoA specificity within the active site binding pocket, and support biochemical results that RipA is a butyryl-CoA transferase. We hypothesize that the end product of the rip operon is butyrate, a known anti-inflammatory, which has been shown to lower NO levels in macrophages. Thus, the results of this molecular study of Y. pestis RipA provide a structural platform for rational inhibitor design, which may lead to a greater understanding of the

RIP-ET: A riparian evapotranspiration package for MODFLOW-2005

Science.gov (United States)

Maddock, Thomas; Baird, Kathryn J.; Hanson, R.T.; Schmid, Wolfgang; Ajami, Hoori

2012-01-01

A new evapotranspiration package for the U.S. Geological Survey's groundwater-flow model, MODFLOW, is documented. The Riparian Evapotranspiration Package (RIP-ET) provides flexibility in simulating riparian and wetland transpiration not provided by the Evapotranspiration (EVT) or Segmented Function Evapotranspiration (ETS1) Packages for MODFLOW 2005. This report describes how the RIP-ET package was conceptualized and provides input instructions, listings and explanations of the source code, and an example. Traditional approaches to modeling evapotranspiration (ET) processes assume a piecewise linear relationship between ET flux and hydraulic head. The RIP-ET replaces this traditional relationship with a segmented, nonlinear dimensionless curve that reflects the eco-physiology of riparian and wetland ecosystems. Evapotranspiration losses from these ecosystems are dependent not only on hydraulic head, but on the plant types present. User-defined plant functional groups (PFGs) are used to elucidate the interaction between plant transpiration and groundwater conditions. Five generalized plant functional groups based on transpiration rates, plant rooting depth, and water tolerance ranges are presented: obligate wetland, shallow-rooted riparian, deep-rooted riparian, transitional riparian and bare ground/open water. Plant functional groups can be further divided into subgroups (PFSGs) based on plant size, density or other characteristics. The RIP-ET allows for partial habitat coverage and mixtures of plant functional subgroups to be present in a single model cell. RIP-ET also distinguishes between plant transpiration and bare-ground evaporation. Habitat areas are designated by polygons; each polygon can contain a mixture of PFSGs and bare ground, and is assigned a surface elevation. This process requires a determination of fractional coverage for each of the plant functional subgroups present in a polygon to account for the mixture of coverage types and resulting

Potential for yield improvement in combined rip-first and crosscut-first rough mill processing

Science.gov (United States)

Ed Thomas; Urs Buehlmann

2016-01-01

Traditionally, lumber cutting systems in rough mills have either first ripped lumber into wide strips and then crosscut the resulting strips into component lengths (rip-first), or first crosscut the lumber into component lengths, then ripped the segments to the required widths (crosscut-first). Each method has its advantages and disadvantages. Crosscut-first typically...

Relevance of Radiocaesium Interception Potential (RIP) on a worldwide scale to assess soil vulnerability to 137Cs contamination

International Nuclear Information System (INIS)

Vandebroek, Louis; Van Hees, May; Delvaux, Bruno; Spaargaren, Otto; Thiry, Yves

2012-01-01

The extent of radiocaesium retention in soil is important to quantify the risk of further foodchain contamination. The Radiocaesium Interception Potential (RIP –, Nature 335, 247–249) is an intrinsic soil parameter which can be used to categorize soils or minerals in terms of their capacity to selectively adsorb radiocaesium. In this study, we measured RIP for a large soil collection (88 soil samples) representative of major FAO soil reference groups on a worldwide scale and tested the possibility to predict the RIP on the basis of other easily accessible or measurable soil data. We also compared RIP values with those obtained from separate chemical extraction experiments. The range of measured RIP values (1.8–13300 mmol kg −1 ) was shown to include nearly all possible cases of agricultural soil contamination. Only Podzols, Andosols and Ferralsols were clearly characterized by a very low RIP ( −1 ). On a worldwide scale, RIP was in fact slightly related to soil reference type or other simple major physicochemical parameters such as clay percentage or organic matter. Conversely our results indicated a link between the RIP and radiocaesium extractability across very different soils. We showed that, with the proposed scale of RIP values, a simple acid extraction method can provide an operational result highly predictive of potential RIP despite very contrasting soil properties. The RIP could be estimated from the empirical equation: RIP = (−31.701 ∗ log(AER) + 58.886) 2 where AER is the fraction of acid-extractable radiocaesium. - Highlights: ► The Radiocaesium Interception Potential (RIP) is an intrinsic soil parameter. ► We measured RIP of 88 different soils representative of major FAO reference groups. ► The range of RIP (1.8–13 343 μmol g −1 ) extended over four orders of magnitude. ► Nearly all possible cases of agricultural soils contamination were represented. ► A simple acid extraction method could be used to predict potential RIP.

Apicomplexa-specific tRip facilitates import of exogenous tRNAs into malaria parasites.

Science.gov (United States)

Bour, Tania; Mahmoudi, Nassira; Kapps, Delphine; Thiberge, Sabine; Bargieri, Daniel; Ménard, Robert; Frugier, Magali

2016-04-26

The malaria-causing Plasmodium parasites are transmitted to vertebrates by mosquitoes. To support their growth and replication, these intracellular parasites, which belong to the phylum Apicomplexa, have developed mechanisms to exploit their hosts. These mechanisms include expropriation of small metabolites from infected host cells, such as purine nucleotides and amino acids. Heretofore, no evidence suggested that transfer RNAs (tRNAs) could also be exploited. We identified an unusual gene in Apicomplexa with a coding sequence for membrane-docking and structure-specific tRNA binding. This Apicomplexa protein-designated tRip (tRNA import protein)-is anchored to the parasite plasma membrane and directs import of exogenous tRNAs. In the absence of tRip, the fitness of the parasite stage that multiplies in the blood is significantly reduced, indicating that the parasite may need host tRNAs to sustain its own translation and/or as regulatory RNAs. Plasmodium is thus the first example, to our knowledge, of a cell importing exogenous tRNAs, suggesting a remarkable adaptation of this parasite to extend its reach into host cell biology.

The effects and regulatory mechanism of RIP3 on RGC-5 necroptosis following elevated hydrostatic pressure.

Science.gov (United States)

Shang, Lei; Ding, Wei; Li, Na; Liao, Lvshuang; Chen, Dan; Huang, Jufang; Xiong, Kun

2017-02-06

Necroptosis is a type of regulated cell death that has been implicated in various diseases. Receptor-interacting protein 3 (RIP3), a member of the RIP family, is an important mediator of the necroptotic pathway. Cleavage of RIP3 at Asp328 by caspase-8 abolishes the kinase activity of RIP3, which is critical for necroptosis. Moreover, RIP3 is significantly upregulated during the early stages of acute high intra-ocular pressure and oxygen glucose deprivation. In this study, the effects of RIP3 during elevated hydrostatic pressure (EHP) were investigated and the possible mechanism through which caspase-8 regulated RIP3 cleavage was explored. Flow cytometry analysis revealed that the number of EHP-induced necrotic retinal ganglion cell 5 (RGC-5) cells was reduced after RIP3-knockdown. Furthermore, malondialdehyde (MDA) levels and glycogen phosphorylase (PYGL) activity in normal RGC-5 cells were much higher than those in RIP3-knockdown cells after EHP. EHP-induced RGC-5 necrosis was significantly reduced after treatment with butylated hydroxyanisole (BHA), a reactive oxygen species (ROS) scavenger. MDA levels and PYGL activity were lower in normal RGC-5 cells than those in cells with caspase-8 inhibition after EHP. Western blot analysis demonstrated that the RIP3 cleavage product was upregulated in cells with caspase-8 inhibition. Additionally, flow cytometry analysis revealed that the number of EHP-induced necrotic RGC-5 cells was increased after caspase-8 inhibition. Our results suggested that RGC-5 necroptosis following EHP was mediated by RIP3 through induction of PYGL activity and subsequent ROS accumulation. Thus, caspase-8 may participate in the regulation of RGC-5 necroptosis via RIP3 cleavage. © The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Structures of the inactive and active states of RIP2 kinase inform on the mechanism of activation.

Directory of Open Access Journals (Sweden)

Erika Pellegrini

Full Text Available Innate immune receptors NOD1 and NOD2 are activated by bacterial peptidoglycans leading to recruitment of adaptor kinase RIP2, which, upon phosphorylation and ubiquitination, becomes a scaffold for downstream effectors. The kinase domain (RIP2K is a pharmaceutical target for inflammatory diseases caused by aberrant NOD2-RIP2 signalling. Although structures of active RIP2K in complex with inhibitors have been reported, the mechanism of RIP2K activation remains to be elucidated. Here we analyse RIP2K activation by combining crystal structures of the active and inactive states with mass spectrometric characterization of their phosphorylation profiles. The active state has Helix αC inwardly displaced and the phosphorylated Activation Segment (AS disordered, whilst in the inactive state Helix αC is outwardly displaced and packed against the helical, non-phosphorylated AS. Biophysical measurements show that the active state is a stable dimer whilst the inactive kinase is in a monomer-dimer equilibrium, consistent with the observed structural differences at the dimer interface. We conclude that RIP2 kinase auto-phosphorylation is intimately coupled to dimerization, similar to the case of BRAF. Our results will help drug design efforts targeting RIP2 as a potential treatment for NOD2-RIP2 related inflammatory diseases.

“I didn't know her, but…”: parasocial mourning of mediated deaths on Facebook RIP pages

DEFF Research Database (Denmark)

Klastrup, Lisbeth

2015-01-01

This article examines the use of six Danish “Rest in Peace” or (RIP) memorial pages. The article focuses on the relation between news media and RIP page use, in relation to general communicative practices on these pages. Based on an analysis of press coverage of the deaths of six young people...... and a close analysis of 1,015 comments extracted from the RIP pages created to memorialize them, it is shown that their deaths attracted considerable media attention, as did the RIP pages themselves. Comment activity seem to reflect the news stories in the way the commenters refer to the context of death...... and the emotional distress they experience, but mainly comments on the RIP pages are conventional expressions of sympathy and “RIP” wishes. The article concludes that public RIP pages might be understood as virtual spontaneous shrines, affording an emerging practice of “RIP-ing.”...

2-HG Inhibits Necroptosis by Stimulating DNMT1-Dependent Hypermethylation of the RIP3 Promoter

Directory of Open Access Journals (Sweden)

Zhentao Yang

2017-05-01

Full Text Available 2-hydroxyglutarate-(2-HG-mediated inhibition of TET2 activity influences DNA hypermethylation in cells harboring mutations of isocitrate dehydrogenases 1 and 2 (IDH1/2. Here, we show that 2-HG also regulates DNA methylation mediated by DNA methyltransferase 1 (DNMT1. DNMT1-dependent hypermethylation of the RIP3 promoter occurred in both IDH1 R132Q knockin mutant mouse embryonic fibroblast (MEFs and 2-HG-treated wild-type (WT MEFs. We found that 2-HG bound to DNMT1 and stimulated its association with the RIP3 promoter, inducing hypermethylation that reduces RIP3 protein and consequently impaired RIP3-dependent necroptosis. In human glioma samples, RIP3 protein levels correlated negatively with IDH1 R132H levels. Furthermore, ectopic expression of RIP3 in transformed IDH1-mutated MEFs inhibited the growth of tumors derived from these cells following transplantation into nude mice. Thus, our research sheds light on a mechanism of 2-HG-induced DNA hypermethylation and suggests that impaired necroptosis contributes to the tumorigenesis driven by IDH1/2 mutations.

RIP3 attenuates the pancreatic damage induced by deletion of ATG7.

Science.gov (United States)

Zhou, Xiaodong; Xie, Li; Xia, Leizhou; Bergmann, Frank; Büchler, Markus W; Kroemer, Guido; Hackert, Thilo; Fortunato, Franco

2017-07-13

Invalidation of pancreatic autophagy entails pancreatic atrophy, endocrine and exocrine insufficiency and pancreatitis. The aim of this study was to investigate whether depletion of Rip3, which is involved in necroptotic signaling, may attenuate the pancreatic atrophy and pancreatitis resulting from autophagy inhibition. Autophagy and necroptosis signaling were evaluated in mice lacking expression of Rip3 in all organs and Atg7 in the pancreas. Acinar cell death, inflammation and fibrosis were evaluated by using of a compendium of immunofluorescence methods and immunoblots. Mice deficient for pancreatic Atg7 developed acute pancreatitis, which progressed to chronic pancreatitis. This phenotype reduces autophagy, increase apoptosis and necroptosis, inflammation and fibrosis, as well as premature death of the animals. Knockout of Rip3 exacerbated the apoptotic death of acinar cells, increased tissue damage, reduced macrophage infiltration and further accelerated the death of the mice with Atg7-deficient pancreas. The pancreatic degeneration induced by autophagy inhibition was exacerbated by Rip3 deletion.

The transcriptional co-factor RIP140 regulates mammary gland development by promoting the generation of key mitogenic signals.

Science.gov (United States)

Nautiyal, Jaya; Steel, Jennifer H; Mane, Meritxell Rosell; Oduwole, Olayiwola; Poliandri, Ariel; Alexi, Xanthippi; Wood, Nicholas; Poutanen, Matti; Zwart, Wilbert; Stingl, John; Parker, Malcolm G

2013-03-01

Nuclear receptor interacting protein (Nrip1), also known as RIP140, is a co-regulator for nuclear receptors that plays an essential role in ovulation by regulating the expression of the epidermal growth factor-like family of growth factors. Although several studies indicate a role for RIP140 in breast cancer, its role in the development of the mammary gland is unclear. By using RIP140-null and RIP140 transgenic mice, we demonstrate that RIP140 is an essential factor for normal mammary gland development and that it functions by mediating oestrogen signalling. RIP140-null mice exhibit minimal ductal elongation with no side-branching, whereas RIP140-overexpressing mice show increased cell proliferation and ductal branching with age. Tissue recombination experiments demonstrate that RIP140 expression is required in both the mammary epithelial and stromal compartments for ductal elongation during puberty and that loss of RIP140 leads to a catastrophic loss of the mammary epithelium, whereas RIP140 overexpression augments the mammary basal cell population and shifts the progenitor/differentiated cell balance within the luminal cell compartment towards the progenitors. For the first time, we present a genome-wide global view of oestrogen receptor-α (ERα) binding events in the developing mammary gland, which unravels 881 ERα binding sites. Unbiased evaluation of several ERα binding sites for RIP140 co-occupancy reveals selectivity and demonstrates that RIP140 acts as a co-regulator with ERα to regulate directly the expression of amphiregulin (Areg), the progesterone receptor (Pgr) and signal transducer and activator of transcription 5a (Stat5a), factors that influence key mitogenic pathways that regulate normal mammary gland development.

RIP studies at AREVA: R&D and applications for Niger and Canada projects

International Nuclear Information System (INIS)

Ling, Y.; Durupt, N.; Banton, N.

2010-01-01

Cominak in Niger owns a large stock of high grade fines which cumulated originally from underground mining discharge water. This ore is too fine to be treated with the current process because it readily blocks the cloths of the belt filters. Cominak plans to build a Resin-In-Pulp (RIP) plant. The RIP technology permits to recover U values without filtration. Some bench scale studies (at AREVA-SEPA) and two trial campaigns (on site) had been successfully conducted to implement the RIP process, which further allows, from economic point of view, a positive feasibility evaluation. As part of the Kiggavik Project managed by Areva Resources Canada (ARC), AREVA-SEPA is also being actively involved in developing a practical, cost-effective and environmentally sound process flowsheet. RIP technology has drawn significant attention due to the relatively low water consumption and capital cost. SEPA's experience with RIP technology together with the newer and better-performance resins makes this technology a viable choice. Three pilot campaigns have been accomplished at SEPA, which is believed to be of great help to reduce technical risk as well as capital risk in the decision making for Kiggavik project. (author)

Confronting dark energy models mimicking ΛCDM epoch with observational constraints: Future cosmological perturbations decay or future Rip?

International Nuclear Information System (INIS)

Astashenok, Artyom V.; Odintsov, Sergei D.

2013-01-01

We confront dark energy models which are currently similar to ΛCDM theory with observational data which include the SNe data, matter density perturbations and baryon acoustic oscillations data. DE cosmology under consideration may evolve to Big Rip, type II or type III future singularity, or to Little Rip or Pseudo-Rip universe. It is shown that matter perturbations data define more precisely the possible deviation from ΛCDM model than consideration of SNe data only. The combined data analysis proves that DE models under consideration are as consistent as ΛCDM model. We demonstrate that growth of matter density perturbations may occur at sufficiently small background density but still before the possible disintegration of bound objects (like clusters of galaxies, galaxies, etc.) in Big Rip, type III singularity, Little Rip or Pseudo-Rip universe. This new effect may bring the future universe to chaotic state well before disintegration or Rip.

The phytopathogenic virulent effector protein RipI induces apoptosis in budding yeast Saccharomyces cerevisiae.

Science.gov (United States)

Deng, Meng-Ying; Sun, Yun-Hao; Li, Pai; Fu, Bei; Shen, Dong; Lu, Yong-Jun

2016-10-01

Virulent protein toxins secreted by the bacterial pathogens can cause cytotoxicity by various molecular mechanisms to combat host cell defense. On the other hand, these proteins can also be used as probes to investigate the defense pathway of host innate immunity. Ralstonia solanacearum, one of the most virulent bacterial phytopathogens, translocates more than 70 effector proteins via type III secretion system during infection. Here, we characterized the cytotoxicity of effector RipI in budding yeast Saccharomyce scerevisiae, an alternative host model. We found that over-expression of RipI resulted in severe growth defect and arginine (R) 117 within the predicted integrase motif was required for inhibition of yeast growth. The phenotype of death manifested the hallmarks of apoptosis. Our data also revealed that RipI-induced apoptosis was independent of Yca1 and mitochondria-mediated apoptotic pathways because Δyca1 and Δaif1 were both sensitive to RipI as compared with the wild type. We further demonstrated that RipI was localized in the yeast nucleus and the N-terminal 1-174aa was required for the localization. High-throughput RNA sequencing analysis showed that upon RipI over-expression, 101 unigenes of yeast ribosome presented lower expression level, and 42 GO classes related to the nucleus or recombination were enriched with differential expression levels. Taken together, our data showed that a nuclear-targeting effector RipI triggers yeast apoptosis, potentially dependent on its integrase function. Our results also provided an alternative strategy to dissect the signaling pathway of cytotoxicity induced by the protein toxins. Copyright © 2016 Elsevier Ltd. All rights reserved.

SimBa: An Efficient Tool for Approximating Rips-Filtration Persistence via Simplicial Batch-Collapse

OpenAIRE

Dey, Tamal K.; Shi, Dayu; Wang, Yusu

2016-01-01

In topological data analysis, a point cloud data P extracted from a metric space is often analyzed by computing the persistence diagram or barcodes of a sequence of Rips complexes built on $P$ indexed by a scale parameter. Unfortunately, even for input of moderate size, the size of the Rips complex may become prohibitively large as the scale parameter increases. Starting with the Sparse Rips filtration introduced by Sheehy, some existing methods aim to reduce the size of the complex so as to ...

Repository Integration Program: RIP performance assessment and strategy evaluation model theory manual and user's guide

International Nuclear Information System (INIS)

1995-11-01

This report describes the theory and capabilities of RIP (Repository Integration Program). RIP is a powerful and flexible computational tool for carrying out probabilistic integrated total system performance assessments for geologic repositories. The primary purpose of RIP is to provide a management tool for guiding system design and site characterization. In addition, the performance assessment model (and the process of eliciting model input) can act as a mechanism for integrating the large amount of available information into a meaningful whole (in a sense, allowing one to keep the ''big picture'' and the ultimate aims of the project clearly in focus). Such an integration is useful both for project managers and project scientists. RIP is based on a '' top down'' approach to performance assessment that concentrates on the integration of the entire system, and utilizes relatively high-level descriptive models and parameters. The key point in the application of such a ''top down'' approach is that the simplified models and associated high-level parameters must incorporate an accurate representation of their uncertainty. RIP is designed in a very flexible manner such that details can be readily added to various components of the model without modifying the computer code. Uncertainty is also handled in a very flexible manner, and both parameter and model (process) uncertainty can be explicitly considered. Uncertainty is propagated through the integrated PA model using an enhanced Monte Carlo method. RIP must rely heavily on subjective assessment (expert opinion) for much of its input. The process of eliciting the high-level input parameters required for RIP is critical to its successful application. As a result, in order for any project to successfully apply a tool such as RIP, an enormous amount of communication and cooperation must exist between the data collectors, the process modelers, and the performance. assessment modelers

Activation of hypothalamic RIP-Cre neurons promotes beiging of WAT via sympathetic nervous system.

Science.gov (United States)

Wang, Baile; Li, Ang; Li, Xiaomu; Ho, Philip Wl; Wu, Donghai; Wang, Xiaoqi; Liu, Zhuohao; Wu, Kelvin Kl; Yau, Sonata Sy; Xu, Aimin; Cheng, Kenneth Ky

2018-04-01

Activation of brown adipose tissue (BAT) and beige fat by cold increases energy expenditure. Although their activation is known to be differentially regulated in part by hypothalamus, the underlying neural pathways and populations remain poorly characterized. Here, we show that activation of rat-insulin-promoter-Cre (RIP-Cre) neurons in ventromedial hypothalamus (VMH) preferentially promotes recruitment of beige fat via a selective control of sympathetic nervous system (SNS) outflow to subcutaneous white adipose tissue (sWAT), but has no effect on BAT Genetic ablation of APPL2 in RIP-Cre neurons diminishes beiging in sWAT without affecting BAT, leading to cold intolerance and obesity in mice. Such defects are reversed by activation of RIP-Cre neurons, inactivation of VMH AMPK, or treatment with a β3-adrenergic receptor agonist. Hypothalamic APPL2 enhances neuronal activation in VMH RIP-Cre neurons and raphe pallidus, thereby eliciting SNS outflow to sWAT and subsequent beiging. These data suggest that beige fat can be selectively activated by VMH RIP-Cre neurons, in which the APPL2-AMPK signaling axis is crucial for this defending mechanism to cold and obesity. © 2018 The Authors.

Bellman Ford algorithm - in Routing Information Protocol (RIP)

Science.gov (United States)

Krianto Sulaiman, Oris; Mahmud Siregar, Amir; Nasution, Khairuddin; Haramaini, Tasliyah

2018-04-01

In a large scale network need a routing that can handle a lot number of users, one of the solutions to cope with large scale network is by using a routing protocol, There are 2 types of routing protocol that is static and dynamic, Static routing is manually route input based on network admin, while dynamic routing is automatically route input formed based on existing network. Dynamic routing is efficient used to network extensively because of the input of route automatic formed, Routing Information Protocol (RIP) is one of dynamic routing that uses the bellman-ford algorithm where this algorithm will search for the best path that traversed the network by leveraging the value of each link, so with the bellman-ford algorithm owned by RIP can optimize existing networks.

Changes in nuclear receptor corepressor RIP140 do not influence mitochondrial content in the cortex.

Science.gov (United States)

Herbst, Eric A F; Bonen, Arend; Holloway, Graham P

2015-10-01

Changes in nuclear receptor interacting protein 140 (RIP140) influences mitochondrial content in skeletal muscle; however, the translation of these findings to the brain has not been investigated. The present study examined the impact of overexpressing and ablating RIP140 on mitochondrial content in muscle and the cortex through examining mRNA, mtDNA, and mitochondrial protein content. Our results show that changes in RIP140 expression significantly alters markers of mitochondrial content in skeletal muscle but not the brain.

Repository Integration Program: RIP performance assessment and strategy evaluation model theory manual and user`s guide

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-11-01

This report describes the theory and capabilities of RIP (Repository Integration Program). RIP is a powerful and flexible computational tool for carrying out probabilistic integrated total system performance assessments for geologic repositories. The primary purpose of RIP is to provide a management tool for guiding system design and site characterization. In addition, the performance assessment model (and the process of eliciting model input) can act as a mechanism for integrating the large amount of available information into a meaningful whole (in a sense, allowing one to keep the ``big picture`` and the ultimate aims of the project clearly in focus). Such an integration is useful both for project managers and project scientists. RIP is based on a `` top down`` approach to performance assessment that concentrates on the integration of the entire system, and utilizes relatively high-level descriptive models and parameters. The key point in the application of such a ``top down`` approach is that the simplified models and associated high-level parameters must incorporate an accurate representation of their uncertainty. RIP is designed in a very flexible manner such that details can be readily added to various components of the model without modifying the computer code. Uncertainty is also handled in a very flexible manner, and both parameter and model (process) uncertainty can be explicitly considered. Uncertainty is propagated through the integrated PA model using an enhanced Monte Carlo method. RIP must rely heavily on subjective assessment (expert opinion) for much of its input. The process of eliciting the high-level input parameters required for RIP is critical to its successful application. As a result, in order for any project to successfully apply a tool such as RIP, an enormous amount of communication and cooperation must exist between the data collectors, the process modelers, and the performance. assessment modelers.

RIP3 Inhibits Inflammatory Hepatocarcinogenesis but Promotes Cholestasis by Controlling Caspase-8- and JNK-Dependent Compensatory Cell Proliferation

Directory of Open Access Journals (Sweden)

Mihael Vucur

2013-08-01

Full Text Available For years, the term “apoptosis” was used synonymously with programmed cell death. However, it was recently discovered that receptor interacting protein 3 (RIP3-dependent “necroptosis” represents an alternative programmed cell death pathway activated in many inflamed tissues. Here, we show in a genetic model of chronic hepatic inflammation that activation of RIP3 limits immune responses and compensatory proliferation of liver parenchymal cells (LPC by inhibiting Caspase-8-dependent activation of Jun-(N-terminal kinase in LPC and nonparenchymal liver cells. In this way, RIP3 inhibits intrahepatic tumor growth and impedes the Caspase-8-dependent establishment of specific chromosomal aberrations that mediate resistance to tumor-necrosis-factor-induced apoptosis and underlie hepatocarcinogenesis. Moreover, RIP3 promotes the development of jaundice and cholestasis, because its activation suppresses compensatory proliferation of cholangiocytes and hepatic stem cells. These findings demonstrate a function of RIP3 in regulating carcinogenesis and cholestasis. Controlling RIP3 or Caspase-8 might represent a chemopreventive or therapeutic strategy against hepatocellular carcinoma and biliary disease.

Reducing the age range of tsunami deposits by 14C dating of rip-up clasts

Science.gov (United States)

Ishizawa, Takashi; Goto, Kazuhisa; Yokoyama, Yusuke; Miyairi, Yosuke; Sawada, Chikako; Takada, Keita

2018-02-01

Erosion by tsunami waves represents an important issue when determining the age of a tsunami deposit, because the age is usually estimated using dating of sediments above and below the deposit. Dating of material within the tsunami deposit, if suitable material is obtainable, can be used to further constrain its age. Eroded sediments are sometimes incorporated within the tsunami deposits as rip-up clasts, which might therefore be used as minimum age dating material. However, the single calibrated 14C age often shows a wide age range because of fluctuations in the calibration curve. Therefore, it remains uncertain whether rip-up clast measurements are useful to constrain the depositional age of tsunami deposits, or not. In this study, we carried out high-resolution 14C dating of tsunami deposits, including rip-up clasts of peat, in Rikuzentakata, northeastern Japan, where numerous rip-up clasts were observed within a tsunami deposit. Sediments above and below the tsunami deposit and a 5 cm large rip-up clast were dated sequentially. Comparison of these dating results with the calibration curve revealed that the clast was inverted. Its age was better constrained based on the stratigraphic order, and we infer that the clast corresponds to approximately 100 years of sedimentation. The oldest age of the clast was consistent with the age of the peat immediately below the tsunami deposit, suggesting that surface sediments probably formed the rip-up clast at the time of the tsunami. Thus, the dating of the rip-up clast was useful to further constrain the depositional age of the tsunami deposit, as we narrowed the tsunami deposit age range by approximately 100 years. Results show that ignoring tsunami-related erosion might lead to overestimation of the tsunami deposit age. For this reason, an appropriate dating site, which is less affected by minor tsunami-related erosion with regards to the paleo-topography, should be explored. We therefore propose a more effective

The role of RIP3 mediated necroptosis in ouabain-induced spiral ganglion neurons injuries.

Science.gov (United States)

Wang, Xi; Wang, Ye; Ding, Zhong-jia; Yue, Bo; Zhang, Peng-zhi; Chen, Xiao-dong; Chen, Xin; Chen, Jun; Chen, Fu-quan; Chen, Yang; Wang, Ren-feng; Mi, Wen-juan; Lin, Ying; Wang, Jie; Qiu, Jian-hua

2014-08-22

Spiral ganglion neuron (SGN) injury is a generally accepted precursor of auditory neuropathy. Receptor-interacting protein 3 (RIP3) has been reported as an important necroptosis pathway mediator that can be blocked by necrostatin-1 (Nec-1). In our study, we sought to identify whether necroptosis participated in SGN injury. Ouabain was applied to establish an SGN injury model. We measured the auditory brain-stem response (ABR) threshold shift as an indicator of the auditory conditions. Positive β3-tubulin immunofluorescence staining indicated the surviving SGNs. RIP3 expression was evaluated using immunofluorescence, quantitative real-time polymerase chain reaction and western blot. SGN injury promoted an increase in RIP3 expression that could be suppressed by application of the necroptosis inhibitor Nec-1. A decreased ABR threshold shift and increased SGN density were observed when Nec-1 was administered with apoptosis inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD). These results demonstrated that necroptosis is an indispensable pathway separately from apoptosis leading to SGN death pathway, in which RIP3 plays an important role. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Global Screening of Antiviral Genes that Suppress Baculovirus Transgene Expression in Mammalian Cells.

Science.gov (United States)

Wang, Chia-Hung; Naik, Nenavath Gopal; Liao, Lin-Li; Wei, Sung-Chan; Chao, Yu-Chan

2017-09-15

Although baculovirus has been used as a safe and convenient gene delivery vector in mammalian cells, baculovirus-mediated transgene expression is less effective in various mammalian cell lines. Identification of the negative regulators in host cells is necessary to improve baculovirus-based expression systems. Here, we performed high-throughput shRNA library screening, targeting 176 antiviral innate immune genes, and identified 43 host restriction factor genes in a human A549 lung carcinoma cell line. Among them, suppression of receptor interaction protein kinase 1 (RIP1, also known as RIPK1) significantly increased baculoviral transgene expression without resulting in significant cell death. Silencing of RIP1 did not affect viral entry or cell viability, but it did inhibit nuclear translocation of the IRF3 and NF-κB transcription factors. Also, activation of downstream signaling mediators (such as TBK1 and IRF7) was affected, and subsequent interferon and cytokine gene expression levels were abolished. Further, Necrostatin-1 (Nec-1)-an inhibitor of RIP1 kinase activity-dramatically increased baculoviral transgene expression in RIP1-silenced cells. Using baculovirus as a model system, this study presents an initial investigation of large numbers of human cell antiviral innate immune response factors against a "nonadaptive virus." In addition, our study has made baculovirus a more efficient gene transfer vector for some of the most frequently used mammalian cell systems.

Learning Styles versus the Rip Van Winkle Syndrome.

Science.gov (United States)

Orsak, Lana

1990-01-01

Rip Van Winkle would not recognize Corsicana (Texas) High School since its curriculum coordinator began implementing learning styles techniques in various pilot programs. Lecturing to rows of bored students has been replaced by students' active involvement in group activities, listening centers, and tactile/kinesthetic exercises on the floor or at…

RIP1 regulates TNF-α-mediated lymphangiogenesis and lymphatic metastasis in gallbladder cancer by modulating the NF-κB-VEGF-C pathway.

Science.gov (United States)

Li, Cheng-Zong; Jiang, Xiao-Jie; Lin, Bin; Hong, Hai-Jie; Zhu, Si-Yuan; Jiang, Lei; Wang, Xiao-Qian; Tang, Nan-Hong; She, Fei-Fei; Chen, Yan-Ling

2018-01-01

Tumor necrosis factor alpha (TNF-α) enhances lymphangiogenesis in gallbladder carcinoma (GBC) via activation of nuclear factor (NF-κB)-dependent vascular endothelial growth factor-C (VEGF-C). Receptor-interacting protein 1 (RIP1) is a multifunctional protein in the TNF-α signaling pathway and is highly expressed in GBC. However, whether RIP1 participates in the signaling pathway of TNF-α-mediated VEGF-C expression that enhances lymphangiogenesis in GBC remains unclear. The RIP1 protein levels in the GBC-SD and NOZ cells upon stimulation with increasing concentrations of TNF-α as indicated was examined using Western blot. Lentiviral RIP1 shRNA and siIκBα were constructed and transduced respectively them into NOZ and GBC-SD cells, and then PcDNA3.1-RIP1 vectors was transduced into siRIP1 cell lines to reverse RIP1 expression. The protein expression of RIP1, inhibitor of NF-κB alpha (IκBα), p-IκBα, TAK1, NF-κB essential modulator were examined through immunoblotting or immunoprecipitation. Moreover, VEGF-C mRNA levels were measured by quantitative real-time polymerase chain reaction, VEGF-C protein levels were measured by immunoblotting and enzyme-linked immunosorbent assay, and VEGF-C promoter and NF-κB activities were quantified using a dual luciferase reporter assay. The association of NF-κB with the VEGF-C promoter was analysed by chromatin immunoprecipitation assay. A three-dimensional coculture method and orthotopic transplantation nude mice model were used to evaluate lymphatic tube-forming and metastasis ability in GBC cells. The expression of RIP1 protein, TNF-α protein and lymphatic vessels in human GBC tissues was examined by immunohistochemistry, and the dependence between RIP1 protein with TNF-α protein and lymphatic vessel density was analysed. TNF-α dose- and time-dependently increased RIP1 protein expression in the GBC-SD and NOZ cells of GBC, and the strongest effect was observed with a concentration of 50 ng/ml. RIP1 is fundamental

NOD1CARD Might Be Using Multiple Interfaces for RIP2-Mediated CARD-CARD Interaction: Insights from Molecular Dynamics Simulation.

Directory of Open Access Journals (Sweden)

Jitendra Maharana

Full Text Available The nucleotide-binding and oligomerization domain (NOD-containing protein 1 (NOD1 plays the pivotal role in host-pathogen interface of innate immunity and triggers immune signalling pathways for the maturation and release of pro-inflammatory cytokines. Upon the recognition of iE-DAP, NOD1 self-oligomerizes in an ATP-dependent fashion and interacts with adaptor molecule receptor-interacting protein 2 (RIP2 for the propagation of innate immune signalling and initiation of pro-inflammatory immune responses. This interaction (mediated by NOD1 and RIP2 helps in transmitting the downstream signals for the activation of NF-κB signalling pathway, and has been arbitrated by respective caspase-recruitment domains (CARDs. The so-called CARD-CARD interaction still remained contradictory due to inconsistent results. Henceforth, to understand the mode and the nature of the interaction, structural bioinformatics approaches were employed. MD simulation of modelled 1:1 heterodimeric complexes revealed that the type-Ia interface of NOD1CARD and the type-Ib interface of RIP2CARD might be the suitable interfaces for the said interaction. Moreover, we perceived three dynamically stable heterotrimeric complexes with an NOD1:RIP2 ratio of 1:2 (two numbers and 2:1. Out of which, in the first trimeric complex, a type-I NOD1-RIP2 heterodimer was found interacting with an RIP2CARD using their type-IIa and IIIa interfaces. However, in the second and third heterotrimer, we observed type-I homodimers of NOD1 and RIP2 CARDs were interacting individually with RIP2CARD and NOD1CARD (in type-II and type-III interface, respectively. Overall, this study provides structural and dynamic insights into the NOD1-RIP2 oligomer formation, which will be crucial in understanding the molecular basis of NOD1-mediated CARD-CARD interaction in higher and lower eukaryotes.

RapidRIP quantifies the intracellular metabolome of 7 industrial strains of E. coli

DEFF Research Database (Denmark)

McCloskey, Douglas; Xu, Julia; Schrübbers, Lars

2018-01-01

Fast metabolite quantification methods are required for high throughput screening of microbial strains obtained by combinatorial or evolutionary engineering approaches. In this study, a rapid RIP-LC-MS/MS (RapidRIP) method for high-throughput quantitative metabolomics was developed and validated...... to quantify the metabolome of seven industrial strains of E. coli revealing significant differences in glycolytic, pentose phosphate, TCA cycle, amino acid, and energy and cofactor metabolites were found. These differences translated to statistically and biologically significant differences in thermodynamics...

Isolation and characterization of an RIP (ribosome-inactivating protein)-like protein from tobacco with dual enzymatic activity.

Science.gov (United States)

Sharma, Neelam; Park, Sang-Wook; Vepachedu, Ramarao; Barbieri, Luigi; Ciani, Marialibera; Stirpe, Fiorenzo; Savary, Brett J; Vivanco, Jorge M

2004-01-01

Ribosome-inactivating proteins (RIPs) are N-glycosidases that remove a specific adenine from the sarcin/ricin loop of the large rRNA, thus arresting protein synthesis at the translocation step. In the present study, a protein termed tobacco RIP (TRIP) was isolated from tobacco (Nicotiana tabacum) leaves and purified using ion exchange and gel filtration chromatography in combination with yeast ribosome depurination assays. TRIP has a molecular mass of 26 kD as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and showed strong N-glycosidase activity as manifested by the depurination of yeast rRNA. Purified TRIP showed immunoreactivity with antibodies of RIPs from Mirabilis expansa. TRIP released fewer amounts of adenine residues from ribosomal (Artemia sp. and rat ribosomes) and non-ribosomal substrates (herring sperm DNA, rRNA, and tRNA) compared with other RIPs. TRIP inhibited translation in wheat (Triticum aestivum) germ more efficiently than in rabbit reticulocytes, showing an IC50 at 30 ng in the former system. Antimicrobial assays using highly purified TRIP (50 microg mL(-1)) conducted against various fungi and bacterial pathogens showed the strongest inhibitory activity against Trichoderma reesei and Pseudomonas solancearum. A 15-amino acid internal polypeptide sequence of TRIP was identical with the internal sequences of the iron-superoxide dismutase (Fe-SOD) from wild tobacco (Nicotiana plumbaginifolia), Arabidopsis, and potato (Solanum tuberosum). Purified TRIP showed SOD activity, and Escherichia coli Fe-SOD was observed to have RIP activity too. Thus, TRIP may be considered a dual activity enzyme showing RIP-like activity and Fe-SOD characteristics.

Holographic Ricci dark energy in Randall-Sundrum braneworld: Avoidance of big rip and steady state future

International Nuclear Information System (INIS)

Feng Chaojun; Zhang Xin

2009-01-01

In the holographic Ricci dark energy (RDE) model, the parameter α plays an important role in determining the evolutionary behavior of the dark energy. When α<1/2, the RDE will exhibit a quintom feature, i.e., the equation of state of dark energy will evolve across the cosmological constant boundary w=-1. Observations show that the parameter α is indeed smaller than 1/2, so the late-time evolution of RDE will be really like a phantom energy. Therefore, it seems that the big rip is inevitable in this model. On the other hand, the big rip is actually inconsistent with the theoretical framework of the holographic model of dark energy. To avoid the big rip, we appeal to the extra dimension physics. In this Letter, we investigate the cosmological evolution of the RDE in the braneworld cosmology. It is of interest to find that for the far future evolution of RDE in a Randall-Sundrum braneworld, there is an attractor solution where the steady state (de Sitter) finale occurs, in stead of the big rip.

Muddy and dolomitic rip-up clasts in Triassic fluvial sandstones: Origin and impact on potential reservoir properties (Argana Basin, Morocco)

Science.gov (United States)

Henares, Saturnina; Arribas, Jose; Cultrone, Giuseppe; Viseras, Cesar

2016-06-01

The significance of rip-up clasts as sandstone framework grains is frequently neglected in the literature being considered as accessory components in bulk sandstone composition. However, this study highlights the great value of muddy and dolomitic rip-up clast occurrence as: (a) information source about low preservation potential from floodplain deposits and (b) key element controlling host sandstone diagenetic evolution and thus ultimate reservoir quality. High-resolution petrographic analysis on Triassic fluvial sandstones from Argana Basin (T6 and T7/T8 units) highlights the significance of different types of rip-up clasts as intrabasinal framework components of continental sediments from arid climates. On the basis of their composition and ductility, three main types are distinguished: (a) muddy rip-up clasts, (b) dolomitic muddy rip-up clasts and (c) dolomite crystalline rip-up clasts. Spatial distribution of different types is strongly facies-related according to grain size. Origin of rip-up clasts is related to erosion of coeval phreatic dolocretes, in different development stages, and associated muddy floodplain sediments. Cloudy cores with abundant inclusions and clear outer rims of dolomite crystals suggest a first replacive and a subsequent displacive growth, respectively. Dolomite crystals are almost stoichiometric. This composition is very similar to that of early sandstone dolomite cement, supporting phreatic dolocretes as dolomite origin in both situations. Sandstone diagenesis is dominated by mechanical compaction and dolomite cementation. A direct correlation exists between: (1) muddy rip-up clast abundance and early reduction of primary porosity by compaction with irreversible loss of intergranular volume (IGV); and (2) occurrence of dolomitic rip-up clasts and dolomite cement nucleation in host sandstone, occluding adjacent pores but preserving IGV. Both processes affect reservoir quality by generation of vertical and 3D fluid flow baffles and

Insulin promotes Rip11 accumulation at the plasma membrane by inhibiting a dynamin- and PI3-kinase-dependent, but Akt-independent, internalisation event.

Science.gov (United States)

Boal, Frédéric; Hodgson, Lorna R; Reed, Sam E; Yarwood, Sophie E; Just, Victoria J; Stephens, David J; McCaffrey, Mary W; Tavaré, Jeremy M

2016-01-01

Rip11 is a Rab11 effector protein that has been shown to be important in controlling the trafficking of several intracellular cargoes, including the fatty acid transporter FAT/CD36, V-ATPase and the glucose transporter GLUT4. We have previously demonstrated that Rip11 translocates to the plasma membrane in response to insulin and here we examine the basis of this regulated phenomenon in more detail. We show that Rip11 rapidly recycles between the cell interior and surface, and that the ability of insulin to increase the appearance of Rip11 at the cell surface involves an inhibition of Rip11 internalisation from the plasma membrane. By contrast the hormone has no effect on the rate of Rip11 translocation towards the plasma membrane. The ability of insulin to inhibit Rip11 internalisation requires dynamin and class I PI3-kinases, but is independent of the activation of the protein kinase Akt; characteristics which are very similar to the mechanism by which insulin inhibits GLUT4 endocytosis. Copyright © 2015. Published by Elsevier Inc.

Environmental Information System Baden-Wuerttemberg, RIPS 2016. Spatial information and planning system

International Nuclear Information System (INIS)

Weissenbach, Kurt; Czommer, Olaf; Ellmenreich, Bastian

2016-01-01

The Spatial Information and Planning System (RIPS), as the overarching component of the Environmental Information System Baden-Wuerttemberg (UIS BW), implements the environmental and nature conservation-specific geoinformation-related requirements taking into account applicable framework conditions. To this end, RIPS offers tailor-made services on the basis of a standardized and in transnational cooperation developed technical kit for the areas of geodata processing and management as well as the development and provision of software components with geo-functions and geodata services as part of the technical and information procedures. The coordination and steering takes place via project development offices, working groups and committees in close coordination with the departments of environmental and nature conservation administration as well as further cooperation and in coordination with other specialist administrations. Taking into account changed framework conditions and new geo-referenced requirements in UIS BW, the present RIPS concept focuses on future-oriented geofunction and geodata management in the field of environmental and nature conservation management as well as the provision of geo-specialized environmental and nature conservation data for policy makers, administrators and the public on innovative technologies Applications and Services. [de

Äripäev hakkab välja andma PR-ajakirja

Index Scriptorium Estoniae

2012-01-01

Ilmuma hakkas Eesti esimene kommunikatsioonispetsialistidele ja -juhtidele mõeldud erialaajakiri Kaja, mille väljaandja on Äripäeva teabekirjastus koostöös Tallinna Ülikooli kommunikatsiooni instituudiga

ANÁLISIS DE LOS REGISTROS INDIVIDUALES DE PRESTACIÓN DE SERVICIOS DE SALUD (RIPS EN CÁNCER EN COLOMBIA

Directory of Open Access Journals (Sweden)

Luz Helena Alba

2016-11-01

Full Text Available

Objetivos: Comparar los registros de atención a pacientes con cáncer en Colombia en el periodo 2009−2013 a través del Registro Individual de Prestación de Servicios de Salud (RIPS, con los registros consignados en la página de la Agencia Internacional Contra el Cáncer: Globocan.

Métodos: Se realizó una búsqueda de información de 27 tipos de cáncer en los RIPS y, a partir de esos datos, se estimaron las tasas de incidencia ajustadas por edad siguiendo la metodología de ajuste directo. Posteriormente, los resultados se compararon con Globocan.

Resultados: Según los RIPS, en el período comprendido entre 2009−2013, se reportaron 110.879 casos incidentes de cáncer; 68.312 en mujeres y 42.509 en hombres. Para la mayoría de los tipos de cáncer se observan tasas de incidencia menores en los registros RIPS respecto a aquellas estimadas por Globocan. De menor a mayor figuran: el cáncer de labio y cavidad oral (0.15:1; próstata (0,33:1; mama (0,74:1; cuello uterino (0,64:1; estómago (0,22:1, colorrectal (0,44:1 y tiroides (0.86:1.

Conclusión: Las diferencias podrían atribuirse a una subestimación presentada en los RIPS; una sobreestimación, en Globocan; o una combinación de las dos. Dada la trayectoria y los mecanismos de verificación de los registros de: Pasto, Cali, Manizales y Bucaramanga, base de la información de Globocan, es probable que los datos de incidencia de los RIPS no se encuentren todavía suficientemente depurados.

ANALYSIS OF INDIVIDUAL RECORDS OF PROVISION OF HEALTH SERVICES (RIPS IN CANCER IN COLOMBIA

ABSTRACT

Objectives: To compare the data for cancer patients care in Colombia during the period 2009- 2013 through the Individual Registration of Health Care Provision (RIPS with records from the International Agency for Research in Cancer (IARC website

Äripäev surub end naisteajakirjade turule / Krista Taim

Index Scriptorium Estoniae

Taim, Krista

2005-01-01

Äripäev hakkab välja andma naisteajakirja Dilemma, lootes saada viiendiku reklaamiturust. Diagramm: Naisteajakirjade reklaamituru jagunemine. Vt. samas: Dilemma hakkab ilmuma kaheksa korda aastas; Eesti Päevaleht ja Eesti Meedia hakkavad tasuta ajalehte välja andma

JMJD3 Is Crucial for the Female AVPV RIP-Cre Neuron-Controlled Kisspeptin-Estrogen Feedback Loop and Reproductive Function.

Science.gov (United States)

Song, Anying; Jiang, Shujun; Wang, Qinghua; Zou, Jianghuan; Lin, Zhaoyu; Gao, Xiang

2017-06-01

The hypothalamic-pituitary-gonadal axis controls development, reproduction, and metabolism. Although most studies have focused on the hierarchy from the brain to the gonad, many questions remain unresolved concerning the feedback from the gonad to the central nervous system, especially regarding the potential epigenetic modifications in hypothalamic neurons. In the present report, we generated genetically modified mice lacking histone H3 lysine 27 (H3K27) demethylase Jumonji domain-containing 3 (JMJD3) in hypothalamic rat-insulin-promoter-expressing neurons (RIP-Cre neurons). The female mutant mice displayed late-onset obesity owing to reduced locomotor activity and decreased energy expenditure. JMJD3 deficiency in RIP-Cre neurons also results in delayed pubertal onset, an irregular estrous cycle, impaired fertility, and accelerated ovarian failure in female mice owing to the dysregulation of the hypothalamic-ovarian axis. We found that JMJD3 directly regulates Kiss1 gene expression by binding to the Kiss1 promoter and triggering H3K27me3 demethylation in the anteroventral periventricular (AVPV) nucleus. Further study confirmed that the aberrations arose from impaired kisspeptin signaling in the hypothalamic AVPV nucleus and subsequent estrogen deficiency. Estrogen replacement therapy can reverse obesity in mutant mice. Moreover, we demonstrated that Jmjd3 is an estrogen target gene in the hypothalamus. These results provide direct genetic and molecular evidence that JMJD3 is a key mediator for the kisspeptin-estrogen feedback loop. Copyright © 2017 Endocrine Society.

ASSESSMENT OF RIP-V1 AND OSPF-V2 PROTOCOL WITH CONSIDERATION OF CONVERGENCE CRITERIA AND SENDING PROTOCOLS TRAFFIC

Directory of Open Access Journals (Sweden)

Hamed Jelodar

2014-03-01

Full Text Available Routing Protocols are underlying principles in networks like internet, transport and mobile. Routing Protocols include a series of rules and algorithms that consider routing metric and select the best way for sending healthy data packets from origin to destination. Dynamic routing protocol compatible to topology has a changeable state. RIP and OSPF are dynamic routing protocol that we consider criteria like convergence and sending protocols traffic assessment RIP first version and OSPF second version. By the test we have done on OPNET stimulation we understood that the OSPF protocol was more efficient than RIP protocol.

Structure and functional regulation of RipA, a mycobacterial enzyme essential for daughter cell separation.

Science.gov (United States)

Ruggiero, Alessia; Marasco, Daniela; Squeglia, Flavia; Soldini, Silvia; Pedone, Emilia; Pedone, Carlo; Berisio, Rita

2010-09-08

Cell separation depends on cell-wall hydrolases that cleave the peptidoglycan layer connecting daughter cells. In Mycobacterium tuberculosis, this process is governed by the predicted endopeptidase RipA. In the absence of this enzyme, the bacterium is unable to divide and exhibits an abnormal phenotype. We here report the crystal structure of a relevant portion of RipA, containing its catalytic-domain and an extra-domain of hitherto unknown function. The structure clearly demonstrates that RipA is produced as a zymogen, which needs to be activated to achieve cell-division. Bacterial cell-wall degradation assays and proteolysis experiments strongly suggest that activation occurs via proteolytic processing of a fully solvent exposed loop identified in the crystal structure. Indeed, proteolytic cleavage at this loop produces an activated form, consisting of the sole catalytic domain. Our work provides the first evidence of self-inhibition in cell-disconnecting enzymes and opens a field for the design of novel antitubercular therapeutics. Copyright © 2010 Elsevier Ltd. All rights reserved.

Pillow seal system at the BigRIPS separator

Energy Technology Data Exchange (ETDEWEB)

Tanaka, K., E-mail: ktanaka@riken.jp; Inabe, N.; Yoshida, K.; Kusaka, K.; Kubo, T.

2013-12-15

Highlights: • Pillow seal system has been installed for a high-intensity RI-beam facility at RIKEN. • It is aimed at facilitating remote maintenance under high residual radiation. • Local radiation shields are integrated with one of the pillow seals. • Pillow seals have been aligned to the beam axis within 1mm accuracy. • A leakage rate of 10{sup –9} Pa m{sup 3}/s has been achieved with our pillow seal system. -- Abstract: We have designed and installed a pillow seal system for the BigRIPS fragment separator at the RIKEN Radioactive Isotope Beam Factory (RIBF) to facilitate remote maintenance in a radioactive environment. The pillow seal system is a device to connect a vacuum chamber and a beam tube. It allows quick attachment and detachment of vacuum connections in the BigRIPS separator and consists of a double diaphragm with a differential pumping system. The leakage rate achieved with this system is as low as 10{sup –9} Pa m{sup 3}/s. We have also designed and installed a local radiation-shielding system, integrated with the pillow seal system, to protect the superconducting magnets and to reduce the heat load on the cryogenic system. We present an overview of the pillow seal and the local shielding systems.

An analytical model for the prediction of rip spacing in intermediate ...

Indian Academy of Sciences (India)

61

study, an analytical model was presented to predict the spacing of channel rip currents (Srip) ... beach and normal wave incidence in two cases with the fixed breaking line and variable one .... On the other hand, in the above relations radiation.

RIP Input Tables From WAPDEG for LA Design Selection: Continuous Pre-Closure Ventilation

International Nuclear Information System (INIS)

K.G. Mon

1999-01-01

The purpose of this calculation is to document the creation of .tables for input into Integrated Probabilistic Simulator for Environmental Systems (RIP) version 5.19.01 (Golder Associates 1998) from Waste Package Degradation (WAPDEG) version 3.09 (CRWMS M and O 1998b. ''Software Routine Report for WAPDEG'' (Version 3.09)) simulations. This calculation details the creation of the RIP input tables (representing waste package corrosion degradation over time) for the License Application Design Selection (LADS) analysis of the effects of continuous pre-closure ventilation. Ventilation during the operational phase of the repository could remove considerable water from the system, as well as reduce temperatures. Pre-closure ventilation is LADS Design Feature 7

Development of heading/ripping systems and immediate roadway support (Report on ECSC contract 6220-62/8/801)

Energy Technology Data Exchange (ETDEWEB)

1977-01-01

The development of a combined heading and ripping system to enable the heading to be advanced while the coal and dirt were taken and discharged separately is discussed. A rotary head ripping machine fitted with cutting picks, dirt stowing machinery and ancillary equipment were developed. Work on the design and testing of powered roadway supports around roadheading machines showed that the problems arising may outweigh any of the possible advantages.

Implementation and modification of a three-dimensional radiation stress formulation for surf zone and rip-current applications

Science.gov (United States)

Kumar, N.; Voulgaris, G.; Warner, John C.

2011-01-01

Regional Ocean Modeling System (ROMS v 3.0), a three-dimensional numerical ocean model, was previously enhanced for shallow water applications by including wave-induced radiation stress forcing provided through coupling to wave propagation models (SWAN, REF/DIF). This enhancement made it suitable for surf zone applications as demonstrated using examples of obliquely incident waves on a planar beach and rip current formation in longshore bar trough morphology (Haas and Warner, 2009). In this contribution, we present an update to the coupled model which implements a wave roller model and also a modified method of the radiation stress term based on Mellor (2008, 2011a,b,in press) that includes a vertical distribution which better simulates non-conservative (i.e., wave breaking) processes and appears to be more appropriate for sigma coordinates in very shallow waters where wave breaking conditions dominate. The improvements of the modified model are shown through simulations of several cases that include: (a) obliquely incident spectral waves on a planar beach; (b) obliquely incident spectral waves on a natural barred beach (DUCK'94 experiment); (c) alongshore variable offshore wave forcing on a planar beach; (d) alongshore varying bathymetry with constant offshore wave forcing; and (e) nearshore barred morphology with rip-channels. Quantitative and qualitative comparisons to previous analytical, numerical, laboratory studies and field measurements show that the modified model replicates surf zone recirculation patterns (onshore drift at the surface and undertow at the bottom) more accurately than previous formulations based on radiation stress (Haas and Warner, 2009). The results of the model and test cases are further explored for identifying the forces operating in rip current development and the potential implication for sediment transport and rip channel development. Also, model analysis showed that rip current strength is higher when waves approach at angles of 5

Identification of RIP1 as a critical mediator of Smac mimetic-mediated sensitization of glioblastoma cells for Drozitumab-induced apoptosis.

Science.gov (United States)

Cristofanon, S; Abhari, B A; Krueger, M; Tchoghandjian, A; Momma, S; Calaminus, C; Vucic, D; Pichler, B J; Fulda, S

2015-04-16

This study aims at evaluating the combination of the tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL)-receptor 2 (TRAIL-R2)-specific antibody Drozitumab and the Smac mimetic BV6 in preclinical glioblastoma models. To this end, the effect of BV6 and/or Drozitumab on apoptosis induction and signaling pathways was analyzed in glioblastoma cell lines, primary glioblastoma cultures and glioblastoma stem-like cells. Here, we report that BV6 and Drozitumab synergistically induce apoptosis and reduce colony formation in several glioblastoma cell lines (combination indextrigger the formation of a cytosolic receptor-interacting protein (RIP) 1/Fas-associated via death domain (FADD)/caspase-8-containing complex and subsequent activation of caspase-8 and -3. BV6- and Drozitumab-induced apoptosis is blocked by the caspase inhibitor zVAD.fmk, pointing to caspase-dependent apoptosis. RNA interference-mediated silencing of RIP1 almost completely abolishes the BV6-conferred sensitization to Drozitumab-induced apoptosis, indicating that the synergism critically depends on RIP1 expression. In contrast, both necrostatin-1, a RIP1 kinase inhibitor, and Enbrel, a TNFα-blocking antibody, do not interfere with BV6/Drozitumab-induced apoptosis, demonstrating that apoptosis occurs independently of RIP1 kinase activity or an autocrine TNFα loop. In conclusion, the rational combination of BV6 and Drozitumab presents a promising approach to trigger apoptosis in glioblastoma, which warrants further investigation.

Phantom cosmology without Big Rip singularity

International Nuclear Information System (INIS)

Astashenok, Artyom V.; Nojiri, Shin'ichi; Odintsov, Sergei D.; Yurov, Artyom V.

2012-01-01

We construct phantom energy models with the equation of state parameter w which is less than -1, w<-1, but finite-time future singularity does not occur. Such models can be divided into two classes: (i) energy density increases with time (“phantom energy” without “Big Rip” singularity) and (ii) energy density tends to constant value with time (“cosmological constant” with asymptotically de Sitter evolution). The disintegration of bound structure is confirmed in Little Rip cosmology. Surprisingly, we find that such disintegration (on example of Sun-Earth system) may occur even in asymptotically de Sitter phantom universe consistent with observational data. We also demonstrate that non-singular phantom models admit wormhole solutions as well as possibility of Big Trip via wormholes.

RIP and OSPF protocols Analysis through GNS-3 and OPNET UMTS Model Suite

Directory of Open Access Journals (Sweden)

Savita Rashmi

2016-01-01

Full Text Available Directing concerning astuteness packages proceed with one concerning Great key systems in amazing web. A coordination tradition démontrâtes Great procédure for correspondance among switches used as a section concerning noteworthy undirected toward affiliation concerning frameworks. On the off chance that you will organizing customs Application Virtualization web like OSPF, RIP, EIGRP, OPNET, IGRP, in like way so on. Great continuation reprobation Convention (RIP goes down from separation route tally in like way noteworthy. Open Shortest Path First (OSPF proceed with an affiliation distance planning estimation. Third time (3G remote frameworks are impressive coordinated toward give spot on remote Internet win, Impressive frameworks are planned for mixed media pacified (Voiced, essence in like way make a recording, enormous core gauge associations, bundle core associations as an outcome area associations. In UMTS fundamental need concerning system proceed coordinated toward give achievable unflactuating concerning Qi’s, for giving Great put down for unflactuating concerning associations, noteworthy UMTS required a fit procédure in like way an apparatus stage. In any case regarding amazing certainty all together that RIP in like way EIGRP depend on upon essentially indistinguishable segment state coordination, Great capabilities in noteworthy convention execution methods can escort coordinated toward fundamental show differentials. Impressive conventions are inspected in light concerning ‘activity sent (packs/seconds’ in like way ’advancement had gotten (bunches/seconds, past moving amazing sum concerning undirected towards, rate in like way break time.

Growth factors FGF8 and FGF2 and their receptor FGFR1, transcriptional factors Msx-1 and MSX-2, and apoptotic factors p19 and RIP5 participate in the early human limb development.

Science.gov (United States)

Becic, Tina; Kero, Darko; Vukojevic, Katarina; Mardesic, Snjezana; Saraga-Babic, Mirna

2018-04-01

The expression pattern of fibroblast growth factors FGF8 and FGF2 and their receptor FGFR1, transcription factors MSX-1 and MSX-2, as well as cell proliferation (Ki-67) and cell death associated caspase-3, p19 and RIP5 factors were analyzed in histological sections of eight 4th-9th-weeks developing human limbs by immunohistochemistry and semi-thin sectioning. Increasing expression of all analyzed factors (except FGF8) characterized both the multilayered human apical ectodermal ridge (AER), sub-ridge mesenchyme (progress zone) and chondrocytes in developing human limbs. While cytoplasmic co-expression of MSX-1 and MSX-2 was observed in both limb epithelium and mesenchyme, p19 displayed strong cytoplasmic expression in non-proliferating cells. Nuclear expression of Ki-67 proliferating cells, and partly of MSX-1 and MSX-2 was detected in the whole limb primordium. Strong expression of factors p19 and RIP5, both in the AER and mesenchyme of human developing limbs indicates their possible involvement in control of cell senescence and cell death. In contrast to animal studies, expression of FGFR1 in the surface ectoderm and p19 in the whole limb primordium might reflect interspecies differences in limb morphology. Expression of FGF2 and downstream RIP5 gene, and transcription factors Msx-1 and MSX-2 did not show human-specific changes in expression pattern. Based on their spatio-temporal expression during human limb development, our study indicates role of FGFs and Msx genes in stimulation of cell proliferation, limb outgrowth, digit elongation and separation, and additionally MSX-2 in control of vasculogenesis. The cascade of orchestrated gene expressions, including the analyzed developmental factors, jointly contribute to the complex human limb development. Copyright © 2018 Elsevier GmbH. All rights reserved.

Screening strategy to generate cell specific recombination: a case report with the RIP-Cre mice.

Science.gov (United States)

Spinelli, Valeria; Martin, Céline; Dorchies, Emilie; Vallez, Emmanuelle; Dehondt, Hélène; Trabelsi, Mohamed-Sami; Tailleux, Anne; Caron, Sandrine; Staels, Bart

2015-10-01

Conditional gene knockout technology is a powerful tool to study the function of a gene in a specific tissue, organ or cell lineage. The most commonly used procedure applies the Cre-LoxP strategy, where the choice of the Cre driver promoter is critical to determine the efficiency and specificity of the system. However, a considered choice of an appropriate promoter does not always protect against the risk of unwanted recombination and the consequent deletion of the gene in other tissues than the desired one(s), due to phenomena of non-specific activation of the Cre transgene. Furthermore, the causes of these phenomena are not completely understood and this can potentially affect every strain of Cre-mice. In our study on the deletion of a same gene in two different tissues, we show that the incidence rate of non-specific recombination in unwanted tissues depends on the Cre driver strain, ranging from 100%, rendering it useless (aP2-Cre strain), to ~5%, which is still compatible with their use (RIP-Cre strain). The use of a simple PCR strategy conceived to detect this occurrence is indispensable when producing a tissue-specific knockout mouse. Therefore, when choosing the Cre-driver promoter, researchers not only have to be careful about its tissue-specificity and timing of activation, but should also include a systematical screening in order to exclude mice in which atypical recombination has occurred and to limit the unnecessary use of laboratory animals in uninterpretable experiments.

Structural studies on a non-toxic homologue of type II RIPs from ...

Indian Academy of Sciences (India)

Structural studies on a non-toxic homologue of type II RIPs from bitter gourd: Molecular basis of non-toxicity, conformational selection and glycan structure. MS accepted http://www.ias.ac.in/jbiosci. THYAGESHWAR CHANDRAN, ALOK SHARMA and M VIJAYAN. J. Biosci. 40(5), October 2015, 929–941, © Indian Academy of ...

Nec-1 Enhances Shikonin-Induced Apoptosis in Leukemia Cells by Inhibition of RIP-1 and ERK1/2

Directory of Open Access Journals (Sweden)

Hongming Pan

2012-06-01

Full Text Available Necrostatin-1 (Nec-1 inhibits necroptosis by allosterically inhibiting the kinase activity of receptor-interacting protein 1 (RIP1, which plays a critical role in necroptosis. RIP1 is a crucial adaptor kinase involved in the activation of NF-κB, production of reactive oxygen species (ROS and the phosphorylation of mitogen activated protein kinases (MAPKs. NF-κB, ROS and MAPKs all play important roles in apoptotic signaling. Nec-1 was regarded as having no effect on apoptosis. Here, we report that Nec-1 increased the rate of nuclear condensation and caspases activation induced by a low concentration of shikonin (SHK in HL60, K562 and primary leukemia cells. siRNA-mediated knockdown of RIP1 significantly enhanced shikonin-induced apoptosis in K562 and HL60 cells. Shikonin treatment alone could slightly inhibit the phosphorylation of ERK1/2 in leukemia cells, and the inhibitory effect on ERK1/2 was significantly augmented by Nec-1. We also found that Nec-1 could inhibit NF-κB p65 translocation to the nucleus at a later stage of SHK treatment. In conclusion, we found that Nec-1 can promote shikonin-induced apoptosis in leukemia cells. The mechanism by which Nec-1 sensitizes shikonin-induced apoptosis appears to be the inhibition of RIP1 kinase-dependent phosphorylation of ERK1/2. To our knowledge, this is the first study to document Nec-1 sensitizes cancer cells to apoptosis.

The dimerization of the yeast cytochrome bc1 complex is an early event and is independent of Rip1.

Science.gov (United States)

Conte, Annalea; Papa, Benedetta; Ferramosca, Alessandra; Zara, Vincenzo

2015-05-01

In Saccharomyces cerevisiae the mature cytochrome bc1 complex exists as an obligate homo-dimer in which each monomer consists of ten distinct protein subunits inserted into or bound to the inner mitochondrial membrane. Among them, the Rieske iron-sulfur protein (Rip1), besides its catalytic role in electron transfer, may be implicated in the bc1 complex dimerization. Indeed, Rip1 has the globular domain containing the catalytic center in one monomer while the transmembrane helix interacts with the adjacent monomer. In addition, the lack of Rip1 leads to the accumulation of an immature bc1 intermediate, only loosely associated with cytochrome c oxidase. In this study we have investigated the biogenesis of the yeast cytochrome bc1 complex using epitope tagged proteins to purify native assembly intermediates. We showed that the dimerization process is an early event during bc1 complex biogenesis and that the presence of Rip1, differently from previous proposals, is not essential for this process. We also investigated the multi-step model of bc1 assembly thereby lending further support to the existence of bona fide subcomplexes during bc1 maturation in the inner mitochondrial membrane. Finally, a new model of cytochrome bc1 complex assembly, in which distinct intermediates sequentially interact during bc1 maturation, has been proposed. Copyright © 2015 Elsevier B.V. All rights reserved.

Coupled RipCAS-DFLOW (CoRD) Software and Data Management System for Reproducible Floodplain Vegetation Succession Modeling

Science.gov (United States)

Turner, M. A.; Miller, S.; Gregory, A.; Cadol, D. D.; Stone, M. C.; Sheneman, L.

2016-12-01

We present the Coupled RipCAS-DFLOW (CoRD) modeling system created to encapsulate the workflow to analyze the effects of stream flooding on vegetation succession. CoRD provides an intuitive command-line and web interface to run DFLOW and RipCAS in succession over many years automatically, which is a challenge because, for our application, DFLOW must be run on a supercomputing cluster via the PBS job scheduler. RipCAS is a vegetation succession model, and DFLOW is a 2D open channel flow model. Data adaptors have been developed to seamlessly connect DFLOW output data to be RipCAS inputs, and vice-versa. CoRD provides automated statistical analysis and visualization, plus automatic syncing of input and output files and model run metadata to the hydrological data management system HydroShare using its excellent Python REST client. This combination of technologies and data management techniques allows the results to be shared with collaborators and eventually published. Perhaps most importantly, it allows results to be easily reproduced via either the command-line or web user interface. This system is a result of collaboration between software developers and hydrologists participating in the Western Consortium for Watershed Analysis, Visualization, and Exploration (WC-WAVE). Because of the computing-intensive nature of this particular workflow, including automating job submission/monitoring and data adaptors, software engineering expertise is required. However, the hydrologists provide the software developers with a purpose and ensure a useful, intuitive tool is developed. Our hydrologists contribute software, too: RipCAS was developed from scratch by hydrologists on the team as a specialized, open-source version of the Computer Aided Simulation Model for Instream Flow and Riparia (CASiMiR) vegetation model; our hydrologists running DFLOW provided numerous examples and help with the supercomputing system. This project is written in Python, a popular language in the

Identificação dos níveis de degradação de matas ripárias com o uso de SIG

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Roseli Mendonça Dias

Full Text Available O presente trabalho objetivou identificar níveis de degradação de matas ripárias com o emprego de Sistema de Informações Geográficas (SIG, para a determinação das categorias de degradação encontradas na Unidade de Gerenciamento de Recursos Hídricos do Tietê-Jacaré, no município de São Carlos-SP. O método consistiu na interpretação visual de imagens de satélite Landsat 5 da área de estudo, em amostragens de campo e no desenvolvimento de procedimentos para a classificação dos níveis de degradação de suas matas ripárias. Foi gerado um mapa das categorias de degradação das matas ripárias, o que permitiu avaliar os locais degradados, com floresta e em estágios de regeneração. A interpretação de imagens de satélite para a identificação dos níveis de degradação das matas ripárias apresenta-se como um instrumento útil para subsidiar informações sobre as matas ripárias das drenagens e nascentes de uma bacia hidrográfica. Outra possibilidade corresponde ao monitoramento do desenvolvimento da degradação ou da recuperação destas matas.

Search for the neutron-rich nuclei in RIKEN-RIPS

Energy Technology Data Exchange (ETDEWEB)

Notani, Masahiro; Aoi, Nori; Fukuda, Naoki [Tokyo Univ. (Japan). Dept. of Physics] [and others

1997-05-01

{sup 64}Ni and {sup 181}Ta target were irradiated with {sup 48}Ca beam (70 AMeV) by R201N experiment in this paper. The production cross sections and yields of F, Ne, Na and Al isotopes were determined by particle identification of RIPS. New three nuclei, {sup 38}Mg and {sup 40},{sup 41}Al were found. Moreover, unstable nuclear isomer {sup 32m}Al was studied by measuring {gamma}-ray emission energy spectrum. The life and rate of isomer were determined. The rate of isomer was different from that of other systems. (S.Y.)

R.I.P. Computer Animal Shelter

CERN Multimedia

2012-01-01

Due to a brutal and unjustified attack on our facilities in front of the CERN Computer Centre, we had to close the CERN Animal Shelter on 5/1/2012 after only 9 months of operation (the shelter was inaugurated on 1/4/2011). With deep sadness we look back to the old days when everything was fine. R.I.P.   The Computer Mice shelter after the attack. More photographs available here.  All surviving mice have been returned to their owners, who have also been advised to "Stop --- Think --- Click" in order to securely browse the Internet and securely read e-mails. Users who have followed this recommendation in the past were less likely to have their computer infected or their computing account compromised. However, still too many users click on malicious web-links and put their computer and account at risk. Thank you all for your support during the last 9 months. The Computer Animal Shelter    

Modelagem da retenção de herbicidas em zonas ripárias Modeling of herbicide retention in riparian zones

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Alexandra P. de Pinho

2006-12-01

Full Text Available O presente trabalho teve como objetivo investigar a retenção de atrazina e picloram, transportados via escoamento superficial, em zona ripária. Para isto, simulou-se um escoamento superficial, contendo uma mistura de caulinita, atrazina e picloram, dentro de zonas ripárias estabelecidas ao longo de plantações de pinheiros do Nordeste do Estado da Geórgia, EUA. Cinco parcelas foram instaladas dentro de zonas ripárias, apresentando declividades diferentes (2, 5, 10, 15 e 20%. Os efeitos da umidade do solo e da presença do horizonte O na retenção dos dois herbicidas foram avaliados. Um modelo exponencial, comumente utilizado na estimativa de redução da DBO e de nutrientes em tratamento por escoamento superficial, foi empregado na estimativa de redução de herbicidas e caulinita em zonas ripárias. O modelo possibilitou estimar com razoável precisão, a remoção de caulinita e atrazina da mistura em escoamento ao longo de zonas ripárias de 10 m de comprimento. Em geral, a declividade foi o parâmetro que apresentou melhor correlação com a retenção dos contaminantes presentes na mistura em escoamento na zona ripária. O horizonte O, mais espesso nas maiores declividades, favoreceu tanto a sedimentação da caulinita como a adsorção da atrazina.This work aimed to investigate the retention of atrazine and picloram, carried by surface flow, in riparian zones. The surface flow, containing a mixture of both herbicides and kaolin, was then simulated within riparian zones established in pine plantations in north-eastern Georgia, USA. Five plots were established within riparian zones, each with a different slope (2, 5, 10, 15 and 20%. The influence of the initial moisture and of the O horizon condition in herbicide retention was analyzed. An exponential model, commonly used for the estimate of biochemical demand of oxygen (BOD and nutrients attenuation in overland flow treatment, was used to estimate the attenuation of kaolin and

Método Expedito para a Análise de Qualidade Ambiental em Zonas Ripárias Urbanas

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Ricardo Siloto da Silva

2012-12-01

Full Text Available Desde o estabelecimento das primeiras cidades, as áreas marginais aos rios são amplamente incorporadas na produção do espaço urbano. Visando contribuir para a reversão dos impactos da urbanização sobre estas áreas,  o trabalho apresenta  um método expedito para análise da qualidade ambiental nas zonas ripárias urbanas. Foi definido um conjunto de variáveis interdisciplinares e critérios de análise, e foram coletados dados em córregos localizados em cidades distintas. Como resultados parciais, o estudo identificou dificuldades quanto ao procedimento de coleta de dados  o que conduziu a alteração dos critérios de análise para o sistema canal fluvial-zona ripária.

To Make Long Character-Marked Cuttings From Low-Grade Yellow-Poplar Lumber - Rip First

Science.gov (United States)

Philip A. Araman

1979-01-01

Long, character-marked furniture cuttings are easily obtained when low-grade (2A and 2B Common) yellow-poplar lumber is first ripped into strips and then crosscut to remove objectionable defects. Overall yields of character-marked material using this procedure were 78% from 1 Common and 2A Common and 70% from 2B Common yellow-poplar lumber. Furthermore, 82% of the 1...

A importância das áreas ripárias para a sustentabilidade hidrológica do uso da terra em microbacias hidrográficas

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Cláudia Mira Attanasio

2012-01-01

Full Text Available Zonas ripárias são áreas de saturação hídrica, permanente ou temporária, cuja principal função é a proteção dos recursos hídricos de uma microbacia. Essa pesquisa comparou a adequação do uso do solo de dois cenários de planejamento agrícola de uma microbacia: o cenário convencional, representando o método usualmente empregado, que apenas considera as classes de capacidade de uso da terra, e o cenário hidrológico, que inclui a delimitação e avaliação das zonas ripárias. Um estudo de caso foi realizado na Microbacia do Ribeirão São João (3.656 ha, no município de Mineiros do Tietê (São Paulo, Brasil. Mapas de Classe de Capacidade de Uso da Terra e de Adequação do Uso do Solo foram elaborados, utilizando o Sistema de Informação Geográfica (SIG, para a construção dos cenários convencional e do proposto. Excluindo a Área de Preservação Permanente (APP, o cenário convencional indicou que 59,0% da área destinada à agricultura está adequadamente utilizada, 28,2% está subutilizada e 2,6% está sobreutilizada. O cenário proposto ou hidrológico, com inclusão da identificação da zona ripária (24,9% da microbacia mostrou que muitas áreas que, no cenário convencional, possuem pouca restrição para o cultivo intensivo, como as classes II e III, são zonas ripárias, de sensibilidade hidrológica. Existem dentro dos limites da zona ripária 38,9% de classe de capacidade de uso III e 49,5% de classe IV. O planejador, desconsiderando a zona ripária, pode colocar em risco áreas vitais que, se degradadas, representam danos para a saúde e resiliência da microbacia.

Surf zone Exchange on a Rip Channeled Beach

Science.gov (United States)

Reniers, A.; Macmahan, J.

2008-12-01

The dispersion and surf zone exchange of GPS-equipped surface drifters observed during the Rip Current EXperiment (RCEX) is examined with help of Lagrangian Coherent Structures (LCSs). LCSs allow for the detection of transport barriers in unsteady flows and are typically applied to shelf-scale circulation systems. Here LCSs are specifically computed to detect the effects of surfzone-originated Very Low Frequency motions (VLFs) with O(10) minute time scale on the cross-shore exchange of floating material using numerical model calculations of the Lagrangian surface velocity at the wave group timescale. After verification with RCEX field observations, the model is run for a range of environmental conditions experienced during the field experiment to assess the effects of VLFs on the cross-shore surf zone exchange. Results are relevant for (but not restricted to) sediment and nutrient exchange, human health, water clarity, and swimmer safety.

Partial rip scenario - a cosmology with a growing cosmological term

International Nuclear Information System (INIS)

Stefancic, H.

2004-01-01

A cosmology with the growing cosmological term is considered. If there is no exchange of energy between vacuum and matter components, the requirement of general covariance implies the time dependence of the gravitational constant G. Irrespectively of the exact functional form of the cosmological term growth, the universe ends in a de Sitter regime with a constant asymptotic Λ, but vanishing G. Although there is no divergence of the scale factor in finite time, such as in the 'Big Rip' scenario, gravitationally bound systems eventually become unbound. In the case of systems bound by non-gravitational forces, there is no unbounding effect, as the asymptotic Λ is insufficiently large to disturb these systems

Stroma-induced Jagged1 expression drives PC3 prostate cancer cell migration; disparate effects of RIP-generated proteolytic fragments on cell behaviour and Notch signaling

Energy Technology Data Exchange (ETDEWEB)

Delury, Craig, E-mail: c.delury@lancaster.ac.uk [Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, LA1 4YQ (United Kingdom); Hart, Claire, E-mail: claire.hart@manchester.ac.uk [Genito Urinary Cancer Research Group, Institute of Cancer Sciences, Paterson Building, The University of Manchester, Manchester Academic Health Science Centre, Wilmslow Road, Manchester, M20 4BX (United Kingdom); Brown, Mick, E-mail: michael.brown@ics.manchester.ac.uk [Genito Urinary Cancer Research Group, Institute of Cancer Sciences, Paterson Building, The University of Manchester, Manchester Academic Health Science Centre, Wilmslow Road, Manchester, M20 4BX (United Kingdom); Clarke, Noel, E-mail: noel.clarke@christie.nhs.uk [Genito Urinary Cancer Research Group, Institute of Cancer Sciences, Paterson Building, The University of Manchester, Manchester Academic Health Science Centre, Wilmslow Road, Manchester, M20 4BX (United Kingdom); Parkin, Edward, E-mail: e.parkin@lancaster.ac.uk [Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, LA1 4YQ (United Kingdom)

2016-03-25

The Notch ligand Jagged1 is subject to regulated intramembrane proteolysis (RIP) which yields a soluble ectodomain (sJag) and a soluble Jagged1 intracellular domain (JICD). The full-length Jagged1 protein enhances prostate cancer (PCa) cell proliferation and is highly expressed in metastatic cells. However, little is known regarding the mechanisms by which Jagged1 or its RIP-generated fragments might promote PCa bone metastasis. In the current study we show that bone marrow stroma (BMS) induces Jagged1 expression in bone metastatic prostate cancer PC3 cells and that this enhanced expression is mechanistically linked to the promotion of cell migration. We also show that RIP-generated Jagged1 fragments exert disparate effects on PC3 cell behaviour and Notch signaling. In conclusion, the expression of both the full-length ligand and its RIP-generated fragments must be considered in tandem when attempting to regulate Jagged1 as a possible PCa therapy. - Highlights: • Bone marrow stroma induces Jagged1 expression in prostate cancer (PCa) PC3 cells. • This enhanced expression of full-length Jagged1 is required for PC3 cell migration. • Proteolytic fragments of Jagged1 exert disparate effects on PC3 cell behaviour. • Effects of fragments on cell behaviour do not correlate with Notch signaling. • Effects of Jagged1 and its fragments on PCa metastasis likely to be complex.

Análise espacial da zona ripária do córrego gleba Cambará, Marumbi-PRSpatial analysis of the riparian zone of the stream Gleba Cambará, Marumbi-PR

OpenAIRE

Oliveira, Tiago Soares de; Oliveira, Éderson Dias

2016-01-01

A vegetação ripária tem uma ampla importância no equilíbrio dos sistemas fluviais, com destaque, principalmente, no ajuste dos processos ecológicos, geomorfológicos e hidrológicos. Assim, o ecossistema ripário, em sua integridade, inclui a dinâmica da zona ripária, sua vegetação e suas interações, desempenhando funções relacionadas à geração do escoamento direto em microbacias, ao aumento da capacidade de armazenamento e à manutenção da qualidade da água, além de promover a estabilidade das m...

Analysis of LOF/TOP excursions in the SNR-300 Zielkern core with a stress controlled rip extension after failure

International Nuclear Information System (INIS)

Royl, P.

1987-07-01

An unprotected loss of flow (ULOF) accident can result in energetic power excursions due to reactivity effects from in-pile fuel motion and compaction after a near midplane failure of fuel pins in unvoided regions of the core (loss of flow driven transient overpower or LOF/TOP excursions). These excursions are strongly mitigated by a propagation of the failure rip, which reduces the fuel compaction and enhances fuel sweep-out. A simple model has been introduced into the SAS3D code in which this propagation is restricted to the expansion of the void zone that is firmed in the coolant channel due to thermal interactions of fuel and sodium (FCI) after failure. The rip propagation is demonstrated in this report in all investigated cases to be a strong mitigator that will limit the fuel compaction effects in the region where they originate

TRACE/PARCS modelling of rips trip transients for Lungmen ABWR

Energy Technology Data Exchange (ETDEWEB)

Chang, C. Y. [Inst. of Nuclear Engineering and Science, National Tsing-Hua Univ., No.101, Kuang-Fu Road, Hsinchu 30013, Taiwan (China); Lin, H. T.; Wang, J. R. [Inst. of Nuclear Energy Research, No. 1000, Wenhua Rd., Longtan Township, Taoyuan County 32546, Taiwan (China); Shih, C. [Inst. of Nuclear Engineering and Science, Dept. of Engineering and System Science, National Tsing-Hua Univ., No.101, Kuang-Fu Road, Hsinchu 30013, Taiwan (China)

2012-07-01

The objectives of this study are to examine the performances of the steady-state results calculated by the Lungmen TRACE/PARCS model compared to SIMULATE-3 code, as well as to use the analytical results of the final safety analysis report (FSAR) to benchmark the Lungmen TRACE/PARCS model. In this study, three power generation methods in TRACE were utilized to analyze the three reactor internal pumps (RIPs) trip transient for the purpose of validating the TRACE/PARCS model. In general, the comparisons show that the transient responses of key system parameters agree well with the FSAR results, including core power, core inlet flow, reactivity, etc. Further studies will be performed in the future using Lungmen TRACE/PARCS model. After the commercial operation of Lungmen nuclear power plant, TRACE/PARCS model will be verified. (authors)

Giant Black Hole Rips Apart Star

Science.gov (United States)

2004-02-01

Thanks to two orbiting X-ray observatories, astronomers have the first strong evidence of a supermassive black hole ripping apart a star and consuming a portion of it. The event, captured by NASA's Chandra and ESA's XMM-Newton X-ray Observatories, had long been predicted by theory, but never confirmed. Astronomers believe a doomed star came too close to a giant black hole after being thrown off course by a close encounter with another star. As it neared the enormous gravity of the black hole, the star was stretched by tidal forces until it was torn apart. This discovery provides crucial information about how these black holes grow and affect surrounding stars and gas. "Stars can survive being stretched a small amount, as they are in binary star systems, but this star was stretched beyond its breaking point," said Stefanie Komossa of the Max Planck Institute for Extraterrestrial Physics (MPE) in Germany, leader of the international team of researchers. "This unlucky star just wandered into the wrong neighborhood." While other observations have hinted stars are destroyed by black holes (events known as "stellar tidal disruptions"), these new results are the first strong evidence. Evidence already exists for supermassive black holes in many galaxies, but looking for tidal disruptions represents a completely independent way to search for black holes. Observations like these are urgently needed to determine how quickly black holes can grow by swallowing neighboring stars. Animation of Star Ripped Apart by Giant Black Hole Star Ripped Apart by Giant Black Hole Observations with Chandra and XMM-Newton, combined with earlier images from the German Roentgen satellite, detected a powerful X-ray outburst from the center of the galaxy RX J1242-11. This outburst, one of the most extreme ever detected in a galaxy, was caused by gas from the destroyed star that was heated to millions of degrees Celsius before being swallowed by the black hole. The energy liberated in the process

Rock gabion, rip-rap, and culvert treatments: Successes and failures in post-fire erosion mitigation, Schultz Fire 2010

Science.gov (United States)

Daniel G. Neary; Karen A. Koestner

2011-01-01

Following the Schultz Fire in June of 2010, several erosion mitigation efforts were undertaken to reduce the impacts of post-fire flooding expected during the 2010 monsoon. One treatment consisted of the placement of large rock rip-rap on targeted fill slopes of a high elevation forest road that contains a buried pipeline supplying water to the city of Flagstaff....

Subunits Rip1p and Cox9p of the respiratory chain contribute to diclofenac-induced mitochondrial dysfunction.

Science.gov (United States)

van Leeuwen, Jolanda S; Orij, Rick; Luttik, Marijke A H; Smits, Gertien J; Vermeulen, Nico P E; Vos, J Chris

2011-03-01

The widely used drug diclofenac can cause serious heart, liver and kidney injury, which may be related to its ability to cause mitochondrial dysfunction. Using Saccharomyces cerevisiae as a model system, we studied the mechanisms of diclofenac toxicity and the role of mitochondria therein. We found that diclofenac reduced cell growth and viability and increased levels of reactive oxygen species (ROS). Strains increasingly relying on respiration for their energy production showed enhanced sensitivity to diclofenac. Furthermore, oxygen consumption was inhibited by diclofenac, suggesting that the drug inhibits respiration. To identify the site of respiratory inhibition, we investigated the effects of deletion of respiratory chain subunits on diclofenac toxicity. Whereas deletion of most subunits had no effect, loss of either Rip1p of complex III or Cox9p of complex IV resulted in enhanced resistance to diclofenac. In these deletion strains, diclofenac did not increase ROS formation as severely as in the wild-type. Our data are consistent with a mechanism of toxicity in which diclofenac inhibits respiration by interfering with Rip1p and Cox9p in the respiratory chain, resulting in ROS production that causes cell death.

Necessary and sufficient conditions for big bangs, bounces, crunches, rips, sudden singularities and extremality events

International Nuclear Information System (INIS)

Cattoen, Celine; Visser, Matt

2005-01-01

Until recently, the physically relevant singularities occurring in FRW cosmologies had traditionally been thought to be limited to the 'big bang', and possibly a 'big crunch'. However, over the last few years, the zoo of cosmological singularities considered in the literature has become considerably more extensive, with 'big rips' and 'sudden singularities' added to the mix, as well as renewed interest in nonsingular cosmological events such as 'bounces' and 'turnarounds'. In this paper we present an extensive catalogue of such cosmological milestones, both at the kinematical and dynamical level. First, using generalized power series, purely kinematical definitions of these cosmological events are provided in terms of the behaviour of the scale factor a(t). The notion of a 'scale-factor singularity' is defined, and its relation to curvature singularities (polynomial and differential) is explored. Second, dynamical information is extracted by using the Friedmann equations (without assuming even the existence of any equation of state) to place constraints on whether or not the classical energy conditions are satisfied at the cosmological milestones. We use these considerations to derive necessary and sufficient conditions for the existence of cosmological milestones such as bangs, bounces, crunches, rips, sudden singularities and extremality events. Since the classification is extremely general and, modulo certain technical assumptions, is complete, the corresponding results are to a high degree model independent: in particular, we provide a characterization of the class of bangs, crunches and sudden singularities for which the dominant energy condition is satisfied

Autophagy suppresses RIP kinase-dependent necrosis enabling survival to mTOR inhibition.

Directory of Open Access Journals (Sweden)

Kevin Bray

Full Text Available mTOR inhibitors are used clinically to treat renal cancer but are not curative. Here we show that autophagy is a resistance mechanism of human renal cell carcinoma (RCC cell lines to mTOR inhibitors. RCC cell lines have high basal autophagy that is required for survival to mTOR inhibition. In RCC4 cells, inhibition of mTOR with CCI-779 stimulates autophagy and eliminates RIP kinases (RIPKs and this is blocked by autophagy inhibition, which induces RIPK- and ROS-dependent necroptosis in vitro and suppresses xenograft growth. Autophagy of mitochondria is required for cell survival since mTOR inhibition turns off Nrf2 antioxidant defense. Thus, coordinate mTOR and autophagy inhibition leads to an imbalance between ROS production and defense, causing necroptosis that may enhance cancer treatment efficacy.

Role of Receptor-Interacting Protein 140 in human fat cells

Directory of Open Access Journals (Sweden)

Stenson Britta M

2010-01-01

Full Text Available Abstract Background Mice lacking Receptor-interacting protein 140 (RIP140 have reduced body fat which at least partly is mediated through increased lipid and glucose metabolism in adipose tissue. In humans, RIP140 is lower expressed in visceral white adipose tissue (WAT of obese versus lean subjects. We investigated the role of RIP140 in human subcutaneous WAT, which is the major fat depot of the body. Methods Messenger RNA levels of RIP140 were measured in samples of subcutaneous WAT from women with a wide variation in BMI and in different human WAT preparations. RIP140 mRNA was knocked down with siRNA in in vitro differentiated adipocytes and the impact on glucose transport and mRNA levels of target genes determined. Results RIP140 mRNA levels in subcutaneous WAT were decreased among obese compared to lean women and increased by weight-loss, but did not associate with mitochondrial DNA copy number. RIP140 expression increased during adipocyte differentiation in vitro and was higher in isolated adipocytes compared to corresponding pieces of WAT. Knock down of RIP140 increased basal glucose transport and mRNA levels of glucose transporter 4 and uncoupling protein-1. Conclusions Human RIP140 inhibits glucose uptake and the expression of genes promoting energy expenditure in the same fashion as the murine orthologue. Increased levels of human RIP140 in subcutaneous WAT of lean subjects may contribute to economize on energy stores. By contrast, the function and expression pattern does not support that RIP140 regulate human obesity.

Loss of Serglycin Promotes Primary Tumor Growth and Vessel Functionality in the RIP1-Tag2 Mouse Model for Spontaneous Insulinoma Formation.

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Andrew Hamilton

Full Text Available The serglycin proteoglycan is mainly expressed by hematopoietic cells where the major function is to retain the content of storage granules and vesicles. In recent years, expression of serglycin has also been found in different forms of human malignancies and a high serglycin expression level has been correlated with a more migratory and invasive phenotype in the case of breast cancer and nasopharyngeal carcinoma. Serglycin has also been implicated in the development of the tumor vasculature in multiple myeloma and hepatocellular carcinoma where reduced expression of serglycin was correlated with a less extensive vasculature. To further investigate the contribution of serglycin to tumor development, we have used the immunocompetent RIP1-Tag2 mouse model of spontaneous insulinoma formation crossed into serglycin deficient mice. For the first time we show that serglycin-deficiency affects orthotopic primary tumor growth and tumor vascular functionality of late stage carcinomas. RIP1-Tag2 mice that lack serglycin develop larger tumors with a higher proliferative activity but unaltered apoptosis compared to normal RIP1-Tag2 mice. The absence of serglycin also enhances the tumor vessel functionality, which is better perfused than in tumors from serglycin wild type mice. The presence of the pro-angiogenic modulators vascular endothelial growth factor and hepatocyte growth factor were decreased in the serglycin deficient mice which suggests a less pro-angiogenic environment in the tumors of these animals. Taken together, we conclude that serglycin affects multiple aspects of spontaneous tumor formation, which strengthens the theory that serglycin acts as an important mediator in the formation and progression of tumors.

Beta-cell specific deletion of Dicer1 leads to defective insulin secretion and diabetes mellitus

DEFF Research Database (Denmark)

Kalis, Martins; Bolmeson, Caroline; Esguerra, Jonathan L.S.

2011-01-01

-cells specific disruption of the Dicer1 gene using the Cre-lox system controlled by the rat insulin promoter (RIP). In contrast to their normoglycaemic control littermates (RIP-Cre(+/-) Dicer1(¿/wt)), RIP-Cre(+/-)Dicer1(flox/flox) mice (RIP-Cre Dicer1(¿/¿)) developed progressive hyperglycaemia and full...... revealed altered islet morphology, marked decreased ß-cell mass, reduced numbers of granules within the ß-cells and reduced granule docking in adult RIP-Cre Dicer1(¿/¿) mice. ß-cell specific Dicer1 deletion did not appear to disrupt fetal and neonatal ß-cell development as 2-week old RIP-Cre Dicer1...

Investigating the little rip and other future singularities of the universe, and validity of the second law of thermodynamics in F(R theory

Directory of Open Access Journals (Sweden)

M Aghaei Abchouyeh

2015-01-01

Full Text Available The future singularities are possible in a universe that is described by F(R theory. In previous studies the occurrence of the singularities in F(R theory have been considered by using a special function for the Hubble parameter and calculating the F(R function for each of the singularities. Using the specified Hubble parameter causes some difficulties in the study of the second law of thermodynamics. In this paper by using the scale factor, the behavior of F(R function near each type of the singularities is considered. We can check the validity of the second law of thermodynamics near the singularities. At first we study the Little Rip and then the other types of singularities are considered. The results show that the second law of thermodynamics is satisfied near the singularity type (I with some special conditions and is violated with some other conditions. it is satisfied near the Little Rip, type (II, (III and (IV singularities

Ameliorating effect of TI-1-162, a hydroxyindenone derivative, against TNBS-induced rat colitis is mediated through suppression of RIP/ASK-1/MAPK signaling.

Science.gov (United States)

Gurung, Pallavi; Banskota, Suhrid; Katila, Nikita; Gautam, Jaya; Kadayat, Tara Man; Choi, Dong-Young; Lee, Eung Seok; Jeong, Tae Cheon; Kim, Jung-Ae

2018-05-15

The pathogenesis of inflammatory bowel disease (IBD) is associated with production of immense pro-inflammatory cytokines including TNF-α. Once generated, TNF-α stimulates production of various pro-inflammatory cytokines and disrupts mucosal barrier by inducing inflamed mucosal epithelial cell death. In the present study, we investigated inhibitory effects of TI-1-162, a hydroxyindenone derivative, against TNF-α-induced and TNBS-induced colon inflammation. TI-1-162 showed inhibitory effect on the TNF-α-induced adhesion of U937 monocytic cells to HT-29 colonic epithelial cells (IC 50 = 0.83 ± 0.12 μM), which is an in vitro model representing the initial step of colitis. In addition, TI-1-162 suppressed TNF-α-stimulated caspase-3 activation and HT-29 cell apoptosis. These in vitro inhibitory activities of TI-1-162 correlated to recovery changes in in vivo colon tissues, such as downregulation of adhesion molecules (ICAM-1, VCAM-1) and chemokines (CCL11, CXCL1, CXCL2, CXCL3, CX3CL1) revealed by gene expression array and Western blot analyses. Such molecular recovery of colon epithelium from TNBS-treated rats corresponded to the recovery in body weight, colon weight/length, and myeloperoxidase level by TI-1-162 (10 and 30 mg/kg/day, orally). In relation to action mechanism, TI-1-162 did not disturb TNF-α binding to its receptor, but suppressed phosphorylation of RIP-1, ASK-1, JNK and p38, and nuclear translocation of NF-kB and AP-1, which corresponded to down regulation of inflammatory cytokines in TNF-α-treated cells (HT-29 and U937) and TNBS-treated rat colon tissues. Taken together, the results indicate that the protective effects of TI-1-162 against colon inflammation and epithelial cell death are associated with its inhibitory action in RIP/ASK-1/MAPK signaling pathway downstream to TNF receptor 1. Copyright © 2018 Elsevier B.V. All rights reserved.

Protective effect of naringenin in experimental ischemic stroke: down-regulated NOD2, RIP2, NF-κB, MMP-9 and up-regulated claudin-5 expression.

Science.gov (United States)

Bai, Xue; Zhang, Xiangjian; Chen, Linyu; Zhang, Jian; Zhang, Lan; Zhao, Xumeng; Zhao, Ting; Zhao, Yuan

2014-08-01

Inflammatory damage plays a pivotal, mainly detrimental role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Naringenin (NG) has gained growing appreciation for its beneficial biological effects through its anti-inflammatory property. Whether this protective effect applies to cerebral ischemic injury, we therefore investigate the potential neuroprotective role of NG and the underlying mechanisms. Focal cerebral ischemia in male Sprague-Dawley rats was induced by permanent middle cerebral artery occlusion (pMCAO) and NG was pre-administered intragastrically once daily for four consecutive days before surgery. Neurological deficit, brain water content and infarct volume were measured at 24 h after stroke. Immunohistochemistry, Western blot and RT-qPCR were used to explore the anti-inflammatory potential of NG in the regulation of NOD2, RIP2 and NF-κB in ischemic cerebral cortex. Additionally, the activities of MMP-9 and claudin-5 were analyzed to detect NG's influence on blood-brain barrier. Compared with pMCAO and Vehicle groups, NG noticeably improved neurological deficit, decreased infarct volume and edema at 24 h after ischemic insult. Consistent with these results, our data also indicated that NG significantly downregulated the expression of NOD2, RIP2, NF-κB and MMP-9, and upregulated the expression of claudin-5 (P < 0.05). The results provided a neuroprotective profile of NG in cerebral ischemia, this effect was likely exerted by down-regulated NOD2, RIP2, NF-κB, MMP-9 and up-regulated claudin-5 expression.

The effects of crosscutting before gang-ripping on dimension part yields from no. 1 and 2A common red oak lumber

Science.gov (United States)

Charles, J. Gatchell; Janice K. Wiedenbeck; Elizabeth S. Walker; Elizabeth S. Walker

1996-01-01

Mills should have the option to crosscut red oak lumber prior to gang-ripping to remove crook and worthless material and to take advantage of the quality differences between board ends. At least half of No: 1 and 2A Common red oak boards will have end-to-end yield differences of at least 10 percent. Preprocessing will cause a slight decrease in overall yield but will...

RIP-seq of BmAgo2-associated small RNAs reveal various types of small non-coding RNAs in the silkworm, Bombyx mori

Science.gov (United States)

2013-01-01

Background Small non-coding RNAs (ncRNAs) are important regulators of gene expression in eukaryotes. Previously, only microRNAs (miRNAs) and piRNAs have been identified in the silkworm, Bombyx mori. Furthermore, only ncRNAs (50-500nt) of intermediate size have been systematically identified in the silkworm. Results Here, we performed a systematic identification and analysis of small RNAs (18-50nt) associated with the Bombyx mori argonaute2 (BmAgo2) protein. Using RIP-seq, we identified various types of small ncRNAs associated with BmAGO2. These ncRNAs showed a multimodal length distribution, with three peaks at ~20nt, ~27nt and ~33nt, which included tRNA-, transposable element (TE)-, rRNA-, snoRNA- and snRNA-derived small RNAs as well as miRNAs and piRNAs. The tRNA-derived fragments (tRFs) were found at an extremely high abundance and accounted for 69.90% of the BmAgo2-associated small RNAs. Northern blotting confirmed that many tRFs were expressed or up-regulated only in the BmNPV-infected cells, implying that the tRFs play a prominent role by binding to BmAgo2 during BmNPV infection. Additional evidence suggested that there are potential cleavage sites on the D, anti-codon and TψC loops of the tRNAs. TE-derived small RNAs and piRNAs also accounted for a significant proportion of the BmAgo2-associated small RNAs, suggesting that BmAgo2 could be involved in the maintenance of genome stability by suppressing the activities of transposons guided by these small RNAs. Finally, Northern blotting was also used to confirm the Bombyx 5.8 s rRNA-derived small RNAs, demonstrating that various novel small RNAs exist in the silkworm. Conclusions Using an RIP-seq method in combination with Northern blotting, we identified various types of small RNAs associated with the BmAgo2 protein, including tRNA-, TE-, rRNA-, snoRNA- and snRNA-derived small RNAs as well as miRNAs and piRNAs. Our findings provide new clues for future functional studies of the role of small RNAs in insect

TALE-Like Effectors Are an Ancestral Feature of the Ralstonia solanacearum Species Complex and Converge in DNA Targeting Specificity.

Science.gov (United States)

Schandry, Niklas; de Lange, Orlando; Prior, Philippe; Lahaye, Thomas

2016-01-01

Ralstonia solanacearum, a species complex of bacterial plant pathogens divided into four monophyletic phylotypes, causes plant diseases in tropical climates around the world. Some strains exhibit a broad host range on solanaceous hosts, while others are highly host-specific as for example some banana-pathogenic strains. Previous studies showed that transcription activator-like (TAL) effectors from Ralstonia, termed RipTALs, are capable of activating reporter genes in planta, if these are preceded by a matching effector binding element (EBE). RipTALs target DNA via their central repeat domain (CRD), where one repeat pairs with one DNA-base of the given EBE. The repeat variable diresidue dictates base repeat specificity in a predictable fashion, known as the TALE code. In this work, we analyze RipTALs across all phylotypes of the Ralstonia solanacearum species complex. We find that RipTALs are prevalent in phylotypes I and IV but absent from most phylotype III and II strains (10/12, 8/14, 1/24, and 1/5 strains contained a RipTAL, respectively). RipTALs originating from strains of the same phylotype show high levels of sequence similarity (>98%) in the N-terminal and C-terminal regions, while RipTALs isolated from different phylotypes show 47-91% sequence similarity in those regions, giving rise to four RipTAL classes. We show that, despite sequence divergence, the base preference for guanine, mediated by the N-terminal region, is conserved across RipTALs of all classes. Using the number and order of repeats found in the CRD, we functionally sub-classify RipTALs, introduce a new simple nomenclature, and predict matching EBEs for all seven distinct RipTALs identified. We experimentally study RipTAL EBEs and uncover that some RipTALs are able to target the EBEs of other RipTALs, referred to as cross-reactivity. In particular, RipTALs from strains with a broad host range on solanaceous hosts cross-react on each other's EBEs. Investigation of sequence divergence between

A Role for Tubular Necroptosis in Cisplatin-Induced AKI

Science.gov (United States)

Xu, Yanfang; Ma, Huabin; Shao, Jing; Wu, Jianfeng; Zhou, Linying; Zhang, Zhirong; Wang, Yuze; Huang, Zhe; Ren, Junming; Liu, Suhuan; Chen, Xiangmei

2015-01-01

Cell death and inflammation in the proximal tubules are the hallmarks of cisplatin-induced AKI, but the mechanisms underlying these effects have not been fully elucidated. Here, we investigated whether necroptosis, a type of programmed necrosis, has a role in cisplatin-induced AKI. We found that inhibition of any of the core components of the necroptotic pathway—receptor-interacting protein 1 (RIP1), RIP3, or mixed lineage kinase domain-like protein (MLKL)—by gene knockout or a chemical inhibitor diminished cisplatin-induced proximal tubule damage in mice. Similar results were obtained in cultured proximal tubular cells. Furthermore, necroptosis of cultured cells could be induced by cisplatin or by a combination of cytokines (TNF-α, TNF-related weak inducer of apoptosis, and IFN-γ) that were upregulated in proximal tubules of cisplatin-treated mice. However, cisplatin induced an increase in RIP1 and RIP3 expression in cultured tubular cells in the absence of cytokine release. Correspondingly, overexpression of RIP1 or RIP3 enhanced cisplatin-induced necroptosis in vitro. Notably, inflammatory cytokine upregulation in cisplatin-treated mice was partially diminished in RIP3- or MLKL-deficient mice, suggesting a positive feedback loop involving these genes and inflammatory cytokines that promotes necroptosis progression. Thus, our data demonstrate that necroptosis is a major mechanism of proximal tubular cell death in cisplatin-induced nephrotoxic AKI. PMID:25788533

Collateral damage: Spread of repeat-induced point mutation from a ...

Indian Academy of Sciences (India)

Unknown

of the erg-3 gene, present in single copy, to the spread of RIP from duplications of adjoining sequences. Ge- ... RIP can spread across as much as 1 kb of unduplicated DNA. ... sequences that are > 500 bp and share > 80% similarity.

Como diferenciar uma marca num mercado pouco heterogéneo: inovação da Rip Curl

OpenAIRE

Real, Isabel Corte

2011-01-01

Mestrado em Marketing A partir de uma paixão pessoal que é o surf, e um interesse cada vez maior pelas novas tecnologias e como elas estão a mudar tudo à nossa volta, surgiu a ideia de criar um projecto para uma marca de surf que tem investido muito em Portugal, percebendo o potencial que o nosso país tem com tantos quilómetros de costa. As conclusões retiradas do quadro teórico e de toda a envolvente externa e interna à Rip Curl permitem apresentar um plano inovador para a criação de u...

Gene Expression Profiling Identifies Important Genes Affected by R2 Compound Disrupting FAK and P53 Complex

International Nuclear Information System (INIS)

Golubovskaya, Vita M.; Ho, Baotran; Conroy, Jeffrey; Liu, Song; Wang, Dan; Cance, William G.

2014-01-01

Focal Adhesion Kinase (FAK) is a non-receptor kinase that plays an important role in many cellular processes: adhesion, proliferation, invasion, angiogenesis, metastasis and survival. Recently, we have shown that Roslin 2 or R2 (1-benzyl-15,3,5,7-tetraazatricyclo[3.3.1.1~3,7~]decane) compound disrupts FAK and p53 proteins, activates p53 transcriptional activity, and blocks tumor growth. In this report we performed a microarray gene expression analysis of R2-treated HCT116 p53 +/+ and p53 −/− cells and detected 1484 genes that were significantly up- or down-regulated (p < 0.05) in HCT116 p53 +/+ cells but not in p53 −/− cells. Among up-regulated genes in HCT p53 +/+ cells we detected critical p53 targets: Mdm-2, Noxa-1, and RIP1. Among down-regulated genes, Met, PLK2, KIF14, BIRC2 and other genes were identified. In addition, a combination of R2 compound with M13 compound that disrupts FAK and Mmd-2 complex or R2 and Nutlin-1 that disrupts Mdm-2 and p53 decreased clonogenicity of HCT116 p53 +/+ colon cancer cells more significantly than each agent alone in a p53-dependent manner. Thus, the report detects gene expression profile in response to R2 treatment and demonstrates that the combination of drugs targeting FAK, Mdm-2, and p53 can be a novel therapy approach

RIP Input Tables From Wapdeg For LA Design Selection: Enhanced Design Alternative IIIb

International Nuclear Information System (INIS)

K.G. Mon; K.G. Mast; J.H. Lee

1999-01-01

The purpose of this calculation is to document the Waste Package Degradation (WAPDEG) version 3.09 (CRWMS M and O 1998b. 'Software Routine Report for WAPDEG' (Version 3.09)) simulations used to analyze degradation and failure of 2-cm thick titanium grade 7 corrosion resistant material (CRM) drip shields as well as degradation and failure of the waste packages over which they are placed. The waste packages are composed of two corrosion resistant materials (CRM) barriers. The outer barrier is composed of 2 cm of Alloy 22 and the inner barrier is composed of 1.5 cm of titanium grade 7. The WAPDEG simulation results are post-processed into tables of drip shield/waste package degradation time histories suitable for use as input into the Integrated Probabilistic Simulator for Environmental Systems (RIP) version 5.19.01 (Golder Associates 1998) computer code. This calculation supports Performance Assessment analysis of the License Application Design Selection (LADS) Enhanced Design Alternative IIIb

Genome Defense Mechanisms in Neurospora and Associated Specialized Proteins

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Ranjan Tamuli

2010-06-01

Full Text Available Neurospora crassa, the filamentous fungus possesses widest array of genome defense mechanisms known to any eukaryotic organism, including a process called repeat-induced point mutation (RIP. RIP is a genome defense mechanism that hypermutates repetitive DNA sequences; analogous to genomic imprinting in mammals. As an impact of RIP, Neurospora possesses many fewer genes in multigene families than expected. A DNA methyltransferase homologue, RID was shown to be essential for RIP. Recently, a variant catalytic subunit of translesion DNA polymerase zeta (Pol zeta has been found to be essential for dominant RIP suppressor phenotype. Meiotic silencing and quelling are two other genome defense mechanisms in Neurospora, and proteins required for these two processes have been identified through genetic screens.

Effect of calcitonin gene-related peptide on the neurogenesis of rat adipose-derived stem cells in vitro.

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Qin Yang

Full Text Available Calcitonin gene-related peptide (CGRP promotes neuron recruitment and neurogenic activity. However, no evidence suggests that CGRP affects the ability of stem cells to differentiate toward neurogenesis. In this study, we genetically modified rat adipose-derived stem cells (ADSCs with the CGRP gene (CGRP-ADSCs and subsequently cultured in complete neural-induced medium. The formation of neurospheres, cellular morphology, and proliferative capacity of ADSCs were observed. In addition, the expression of the anti-apoptotic protein Bcl-2 and special markers of neural cells, such as Nestin, MAP2, RIP and GFAP, were evaluated using Western blot and immunocytochemistry analysis. The CGRP-ADSCs displayed a greater proliferation than un-transduced (ADSCs and Vector-transduced (Vector-ADSCs ADSCs (p<0.05, and lower rates of apoptosis, associated with the incremental expression of Bcl-2, were also observed for CGRP-ADSCs. Moreover, upon neural induction, CGRP-ADSCs formed markedly more and larger neurospheres and showed round cell bodies with more branching extensions contacted with neighboring cells widely. Furthermore, the expression levels of Nestin, MAP2, and RIP in CGRP-ADSCs were markedly increased, resulting in higher levels than the other groups (p<0.05; however, GFAP was distinctly undetectable until day 7, when slight GFAP expression was detected among all groups. Wnt signals, primarily Wnt 3a, Wnt 5a and β-catenin, regulate the neural differentiation of ADSCs, and CGRP gene expression apparently depends on canonical Wnt signals to promote the neurogenesis of ADSCs. Consequently, ADSCs genetically modified with CGRP exhibit stronger potential for differentiation and neurogenesis in vitro, potentially reflecting the usefulness of ADSCs as seed cells in therapeutic strategies for spinal cord injury.

A novel Ras-interacting protein required for chemotaxis and cyclic adenosine monophosphate signal relay in Dictyostelium.

Science.gov (United States)

Lee, S; Parent, C A; Insall, R; Firtel, R A

1999-09-01

We have identified a novel Ras-interacting protein from Dictyostelium, RIP3, whose function is required for both chemotaxis and the synthesis and relay of the cyclic AMP (cAMP) chemoattractant signal. rip3 null cells are unable to aggregate and lack receptor activation of adenylyl cyclase but are able, in response to cAMP, to induce aggregation-stage, postaggregative, and cell-type-specific gene expression in suspension culture. In addition, rip3 null cells are unable to properly polarize in a cAMP gradient and chemotaxis is highly impaired. We demonstrate that cAMP stimulation of guanylyl cyclase, which is required for chemotaxis, is reduced approximately 60% in rip3 null cells. This reduced activation of guanylyl cyclase may account, in part, for the defect in chemotaxis. When cells are pulsed with cAMP for 5 h to mimic the endogenous cAMP oscillations that occur in wild-type strains, the cells will form aggregates, most of which, however, arrest at the mound stage. Unlike the response seen in wild-type strains, the rip3 null cell aggregates that form under these experimental conditions are very small, which is probably due to the rip3 null cell chemotaxis defect. Many of the phenotypes of the rip3 null cell, including the inability to activate adenylyl cyclase in response to cAMP and defects in chemotaxis, are very similar to those of strains carrying a disruption of the gene encoding the putative Ras exchange factor AleA. We demonstrate that aleA null cells also exhibit a defect in cAMP-mediated activation of guanylyl cyclase similar to that of rip3 null cells. A double-knockout mutant (rip3/aleA null cells) exhibits a further reduction in receptor activation of guanylyl cyclase, and these cells display almost no cell polarization or movement in cAMP gradients. As RIP3 preferentially interacts with an activated form of the Dictyostelium Ras protein RasG, which itself is important for cell movement, we propose that RIP3 and AleA are components of a Ras

Triple-Loaded Suture Anchors Versus a Knotless Rip Stop Construct in a Single-Row Rotator Cuff Repair Model.

Science.gov (United States)

Noyes, Matthew P; Lederman, Evan; Adams, Christopher R; Denard, Patrick J

2018-05-01

To compare the biomechanical properties of single-row repair with triple-loaded (TL) anchor repair versus a knotless rip stop (KRS) repair in a rotator cuff repair model. Rotator cuff tears were created in 8 cadaveric matched-pair specimens and repaired with a TL anchor or KRS construct. In the TL construct, anchors were placed in the greater tuberosity and then all suture limbs were passed through the rotator cuff as simple sutures and tied. In the KRS construct, a 2-mm suture tape was passed through the tendon in an inverted mattress fashion, and a free suture was passed medial to the suture tape to create a rip-stop. Then, the suture tape and free suture were secured with knotless anchors. Displacement was observed with video tracking after cyclic loading, and specimens were loaded to failure. The mean load to failure was 438 ± 59 N in TL anchor repairs compared with 457 ± 110 N in KRS repairs (P = .582). The mean displacement with cyclic loading was 3.8 ± 1.6 mm in TL anchor repairs versus 4.3 ± 1.8 mm in the KRS group (P = .297). Mode of failure was consistent in both groups, with 6 of 8 failures in the TL anchor group and 7 of 8 failures in KRS group occurring from anchor pullout. There is no statistical difference in load to failure and cyclic loading between TL anchor and KRS single-row repair techniques. KRS repair technique may be an alternative method of repairing full-thickness supraspinatus tendon tears with a single-row construct. Copyright © 2018 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Gene expression in periodontal tissues following treatment

Directory of Open Access Journals (Sweden)

Eisenacher Martin

2008-07-01

Full Text Available Abstract Background In periodontitis, treatment aimed at controlling the periodontal biofilm infection results in a resolution of the clinical and histological signs of inflammation. Although the cell types found in periodontal tissues following treatment have been well described, information on gene expression is limited to few candidate genes. Therefore, the aim of the study was to determine the expression profiles of immune and inflammatory genes in periodontal tissues from sites with severe chronic periodontitis following periodontal therapy in order to identify genes involved in tissue homeostasis. Gingival biopsies from 12 patients with severe chronic periodontitis were taken six to eight weeks following non-surgical periodontal therapy, and from 11 healthy controls. As internal standard, RNA of an immortalized human keratinocyte line (HaCaT was used. Total RNA was subjected to gene expression profiling using a commercially available microarray system focusing on inflammation-related genes. Post-hoc confirmation of selected genes was done by Realtime-PCR. Results Out of the 136 genes analyzed, the 5% most strongly expressed genes compared to healthy controls were Interleukin-12A (IL-12A, Versican (CSPG-2, Matrixmetalloproteinase-1 (MMP-1, Down syndrome critical region protein-1 (DSCR-1, Macrophage inflammatory protein-2β (Cxcl-3, Inhibitor of apoptosis protein-1 (BIRC-1, Cluster of differentiation antigen 38 (CD38, Regulator of G-protein signalling-1 (RGS-1, and Finkel-Biskis-Jinkins murine osteosarcoma virus oncogene (C-FOS; the 5% least strongly expressed genes were Receptor-interacting Serine/Threonine Kinase-2 (RIP-2, Complement component 3 (C3, Prostaglandin-endoperoxide synthase-2 (COX-2, Interleukin-8 (IL-8, Endothelin-1 (EDN-1, Plasminogen activator inhibitor type-2 (PAI-2, Matrix-metalloproteinase-14 (MMP-14, and Interferon regulating factor-7 (IRF-7. Conclusion Gene expression profiles found in periodontal tissues following

Identification of interacting proteins of retinoid-related orphan nuclear receptor gamma in HepG2 cells

Directory of Open Access Journals (Sweden)

Ze-Min Huang1,#, Jun Wu2,#, Zheng-Cai Jia1, Yi Tian1, Jun Tang3, Yan Tang1, Ying Wang2, Yu-Zhang Wu1,* & Bing Ni1,*

2012-06-01

Full Text Available The retinoid-related orphan nuclear receptor gamma (RORγplays critical roles in regulation of development, immunity andmetabolism. As transcription factor usually forms a proteincomplex to function, thus capturing and dissecting of theRORγ protein complex will be helpful for exploring themechanisms underlying those functions. After construction ofthe recombinant tandem affinity purification (TAP plasmid,pMSCVpuro RORγ-CTAP(SG, the nuclear localization ofRORγ-CTAP(SG fusion protein was verified. Followingisolation of RORγ protein complex by TAP strategy, sevencandidate interacting proteins were identified. Finally, the heatshock protein 90 (HSP90 and receptor-interacting protein 140(RIP140 were confirmed to interplay with RORγ byco-immunoprecipitation. Interference of HSP90 or/and RIP140genes resulted in dramatically decreased expression ofCYP2C8 gene, the RORγ target gene. Data from this studydemonstrate that HSP90 and RIP140 proteins interact withRORγ protein in a complex format and function asco-activators in the RORγ-mediated regulatory processes ofHepG2 cells.

Caracterização e distribuição espacial dos sedimentos depositados numa zona ripária reflorestada

OpenAIRE

Renata Santos Momoli

2006-01-01

As atividades agrícolas no Estado de São Paulo, foram responsáveis pela supressão da cobertura vegetal original do solo e, sua conseqüente degradação. A vegetação nativa foi gradativamente substituída por culturas como café, pastagem, citros e cana-de-açúcar, durante séculos de ocupação e uso da terra. A recomposição da cobertura florestal auxilia na prevenção da erosão do solo e na redução dos impactos causados. A floresta ripária retém os sedimentos resultantes do desprendimento do solo à m...

Pancreatic beta-cell overexpression of the glucagon receptor gene results in enhanced beta-cell function and mass

DEFF Research Database (Denmark)

Gelling, Richard W; Vuguin, Patricia M; Du, Xiu Quan

2009-01-01

in vivo, we generated mice overexpressing the Gcgr specifically on pancreatic beta-cells (RIP-Gcgr). In vivo and in vitro insulin secretion in response to glucagon and glucose was increased 1.7- to 3.9-fold in RIP-Gcgr mice compared with controls. Consistent with the observed increase in insulin release...

RIP INPUT TABLES FROM WAPDEG FOR LA DESIGN SELECTION: ENHANCED DESIGN ALTERNATIVE V

International Nuclear Information System (INIS)

K. Mon

1999-01-01

The purpose of this calculation is to document (1) the Waste Package Degradation (WAPDEG) version 3.09 (CRWMS M and O 1998b, Software Routine Report for WAPDEG (Version 3.09)) simulations used to analyze degradation and failure of 2-cm thick titanium grade 7 corrosion resistant material (CRM) drip shields (that are placed over waste packages composed of a 2-cm thick Alloy 22 corrosion resistant material (CRM) as the outer barrier and an unspecified material to provide structural support as the inner barrier) as well as degradation and failure of the waste packages themselves, and (2) post-processing of these results into tables of drip shield/waste package degradation time histories suitable for use as input into the Integrated Probabilistic Simulator for Environmental Systems (RIP) version 5.19.01 (Golder Associates 1998) computer code. Performance credit of the inner barrier material is not taken in this calculation. This calculation supports Performance Assessment analysis of the License Application Design Selection (LADS) Enhanced Design Alternative V. Additional details concerning the Enhanced Design Alternative V are provided in a Design Input Request (CRWMS M and O 1999e, Design Input Request for LADS Phase II EDA Evaluations, Item 3)

May the Soul of the IFS Financial System Definition RIP in Developing Countries

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Simplice A. Asongu

2015-03-01

Full Text Available In this paper, we dissect with great acuteness contemporary insufficiencies of the IFS (2008 definition of the financial system and conclude from sound theoretical underpinnings and empirical justifications that the foundation, on which it is based, while solid for developed countries, holds less ground in developing countries. Perhaps one of the deepest empirical hollows in the financial development literature has been the equation of financial depth in the perspective of money supply to liquid liabilities. This equation has put on the margin (and skewed burgeoning phenomena of mobile banking, knowledge economy (KE, inequality…etc. We conclude that the informal financial sector, a previously missing component in the IFS conception and definition of the financial system can only be marginalized at the cost of misunderstanding recent burgeoning trends in mobile phone penetration, KE and poverty. Hence, the IFS definition has incontrovertibly fought its final dead battle and lost in the face of soaring trends highlighted above. Despite the plethora of econometric and policy-making sins the definition has committed in developing countries through bias estimates and misleading inferences, may its soul RIP.

Enhanced quantitative resistance against fungal disease by combinatorial expression of different barley antifungal proteins in transgenic tobacco

DEFF Research Database (Denmark)

Jach, G; Görnhardt, B; Mundy, J

1995-01-01

cDNAs encoding three proteins from barley (Hordeum vulgare), a class-II chitinase (CHI), a class-II beta-1,3-glucanase (GLU) and a Type-I ribosome-inactivating protein (RIP) were expressed in tobacco plants under the control of the CaMV 35S-promoter. High-level expression of the transferred genes...... was detected in the transgenic plants by Northern and Western blot analysis. The leader peptides in CHI and GLU led to accumulation of these proteins in the intercellular space of tobacco leaves. RIP, which is naturally deposited in the cytosol of barley endosperm cells, was expressed either in its original...... cytosolic form or fused to a plant secretion peptide (spRIP). Fungal infection assays revealed that expression of the individual genes in each case resulted in an increased protection against the soilborne fungal pathogen Rhizoctonia solani, which infects a range of plant species including tobacco...

RNAi Mediated curcin precursor gene silencing in Jatropha (Jatropha curcas L.).

Science.gov (United States)

Patade, Vikas Yadav; Khatri, Deepti; Kumar, Kamal; Grover, Atul; Kumari, Maya; Gupta, Sanjay Mohan; Kumar, Devender; Nasim, Mohammed

2014-07-01

Curcin, a type I ribosomal inhibiting protein-RIP, encoded by curcin precursor gene, is a phytotoxin present in Jatropha (Jatropha curcas L.). Here, we report designing of RNAi construct for the curcin precursor gene and further its genetic transformation of Jatropha to reduce its transcript expression. Curcin precursor gene was first cloned from Jatropha strain DARL-2 and part of the gene sequence was cloned in sense and antisense orientation separated by an intron sequence in plant expression binary vector pRI101 AN. The construction of the RNAi vector was confirmed by double digestion and nucleotide sequencing. The vector was then mobilized into Agrobacterium tumefaciens strain GV 3101 and used for tissue culture independent in planta transformation protocol optimized for Jatropha. Germinating seeds were injured with a needle before infection with Agrobacterium and then transferred to sterilized sand medium. The seedlings were grown for 90 days and genomic DNA was isolated from leaves for transgenic confirmation based on real time PCR with NPT II specific dual labeled probe. Result of the transgenic confirmation analysis revealed presence of the gene silencing construct in ten out of 30 tested seedlings. Further, quantitative transcript expression analysis of the curcin precursor gene revealed reduction in the transcript abundance by more than 98% to undetectable level. The transgenic plants are being grown in containment for further studies on reduction in curcin protein content in Jatropha seeds.

Carfilzomib en el tratamiento de mieloma múltiple: revisión sistemática de la literatura y experiencia colombiana basada en RIPS / Carfilzomib for the Treatment of Multiple Myeloma: Systematic Review of the Literature and Colombian Experience Based on RIPS / Carfilzomib no tratamento do mieloma múltiplo: revisão da literatura e da experiência colombiana baseada em RIPS

Directory of Open Access Journals (Sweden)

Camilo Castañeda, MD.

2014-11-01

Full Text Available Introducción: El mieloma múltiple es un tumor maligno y progresivo de las células B asociado a lesiones osteolíticas, inmunodeficiencia y disfunción renal que ha sido tratado desde 2008 con bortezomib con el cual se logró un aumento del tiempo de sobrevida de los pacientes, sin embargo su uso se vio limitado por efectos adversos dependientes de la dosis, en especial la neuropatía periférica dolorosa. Recientemente ha entrado en uso carfilzomib (agente inhibidor de proteosoma de segunda generación aprobado por la FDA en 2012 como agente único para tratamiento de enfermedad refractaria y recaídas de mieloma múltiple. Objetivo: Realizar una revisión de la literatura y determinar la experiencia colombiana con el medicamento carfilzomib teniendo en cuenta las estadísticas nacionales consignadas en los registros individuales de prestación de servicios de salud. Además se describe la situación de un caso clínico. Metodología: La revisión se hizo con base en literatura indexada en PubMed; como criterio de inclusión se tuvo en cuenta que los artículos a revisar fueran estudios clínicos de fase 2 y 3 de carfilzomib en manejo de mieloma múltiple. Respecto a la experiencia colombiana se identificaron 37 pacientes colombianos con mieloma múltiple diagnosticado entre 2003 y 2012 y a quienes se hubiera prescrito carfilzomib, teniendo en cuenta información proporcionada por Biotoscana. Resultados: En total se localizaron 8 estudios clínicos con asignación al azar que evidencian efectos adversos no hematológicos como fatiga (367 de los 678 pacientes, 54%, y náusea (323 pacientes, 48%. En el caso de los RIPS, de los 37 pacientes, 22 pacientes recibieron de 1 a 8 ciclos de carfilzomib (promedio 3.0, mediana 3. Se evaluó la respuesta clínica en 9 de ellos, encontrándose 4 pacientes (22% en respuesta parcial muy buena, 4 pacientes (22% en respuesta parcial, 1 paciente (6% con enfermedad estable. Conclusiones: Se encontró diferencia

Status of beam line detectors for the BigRIPS fragment separator at RIKEN RI Beam Factory. Issues on high rates and resolution

International Nuclear Information System (INIS)

Sato, Yuki; Fukuda, Naoki; Takeda, Hiroyuki

2015-01-01

A multiple sampling ionization chamber (MUSIC) and parallel-plate avalanche counters (PPACs) were installed within the superconducting in-flight separator, named BigRIPS, at the RIKEN Nishina Center for particle identification of RI beams. The MUSIC detector showed negligible charge collection inefficiency from recombination of electrons and ions, up to a 99-kcps incidence rate for high-energy heavy ions. For the PPAC detectors, the electrical discharge durability for incident heavy ions was improved by changing the electrode material. Finally, we designed a single crystal diamond detector, which is under development for TOF measurements of high-energy heavy ions, that has a very fast response time (pulse width <1 ns). (author)

Status of Beam Line Detectors for the BigRIPS Fragment Separator at RIKEN RI Beam Factory: Issues on High Rates and Resolution

Science.gov (United States)

Sato, Yuki; Fukuda, Naoki; Takeda, Hiroyuki; Kameda, Daisuke; Suzuki, Hiroshi; Shimizu, Yohei; Ahn, DeukSoon; Murai, Daichi; Inabe, Naohito; Shimaoka, Takehiro; Tsubota, Masakatsu; Kaneko, Junichi H.; Chayahara, Akiyoshi; Umezawa, Hitoshi; Shikata, Shinichi; Kumagai, Hidekazu; Murakami, Hiroyuki; Sato, Hiromi; Yoshida, Koichi; Kubo, Toshiyuki

A multiple sampling ionization chamber (MUSIC) and parallel-plate avalanche counters (PPACs) were installed within the superconducting in-flight separator, named BigRIPS, at the RIKEN Nishina Center for particle identification of RI beams. The MUSIC detector showed negligible charge collection inefficiency from recombination of electrons and ions, up to a 99-kcps incidence rate for high-energy heavy ions. For the PPAC detectors, the electrical discharge durability for incident heavy ions was improved by changing the electrode material. Finally, we designed a single crystal diamond detector, which is under development for TOF measurements of high-energy heavy ions, that has a very fast response time (pulse width <1 ns).

The Avoidance of the Little Sibling of the Big Rip Abrupt Event by a Quantum Approach

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Imanol Albarran

2018-02-01

Full Text Available We address the quantisation of a model that induces the Little Sibling of the Big Rip (LSBR abrupt event, where the dark energy content is described by means of a phantom-like fluid or a phantom scalar field. The quantisation is done in the framework of the Wheeler–DeWitt (WDW equation and imposing the DeWitt boundary condition; i.e., the wave function vanishes close to the abrupt event. We analyse the WDW equation within two descriptions: First, when the dark energy content is described with a perfect fluid. This leaves the problem with the scale factor as the single degree of freedom. Second, when the dark energy content is described with a phantom scalar field in such a way that an additional degree of freedom is incorporated. Here, we have applied the Born–Oppenheimer (BO approximation in order to simplify the WDW equation. In all cases, the obtained wave function vanishes when the LSBR takes place, thus fulfilling the DeWitt boundary condition.

More on the holographic Ricci dark energy model: smoothing Rips through interaction effects?

Science.gov (United States)

Bouhmadi-López, Mariam; Errahmani, Ahmed; Ouali, Taoufik; Tavakoli, Yaser

2018-04-01

The background cosmological dynamics of the late Universe is analysed on the framework of a dark energy model described by an holographic Ricci dark energy component. Several kind of interactions between the dark energy and the dark matter components are considered herein. We solve the background cosmological dynamics for the different choices of interactions with the aim to analyse not only the current evolution of the universe but also its asymptotic behaviour and, in particular, possible future singularities removal. We show that in most of the cases, the Big Rip singularity, a finger print of this model in absence of an interaction between the dark sectors, is substituted by a de Sitter or a Minkowski state. Most importantly, we found two new future bouncing solutions leading to two possible asymptotic behaviours, we named Little Bang and Little Sibling of the Big Bang. At a Little Bang, as the size of the universe shrinks to zero in an infinite cosmic time, the Hubble rate and its cosmic time derivative blow up. In addition, at a Little sibling of the Big Bang, as the size of the universe shrinks to zero in an infinite cosmic time, the Hubble rate blows up but its cosmic time derivative is finite. These two abrupt events can happen as well in the past.

More on the holographic Ricci dark energy model: smoothing Rips through interaction effects?

Science.gov (United States)

Bouhmadi-López, Mariam; Errahmani, Ahmed; Ouali, Taoufik; Tavakoli, Yaser

2018-01-01

The background cosmological dynamics of the late Universe is analysed on the framework of a dark energy model described by an holographic Ricci dark energy component. Several kind of interactions between the dark energy and the dark matter components are considered herein. We solve the background cosmological dynamics for the different choices of interactions with the aim to analyse not only the current evolution of the universe but also its asymptotic behaviour and, in particular, possible future singularities removal. We show that in most of the cases, the Big Rip singularity, a finger print of this model in absence of an interaction between the dark sectors, is substituted by a de Sitter or a Minkowski state. Most importantly, we found two new future bouncing solutions leading to two possible asymptotic behaviours, we named Little Bang and Little Sibling of the Big Bang. At a Little Bang, as the size of the universe shrinks to zero in an infinite cosmic time, the Hubble rate and its cosmic time derivative blow up. In addition, at a Little sibling of the Big Bang, as the size of the universe shrinks to zero in an infinite cosmic time, the Hubble rate blows up but its cosmic time derivative is finite. These two abrupt events can happen as well in the past.

Receptor-interacting Protein 140 Overexpression Promotes Neuro-2a Neuronal Differentiation by ERK1/2 Signaling

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Xiao Feng

2015-01-01

Full Text Available Background: Abnormal neuronal differentiation plays an important role in central nervous system (CNS development abnormalities such as Down syndrome (DS, a disorder that results directly from overexpression of genes in trisomic cells. Receptor-interacting protein 140 (RIP140 is significantly upregulated in DS brains, suggesting its involvement in DS CNS development abnormalities. However, the role of RIP140 in neuronal differentiation is still not clear. The current study aimed to investigate the effect of RIP140 overexpression on the differentiation of neuro-2a (N2a neuroblastoma cells, in vitro. Methods: Stably RIP140-overexpressing N2a (N2a-RIP140 cells were used as a neurodevelopmental model, and were constructed by lipofection and overexpression validated by real-time polymerase chain reaction and Western blot. Retinoic acid (RA was used to stimulate N2a differentiation. Combining the expression of Tuj1 at the mRNA and protein levels, the percentage of cells baring neurites, and the number of neurites per cell body was semi-quantified to determine the effect of RIP140 on differentiation of N2a cells. Furthermore, western blot and the ERK1/2 inhibitor U0126 were used to identify the specific signaling pathway by which RIP140 induces differentiation of N2a cells. Statistical significance of the differences between groups was determined by one-way analysis of variance followed by the Dunnett test. Results: Compared to untransfected N2a cells RIPl40 expression in N2a-RIP140 cells was remarkably upregulated at both the mRNA and protein levels. N2a-RIP140 cells had a significantly increased percentage of cells baring neurites, and numbers of neurites per cell, as compared to N2a cells, in the absence and presence of RA (P < 0.05. In addition, Tuj1, a neuronal biomarker, was strongly upregulated in N2a-RIP140 cells (P < 0.05 and phosphorylated ERK1/2 (p-ERK1/2 levels in N2a-RIP140 cells were dramatically increased, while differentiation was

RIP INPUT TABLES FROM WAPDEG FOR LA DESIGN SELECTION: HIGHER THERMAL LOADING

International Nuclear Information System (INIS)

K. Mon

1999-01-01

The purpose of this calculation is to document (1) the Waste Package Degradation (WAPDEG) version 3.09 (CRWMS M and O 1998b. Software Routine Report for WAPDEG (Version 3.09)) simulations used to analyze waste package degradation and failure under the repository exposure conditions characterized by the higher thermal loading repository design feature and, (2) post-processing of these results into tables of waste package degradation time histories suitable for use as input into the Integrated Probabilistic Simulator for Environmental Systems version 5.19.01 (RIP) computer program (Golder Associates 1998). Specifically, the WAPDEG simulations discussed in this calculation correspond to waste package emplacement conditions (repository environment and design) defined in the Total System Performance Assessment-Viability Assessment (TSPA-VA), with the exception that the higher thermal loading Design Feature (Design Feature 26) of the License Application Design Selection (LADS) analysis was analyzed. Higher thermal loading would keep the drift temperature above the boiling point of water for a longer period of time, thereby minimizing moisture around the waste packages during a longer post-closure period. The higher thermal loading would also affect the surrounding rock, which may have adverse effects. The only failure mechanism of this feature would be if the effects on the surrounding rock were determined to be unacceptable. As a result of the change in waste package placement relative to the TSPA-VA base-case design, different temperature and relative humidity time histories at the waste package surface are calculated (input to the WAPDEG simulations), and consequently different waste package failure histories (as calculated by WAPDEG) result

RIP Input Tables from WAPDEG for LA Design Selection: Enhanced Design Alternative II-3

International Nuclear Information System (INIS)

A.M. Monib

1999-01-01

The purpose of this calculation is to document (1) the Waste Package Degradation (WAPDEG) version 3.09 (CRWMS M and O 1998b. ''Software Routine Report for WAPDEG'' (Version 3.09)) simulations used to analyze degradation and failure of 2-cm thick titanium grade 7 corrosion resistant material (CRM) drip shields (that are placed over waste packages composed of a 2-cm thick Alloy 22 corrosion resistant material (CRM) as the outer barrier and an unspecified material to provide structural support as the inner barrier) as well as degradation and failure of the waste packages themselves, and (2) post-processing of these results into tables of drip shield/waste package degradation time histories suitable for use as input into the Integrated Probabilistic Simulator for Environmental Systems (RIP) version 5.19.01 (Golder Associates 1998) computer code. This calculation supports Performance Assessment analysis of the License Application Design Selection (LADS) Enhanced Design Alternative (EDA) II-3. The aging period in the EDA II design (CRWMS M and O 1999f. ''Design Input Request for LADS Phase II EDA Evaluations'', Item 1 Row 9 Column 3) was replaced in the case of EDA II-3 with 25 years preclosure ventilation, leading to a total of 50 years preclosure ventilation. The waste packages are line loaded in the repository and no backfill is used

Studying RNA-protein interactions in vivo by RNA immunoprecipitation

DEFF Research Database (Denmark)

Selth, Luke A; Close, Pierre; Svejstrup, Jesper Q

2011-01-01

and have significant effects on gene expression. RNA immunoprecipitation (RIP) is a powerful technique used to detect direct and indirect interactions between individual proteins and specific RNA molecules in vivo. Here, we describe RIP methods for both yeast and mammalian cells.......The crucial roles played by RNA-binding proteins in all aspects of RNA metabolism, particularly in the regulation of transcription, have become increasingly evident. Moreover, other factors that do not directly interact with RNA molecules can nevertheless function proximally to RNA polymerases...

Enhancement of 9α-Hydroxy-4-androstene-3,17-dione Production from Soybean Phytosterols by Deficiency of a Regulated Intramembrane Proteolysis Metalloprotease in Mycobacterium neoaurum.

Science.gov (United States)

Xiong, Liang-Bin; Sun, Wan-Ju; Liu, Yong-Jun; Wang, Feng-Qing; Wei, Dong-Zhi

2017-12-06

Modification of the sterol catabolism pathway in mycobacteria may result in the accumulation of some valuable steroid pharmaceutical intermediates, such as 9α-hydroxy-4-androstene-3,17-dione (9-OHAD). In previous work, sigma factor D (SigD) was identified as a negative factor of the 9-OHAD production in Mycobacterium neoaurum. Here, the deficiency of rip1 putatively coding for a regulated intramembrane proteolysis metalloprotease (Rip1), which could cleave the negative regulator of SigD (anti-SigD), enhanced the transcription of some key genes (choM1, kshA, and hsd4A) in the sterol catabolic pathway. Furthermore, the deletion of rip1 increased the consumption of phytosterols by 37.8% after 96 h of growth in M. neoaurum. The production of 9-OHAD in the engineered M. neoaurumΔkstD1ΔkstD2ΔkstD3Δrip1 (MnΔk123Δrip1) strain was ultimately increased by 27.3% compared to that in its parental strain M. neoaurumΔkstD1ΔkstD2ΔkstD3 (MnΔk123). This study further confirms the important role of SigD-related factors in the catabolism of sterols.

Efeitos de alterações na zona ripária sobre a integridade de igarapés amazônicos no Baixo rio Teles Pires, Norte de Mato Grosso

OpenAIRE

Bleich, Monica Elisa

2015-01-01

Na bacia Amazônica existem muitos riachos, localmente denominados de igarapés, inseridos em paisagens heterogêneas, considerando as variações naturais das condições geomorfológicas, os períodos hidrológicos e a degradação promovida pelo desmatamento, principalmente na borda sul da bacia. Logo, o objetivo do presente estudo foi avaliar os impactos de alterações na cobertura florestal ripária sobre a estrutura do ecossistema em igarapés de cabeceira no baixo rio Teles Pires, norte de Mato Gross...

CELF1 preferentially binds to exon-intron boundary and regulates alternative splicing in HeLa cells.

Science.gov (United States)

Xia, Heng; Chen, Dong; Wu, Qijia; Wu, Gang; Zhou, Yanhong; Zhang, Yi; Zhang, Libin

2017-09-01

The current RIP-seq approach has been developed for the identification of genome-wide interaction between RNA binding protein (RBP) and the bound RNA transcripts, but still rarely for identifying its binding sites. In this study, we performed RIP-seq experiments in HeLa cells using a monoclonal antibody against CELF1. Mapping of the RIP-seq reads showed a biased distribution at the 3'UTR and intronic regions. A total of 15,285 and 1384 CELF1-specific sense and antisense peaks were identified using the ABLIRC software tool. Our bioinformatics analyses revealed that 5' and 3' splice site motifs and GU-rich motifs were highly enriched in the CELF1-bound peaks. Furthermore, transcriptome analyses revealed that alternative splicing was globally regulated by CELF1 in HeLa cells. For example, the inclusion of exon 16 of LMO7 gene, a marker gene of breast cancer, is positively regulated by CELF1. Taken together, we have shown that RIP-seq data can be used to decipher RBP binding sites and reveal an unexpected landscape of the genome-wide CELF1-RNA interactions in HeLa cells. In addition, we found that CELF1 globally regulates the alternative splicing by binding the exon-intron boundary in HeLa cells, which will deepen our understanding of the regulatory roles of CELF1 in the pre-mRNA splicing process. Copyright © 2017 Elsevier B.V. All rights reserved.

The quantum realm of the ''Little Sibling'' of the Big Rip singularity

International Nuclear Information System (INIS)

Albarran, Imanol; Bouhmadi-López, Mariam; Cabral, Francisco; Martín-Moruno, Prado

2015-01-01

We analyse the quantum behaviour of the ''Little Sibling'' of the Big Rip singularity (LSBR) [1]. The quantisation is carried within the geometrodynamical approach given by the Wheeler-DeWitt (WDW) equation. The classical model is based on a Friedmann-Lemaître-Robertson-Walker Universe filled by a perfect fluid that can be mapped to a scalar field with phantom character. We analyse the WDW equation in two setups. In the first step, we consider the scale factor as the single degree of freedom, which from a classical perspective parametrises both the geometry and the matter content given by the perfect fluid. We then solve the WDW equation within a WKB approximation, for two factor ordering choices. On the second approach, we consider the WDW equation with two degrees of freedom: the scale factor and a scalar field. We solve the WDW equation, with the Laplace-Beltrami factor-ordering, using a Born-Oppenheimer approximation. In both approaches, we impose the DeWitt (DW) condition as a potential criterion for singularity avoidance. We conclude that in all the cases analysed the DW condition can be verified, which might be an indication that the LSBR can be avoided or smoothed in the quantum approach

Transcriptomic-Wide Discovery of Direct and Indirect HuR RNA Targets in Activated CD4+ T Cells.

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Patsharaporn Techasintana

Full Text Available Due to poor correlation between steady state mRNA levels and protein product, purely transcriptomic profiling methods may miss genes posttranscriptionally regulated by RNA binding proteins (RBPs and microRNAs (miRNAs. RNA immunoprecipitation (RIP methods developed to identify in vivo targets of RBPs have greatly elucidated those mRNAs which may be regulated via transcript stability and translation. The RBP HuR (ELAVL1 and family members are major stabilizers of mRNA. Many labs have identified HuR mRNA targets; however, many of these analyses have been performed in cell lines and oftentimes are not independent biological replicates. Little is known about how HuR target mRNAs behave in conditional knock-out models. In the present work, we performed HuR RIP-Seq and RNA-Seq to investigate HuR direct and indirect targets using a novel conditional knock-out model of HuR genetic ablation during CD4+ T activation and Th2 differentiation. Using independent biological replicates, we generated a high coverage RIP-Seq data set (>160 million reads that was analyzed using bioinformatics methods specifically designed to find direct mRNA targets in RIP-Seq data. Simultaneously, another set of independent biological replicates were sequenced by RNA-Seq (>425 million reads to identify indirect HuR targets. These direct and indirect targets were combined to determine canonical pathways in CD4+ T cell activation and differentiation for which HuR plays an important role. We show that HuR may regulate genes in multiple canonical pathways involved in T cell activation especially the CD28 family signaling pathway. These data provide insights into potential HuR-regulated genes during T cell activation and immune mechanisms.

The pmr gene, encoding a Ca2+-ATPase, is required for calcium and manganese homeostasis and normal development of hyphae and conidia in Neurospora crassa.

Science.gov (United States)

Bowman, Barry J; Abreu, Stephen; Johl, Jessica K; Bowman, Emma Jean

2012-11-01

The pmr gene is predicted to encode a Ca(2+)-ATPase in the secretory pathway. We examined two strains of Neurospora crassa that lacked PMR: the Δpmr strain, in which pmr was completely deleted, and pmr(RIP), in which the gene was extensively mutated. Both strains had identical, complex phenotypes. Compared to the wild type, these strains required high concentrations of calcium or manganese for optimal growth and had highly branched, slow-growing hyphae. They conidiated poorly, and the shape and size of the conidia were abnormal. Calcium accumulated in the Δpmr strains to only 20% of the wild-type level. High concentrations of MnCl(2) (1 to 5 mM) in growth medium partially suppressed the morphological defects but did not alter the defect in calcium accumulation. The Δpmr Δnca-2 double mutant (nca-2 encodes a Ca(2+)-ATPase in the plasma membrane) accumulated 8-fold more calcium than the wild type, and the morphology of the hyphae was more similar to that of wild-type hyphae. Previous experiments failed to show a function for nca-1, which encodes a SERCA-type Ca(2+)-ATPase in the endoplasmic reticulum (B. J. Bowman, S. Abreu, E. Margolles-Clark, M. Draskovic, and E. J. Bowman, Eukaryot. Cell 10:654-661, 2011). The pmr(RIP) Δnca-1 double mutant accumulated small amounts of calcium, like the Δpmr strain, but exhibited even more extreme morphological defects. Thus, PMR can apparently replace NCA-1 in the endoplasmic reticulum, but NCA-1 cannot replace PMR. The morphological defects in the Δpmr strain are likely caused, in part, by insufficient concentrations of calcium and manganese in the Golgi compartment; however, PMR is also needed to accumulate normal levels of calcium in the whole cell.

Interaction and modulation of two antagonistic cell wall enzymes of mycobacteria.

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Erik C Hett

2010-07-01

Full Text Available Bacterial cell growth and division require coordinated cell wall hydrolysis and synthesis, allowing for the removal and expansion of cell wall material. Without proper coordination, unchecked hydrolysis can result in cell lysis. How these opposing activities are simultaneously regulated is poorly understood. In Mycobacterium tuberculosis, the resuscitation-promoting factor B (RpfB, a lytic transglycosylase, interacts and synergizes with Rpf-interacting protein A (RipA, an endopeptidase, to hydrolyze peptidoglycan. However, it remains unclear what governs this synergy and how it is coordinated with cell wall synthesis. Here we identify the bifunctional peptidoglycan-synthesizing enzyme, penicillin binding protein 1 (PBP1, as a RipA-interacting protein. PBP1, like RipA, localizes both at the poles and septa of dividing cells. Depletion of the ponA1 gene, encoding PBP1 in M. smegmatis, results in a severe growth defect and abnormally shaped cells, indicating that PBP1 is necessary for viability and cell wall stability. Finally, PBP1 inhibits the synergistic hydrolysis of peptidoglycan by the RipA-RpfB complex in vitro. These data reveal a post-translational mechanism for regulating cell wall hydrolysis and synthesis through protein-protein interactions between enzymes with antagonistic functions.

Plant Ribosome-Inactivating Proteins: Progesses, Challenges and Biotechnological Applications (and a Few Digressions

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Maria Serena Fabbrini

2017-10-01

Full Text Available Plant ribosome-inactivating protein (RIP toxins are EC3.2.2.22 N-glycosidases, found among most plant species encoded as small gene families, distributed in several tissues being endowed with defensive functions against fungal or viral infections. The two main plant RIP classes include type I (monomeric and type II (dimeric as the prototype ricin holotoxin from Ricinus communis that is composed of a catalytic active A chain linked via a disulphide bridge to a B-lectin domain that mediates efficient endocytosis in eukaryotic cells. Plant RIPs can recognize a universally conserved stem-loop, known as the α-sarcin/ ricin loop or SRL structure in 23S/25S/28S rRNA. By depurinating a single adenine (A4324 in 28S rat rRNA, they can irreversibly arrest protein translation and trigger cell death in the intoxicated mammalian cell. Besides their useful application as potential weapons against infected/tumor cells, ricin was also used in bio-terroristic attacks and, as such, constitutes a major concern. In this review, we aim to summarize past studies and more recent progresses made studying plant RIPs and discuss successful approaches that might help overcoming some of the bottlenecks encountered during the development of their biomedical applications.

Chromosome-level genome map provides insights into diverse defense mechanisms in the medicinal fungus Ganoderma sinense

Science.gov (United States)

Zhu, Yingjie; Xu, Jiang; Sun, Chao; Zhou, Shiguo; Xu, Haibin; Nelson, David R.; Qian, Jun; Song, Jingyuan; Luo, Hongmei; Xiang, Li; Li, Ying; Xu, Zhichao; Ji, Aijia; Wang, Lizhi; Lu, Shanfa; Hayward, Alice; Sun, Wei; Li, Xiwen; Schwartz, David C.; Wang, Yitao; Chen, Shilin

2015-01-01

Fungi have evolved powerful genomic and chemical defense systems to protect themselves against genetic destabilization and other organisms. However, the precise molecular basis involved in fungal defense remain largely unknown in Basidiomycetes. Here the complete genome sequence, as well as DNA methylation patterns and small RNA transcriptomes, was analyzed to provide a holistic overview of secondary metabolism and defense processes in the model medicinal fungus, Ganoderma sinense. We reported the 48.96 Mb genome sequence of G. sinense, consisting of 12 chromosomes and encoding 15,688 genes. More than thirty gene clusters involved in the biosynthesis of secondary metabolites, as well as a large array of genes responsible for their transport and regulation were highlighted. In addition, components of genome defense mechanisms, namely repeat-induced point mutation (RIP), DNA methylation and small RNA-mediated gene silencing, were revealed in G. sinense. Systematic bioinformatic investigation of the genome and methylome suggested that RIP and DNA methylation combinatorially maintain G. sinense genome stability by inactivating invasive genetic material and transposable elements. The elucidation of the G. sinense genome and epigenome provides an unparalleled opportunity to advance our understanding of secondary metabolism and fungal defense mechanisms. PMID:26046933

RIP Input Tables From WAPDEG for LA Design Selection: Continuous Post-Closure Ventilation Design- Open Loop

International Nuclear Information System (INIS)

K.G. Mon; P.K. Mast; R. Howard; J.H. Lee

1999-01-01

The purpose of this calculation is to document (1) the Waste Package Degradation (WAPDEG) version 3.09 (CRWMS M and O 1998b). Software Routine Report for WAPDEG (Version 3.09) simulations used to analyze waste package degradation and failure under the repository exposure conditions characterized by the open loop option of the post-closure ventilation design and, (2) post-processing of these results into tables of waste package degradation time histories suitable for use as input into the Integrated Probabilistic Simulator for Environmental Systems version 5.19.0 1 (RIP) computer program (Golder Associates 1998). Specifically, the WAPDEG simulations discussed in this calculation correspond to waste package emplacement conditions (repository environment and design) defined in the Total System Performance Assessment-Viability Assessment (TSPA-VA), with the exception that the open loop option of the post-closure ventilation License Application Design Selection (LADS) Design Alternative (Design Alternative 3b) was analyzed. The open loop post-closure ventilation design alternative, under which airways to the surface remain open after repository closure, could result in substantial cooling and drying of the potential repository. In open loop post-closure ventilation, expanded air heated by waste decay would move up an exhaust shaft, pulling denser, cooler air into the repository through intake shafts. The exchange of air with the atmosphere could remove more heat and moisture. As a result of the enhanced ventilation relative to the TSPA-VA base-case design, different temperature and relative humidity time histories at the waste package surface are calculated (input to the WAPDEG simulations), and consequently different waste package failure histories (as calculated by WAPDEG) result

Antiviral activities of Radix Isatidis polysaccharide against type II herpes simplex virus in vitro

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Chunmei WANG

2018-03-01

Full Text Available Abstract This study investigated the antiviral activities of Radix Isatidis polysaccharide (RIP against type II herpes simplex virus (HSV-2 in vitro. RIP was prepared from the Radix Isatidis root. The toxicity of RIP on Vero cells was detected. The direct killing effect of RIP on HSV-2, inhibitory effect of RIP on HSV-2 replication and inhibitory effect of RIP on HSV-2 adsorption were determined. Results showed that, RIP in concentration range of 25-800 mg/L had no toxic effect on Vero cells. RIP with different concentrations could not directly inactivate the HSV-2. The effective rates on inhibition of HSV-2 replication and adsorption in 800 mg/L RIP group were 71.57% and 48.37%, respectively, which were the highest among different groups. In conclusion, RIP has the antiviral effect against HSV-2 in vitro. This effect mainly occurs in inhibiting the virus duplication and adsorption.

The Plant Ribosome-Inactivating Proteins Play Important Roles in Defense against Pathogens and Insect Pest Attacks

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Feng Zhu

2018-02-01

Full Text Available Ribosome-inactivating proteins (RIPs are toxic N-glycosidases that depurinate eukaryotic and prokaryotic rRNAs, thereby arresting protein synthesis during translation. RIPs are widely found in various plant species and within different tissues. It is demonstrated in vitro and in transgenic plants that RIPs have been connected to defense by antifungal, antibacterial, antiviral, and insecticidal activities. However, the mechanism of these effects is still not completely clear. There are a number of reviews of RIPs. However, there are no reviews on the biological functions of RIPs in defense against pathogens and insect pests. Therefore, in this report, we focused on the effect of RIPs from plants in defense against pathogens and insect pest attacks. First, we summarize the three different types of RIPs based on their physical properties. RIPs are generally distributed in plants. Then, we discuss the distribution of RIPs that are found in various plant species and in fungi, bacteria, algae, and animals. Various RIPs have shown unique bioactive properties including antibacterial, antifungal, antiviral, and insecticidal activity. Finally, we divided the discussion into the biological roles of RIPs in defense against bacteria, fungi, viruses, and insects. This review is focused on the role of plant RIPs in defense against bacteria, fungi, viruses, and insect attacks. The role of plant RIPs in defense against pathogens and insects is being comprehended currently. Future study utilizing transgenic technology approaches to study the mechanisms of RIPs will undoubtedly generate a better comprehending of the role of plant RIPs in defense against pathogens and insects. Discovering additional crosstalk mechanisms between RIPs and phytohormones or reactive oxygen species (ROS against pathogen and insect infections will be a significant subject in the field of biotic stress study. These studies are helpful in revealing significance of genetic control that can

RNA Binding Proteins Posttranscriptionally Regulate Genes Involved In Oncogenesis

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2010-06-01

HuR using RNA immunoprecipitations applied to m icroarray chip s ( RIP-Chip) in estrogen positiv e (ER+) and estrogen negative (ER-) breast ca ncer...CALM2 mRNAs, were identified and validated by quantitative RT-PCR and biotin pull- down analysis. Conclusion: This is the first report of a side-by...labeled amplified cDNA) were quantitated using a Nanodrop™ (Thermo Fisher Scientific, Waltham, MA) spectrophotometer. RNA quality and integrity were

Estrutura e classificação de um remanescente de floresta ripária no município de Lages, SC

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André Rosalvo Terra Nascimento

2011-06-01

Full Text Available Este estudo objetiva descrever a diversidade e investigar aspectos da classificação de um remanescente de floresta ripária na região de Lages, estado de Santa Catarina. Usando o método de parcelas foram alocadas vinte e cinco unidades amostrais ao longo do curso de água, sendo mensuradas todas as espécies arbóreas com diâmetro à altura do peito (DAP maior ou igual a 5 cm. A comunidade apresentou um dossel multiestratificado com espécies emergentes de grande porte e uma riqueza de 67 espécies arbóreas. A distribuição em diâmetro evidenciou uma comunidade autoregenerativa, com um grande número de indivíduos de pequenos diâmetros, os quais juntamente com as árvores de grande porte, somaram altos valores de área basal e densidade por hectare. A classificação separou os trechos mais desenvolvidos com maior área basal e complexidade com a presença de Cabralea canjerana e Myrcia hatschbachii dos trechos mais instáveis e com presença das espécies mais generalistas Celtis iguanaea e Ilex brevicuspis, denotando uma grande variabilidade ambiental nesse tipo de floresta.

The nuclear receptor ERβ engages AGO2 in regulation of gene transcription, RNA splicing and RISC loading.

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Tarallo, Roberta; Giurato, Giorgio; Bruno, Giuseppina; Ravo, Maria; Rizzo, Francesca; Salvati, Annamaria; Ricciardi, Luca; Marchese, Giovanna; Cordella, Angela; Rocco, Teresa; Gigantino, Valerio; Pierri, Biancamaria; Cimmino, Giovanni; Milanesi, Luciano; Ambrosino, Concetta; Nyman, Tuula A; Nassa, Giovanni; Weisz, Alessandro

2017-10-06

The RNA-binding protein Argonaute 2 (AGO2) is a key effector of RNA-silencing pathways It exerts a pivotal role in microRNA maturation and activity and can modulate chromatin remodeling, transcriptional gene regulation and RNA splicing. Estrogen receptor beta (ERβ) is endowed with oncosuppressive activities, antagonizing hormone-induced carcinogenesis and inhibiting growth and oncogenic functions in luminal-like breast cancers (BCs), where its expression correlates with a better prognosis of the disease. Applying interaction proteomics coupled to mass spectrometry to characterize nuclear factors cooperating with ERβ in gene regulation, we identify AGO2 as a novel partner of ERβ in human BC cells. ERβ-AGO2 association was confirmed in vitro and in vivo in both the nucleus and cytoplasm and is shown to be RNA-mediated. ChIP-Seq demonstrates AGO2 association with a large number of ERβ binding sites, and total and nascent RNA-Seq in ERβ + vs ERβ - cells, and before and after AGO2 knock-down in ERβ + cells, reveals a widespread involvement of this factor in ERβ-mediated regulation of gene transcription rate and RNA splicing. Moreover, isolation and sequencing by RIP-Seq of ERβ-associated long and small RNAs in the cytoplasm suggests involvement of the nuclear receptor in RISC loading, indicating that it may also be able to directly control mRNA translation efficiency and stability. These results demonstrate that AGO2 can act as a pleiotropic functional partner of ERβ, indicating that both factors are endowed with multiple roles in the control of key cellular functions.

Functional Outcome and Healing of Large and Massive Rotator Cuff Tears Repaired With a Load-Sharing Rip-Stop Construct.

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Noyes, Matthew P; Ladermann, Alexandre; Denard, Patrick J

2017-09-01

To prospectively review functional outcomes and healing rates of large and massive rotator cuff tears repaired with a load-sharing rip-stop (LSRS) technique. Twenty-one consecutive patients underwent arthroscopic rotator cuff repair with an LSRS construct between January and December 2014. Seventeen patients with a minimum of 2 years' follow-up were included. Four patients did not complete clinical evaluations and functional outcome scores at a minimum of 2 years' follow-up and were lost to follow-up. Ultrasound imaging was used to assess for rotator cuff healing at a minimum of 6 months postoperatively. Range of motion, strength, and functional outcome scores were evaluated at final follow-up. Mean active forward elevation improved from 109° preoperatively to 153° postoperatively, and mean supraspinatus strength improved by 1 strength grade, from 3.5 preoperatively to 4.4 postoperatively. When we compared preoperative and postoperative values, the American Shoulder and Elbow Surgeons score improved from 40.8 to 89.5, the Single Assessment Numeric Evaluation score improved from 32.8 to 83.1, the Simple Shoulder Test score improved from 3.8 to 10.3, and the pain score on a visual analog scale decreased from 4.8 to 0.8 (P rotator cuff tears. This construct may be an alternative for tears not amenable to double-row repair. Level IV, therapeutic case series. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

QNB: differential RNA methylation analysis for count-based small-sample sequencing data with a quad-negative binomial model.

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Liu, Lian; Zhang, Shao-Wu; Huang, Yufei; Meng, Jia

2017-08-31

As a newly emerged research area, RNA epigenetics has drawn increasing attention recently for the participation of RNA methylation and other modifications in a number of crucial biological processes. Thanks to high throughput sequencing techniques, such as, MeRIP-Seq, transcriptome-wide RNA methylation profile is now available in the form of count-based data, with which it is often of interests to study the dynamics at epitranscriptomic layer. However, the sample size of RNA methylation experiment is usually very small due to its costs; and additionally, there usually exist a large number of genes whose methylation level cannot be accurately estimated due to their low expression level, making differential RNA methylation analysis a difficult task. We present QNB, a statistical approach for differential RNA methylation analysis with count-based small-sample sequencing data. Compared with previous approaches such as DRME model based on a statistical test covering the IP samples only with 2 negative binomial distributions, QNB is based on 4 independent negative binomial distributions with their variances and means linked by local regressions, and in the way, the input control samples are also properly taken care of. In addition, different from DRME approach, which relies only the input control sample only for estimating the background, QNB uses a more robust estimator for gene expression by combining information from both input and IP samples, which could largely improve the testing performance for very lowly expressed genes. QNB showed improved performance on both simulated and real MeRIP-Seq datasets when compared with competing algorithms. And the QNB model is also applicable to other datasets related RNA modifications, including but not limited to RNA bisulfite sequencing, m 1 A-Seq, Par-CLIP, RIP-Seq, etc.

Studies on a novel peptide isolated and purified from rat insulinoma tissue

Energy Technology Data Exchange (ETDEWEB)

Al-Akhras, G N

1987-01-01

Rat insulinoma peptide (RIP) which appears to be either a fragment of, or an altered rat C-peptide was isolated and purified by dialysis. The purity of this peptide was investigated using polyacrylamide gel electrophoresis with sodium dodecyl sulfate, isoelectric focusing, and high performance liquid chromatography. RIP may contain two peptides similar to each other but differing in their isoelectric points. The molecular weight of RIP was found to be 1982 daltons by fast atoms bombardment mass spectrometry giving a chain length of approximately 22 amino acid residues. From information obtained using radioimmunoassay employing antiserum R901, RIP appears to share a common C-terminus with rat C-peptide. A radioimmunoassay for RIP was developed using the purified RIP as immunogen and for standards and tracers. An indirect enzyme linked immunosorbent assay (ELISA) for rat insulinoma peptide was developed using purified RIP for immunogen and semi-purified RIP as a standard.

Predicting radiocaesium sorption characteristics with soil chemical properties for Japanese soils.

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Uematsu, Shinichiro; Smolders, Erik; Sweeck, Lieve; Wannijn, Jean; Van Hees, May; Vandenhove, Hildegarde

2015-08-15

The high variability of the soil-to-plant transfer factor of radiocaesium (RCs) compels a detailed analysis of the radiocaesium interception potential (RIP) of soil, which is one of the specific factors ruling the RCs transfer. The range of the RIP values for agricultural soils in the Fukushima accident affected area has not yet been fully surveyed. Here, the RIP and other major soil chemical properties were characterised for 51 representative topsoils collected in the vicinity of the Fukushima contaminated area. The RIP ranged a factor of 50 among the soils and RIP values were lower for Andosols compared to other soils, suggesting a role of soil mineralogy. Correlation analysis revealed that the RIP was most strongly and negatively correlated to soil organic matter content and oxalate extractable aluminium. The RIP correlated weakly but positively to soil clay content. The slope of the correlation between RIP and clay content showed that the RIP per unit clay was only 4.8 mmol g(-1) clay, about threefold lower than that for clays of European soils, suggesting more amorphous minerals and less micaceous minerals in the clay fraction of Japanese soils. The negative correlation between RIP and soil organic matter may indicate that organic matter can mask highly selective sorption sites to RCs. Multiple regression analysis with soil organic matter and cation exchange capacity explained the soil RIP (R(2)=0.64), allowing us to map soil RIP based on existing soil map information. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of an Inertia-Increased ABWR Internal Pump

International Nuclear Information System (INIS)

Shirou Takahashi; Kousei Umemori; Kooji Shiina; Tetsuya Totani; Akihiro Sakashita; Norimichi Yamashita; Takahisa Kondo

2002-01-01

It is possible to simplify the reactor internal pump power supply system in the ABWR without affecting the core flow supply when a trip of all RIPs event occurs by eliminating the motor-generator sets and increasing the rotating inertia of the RIPs. This inertia increase due to an additional flywheel, which leads to a gain in weight and length, requires a larger diameter nozzle with a thicker sleeve. However, a thicker sleeve nozzle and a longer and heavier motor casing may change the RIP performance. In the present study, the inertia-increased RIP was verified through full-scale tests. The rotating inertia time constant for coast-down characteristics (behavior of the RIP speed in the event of power loss) for the inertia-increased RIP was doubled compared with the current RIP. The inertia-increased RIP with the thicker sleeve nozzle maintained good performance and its power supply system without motor-generator sets was judged appropriate for the ABWR. (authors)

Biomechanical validation of load-sharing rip-stop fixation for the repair of tissue-deficient rotator cuff tears.

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Burkhart, Stephen S; Denard, Patrick J; Konicek, John; Hanypsiak, Bryan T

2014-02-01

Poor-quality tendon is one of the most difficult problems the surgeon must overcome in achieving secure fixation during rotator cuff repair. A load-sharing rip-stop construct (LSRS) has recently been proposed as a method for improving fixation strength, but the biomechanical properties of this construct have not yet been examined. To compare the strength of the LSRS construct to that of single-row fixation for rotator cuff repair. Controlled laboratory study. Rotator cuff tears were created in 6 cadaveric matched-pair specimens and repaired with a single row or an LSRS. In the LSRS repair, a 2-mm suture tape was placed as an inverted mattress stitch in the rotator cuff, and sutures from 2 anchors were placed as simple stitches that passed medial to the suture tape. The suture tape limbs were secured with knotless anchors laterally before sutures were tied from the medial anchors. Displacement was observed with video tracking after cyclic loading, and specimens were loaded to failure. The mean load to failure was 371 ± 102 N in single-row repairs compared with 616 ± 185 N in LSRS repairs (P = .031). There was no difference in displacement with cyclic loading between the groups (3.3 ± 0.8 mm vs. 3.5 ± 1.1 mm; P = .561). In the single-row group, 4 of 6 failures occurred at the suture-tendon interface. In the LSRS group, only 1 failure occurred at the suture-tendon interface. The ultimate failure load of the LSRS construct for rotator cuff repair was 1.7 times that of a single-row construct in a cadaveric model. The LSRS rotator cuff repair construct may be useful in the repair of difficult tears such as massive tears, medial tears, and tears with tendon loss.

NOD2, RIP2 and IRF5 Play a Critical Role in the Type I Interferon Response to Mycobacterium tuberculosis

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Jiang, Zhaozhao; Fortune, Sarah M.; Coulombe, Francois; Behr, Marcel A.; Fitzgerald, Katherine A.; Sassetti, Christopher M.; Kelliher, Michelle A.

2009-01-01

While the recognition of microbial infection often occurs at the cell surface via Toll-like receptors, the cytosol of the cell is also under surveillance for microbial products that breach the cell membrane. An important outcome of cytosolic recognition is the induction of IFNα and IFNβ, which are critical mediators of immunity against both bacteria and viruses. Like many intracellular pathogens, a significant fraction of the transcriptional response to Mycobacterium tuberculosis infection depends on these type I interferons, but the recognition pathways responsible remain elusive. In this work, we demonstrate that intraphagosomal M. tuberculosis stimulates the cytosolic Nod2 pathway that responds to bacterial peptidoglycan, and this event requires membrane damage that is actively inflicted by the bacterium. Unexpectedly, this recognition triggers the expression of type I interferons in a Tbk1- and Irf5-dependent manner. This response is only partially impaired by the loss of Irf3 and therefore, differs fundamentally from those stimulated by bacterial DNA, which depend entirely on this transcription factor. This difference appears to result from the unusual peptidoglycan produced by mycobacteria, which we show is a uniquely potent agonist of the Nod2/Rip2/Irf5 pathway. Thus, the Nod2 system is specialized to recognize bacteria that actively perturb host membranes and is remarkably sensitive to mycobacteria, perhaps reflecting the strong evolutionary pressure exerted by these pathogens on the mammalian immune system. PMID:19578435

The global nitrogen regulator, FNR1, regulates fungal nutrition-genes and fitness during Fusarium oxysporum pathogenesis.

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Divon, Hege Hvattum; Ziv, Carmit; Davydov, Olga; Yarden, Oded; Fluhr, Robert

2006-11-01

SUMMARY Fusarium oxysporum is a soil-borne pathogen that infects plants through the roots and uses the vascular system for host ingress. Specialized for this route of infection, F. oxysporum is able to adapt to the scarce nutrient environment in the xylem vessels. Here we report the cloning of the F. oxysporum global nitrogen regulator, Fnr1, and show that it is one of the determinants for fungal fitness during in planta growth. The Fnr1 gene has a single conserved GATA-type zinc finger domain and is 96% and 48% identical to AREA-GF from Gibberella fujikuroi, and NIT2 from Neurospora crassa, respectively. Fnr1 cDNA, expressed under a constitutive promoter, was able to complement functionally an N. crassa nit-2(RIP) mutant, restoring the ability of the mutant to utilize nitrate. Fnr1 disruption mutants showed high tolerance to chlorate and reduced ability to utilize several secondary nitrogen sources such as amino acids, hypoxanthine and uric acid, whereas growth on favourable nitrogen sources was not affected. Fnr1 disruption also abolished in vitro expression of nutrition genes, normally induced during the early phase of infection. In an infection assay on tomato seedlings, infection rate of disruption mutants was significantly delayed in comparison with the parental strain. Our results indicate that FNR1 mediates adaptation to nitrogen-poor conditions in planta through the regulation of secondary nitrogen acquisition, and as such acts as a determinant for fungal fitness during infection.

Development of inertia-increased reactor internal pump

International Nuclear Information System (INIS)

Tanaka, Masaaki; Matsumura, Seiichi; Kikushima, Jun; Kawamura, Shinichi; Yamashita, Norimichi; Kurosaki, Toshikazu; Kondo, Takahisa

2000-01-01

The Reactor Internal Pump (RIP) was adopted for the Reactor Recirculation System (RRS) of Advanced Boiling Water Reactor (ABWR) plants, and ten RIPs are located at the bottom of the reactor pressure vessel. In order to simplify the power supply system for the RIPs, a new inertia-increased RIP was developed, which allows to eliminate the Motor-Generator (M-G) sets. The rotating inertia was increased approximately 2.5 times of current RIP inertia by addition of flywheel on its main shaft. A full scale proving test of the inertia-increased RIP under actual plant operating conditions using full scale test loop was performed to evaluate vibration characteristics and coast down characteristics. From the results of this proving test, the validity of the new inertia-increased RIP and its power supply system (without M-G sets) was confirmed. (author)

Cylindromatosis mediates neuronal cell death in vitro and in vivo.

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Ganjam, Goutham K; Terpolilli, Nicole Angela; Diemert, Sebastian; Eisenbach, Ina; Hoffmann, Lena; Reuther, Christina; Herden, Christiane; Roth, Joachim; Plesnila, Nikolaus; Culmsee, Carsten

2018-01-19

The tumor-suppressor cylindromatosis (CYLD) is a deubiquitinating enzyme and key regulator of cell proliferation and inflammation. A genome-wide siRNA screen linked CYLD to receptor interacting protein-1 (RIP1) kinase-mediated necroptosis; however, the exact mechanisms of CYLD-mediated cell death remain unknown. Therefore, we investigated the precise role of CYLD in models of neuronal cell death in vitro and evaluated whether CYLD deletion affects brain injury in vivo. In vitro, downregulation of CYLD increased RIP1 ubiquitination, prevented RIP1/RIP3 complex formation, and protected neuronal cells from oxidative death. Similar protective effects were achieved by siRNA silencing of RIP1 or RIP3 or by pharmacological inhibition of RIP1 with necrostatin-1. In vivo, CYLD knockout mice were protected from trauma-induced brain damage compared to wild-type littermate controls. These findings unravel the mechanisms of CYLD-mediated cell death signaling in damaged neurons in vitro and suggest a cell death-mediating role of CYLD in vivo.

Molecular cloning and functional analysis of nucleotide-binding oligomerization domain-containing protein 1 in rainbow trout, Oncorhynchus mykiss.

Science.gov (United States)

Jang, Ju Hye; Kim, Hyun; Kim, Yu Jin; Cho, Ju Hyun

2016-04-01

NOD1 has important roles in innate immunity as sensor of microbial components derived from bacterial peptidoglycan. In this study, we identified genes encoding components of the NOD1 signaling pathway, including NOD1 (OmNOD1) and RIP2 (OmRIP2) from rainbow trout, Oncorhynchus mykiss, and investigated whether OmNOD1 has immunomodulating activity in a rainbow trout hepatoma cell line RTH-149 treated with NOD1-specific ligand (iE-DAP). The deduced amino acid sequence of OmNOD1 contained conserved CARD, NOD and LRR domains. Loss-of-function and gain-of-function experiments indicated that OmNOD1 is involved in the expression of pro-inflammatory cytokines. Silencing of OmNOD1 in RTH-149 cells treated with iE-DAP decreased the expression of IL-1β, IL-6, IL-8 and TNF-α. Conversely, overexpression of OmNOD1 resulted in up-regulation of IL-1β, IL-6, IL-8 and TNF-α expression. In addition, RIP2 inhibitor (gefitinib) significantly decreased the expression of these pro-inflammatory cytokines induced by iE-DAP in RTH-149 cells. These findings highlight the important role of NOD1 signaling pathway in fish in eliciting innate immune response. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of a simplified statistical methodology for nuclear fuel rod internal pressure calculation

International Nuclear Information System (INIS)

Kim, Kyu Tae; Kim, Oh Hwan

1999-01-01

A simplified statistical methodology is developed in order to both reduce over-conservatism of deterministic methodologies employed for PWR fuel rod internal pressure (RIP) calculation and simplify the complicated calculation procedure of the widely used statistical methodology which employs the response surface method and Monte Carlo simulation. The simplified statistical methodology employs the system moment method with a deterministic statistical methodology employs the system moment method with a deterministic approach in determining the maximum variance of RIP. The maximum RIP variance is determined with the square sum of each maximum value of a mean RIP value times a RIP sensitivity factor for all input variables considered. This approach makes this simplified statistical methodology much more efficient in the routine reload core design analysis since it eliminates the numerous calculations required for the power history-dependent RIP variance determination. This simplified statistical methodology is shown to be more conservative in generating RIP distribution than the widely used statistical methodology. Comparison of the significances of each input variable to RIP indicates that fission gas release model is the most significant input variable. (author). 11 refs., 6 figs., 2 tabs

Development of ABWR inertia-increased reactor internal pump and thicker sleeve nozzle

International Nuclear Information System (INIS)

Takahashi, Shirou; Shiina, Kouji; Matsumura, Seiichi

2002-01-01

The conventional reactor internal pumps (RIPs) in the ABWR have an inertia moment coming from the shafts and Motor-Generator sets, enabling the RIPs to continue running for a few seconds, when a trip of all RIPs event occurs. It is possible to simplify the RIPs' power supply system without affecting the core flow supply when the above event occurs by eliminating M-G sets, if the rotating inertia is increased. This inertia increase due to an additional flywheel, which leads to gains in weight and length, requires the larger diameter nozzle with the thicker sleeve. However, too large a nozzle diameter may change the hydraulic performance. In authors' previous study, the optimum nozzle diameter (492 mm) was selected through 1/5-scale test. In this study, the 492 mm nozzle and the inertia-increased RIP were verified through the full-scale tests. The rotating inertia time constant on coastdown characteristics (behavior of the RIP speed in the event of power loss) for the inertia-increased RIP doubled compared with the current RIP. The casing and the shaft vibration were also confirmed to satisfy the design criteria. Moreover, hydraulic performance and heat increase in the motor casing due to the flywheel were evaluated. The inertia increased RIP with the 492 mm nozzle maintained good performance. (author)

New ribosome-inactivating proteins with polynucleotide:adenosine glycosidase and antiviral activities from Basella rubra L. and bougainvillea spectabilis Willd.

Science.gov (United States)

Bolognesi, A; Polito, L; Olivieri, F; Valbonesi, P; Barbieri, L; Battelli, M G; Carusi, M V; Benvenuto, E; Del Vecchio Blanco, F; Di Maro, A; Parente, A; Di Loreto, M; Stirpe, F

1997-12-01

New single-chain (type 1) ribosome-inactivating proteins (RIPs) were isolated from the seeds of Basella rubra L. (two proteins) and from the leaves of Bougainvillea spectabilis Willd. (one protein). These RIPs inhibit protein synthesis both in a cell-free system, with an IC50 (concentration causing 50% inhibition) in the 10(-10) M range, and by various cell lines, with IC50S in the 10(-8)-10(-6) M range. All three RIPs released adenine not only from rat liver ribosomes but also from Escherichia coli rRNA, polyadenylic acid, herring sperm DNA, and artichoke mottled crinkle virus (AMCV) genomic RNA, thus being polynucleotide:adenosine glycosidases. The proteins from Basella rubra had toxicity to mice similar to that of most type 1 RIPs (Barbieri et al., 1993, Biochim Biophys Acta 1154: 237-282) with an LD50 (concentration that is 50% lethal) Bougainvillea spectabilis had an LD50 > 32 mg.kg-1. The N-terminal sequence of the two RIPs from Basella rubra had 80-93% identity, whereas it differed from the sequence of the RIP from Bougainvillea spectabilis. When tested with antibodies against various RIPs, the RIPs from Basella gave some cross-reactivity with sera against dianthin 32, and weak cross-reactivity with momordin I and momorcochin-S, whilst the RIP from Bougainvillea did not cross-react with any antiserum tested. An RIP from Basella rubra and one from Bougainvillea spectabilis were tested for antiviral activity, and both inhibited infection of Nicotiana benthamiana by AMCV.

The Necrosome Promotes Pancreas Oncogenesis via CXCL1 and Mincle Induced Immune Suppression

Science.gov (United States)

Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Giao Ly, Nancy Ngoc; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Barilla, Rocky; Daley, Donnele; Greco, Stephanie H.; Torres-Hernandez, Alejandro; Pergamo, Matthew; Ochi, Atsuo; Zambirinis, Constantinos P.; Pansari, Mridul; Rendon, Mauricio; Tippens, Daniel; Hundeyin, Mautin; Mani, Vishnu R.; Hajdu, Cristina; Engle, Dannielle; Miller, George

2016-01-01

Neoplastic pancreatic epithelial cells are widely believed to die via Caspase 8-dependant apoptotic cell death and chemotherapy is thought to further promote tumor apoptosis1. Conversely, disruption of apoptosis is a basic modality cancer cells exploit for survival2,3. However, the role of necroptosis, or programmed necrosis, in pancreatic ductal adenocarcinoma (PDA) is uncertain. There are a multitude of potential inducers of necroptosis in PDA including ligation of TNFR1, CD95, TRAIL receptors, Toll-like receptors, ROS, and Chemotherapeutics4,5. Here we report that the principal components of the necrosome, RIP1 and RIP3, are highly expressed in PDA and are further upregulated by chemotherapy. Blockade of the necrosome in vitro promoted cancer cell proliferation and induced an aggressive oncogenic phenotype. By contrast, in vivo RIP3 deletion or RIP1 inhibition was protective against oncogenic progression and was associated with the development of a highly immunogenic myeloid and T cell infiltrate. The immune-suppressive tumor microenvironment (TME) associated with intact RIP1/RIP3 signaling was in-part contingent on necroptosis-induced CXCL1 expression whereas CXCL1 blockade was protective against PDA. Moreover, we found that cytoplasmic SAP130 was expressed in PDA in a RIP1/RIP3-dependent manner, and Mincle – its cognate receptor – was upregulated in tumor-infiltrating myeloid cells. Mincle ligation by SAP130 promoted oncogenesis whereas Mincle deletion was protective and phenocopied the immunogenic reprogramming of the TME characteristic of RIP3 deletion. Cellular depletion experiments suggested that whereas inhibitory macrophages promote tumorigenesis in PDA, they lose their immune-suppressive effects in the context of RIP3 or Mincle deletion. As such, T cells which are dispensable to PDA progression in hosts with intact RIP3 or Mincle signaling become reprogrammed into indispensable mediators of anti-tumor immunity in absence of RIP3 or Mincle. Our work

Planeeringut ei saadud 8 päevaga

Index Scriptorium Estoniae

2010-01-01

Tartu Ringkonnakohtu otsusest Ain Seppiku, Sulev Seppiku ja Siim Seppiku ning ajalehe Äripäev vahel. Äripäev lükkab ümber andmed selle kohta, nagu oleks nn Antennideväljaku krundi detailplaneering kehtestatud 8 päevaga. Vastukaja artiklitele: Soe, Ralf-Martin. Sulev Seppik tegi Viimsis imet. // Äripäev (2007/Mar/1), lk. 4-5 ; Arumäe, Urmas. Viimsi võim ei tegele maaäriga. // Äripäev (2007/Mar/13), lk. 27 ; Soe, Ralf-Martin. Viimsi võtmeisikute tehingutel kahtlane maik. // Äripäev (2007/Mar/23), lk. 12-13

Necroptosis Mediates TNF-Induced Toxicity of Hippocampal Neurons

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Shan Liu

2014-01-01

Full Text Available Tumor necrosis factor-α (TNF-α is a critical proinflammatory cytokine regulating neuroinflammation. Elevated levels of TNF-α have been associated with various neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. However, the signaling events that lead to TNF-α-initiated neurotoxicity are still unclear. Here, we report that RIP3-mediated necroptosis, a form of regulated necrosis, is activated in the mouse hippocampus after intracerebroventricular injection of TNF-α. RIP3 deficiency attenuates TNF-α-initiated loss of hippocampal neurons. Furthermore, we characterized the molecular mechanism of TNF-α-induced neurotoxicity in HT-22 hippocampal neuronal cells. HT-22 cells are sensitive to TNF-α only upon caspase blockage and subsequently undergo necrosis. The cell death is suppressed by knockdown of CYLD or RIP1 or RIP3 or MLKL, suggesting that this necrosis is necroptosis and mediated by CYLD-RIP1-RIP3-MLKL signaling pathway. TNF-α-induced necroptosis of HT-22 cells is largely independent of both ROS accumulation and calcium influx although these events have been shown to be critical for necroptosis in certain cell lines. Taken together, these data not only provide the first in vivo evidence for a role of RIP3 in TNF-α-induced toxicity of hippocampal neurons, but also demonstrate that TNF-α promotes CYLD-RIP1-RIP3-MLKL-mediated necroptosis of hippocampal neurons largely bypassing ROS accumulation and calcium influx.

Heterochromatin protein 1 (HP1a positively regulates euchromatic gene expression through RNA transcript association and interaction with hnRNPs in Drosophila.

Directory of Open Access Journals (Sweden)

Lucia Piacentini

2009-10-01

Full Text Available Heterochromatin Protein 1 (HP1a is a well-known conserved protein involved in heterochromatin formation and gene silencing in different species including humans. A general model has been proposed for heterochromatin formation and epigenetic gene silencing in different species that implies an essential role for HP1a. According to the model, histone methyltransferase enzymes (HMTases methylate the histone H3 at lysine 9 (H3K9me, creating selective binding sites for itself and the chromodomain of HP1a. This complex is thought to form a higher order chromatin state that represses gene activity. It has also been found that HP1a plays a role in telomere capping. Surprisingly, recent studies have shown that HP1a is present at many euchromatic sites along polytene chromosomes of Drosophila melanogaster, including the developmental and heat-shock-induced puffs, and that this protein can be removed from these sites by in vivo RNase treatment, thus suggesting an association of HP1a with the transcripts of many active genes. To test this suggestion, we performed an extensive screening by RIP-chip assay (RNA-immunoprecipitation on microarrays, and we found that HP1a is associated with transcripts of more than one hundred euchromatic genes. An expression analysis in HP1a mutants shows that HP1a is required for positive regulation of these genes. Cytogenetic and molecular assays show that HP1a also interacts with the well known proteins DDP1, HRB87F, and PEP, which belong to different classes of heterogeneous nuclear ribonucleoproteins (hnRNPs involved in RNA processing. Surprisingly, we found that all these hnRNP proteins also bind heterochromatin and are dominant suppressors of position effect variegation. Together, our data show novel and unexpected functions for HP1a and hnRNPs proteins. All these proteins are in fact involved both in RNA transcript processing and in heterochromatin formation. This suggests that, in general, similar epigenetic mechanisms

Genome-wide RIP-Chip analysis of translational repressor-bound mRNAs in the Plasmodium gametocyte

KAUST Repository

Guerreiro, Ana; Deligianni, Elena; Santos, Jorge M; Silva, Patricia AGC; Louis, Christos; Pain, Arnab; Janse, Chris J; Franke-Fayard, Blandine; Carret, Celine K; Siden-Kiamos, Inga; Mair, Gunnar R

2014-01-01

of RNA polymerase II transcription. Using GFP-tagging, we validate the repression phenotype of selected genes and identify mRNAs relying on the 5′ untranslated region for translational control. Gene deletion reveals a novel protein located in the ookinete

Identification and biochemical analysis of Slac2-c/MyRIP as a Rab27A-, myosin Va/VIIa-, and actin-binding protein.

Science.gov (United States)

Kuroda, Taruho S; Fukuda, Mitsunori

2005-01-01

Slac2-c/MyRIP is a specific Rab27A-binding protein that contains an N-terminal synaptotagmin-like protein (Slp) homology domain (SHD, a newly identified GTP-Rab27A-binding motif), but in contrast to the Slp family proteins, it lacks C-terminal tandem C2 domains. In vitro Slac2-c simultaneously directly interacts with both Rab27A and an actin-based motor protein, myosin Va, via its N-terminal SHD and middle region, respectively, consistent with the fact that the overall structure of Slac2-c is similar to that of Slac2-a/melanophilin, a linker protein between Rab27A and myosin Va in the melanosome transport in melanocytes. Unlike Slac2-a, however, the middle region of Slac2-c interacts with two types of myosins, myosin Va and myosin VIIa. In addition, the most C-terminal part of both Slac2-a and Slac2-c functions as an actin-binding domain: it directly interacts with globular and fibrous actin in vitro, and the actin-binding domain of Slac2-a and Slac2-c colocalizes with actin filaments when it is expressed in living cells (i.e., PC12 cells and mouse melanocytes). In this chapter we describe the methods that have been used to analyze the protein-protein interactions of Slac2-c, specifically with Rab27A, myosin Va/VIIa, and actin.

The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression.

Science.gov (United States)

Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Giao Ly, Nancy Ngoc; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Barilla, Rocky; Daley, Donnele; Greco, Stephanie H; Torres-Hernandez, Alejandro; Pergamo, Matthew; Ochi, Atsuo; Zambirinis, Constantinos P; Pansari, Mridul; Rendon, Mauricio; Tippens, Daniel; Hundeyin, Mautin; Mani, Vishnu R; Hajdu, Cristina; Engle, Dannielle; Miller, George

2016-04-14

Neoplastic pancreatic epithelial cells are believed to die through caspase 8-dependent apoptotic cell death, and chemotherapy is thought to promote tumour apoptosis. Conversely, cancer cells often disrupt apoptosis to survive. Another type of programmed cell death is necroptosis (programmed necrosis), but its role in pancreatic ductal adenocarcinoma (PDA) is unclear. There are many potential inducers of necroptosis in PDA, including ligation of tumour necrosis factor receptor 1 (TNFR1), CD95, TNF-related apoptosis-inducing ligand (TRAIL) receptors, Toll-like receptors, reactive oxygen species, and chemotherapeutic drugs. Here we report that the principal components of the necrosome, receptor-interacting protein (RIP)1 and RIP3, are highly expressed in PDA and are further upregulated by the chemotherapy drug gemcitabine. Blockade of the necrosome in vitro promoted cancer cell proliferation and induced an aggressive oncogenic phenotype. By contrast, in vivo deletion of RIP3 or inhibition of RIP1 protected against oncogenic progression in mice and was associated with the development of a highly immunogenic myeloid and T cell infiltrate. The immune-suppressive tumour microenvironment associated with intact RIP1/RIP3 signalling depended in part on necroptosis-induced expression of the chemokine attractant CXCL1, and CXCL1 blockade protected against PDA. Moreover, cytoplasmic SAP130 (a subunit of the histone deacetylase complex) was expressed in PDA in a RIP1/RIP3-dependent manner, and Mincle--its cognate receptor--was upregulated in tumour-infiltrating myeloid cells. Ligation of Mincle by SAP130 promoted oncogenesis, whereas deletion of Mincle protected against oncogenesis and phenocopied the immunogenic reprogramming of the tumour microenvironment that was induced by RIP3 deletion. Cellular depletion suggested that whereas inhibitory macrophages promote tumorigenesis in PDA, they lose their immune-suppressive effects when RIP3 or Mincle is deleted. Accordingly, T cells

Receptor Interacting Protein 3-Mediated Necroptosis Promotes Lipopolysaccharide-Induced Inflammation and Acute Respiratory Distress Syndrome in Mice.

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Linlin Wang

Full Text Available Necrosis amplifies inflammation and plays important roles in acute respiratory distress syndrome (ARDS. Necroptosis is a newly identified programmed necrosis that is mediated by receptor interacting protein 3 (RIP3. However, the potential involvement and impact of necroptosis in lipopolysaccharide (LPS-induced ARDS remains unknown. We therefore explored the role and mechanism of RIP3-mediated necroptosis in LPS-induced ARDS. Mice were instilled with increasing doses of LPS intratracheally to induce different degrees of ARDS. Lung tissues were harvested for histological and TUNEL staining and western blot for RIP3, p-RIP3, X-linked inhibitor of apoptosis protein (XIAP, mixed lineage kinase domain-like protein (MLKL, total and cleaved caspases-3/8. Then, wild-type and RIP3 knock-out mice were induced ARDS with 30 mg/kg LPS. Pulmonary cellular necrosis was labeled by the propidium Iodide (PI staining. Levels of TNF-a, Interleukin (IL-1β, IL-6, IL-1α, IL-10 and HMGB1, tissue myeloperoxidase (MPO activity, neutrophil counts and total protein concentration were measured. Results showed that in high dose LPS (30mg/kg and 40mg/kg -induced severe ARDS, RIP3 protein was increased significantly, accompanied by increases of p-RIP3 and MLKL, while in low dose LPS (10mg/kg and 20mg/kg -induced mild ARDS, apoptosis was remarkably increased. In LPS-induced severe ARDS, RIP3 knock-out alleviated the hypothermia symptom, increased survival rate and ameliorated the lung tissue injury RIP3 depletion also attenuated LPS-induced increase in IL-1α/β, IL-6 and HMGB1 release, decreased tissue MPO activity, and reduced neutrophil influx and total protein concentration in BALF in severe ARDS. Further, RIP3 depletion reduced the necrotic cells in the lung and decreased the expression of MLKL, but had no impact on cleaved caspase-3 in LPS-induced ARDS. It is concluded that RIP3-mediated necroptosis is a major mechanism of enhanced inflammation and lung tissue injury in

Towards estimation of respiratory muscle effort with respiratory inductance plethysmography signals and complementary ensemble empirical mode decomposition.

Science.gov (United States)

Chen, Ya-Chen; Hsiao, Tzu-Chien

2018-07-01

Respiratory inductance plethysmography (RIP) sensor is an inexpensive, non-invasive, easy-to-use transducer for collecting respiratory movement data. Studies have reported that the RIP signal's amplitude and frequency can be used to discriminate respiratory diseases. However, with the conventional approach of RIP data analysis, respiratory muscle effort cannot be estimated. In this paper, the estimation of the respiratory muscle effort through RIP signal was proposed. A complementary ensemble empirical mode decomposition method was used, to extract hidden signals from the RIP signals based on the frequency bands of the activities of different respiratory muscles. To validate the proposed method, an experiment to collect subjects' RIP signal under thoracic breathing (TB) and abdominal breathing (AB) was conducted. The experimental results for both the TB and AB indicate that the proposed method can be used to loosely estimate the activities of thoracic muscles, abdominal muscles, and diaphragm. Graphical abstract ᅟ.

Inductive plethysmography potential as a surrogate for ventilatory measurements during rest and moderate physical exercise

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Ramona Cabiddu

2016-01-01

Full Text Available Background: Portable respiratory inductive plethysmography (RIP systems have been validated for ventilatory assessment during resting conditions and during incremental treadmill exercise. However, in clinical settings and during field-based exercise, intensity is usually constant and submaximal. A demonstration of the ability of RIP to detect respiratory measurements accurately during constant intensity conditions would promote and validate the routine use of portable RIP devices as an alternative to ergospirometry (ES, the current gold standard technique for ventilatory measures. Objective: To investigate the agreement between respiratory variables recorded by a portable RIP device and by ES during rest and constant intensity exercise. Method: Tidal volume (VT, respiratory rate (RR and minute ventilation (VE were concurrently acquired by portable RIP and ES in seven healthy male volunteers during standing rest position and constant intensity treadmill exercise. Results: Significant agreement was found between RIP and ES acquisitions during the standing rest position and constant intensity treadmill exercise for RR and during the standing rest position for VE. Conclusion: Our results suggest that portable RIP devices might represent a suitable alternative to ES during rest and during constant submaximal exercise.

Development of a Respiratory Inductive Plethysmography Module Supporting Multiple Sensors for Wearable Systems

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Zhengbo Zhang

2012-09-01

Full Text Available In this paper, we present an RIP module with the features of supporting multiple inductive sensors, no variable frequency LC oscillator, low power consumption, and automatic gain adjustment for each channel. Based on the method of inductance measurement without using a variable frequency LC oscillator, we further integrate pulse amplitude modulation and time division multiplexing scheme into a module to support multiple RIP sensors. All inductive sensors are excited by a high-frequency electric current periodically and momentarily, and the inductance of each sensor is measured during the time when the electric current is fed to it. To improve the amplitude response of the RIP sensors, we optimize the sensing unit with a matching capacitor parallel with each RIP sensor forming a frequency selection filter. Performance tests on the linearity of the output with cross-sectional area and the accuracy of respiratory volume estimation demonstrate good linearity and accurate lung volume estimation. Power consumption of this new RIP module with two sensors is very low. The performance of respiration measurement during movement is also evaluated. This RIP module is especially desirable for wearable systems with multiple RIP sensors for long-term respiration monitoring.

Ringkonnakohtu otsus

Index Scriptorium Estoniae

2010-01-01

Tartu ringkonnakohtu otsusest Ain Seppiku, Sulev Seppiku ja Siim Seppiku ning ajalehe Äripäev vahel. Äripäev lükkab ümber andmed, nagu oleks Seppikutel seos nn allilmaga, nn ühiskassaga ja Oleg Lvoviga. Skeem. Vastukaja artiklitele: Raidla, Peeter. Kas Keskerakonna rahal on märk küljes? // Äripäev (2007/Mar/16), lk. 12-15 ; Raidla, Peeter. Kust võis tulla Seppikute raha? // Äripäev (2007/Mar/16), lk. 14-15

Journal of Genetics | Indian Academy of Sciences

Indian Academy of Sciences (India)

Keywords. Spore killer; meiotic drive; Neurospora crassa; RIP. Abstract. A convenient assay to score repeat-induced point mutation (RIP) in Neurospora employs the erg-3 locus as a mutagenesis target. Using this assay we screened 132 wild-isolated Neurospora crassa strains for ability to dominantly suppress RIP.

The Cytotoxicity of Elderberry Ribosome-Inactivating Proteins Is Not Solely Determined by Their Protein Translation Inhibition Activity.

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Chenjing Shang

Full Text Available Although the protein translation inhibition activity of ribosome inactivating proteins (RIPs is well documented, little is known about the contribution of the lectin chain to the biological activity of these proteins. In this study, we compared the in vitro and intracellular activity of several S. nigra (elderberry RIPs and non-RIP lectins. Our data demonstrate that RIPs from elderberry are much more toxic to HeLa cells than to primary fibroblasts. Differences in the cytotoxicity between the elderberry proteins correlated with differences in glycan specificity of their lectin domain, cellular uptake efficiency and intracellular destination. Despite the fact that the bulk of the RIPs accumulated in the lysosomes and partly in the Golgi apparatus, we could demonstrate effective inhibition of protein synthesis in cellula. As we also observed cytotoxicity for non-RIP lectins, it is clear that the lectin chain triggers additional pathways heralding cell death. Our data suggest that one of these pathways involves the induction of autophagy.

STAT5 activity in pancreatic beta-cells influences the severity of diabetes in animal models of type 1 and 2 diabetes

DEFF Research Database (Denmark)

Jackerott, Malene; Møldrup, Annette; Thams, Peter

2006-01-01

Pancreatic beta-cell growth and survival and insulin production are stimulated by growth hormone and prolactin through activation of the transcription factor signal transducer and activator of transcription (STAT)5. To assess the role of STAT5 activity in beta-cells in vivo, we generated transgen...... and type 2 diabetes....... reduced beta-cell proliferation at 6 months of age. The inhibitory effect of high-fat diet or leptin on insulin secretion was diminished in isolated islets from RIP-DNSTAT5 mice compared with wild-type islets. Upon multiple low-dose streptozotocin treatment, RIP-DNSTAT5 mice exhibited higher plasma...... of glucose tolerance, whereas RIP-CASTAT5 mice were more glucose tolerant and less hyperleptinemic than wild-type mice. Although the pancreatic insulin content and relative beta-cell area were increased in high-fat diet-fed RIP-DNSTAT5 mice compared with wild-type or RIP-CASTAT5 mice, RIP-DNSTAT5 mice showed...

Journal of Biosciences | Indian Academy of Sciences

Indian Academy of Sciences (India)

Previous studies from our laboratory showed that chromosome segment duplications (Dps) longer than ∼300 kbp can dominantly suppress RIP, presumably by titration of the RIP machinery, and that although Dps < 200 kbp did not individually suppress RIP, they could do so in homozygous and multiply heterozygous ...

Hypoxic regulation of the expression of genes encoded estrogen related proteins in U87 glioma cells: eff ect of IRE1 inhibition.

Science.gov (United States)

Minchenko, D O; Riabovol, O O; Ratushna, O O; Minchenko, O H

2017-01-01

The aim of the present study was to examine the effect of inhibition of endoplasmic reticulum stress signaling, mediated by IRE1 (inositol requiring enzyme 1), which is a central mediator of the unfolded protein response on the expression of genes encoded estrogen related proteins (NRIP1/RIP140, TRIM16/EBBP, ESRRA/NR3B1, FAM162A/E2IG5, PGRMC2/PMBP, and SLC39A6/LIV-1) and their hypoxic regulation in U87 glioma cells for evaluation of their possible significance in the control of glioma cells proliferation. The expression of NRIP1, EBBP, ESRRA, E2IG5, PGRMC2, and SLC39A6 genes in U87 glioma cells, transfected by empty vector pcDNA3.1 (control) and cells without IRE1 signaling enzyme function (transfected by dnIRE1) upon hypoxia, was studied by a quantitative polymerase chain reaction. Inhibition of both enzymatic activities (kinase and endoribonuclease) of IRE1 signaling enzyme function up-regulates the expression of EBBP, E2IG5, PGRMC2, and SLC39A6 genes is in U87 glioma cells in comparison with the control glioma cells, with more significant changes for E2IG5 and PGRMC2 genes. At the same time, the expression of NRIP1 and ESRRA genes is strongly down-regulated in glioma cells upon inhibition of IRE1. We also showed that hypoxia increases the expression of E2IG5, PGRMC2, and EBBP genes and decreases NRIP1 and ESRRA genes expression in control glioma cells. Furthermore, the inhibition of IRE1 in U87 glioma cells decreases the eff ect of hypoxia on the expression of E2IG5 and PGRMC2 genes, eliminates hypoxic regulation of NRIP1 gene, and enhances the sensitivity of ESRRA gene to hypoxic condition. Furthermore, the expression of SLC39A6 gene is resistant to hypoxia in both the glioma cells with and without IRE1 signaling enzyme function. Results of this investigation demonstrate that inhibition of IRE1 signaling enzyme function affects the expression of NRIP1, EBBP, ESRRA, E2IG5, PGRMC2, and SLC39A6 genes in U87 glioma cells in gene specific manner and these changes

Quantum computation in decoherence-free subspace via cavity-decay-assisted adiabatic passage

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FENG Xunli

2015-08-01

Full Text Available The scalar phantom field Φ leads to various catastrophic fates of the universe including big rip,little rip and other future singularity depending on the choice of its potential.For example,little rip stems from a quadratic potential in general relativity.We suggest a new mechanism to avoid little rip in the 1/R gravity.The phantom field with different potentials,including quadratic,cubic and quantic potentials are studied via numerical calculation in the 1/R gravity with R2 correction.The singularity is avoidable under all these potentials.

The pokeweed leaf mRNA transcriptome and its regulation by jasmonic acid.

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Kira C.M. Neller

2016-03-01

Full Text Available The American pokeweed plant, Phytolacca americana, is recognized for synthesizing pokeweed antiviral protein (PAP, a ribosome inactivating protein (RIP that inhibits the replication of several plant and animal viruses. The plant is also a heavy metal accumulator with applications in soil remediation. However, little is known about pokeweed stress responses, as large-scale sequencing projects have not been performed for this species. Here, we sequenced the mRNA transcriptome of pokeweed in the presence and absence of jasmonic acid (JA, a hormone mediating plant defense. Trinity-based de novo assembly of mRNA from leaf tissue and BLASTx homology searches against public sequence databases resulted in the annotation of 59 096 transcripts. Differential expression analysis identified JA-responsive genes that may be involved in defense against pathogen infection and herbivory. We confirmed the existence of several PAP isoforms and cloned a potentially novel isoform of PAP. Expression analysis indicated that PAP isoforms are differentially responsive to JA, perhaps indicating specialized roles within the plant. Finally, we identified 52 305 natural antisense transcript pairs, four of which comprised PAP isoforms, suggesting a novel form of RIP gene regulation. This transcriptome-wide study of a Phytolaccaceae family member provides a source of new genes that may be involved in stress tolerance in this plant. The sequences generated in our study have been deposited in the SRA database under project # SRP069141.

Assessment of upper tropospheric and stratospheric water vapor and ozone in reanalyses as part of S-RIP

Science.gov (United States)

Davis, Sean M.; Hegglin, Michaela I.; Fujiwara, Masatomo; Dragani, Rossana; Harada, Yayoi; Kobayashi, Chiaki; Long, Craig; Manney, Gloria L.; Nash, Eric R.; Potter, Gerald L.; Tegtmeier, Susann; Wang, Tao; Wargan, Krzysztof; Wright, Jonathon S.

2017-10-01

Reanalysis data sets are widely used to understand atmospheric processes and past variability, and are often used to stand in as "observations" for comparisons with climate model output. Because of the central role of water vapor (WV) and ozone (O3) in climate change, it is important to understand how accurately and consistently these species are represented in existing global reanalyses. In this paper, we present the results of WV and O3 intercomparisons that have been performed as part of the SPARC (Stratosphere-troposphere Processes and their Role in Climate) Reanalysis Intercomparison Project (S-RIP). The comparisons cover a range of timescales and evaluate both inter-reanalysis and observation-reanalysis differences. We also provide a systematic documentation of the treatment of WV and O3 in current reanalyses to aid future research and guide the interpretation of differences amongst reanalysis fields.The assimilation of total column ozone (TCO) observations in newer reanalyses results in realistic representations of TCO in reanalyses except when data coverage is lacking, such as during polar night. The vertical distribution of ozone is also relatively well represented in the stratosphere in reanalyses, particularly given the relatively weak constraints on ozone vertical structure provided by most assimilated observations and the simplistic representations of ozone photochemical processes in most of the reanalysis forecast models. However, significant biases in the vertical distribution of ozone are found in the upper troposphere and lower stratosphere in all reanalyses.In contrast to O3, reanalysis estimates of stratospheric WV are not directly constrained by assimilated data. Observations of atmospheric humidity are typically used only in the troposphere, below a specified vertical level at or near the tropopause. The fidelity of reanalysis stratospheric WV products is therefore mainly dependent on the reanalyses' representation of the physical drivers that

Relationship between the adsorption species of cesium and radiocesium interception potential in soils and minerals: an EXAFS study

International Nuclear Information System (INIS)

Fan, Qiaohui; Yamaguchi, Noriko; Tanaka, Masato; Tsukada, Hirofumi; Takahashi, Yoshio

2014-01-01

This study examined the radiocesium (RCs) interception potential (RIP), cation exchange capacity (CEC), total organic carbon (TOC) content, and adsorption species in soils and minerals by using extended X-ray absorption fine structure (EXAFS) spectroscopy. The RIP related to Cs + adsorption by frayed-edge site (FES) has often been used to measure the mobility and bioavailability of RCs in the environment. This study found that the presence of organic matter (OM) can reduce RIP to a certain extent. The adsorption amount (=Q T ) in soil was obviously correlated to RIP at a small [Cs + ] region, whereas a linear relationship between Q T and CEC was observed at a large [Cs + ] region. Both the inner-sphere (IS) and outer-sphere (OS) complexes of Cs + were observed through EXAFS at a molecular scale. The linear correlation between log (RIP/CEC) and the ratio of the coordination number (CN) of IS (=CN IS ) and OS (=CN OS ) complexes noted as CN IS /(CN IS + CN OS ) suggested that the ratio of CN is very sensitive to Cs + adsorption species with variable RIP and CEC. The adsorption species of Cs + in soil was mainly dependent on the clay mineral content of soil. RIP was affected not only by FES but also by other strong adsorption sites, such as the interlayers and cavities identified as the IS complex in EXAFS analysis. Findings indicated that the EXAFS approach is a powerful and efficient tool to explore the behavior of Cs + in a given environment. - Highlights: • The relationship of Cs + species on soils and minerals and RIP was firstly clarified in this study. • Coordination number of Cs + was very sensitive to Cs + adsorption species with variable RIP and CEC. • This finding can be used as a basis for understanding of Cs + behavior in nature

Small-molecule inhibitor leads of ribosome-inactivating proteins developed using the doorstop approach.

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Yuan-Ping Pang

2011-03-01

Full Text Available Ribosome-inactivating proteins (RIPs are toxic because they bind to 28S rRNA and depurinate a specific adenine residue from the α-sarcin/ricin loop (SRL, thereby inhibiting protein synthesis. Shiga-like toxins (Stx1 and Stx2, produced by Escherichia coli, are RIPs that cause outbreaks of foodborne diseases with significant morbidity and mortality. Ricin, produced by the castor bean plant, is another RIP lethal to mammals. Currently, no US Food and Drug Administration-approved vaccines nor therapeutics exist to protect against ricin, Shiga-like toxins, or other RIPs. Development of effective small-molecule RIP inhibitors as therapeutics is challenging because strong electrostatic interactions at the RIP•SRL interface make drug-like molecules ineffective in competing with the rRNA for binding to RIPs. Herein, we report small molecules that show up to 20% cell protection against ricin or Stx2 at a drug concentration of 300 nM. These molecules were discovered using the doorstop approach, a new approach to protein•polynucleotide inhibitors that identifies small molecules as doorstops to prevent an active-site residue of an RIP (e.g., Tyr80 of ricin or Tyr77 of Stx2 from adopting an active conformation thereby blocking the function of the protein rather than contenders in the competition for binding to the RIP. This work offers promising leads for developing RIP therapeutics. The results suggest that the doorstop approach might also be applicable in the development of other protein•polynucleotide inhibitors as antiviral agents such as inhibitors of the Z-DNA binding proteins in poxviruses. This work also calls for careful chemical and biological characterization of drug leads obtained from chemical screens to avoid the identification of irrelevant chemical structures and to avoid the interference caused by direct interactions between the chemicals being screened and the luciferase reporter used in screening assays.

Role of necroptosis in autophagy signaling during hepatic ischemia and reperfusion

Energy Technology Data Exchange (ETDEWEB)

Hong, Jeong-Min; Kim, Seok-Joo; Lee, Sun-Mee, E-mail: sunmee@skku.edu

2016-10-01

Ischemia and reperfusion (I/R) is a complex phenomenon involving massive inflammation and cell death. Necroptosis refers to a newly described cell death as “programmed necrosis” that is controlled by receptor-interacting protein kinase (RIP) 1 and RIP3, which is involved in the pathogenesis of several inflammatory diseases. Autophagy is an essential cytoprotective system that is rapidly activated in response to various stimuli and involves crosstalk between different modes of cell death and inflammation. In this study, we investigated pattern changes in necroptosis and its role in autophagy signaling during hepatic I/R. Male C57BL/6 mice were subjected to 60 min of ischemia followed by 3 h reperfusion. Necrostatin-1 (Nec-1, a necroptosis inhibitor; 1.65 mg/kg) was administered intraperitoneally 5 min before reperfusion. Hepatic I/R significantly increased the level of RIP3, phosphorylated RIP1 and RIP3 protein expression, and RIP1/RIP3 necrosome formation, which were attenuated by Nec-1. I/R also significantly increased serum levels of alanine aminotransferase, tumor necrosis factor-α, and interleukin-6, which were attenuated by Nec-1. Meanwhile, hepatic I/R activated autophagy and mitophagy, as evidenced by increased LC3-II, PINK1, and Parkin, and decreased sequestosome 1/p62 protein expression. Nec-1 attenuated these changes and attenuated the increased levels of autophagy-related protein (ATG) 3, ATG7, Rab7, and cathepsin B protein expression during hepatic I/R. Moreover, hepatic I/R activated the extracellular signal-regulated kinase (ERK) pathway, and Nec-1 attenuated this increase. Taken together, our findings suggest that necroptosis contributes to hepatic damage during I/R, which induces autophagy via ERK activation. - Highlights: • Hepatic I/R induces RIP1/RIP3-dependent necroptosis. • Necroptosis contributes to hepatic I/R injury. • Necroptosis activates autophagic flux via ERK activation during hepatic I/R.

Stereotactic body radiotherapy for Stage I lung cancer with chronic obstructive pulmonary disease. Special reference to survival and radiation-induced pneumonitis

International Nuclear Information System (INIS)

Inoue, Toshihiko; Shiomi, Hiroya; Oh, Ryoong-Jin

2015-01-01

This retrospective study aimed to evaluate radiation-induced pneumonitis (RIP) and a related condition that we define in this report — prolonged minimal RIP (pmRIP) — after stereotactic body radiotherapy (SBRT) for Stage I primary lung cancer in patients with chronic obstructive pulmonary disease (COPD). We assessed 136 Stage I lung cancer patients with COPD who underwent SBRT. Airflow limitation on spirometry was classified into four Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades, with minor modifications: GOLD 1 (mild), GOLD 2 (moderate), GOLD 3 (severe) and GOLD 4 (very severe). On this basis, we defined two subgroups: COPD-free (COPD -) and COPD-positive (COPD +). There was no significant difference in overall survival or cause-specific–survival between these groups. Of the 136 patients, 44 (32%) had pmRIP. Multivariate analysis showed that COPD and the Brinkman index were statistically significant risk factors for the development of pmRIP. COPD and the Brinkman index were predictive factors for pmRIP, although our findings also indicate that SBRT can be tolerated in early lung cancer patients with COPD. (author)

Upgraded prototype-reactor internal pump for ABWR

International Nuclear Information System (INIS)

Kumagai, Mikio; Amemori, Shiro; Saito, Takehiko

1988-01-01

In 1983, Toshiba, using their own technology, manufactured a commercial grade reactor internal pump (RIP). Recently, however, a licensing agreement with KSB of West Germany covering the RIP technology, has combined the know-how of KSB with Toshiba's technology to produce a truly high-quality prototype RIP. The pump produces the required coreflow for ABWR at low speed and with high efficiency, and simply by increasing the pump speed to the prior level, the coreflow can be further increased for such advantages as improved fuel cycle economy. Here, the advanced features and test results of the RIP are summarized. (author)

RIP Input Tables From WAPDEG for LA Design Selection: Repository Horizon Elevation - 2-Level AML 50% and Near Maximum

International Nuclear Information System (INIS)

B.E. Bullard

1999-01-01

The purpose of this calculation is to document the WAPDEG version 3.09 (CRWMS M and O 1998b). Software Routine Report for WAPDEG (Version 3.09) simulations used to analyze waste package degradation and failure under the repository exposure conditions characterized by a two-tier thermal loading repository design. Also documented is the post-processing of these results into tables of waste-package-degradation-time histories suitable for use as input into the Integrated Probabilistic Simulator for Environmental Systems (RIP) version 5.19.01 (Golder Associates 1998) computer program. Specifically, the WAPDEG simulations discussed in this calculation correspond to waste package emplacement conditions (repository environment and design) as defined in the Total System Performance Assessment-Viability Assessment (CRWMS M and O 1998a). Total System Performance Assessment-Viability Assessment (TSPA-VA) Analyses Technical Basis Document--Chapter 5, Waste Package Degradation Modeling And Abstraction, pp. 5-27 to 5-29, with the exception that a two-tier thermal loading design feature as specified in the License Application Design Selection (LADS) study was analyzed. The particular design feature evaluated in this report is a modification of the repository horizon elevation and layout within the Topopah Springs Member of Yucca Mountain. Specifically, the modification consists of adding a second level, 50-m above the base case repository layout. Two options were considered, representing two variations in thermal loading. In Design Feature 25e (designated DF25e), each level has an Areal Mass Loading (AML) of 42.5 MTU/acre (i.e., half the VA base case). In Design Feature 25f (designated DF25), each level has an AML of 64MTU/acre. As a result of the change in waste package placement relative to the TSPA-VA base-case design, different temperature and relative humidity time histories at the waste package surface are calculated (input to the WAPDEG simulations), and consequently

Ministeeriumid toidavad parasiite / Madli Zobel, Kristina Traks

Index Scriptorium Estoniae

Zobel, Madli, 1976-

2000-01-01

Ministeeriumid peavad üleval kümneid erialaliitusid, mille mõttekus ja kasutegur on küsitav. Tabel: Raha, mis läheb sel aastal liitude toetuseks. Vastuseks vt. Äripäev Mar/29 lk. 26 P. Teppi art., A. Runge art. Äripäev Mar/31 lk. 27, J. Rausi art. Äripäev Apr/6 lk. 27

Ribosome-Inactivating Proteins from Plants: A Historical Overview

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Andrea Bolognesi

2016-11-01

Full Text Available This review provides a historical overview of the research on plant ribosome-inactivating proteins (RIPs, starting from the first studies at the end of eighteenth century involving the purification of abrin and ricin, as well as the immunological experiments of Paul Erlich. Interest in these plant toxins was revived in 1970 by the observation of their anticancer activity, which has given rise to a large amount of research contributing to the development of various scientific fields. Biochemistry analyses succeeded in identifying the enzymatic activity of RIPs and allowed for a better understanding of the ribosomal machinery. Studies on RIP/cell interactions were able to detail the endocytosis and intracellular routing of ricin, thus increasing our knowledge of how cells handle exogenous proteins. The identification of new RIPs and the finding that most RIPs are single-chain polypeptides, together with their genetic sequencing, has aided in the development of new phylogenetic theories. Overall, the biological properties of these proteins, including their abortifacient, anticancer, antiviral and neurotoxic activities, suggest that RIPs could be utilized in agriculture and in many biomedical fields, including clinical drug development.

Risk Reduction and Soil Ecosystem Restoration in an Active Oil Producing Area in an Ecologically Sensitive Setting

Energy Technology Data Exchange (ETDEWEB)

Kerry L. Sublette; Greg Thoma; Kathleen Duncan

2006-01-01

The empowerment of small independent oil and gas producers to solve their own remediation problems will result in greater environmental compliance and more effective protection of the environment as well as making small producers more self-reliant. In Chapter 1 we report on the effectiveness of a low-cost method of remediation of a combined spill of crude oil and brine in the Tallgrass Prairie Preserve in Osage County, OK. Specifically, we have used hay and fertilizer as amendments for remediation of both the oil and the brine. No gypsum was used. Three spills of crude oil plus produced water brine were treated with combinations of ripping, fertilizers and hay, and a downslope interception trench in an effort to demonstrate an inexpensive, easily implemented, and effective remediation plan. There was no statistically significant effect of treatment on the biodegradation of crude oil. However, TPH reduction clearly proceeded in the presence of brine contamination. The average TPH half-life considering all impacted sites was 267 days. The combination of hay addition, ripping, and a downslope interception trench was superior to hay addition with ripping, or ripping plus an interception trench in terms of rates of sodium and chloride leaching from the impacted sites. Reductions in salt inventories (36 months) were 73% in the site with hay addition, ripping and an interception trench, 40% in the site with hay addition and ripping only, and < 3% in the site with ripping and an interception trench.

Kto samõi bogatõi v Estonii / Sten-Aleks Pihlak, Kärt Blumberg, Lemmi Kann

Index Scriptorium Estoniae

Pihlak, Sten-Aleks

2008-01-01

Eesti laevatranspordi kolmik - Ain Hanschmidt, Enn Pant ja Kalev Järvelill on Äripäeva rikaste edetabelis esimesed. Viimaste kuude suure aktsiahinnalanguse tõttu on paljud Äripäeva rikaste edetabelis olijad kaotanud igast kolmest kroonist kaks. Artiklis selgitatakse miks on Äripäeva Rikaste TOPis vähe naisi. Lisad: Iz TOP-500 samõhh bogatõhh ljudei v Estonii; Reitingi bogatshei za prezhnije godõ; Metodika

Necroptosis mediates the antineoplastic effects of the soluble fraction of polysaccharide from red wine in Walker-256 tumor-bearing rats.

Science.gov (United States)

Stipp, Maria Carolina; Bezerra, Iglesias de Lacerda; Corso, Claudia Rita; Dos Reis Livero, Francislaine A; Lomba, Luiz Alexandre; Caillot, Adriana Rute Cordeiro; Zampronio, Aleksander Roberto; Queiroz-Telles, José Ederaldo; Klassen, Giseli; Ramos, Edneia A S; Sassaki, Guilherme Lanzi; Acco, Alexandra

2017-03-15

Polysaccharides are substances that modify the biological response to several stressors. The present study investigated the antitumor activity of the soluble fraction of polysaccharides (SFP), extracted from cabernet franc red wine, in Walker-256 tumor-bearing rats. The monosaccharide composition had a complex mixture, suggesting the presence of arabinoglactans, mannans, and pectins. Treatment with SFP (30 and 60mg/kg, oral) for 14days significantly reduced the tumor weight and volume compared with controls. Treatment with 60mg/kg SFP reduced blood monocytes and neutrophils, reduced the tumor activity of N-acetylglucosaminidase, myeloperoxidase, and nitric oxide, increased blood lymphocytes, and increased the levels of tumor necrosis factor α (TNF-α) in tumor tissue. Treatment with SFP also induced the expression of the cell necroptosis-related genes Rip1 and Rip3. The antineoplastic effect of SFP appears to be attributable to its action on the immune system by controlling the tumor microenvironment and stimulating TNF-α production, which may trigger the necroptosis pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

The RNA binding protein HuR differentially regulates unique subsets of mRNAs in estrogen receptor negative and estrogen receptor positive breast cancer

Directory of Open Access Journals (Sweden)

Chen Jing

2010-04-01

Full Text Available Abstract Background The discordance between steady-state levels of mRNAs and protein has been attributed to posttranscriptional control mechanisms affecting mRNA stability and translation. Traditional methods of genome wide microarray analysis, profiling steady-state levels of mRNA, may miss important mRNA targets owing to significant posttranscriptional gene regulation by RNA binding proteins (RBPs. Methods The ribonomic approach, utilizing RNA immunoprecipitation hybridized to microarray (RIP-Chip, provides global identification of putative endogenous mRNA targets of different RBPs. HuR is an RBP that binds to the AU-rich elements (ARE of labile mRNAs, such as proto-oncogenes, facilitating their translation into protein. HuR has been shown to play a role in cancer progression and elevated levels of cytoplasmic HuR directly correlate with increased invasiveness and poor prognosis for many cancers, including those of the breast. HuR has been described to control genes in several of the acquired capabilities of cancer and has been hypothesized to be a tumor-maintenance gene, allowing for cancers to proliferate once they are established. Results We used HuR RIP-Chip as a comprehensive and systematic method to survey breast cancer target genes in both MCF-7 (estrogen receptor positive, ER+ and MDA-MB-231 (estrogen receptor negative, ER- breast cancer cell lines. We identified unique subsets of HuR-associated mRNAs found individually or in both cell types. Two novel HuR targets, CD9 and CALM2 mRNAs, were identified and validated by quantitative RT-PCR and biotin pull-down analysis. Conclusion This is the first report of a side-by-side genome-wide comparison of HuR-associated targets in wild type ER+ and ER- breast cancer. We found distinct, differentially expressed subsets of cancer related genes in ER+ and ER- breast cancer cell lines, and noted that the differential regulation of two cancer-related genes by HuR was contingent upon the cellular

RIPPED TO DEATH

OpenAIRE

Weinlich, Ricardo; Dillon, Christopher P; Green, Douglas R

2011-01-01

An old puzzle in the field of cell death was recently solved: the mysterious embryonic lethality of animals deficient either in caspase-8 or FADD, proteins involved in a pathway of apoptosis. This lethality is caused by a failure to develop the yolk sac vasculature rather than a lack of apoptosis. Remarkably, development is rescued by ablation of either of two Receptor Interacting Protein Kinases (RIPKs). Despite being well-known cell killers, caspase-8 and FADD act together to block RIPK-med...

H1 antihistamines in allergic rhinitis: The molecular pathways of interleukin and toll - like receptor systems

Directory of Open Access Journals (Sweden)

Jonny Karunia Fajar

2016-03-01

Full Text Available The complex interaction between inflammatory mediators in allergic rhinitis (AR is determined by the role of genetic polymorphisms, including interleukin (IL and toll-like receptor (TLR genes. This study aimed to discuss the effects of H1-antihistamines on IL and TLR systems. Several ILs involved in AR pathogenesis are: IL-4 (rs2243250, rs1800925, rs1801275, rs2227284, rs2070874, IL-6 (rs1800795, rs1800797, IL-10 (rs1800871, rs1800872, IL-12R (rs438421, IL-13 (rs1800925, rs20541, IL-17 (rs3819024, IL-18 (rs360721, rs360718, rs360717, rs187238, IL-23R (rs7517847, and IL-27 (rs153109, rs17855750. In the IL system, histamines stimulate the IL production in Type 2 helper T (Th2 cells through protein kinase A (PKA, janus kinase-signal transducer and activator of transcription (JAK-STAT pathway, and the activation of H1-histamine receptor and histidine decarboxylase (HDC genes. On contrary, antihistamines down-regulate the H1-histamine receptor gene expression through the transcription suppression of HDC and IL genes and suppress histamine basal signaling through the inverse agonistic activity. TLRs involved in AR pathogenesis are TLR2 (rs4696480, rs3804099, rs5743708, TLR4 (rs4986790, TLR6 (rs2381289, TLR7 (rs179008, rs5935438, TRL8 (rs2407992, rs5741883, rs17256081, rs4830805, rs3788935, rs178998, and TLR10 (rs11466651. In the TLR system, histamines trigger the TLR expression by stimulating interferon-γ (IFN-γ to up-regulate mast cells and by stimulating receptor-interacting protein (RIP to activate IκB kinase-β. Contrastingly, antihistamines suppress TIR-domain-containing adaptor protein inducing IFN-β (TRIF and RIP protein and thus inhibit the expression of TLR. In addition, several studies indicated that H1-antihistamines inhibit the IL and TLR systems indirectly.

Ilmus põhjalik raamat intellektuaalsest omandist / Pirjo Ant, Kairi Kurisoo ; intervjueerinud Mari Sarv

Index Scriptorium Estoniae

Ant, Pirjo

2009-01-01

Autorid räägivad intellektuaalsest omandist ja oma raamatust: Kurisoo, Kairi ; Kaur, Viive ; Ant, Pirjo. Intellektuaalne omand. Tallinn : Äripäeva Kirjastus, 2009. (Juht ja seadus. Äripäeva raamat)

Impact of reduced ignition propensity cigarette regulation on consumer smoking behavior and quit intentions: evidence from 6 waves (2004–11) of the ITC Four Country Survey

Science.gov (United States)

2013-01-01

Background Although on the decline, smoking-related fires remain a leading cause of fire death in the United States and United Kingdom and account for over 10% of fire-related deaths worldwide. This has prompted lawmakers to enact legislation requiring manufacturers to implement reduced ignition propensity (RIP) safety standards for cigarettes. The current research evaluates how implementation of RIP safety standards in different countries influenced smokers’ perceptions of cigarette self-extinguishment, frequency of extinguishment, and the impact on consumer smoking behaviors, including cigarettes smoked per day and planning to quit. Methods Participants for this research come from Waves 3 through 8 of the International Tobacco Control (ITC) Four Country Survey conducted longitudinally from 2004 through 2011 in the United States, United Kingdom, Australia, and Canada. Results Perceptions of cigarette self-extinguishment and frequency of extinguishment increased concurrently with an increase in the prevalence of RIP safety standards for cigarettes. Presence of RIP safety standards was also associated with a greater intention to quit smoking, but was not associated with the number of cigarettes smoked per day. Intention to quit was higher among those who were more likely to report that their cigarettes self-extinguish sometimes and often, but we found no evidence of an interaction between frequency of extinguishment and RIP safety standards on quit intentions. Conclusions Overall, because these standards largely do not influence consumer smoking behavior, RIP implementation may significantly reduce the number of cigarette-related fires and the associated death and damages. Further research should assess how implementation of RIP safety standards has influenced smoking-related fire incidence, deaths, and other costs associated with smoking-related fires. PMID:24359292

Impact of reduced ignition propensity cigarette regulation on consumer smoking behavior and quit intentions: evidence from 6 waves (2004-11) of the ITC Four Country Survey.

Science.gov (United States)

Adkison, Sarah E; O'Connor, Richard J; Borland, Ron; Yong, Hua-Hie; Cummings, K Michael; Hammond, David; Fong, Geoffrey T

2013-12-21

Although on the decline, smoking-related fires remain a leading cause of fire death in the United States and United Kingdom and account for over 10% of fire-related deaths worldwide. This has prompted lawmakers to enact legislation requiring manufacturers to implement reduced ignition propensity (RIP) safety standards for cigarettes. The current research evaluates how implementation of RIP safety standards in different countries influenced smokers' perceptions of cigarette self-extinguishment, frequency of extinguishment, and the impact on consumer smoking behaviors, including cigarettes smoked per day and planning to quit. Participants for this research come from Waves 3 through 8 of the International Tobacco Control (ITC) Four Country Survey conducted longitudinally from 2004 through 2011 in the United States, United Kingdom, Australia, and Canada. Perceptions of cigarette self-extinguishment and frequency of extinguishment increased concurrently with an increase in the prevalence of RIP safety standards for cigarettes. Presence of RIP safety standards was also associated with a greater intention to quit smoking, but was not associated with the number of cigarettes smoked per day. Intention to quit was higher among those who were more likely to report that their cigarettes self-extinguish sometimes and often, but we found no evidence of an interaction between frequency of extinguishment and RIP safety standards on quit intentions. Overall, because these standards largely do not influence consumer smoking behavior, RIP implementation may significantly reduce the number of cigarette-related fires and the associated death and damages. Further research should assess how implementation of RIP safety standards has influenced smoking-related fire incidence, deaths, and other costs associated with smoking-related fires.

Fuzzy modeling and control of rotary inverted pendulum system using LQR technique

International Nuclear Information System (INIS)

Fairus, M A; Mohamed, Z; Ahmad, M N

2013-01-01

Rotary inverted pendulum (RIP) system is a nonlinear, non-minimum phase, unstable and underactuated system. Controlling such system can be a challenge and is considered a benchmark in control theory problem. Prior to designing a controller, equations that represent the behaviour of the RIP system must be developed as accurately as possible without compromising the complexity of the equations. Through Takagi-Sugeno (T-S) fuzzy modeling technique, the nonlinear system model is then transformed into several local linear time-invariant models which are then blended together to reproduce, or approximate, the nonlinear system model within local region. A parallel distributed compensation (PDC) based fuzzy controller using linear quadratic regulator (LQR) technique is designed to control the RIP system. The results show that the designed controller able to balance the RIP system

Väikeaktsionäril on õigus teada / Aku Sorainen ; interv. Lauri Matsulevitsh

Index Scriptorium Estoniae

Sorainen, Aku

2006-01-01

Aktsionäri õigustest teabele aktsiaseltsi tegevuse kohta. Intervjuu Investorite Liidu juhatuse liikme ja vandeadvokaadi Aku Soraineniga. Vt ka Äripäev 22.05.2006, lk. 8 ja 23.05.2006 Äripäeva juhtkirja

Tumor protein D52 expression is post-transcriptionally regulated by T-cell intercellular antigen (TIA) 1 and TIA-related protein via mRNA stability.

Science.gov (United States)

Motohashi, Hiromi; Mukudai, Yoshiki; Ito, Chihiro; Kato, Kosuke; Shimane, Toshikazu; Kondo, Seiji; Shirota, Tatsuo

2017-05-04

Although tumor protein D52 (TPD52) family proteins were first identified nearly 20 years ago, their molecular regulatory mechanisms remain unclear. Therefore, we investigated the post-transcriptional regulation of TPD52 family genes. An RNA immunoprecipitation (RIP) assay showed the potential binding ability of TPD52 family mRNAs to several RNA-binding proteins, and an RNA degradation assay revealed that TPD52 is subject to more prominent post-transcriptional regulation than are TPD53 and TPD54. We subsequently focused on the 3'-untranslated region (3'-UTR) of TPD52 as a cis -acting element in post-transcriptional gene regulation. Several deletion mutants of the 3'-UTR of TPD52 mRNA were constructed and ligated to the 3'-end of a reporter green fluorescence protein gene. An RNA degradation assay revealed that a minimal cis -acting region, located in the 78-280 region of the 5'-proximal region of the 3'-UTR, stabilized the reporter mRNA. Biotin pull-down and RIP assays revealed specific binding of the region to T-cell intracellular antigen 1 (TIA-1) and TIA-1-related protein (TIAR). Knockdown of TIA-1/TIAR decreased not only the expression, but also the stability of TPD52 mRNA; it also decreased the expression and stability of the reporter gene ligated to the 3'-end of the 78-280 fragment. Stimulation of transforming growth factor-β and epidermal growth factor decreased the binding ability of these factors, resulting in decreased mRNA stability. These results indicate that the 78-280 fragment and TIA-1/TIAR concordantly contribute to mRNA stability as a cis -acting element and trans -acting factor(s), respectively. Thus, we here report the specific interactions between these elements in the post-transcriptional regulation of the TPD52 gene. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Variability of the soil-to-plant radiocaesium transfer factor for Japanese soils predicted with soil and plant properties.

Science.gov (United States)

Uematsu, Shinichiro; Vandenhove, Hildegarde; Sweeck, Lieve; Van Hees, May; Wannijn, Jean; Smolders, Erik

2016-03-01

Food chain contamination with radiocaesium (RCs) in the aftermath of the Fukushima accident calls for an analysis of the specific factors that control the RCs transfer. Here, soil-to-plant transfer factors (TF) of RCs for grass were predicted from the potassium concentration in soil solution (mK) and the Radiocaesium Interception Potential (RIP) of the soil using existing mechanistic models. The mK and RIP were (a) either measured for 37 topsoils collected from the Fukushima accident affected area or (b) predicted from the soil clay content and the soil exchangeable potassium content using the models that had been calibrated for European soils. An average ammonium concentration was used throughout in the prediction. The measured RIP ranged 14-fold and measured mK varied 37-fold among the soils. The measured RIP was lower than the RIP predicted from the soil clay content likely due to the lower content of weathered micas in the clay fraction of Japanese soils. Also the measured mK was lower than that predicted. As a result, the predicted TFs relying on the measured RIP and mK were, on average, about 22-fold larger than the TFs predicted using the European calibrated models. The geometric mean of the measured TFs for grass in the affected area (N = 82) was in the middle of both. The TFs were poorly related to soil classification classes, likely because soil fertility (mK) was obscuring the effects of the soil classification related to the soil mineralogy (RIP). This study suggests that, on average, Japanese soils are more vulnerable than European soils at equal soil clay and exchangeable K content. The affected regions will be targeted for refined model validation. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Chimeric Peptide Composed of a Dermaseptin Derivative and an RNA III-Inhibiting Peptide Prevents Graft-Associated Infections by Antibiotic-Resistant Staphylococci

Science.gov (United States)

Balaban, Naomi; Gov, Yael; Giacometti, Andrea; Cirioni, Oscar; Ghiselli, Roberto; Mocchegiani, Federico; Orlando, Fiorenza; D'Amato, Giuseppina; Saba, Vittorio; Scalise, Giorgio; Bernes, Sabina; Mor, Amram

2004-01-01

Staphylococcal bacteria are a prevalent cause of infections associated with foreign bodies and indwelling medical devices. Bacteria are capable of escaping antibiotic treatment through encapsulation into biofilms. RNA III-inhibiting peptide (RIP) is a heptapeptide that inhibits staphylococcal biofilm formation by obstructing quorum-sensing mechanisms. K4-S4(1-13)a is a 13-residue dermaseptin derivative (DD13) believed to kill bacteria via membrane disruption. We tested each of these peptides as well as a hybrid construct, DD13-RIP, for their ability to inhibit bacterial proliferation and suppress quorum sensing in vitro and for their efficacy in preventing staphylococcal infection in a rat graft infection model with methicillin-resistant Staphylococcus aureus (MRSA) or S. epidermidis (MRSE). In vitro, proliferation assays demonstrated that RIP had no inhibitory effect, while DD13-RIP and DD13 were equally effective, and that the chimeric peptide but not DD13 was slightly more effective than RIP in inhibiting RNA III synthesis, a regulatory RNA molecule important for staphylococcal pathogenesis. In vivo, the three peptides reduced graft-associated bacterial load in a dose-dependent manner, but the hybrid peptide was most potent in totally preventing staphylococcal infections at the lowest dose. In addition, each of the peptides acted synergistically with antibiotics. The data indicate that RIP and DD13 act in synergy by attacking bacteria simultaneously by two different mechanisms. Such a chimeric peptide may be useful for coating medical devices to prevent drug-resistant staphylococcal infections. PMID:15215107

Arendaja näitab jõudu. 85 hektarit maad ajas taas tülli Jõelähtme vallajuhid / Koit Brinkmann ; kommenteerinud Art Kuum, Andrus Umboja

Index Scriptorium Estoniae

Brinkmann, Koit

2011-01-01

10 aastat tagasi omandas Jõelähtme Arendusgrupp soodsalt Jõelähtme vallas mereäärse kinnistu, kuid pidi suurema osa ostusummast tasuma alles 2011. aastal. Nüüd sõlmis firma vallaga kokkuleppe, mille suhtes on Reformierakonda kuuluv vallavanem ning IRL-i liikmest vallavolikogu esimees eri meelt. Vt. ka Koit Brinkmanni art. Art Kuum: Laheranna lepingu tingimusi pole muudetud. Äripäev, 26. mai, lk. 8 ja Sulev Valneri art. Äripäev rikkus head ajakirjandustava. Äripäev, 12. aug., lk. 10

Pakendiaktsiis ei saa olla turukaitsemehhanism / Ilona Eskelinen

Index Scriptorium Estoniae

Eskelinen, Ilona

2004-01-01

Vastukaja R. Raaga art. "Pakendiaktsiisid ja tegelikkus", Äripäev 13. sep. 2004. lk. 26. Vaata ka P. Eeki art. "Pakendiaktsiis - hirmul on suured silmad", Äripäev 19. aug. 2004, lk. 23. Pakendiaktsiisi seaduse muutmise eelnõust

Climatology and interannual variability of dynamic variables in multiple reanalyses evaluated by the SPARC Reanalysis Intercomparison Project (S-RIP)

Science.gov (United States)

Long, Craig S.; Fujiwara, Masatomo; Davis, Sean; Mitchell, Daniel M.; Wright, Corwin J.

2017-12-01

Two of the most basic parameters generated from a reanalysis are temperature and winds. Temperatures in the reanalyses are derived from conventional (surface and balloon), aircraft, and satellite observations. Winds are observed by conventional systems, cloud tracked, and derived from height fields, which are in turn derived from the vertical temperature structure. In this paper we evaluate as part of the SPARC Reanalysis Intercomparison Project (S-RIP) the temperature and wind structure of all the recent and past reanalyses. This evaluation is mainly among the reanalyses themselves, but comparisons against independent observations, such as HIRDLS and COSMIC temperatures, are also presented. This evaluation uses monthly mean and 2.5° zonal mean data sets and spans the satellite era from 1979-2014. There is very good agreement in temperature seasonally and latitudinally among the more recent reanalyses (CFSR, MERRA, ERA-Interim, JRA-55, and MERRA-2) between the surface and 10 hPa. At lower pressures there is increased variance among these reanalyses that changes with season and latitude. This variance also changes during the time span of these reanalyses with greater variance during the TOVS period (1979-1998) and less variance afterward in the ATOVS period (1999-2014). There is a distinct change in the temperature structure in the middle and upper stratosphere during this transition from TOVS to ATOVS systems. Zonal winds are in greater agreement than temperatures and this agreement extends to lower pressures than the temperatures. Older reanalyses (NCEP/NCAR, NCEP/DOE, ERA-40, JRA-25) have larger temperature and zonal wind disagreement from the more recent reanalyses. All reanalyses to date have issues analysing the quasi-biennial oscillation (QBO) winds. Comparisons with Singapore QBO winds show disagreement in the amplitude of the westerly and easterly anomalies. The disagreement with Singapore winds improves with the transition from TOVS to ATOVS observations

Identification, characterization and structure analysis of a type I ribosome-inactivating protein from Sapium sebiferum (Euphorbiaceae)

Energy Technology Data Exchange (ETDEWEB)

Wu, Ying [Key Laboratory of Ion Beam Bioengineering and Bioenergy Forest Research Center of State Forestry Administration, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, Anhui (China); School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui (China); College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, Henan (China); Mao, Yingji [Key Laboratory of Ion Beam Bioengineering and Bioenergy Forest Research Center of State Forestry Administration, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, Anhui (China); School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui (China); Jin, Shan; Hou, Jinyan; Du, Hua [Key Laboratory of Ion Beam Bioengineering and Bioenergy Forest Research Center of State Forestry Administration, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, Anhui (China); Yang, Minglei, E-mail: yml888@mail.ustc.edu.cn [Key Laboratory of Ion Beam Bioengineering and Bioenergy Forest Research Center of State Forestry Administration, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, Anhui (China); Wu, Lifang, E-mail: lfwu@ipp.ac.cn [Key Laboratory of Ion Beam Bioengineering and Bioenergy Forest Research Center of State Forestry Administration, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, Anhui (China); School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui (China)

2015-08-07

Ribosome-inactivating proteins (RIPs) are N-glycosidases (EC3.2.2.22) that universally inactivate the ribosome, thereby inhibiting protein biosynthesis. In this study, a novel type I RIPs named SEBIN was identified in Sapium sebiferum. Nuclear acid depurine experiment showed that SEBIN had rRNA N-Glycosidase activity. Further experiment indicated that SEBIN significantly inhibited Caenorhabditis elegans development as well as resulted in worm cell apoptosis. This is the first report to evaluate RIPs toxicity using C. elegans. We proposed that SEBIN may impaire C. elegans reproduction in a DNA-damage manner besides traditional protein synthesis inhibition approach. The predicted 3D structure was modeled using threading and ab initio modeling, and the r-RNA binding residue of SEBIN was identified through the protein-ligand docking approach. It showed the amino acid residues, Glu195, Asn81, Ala82, Tyr83, Glu164, Ser163, Ile159 and Arg167, played critical roles in catalytic process. Our results provided the theoretical foundation of structure–function relationships between enzymatic properties, toxicity and structural characterization of SEBIN. - Graphical abstract: Superposition of main chains of ricin (cyan) and SEBIN (brown), and adenine binding site residues of SEBIN. - Highlights: • A Ribosome-inactivating proteins gene (SEBIN) was isolated from Sapium sebiferum. • SEBIN had DNase activity besides widely reported ribosome inactivation via N-glycosidases activity. • SEBIN significantly inhibited Caenorhabditis elegans development in vivo. • SEBIN may impaire C. elegans reproduction in a DNA-damage manner with the aid of mutant strains hus-1 and clk-2. • The possible active sites between SEBIN and the adenine of rRNA were predicted.

Identification, characterization and structure analysis of a type I ribosome-inactivating protein from Sapium sebiferum (Euphorbiaceae)

International Nuclear Information System (INIS)

Wu, Ying; Mao, Yingji; Jin, Shan; Hou, Jinyan; Du, Hua; Yang, Minglei; Wu, Lifang

2015-01-01

Ribosome-inactivating proteins (RIPs) are N-glycosidases (EC3.2.2.22) that universally inactivate the ribosome, thereby inhibiting protein biosynthesis. In this study, a novel type I RIPs named SEBIN was identified in Sapium sebiferum. Nuclear acid depurine experiment showed that SEBIN had rRNA N-Glycosidase activity. Further experiment indicated that SEBIN significantly inhibited Caenorhabditis elegans development as well as resulted in worm cell apoptosis. This is the first report to evaluate RIPs toxicity using C. elegans. We proposed that SEBIN may impaire C. elegans reproduction in a DNA-damage manner besides traditional protein synthesis inhibition approach. The predicted 3D structure was modeled using threading and ab initio modeling, and the r-RNA binding residue of SEBIN was identified through the protein-ligand docking approach. It showed the amino acid residues, Glu195, Asn81, Ala82, Tyr83, Glu164, Ser163, Ile159 and Arg167, played critical roles in catalytic process. Our results provided the theoretical foundation of structure–function relationships between enzymatic properties, toxicity and structural characterization of SEBIN. - Graphical abstract: Superposition of main chains of ricin (cyan) and SEBIN (brown), and adenine binding site residues of SEBIN. - Highlights: • A Ribosome-inactivating proteins gene (SEBIN) was isolated from Sapium sebiferum. • SEBIN had DNase activity besides widely reported ribosome inactivation via N-glycosidases activity. • SEBIN significantly inhibited Caenorhabditis elegans development in vivo. • SEBIN may impaire C. elegans reproduction in a DNA-damage manner with the aid of mutant strains hus-1 and clk-2. • The possible active sites between SEBIN and the adenine of rRNA were predicted

Radiocesium sorption in relation to clay mineralogy of paddy soils in Fukushima, Japan

Energy Technology Data Exchange (ETDEWEB)

Nakao, Atsushi, E-mail: na_4_ka_triplochiton@kpu.ac.jp [Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Hangi-cho 1-5, Shimogamo, Sakyo-ku, Kyoto 606-8522 (Japan); Ogasawara, Sho [Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Hangi-cho 1-5, Shimogamo, Sakyo-ku, Kyoto 606-8522 (Japan); Sano, Oki; Ito, Toyoaki [Field Science Center, Graduate School of Agricultural Science, Tohoku University, Naruko-Onsen 232-3, Osaki, Miyagi 989-6711 (Japan); Yanai, Junta [Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Hangi-cho 1-5, Shimogamo, Sakyo-ku, Kyoto 606-8522 (Japan)

2014-01-01

Relationships between Radiocesium Interception Potential (RIP) and mineralogical characteristics of the clay fraction isolated from 97 paddy soils (Hama-dori, n = 25; Naka-dori, n = 36; Aizu, n = 36) in Fukushima Prefecture, Japan were investigated to clarify the mineralogical factors controlling the {sup 137}Cs retention ability of soils (half-life 30.1 y). Of all the fission products released by the Fukushima accident, {sup 137}Cs is the most important long-term contributor to the environmental contamination. The RIP, a quantitative index of the {sup 137}Cs retention ability, was determined for the soil clays. The composition of clay minerals in the soil clays was estimated from peak areas obtained using X-ray diffraction (XRD) analyses. The predominant clay mineral was smectite in soils from Hama-dori and Aizu, while this was variable for those from Naka-dori. Native K content of the soil clays was found to be an indicator of the amount of micaceous minerals. The average RIP for the 97 soil clays was 7.8 mol kg{sup −1}, and ranged from 2.4 mol kg{sup −1} to 19.4 mol kg{sup −1}. The RIP was significantly and positively correlated with native K content for each of the geographical regions, Hama-dori (r = 0.76, p < 0.001), Naka-dori (r = 0.43, p < 0.05), and Aizu (r = 0.76, P < 0.001), while it was not related to the relative abundance of smectite. The linear relationship between RIP and native K content not only indicate a large contribution of micaceous minerals to the {sup 137}Cs retention ability of the soil clays, but also could be used to predict the {sup 137}Cs retention ability of soil clays for other paddy fields in Fukushima and other areas. - Highlights: • RIP was measured for 97 paddy soils from Fukushima to assess {sup 137}Cs retention ability. • The dominant clay mineral was smectite, but this did not control RIP. • RIP was positively correlated with native K content. • Micaceous minerals were found to control the {sup 137}Cs retention

Programmed necrosis and necroptosis – molecular mechanisms

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Agata Giżycka

2015-12-01

Full Text Available Programmed necrosis has been proven vital for organism development and homeostasis maintenance. Its regulatory effects on functional activity of the immune system, as well as on pathways regulating the death mechanisms in cells with diminished apoptotic activity, including malignant cells, have been confirmed. There is also increasing evidence indicating necrosis involvement in many human pathologies. Contrary to previous beliefs, necrosis is not only a passive, pathological, gene-independent process. However, the current knowledge regarding molecular regulation of programmed necrosis is scarce. In part this is due to the multiplicity and complexity of signaling pathways involved in programmed necrosis, as well as the absence of specific cellular markers identifying this process, but also the ambiguous and imprecise international terminology. This review presents the current state of the art on molecular mechanisms of programmed necrosis. In particular, its specific and frequent form, necroptosis, is discussed. The role of RIP1 and RIP3 kinases in this process is presented, as well as the diverse pathways induced by ligation of tumor necrosis factor α, to its receptor, TNFR1, i.e. cell survival, apoptosis or necroptosis.

Genes and Gene Therapy

Science.gov (United States)

... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

Kas internet muudab meid rumalamaks? / Liis Kängsepp

Index Scriptorium Estoniae

Kängsepp, Liis, 1981-

2012-01-01

Raamatust: Carr, Nicholas. Triiv madalikule : mida Internet meie ajuga teeb / tõlkija Tiina Randus. Tallinn : Äripäev, 2012. (Äripäeva raamat). Ka intervjuu Tallinna Ülikooli dotsendi Kristjan Pordiga raamatus esitatud väidetest interneti mõjust inimesele

Caracterización de los efectos de la administración de la lectina antinutricional nigrina de corteza de Sambucus nigra L. y efecto sinérgico con los polifenoles del té verde

OpenAIRE

Cabrero Lobato, Patricia

2012-01-01

Las proteínas inactivadoras de ribosomas (RIPs) son enzimas con actividad N-glicosidasa del ARN ribosómico. Algunas poseen dos cadenas una con actividad enzimática y otra con actividad lectina (RIPs de tipo dos). Entre estas RIPs se encuentra la nigrina b presente en la corteza de Sambucus nigra L. La nigrina b presenta toxicidad selectiva en función de la dosis y la vía de administración. El blanco son las células de las criptas del intestino delgado. Nuestra hipótesis es que los efectos tóx...

Studying reaction products in a lithium thionyl chloride cell

International Nuclear Information System (INIS)

Vol'fkovich, Yu.M.; Sosenkin, V.E.; Nikol'skaya, N.F.; Blinov, I.A.

1999-01-01

Change in the mass, volume and chemical composition of reaction insoluble products (RIP) formed in the course of discharge of thionyl chloride lithium cells under different conditions has been studied by the methods of gravimetry, volumetry and element analysis. It has been ascertained that the measured volume and mass of RIP essentially (by a factor of 1.1-1.8) exceed the calculated values, proceeding from the reaction stoichiometry. Besides lithium chloride and sulfur during discharge additional RIP is formed as LiAlCl 4 · SOCl 2 solvate, its share increasing with temperature decrease, increase in current density and electrolyte concentration [ru

Proteolysis of virulence regulator ToxR is associated with entry of Vibrio cholerae into a dormant state.

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Salvador Almagro-Moreno

2015-04-01

Full Text Available Vibrio cholerae O1 is a natural inhabitant of aquatic environments and causes the diarrheal disease, cholera. Two of its primary virulence regulators, TcpP and ToxR, are localized in the inner membrane. TcpP is encoded on the Vibrio Pathogenicity Island (VPI, a horizontally acquired mobile genetic element, and functions primarily in virulence gene regulation. TcpP has been shown to undergo regulated intramembrane proteolysis (RIP in response to environmental conditions that are unfavorable for virulence gene expression. ToxR is encoded in the ancestral genome and is present in non-pathogenic strains of V. cholerae, indicating it has roles outside of the human host. In this study, we show that ToxR undergoes RIP in V. cholerae in response to nutrient limitation at alkaline pH, a condition that occurs during the stationary phase of growth. This process involves the site-2 protease RseP (YaeL, and is dependent upon the RpoE-mediated periplasmic stress response, as deletion mutants for the genes encoding these two proteins cannot proteolyze ToxR under nutrient limitation at alkaline pH. We determined that the loss of ToxR, genetically or by proteolysis, is associated with entry of V. cholerae into a dormant state in which the bacterium is normally found in the aquatic environment called viable but nonculturable (VBNC. Strains that can proteolyze ToxR, or do not encode it, lose culturability, experience a change in morphology associated with cells in VBNC, yet remain viable under nutrient limitation at alkaline pH. On the other hand, mutant strains that cannot proteolyze ToxR remain culturable and maintain the morphology of cells in an active state of growth. Overall, our findings provide a link between the proteolysis of a virulence regulator and the entry of a pathogen into an environmentally persistent state.

Expression profiles of putative defence-related proteins in oil palm (Elaeis guineensis) colonized by Ganoderma boninense.

Science.gov (United States)

Tan, Yung-Chie; Yeoh, Keat-Ai; Wong, Mui-Yun; Ho, Chai-Ling

2013-11-01

Basal stem rot (BSR) is a major disease of oil palm caused by a pathogenic fungus, Ganoderma boninense. However, the interaction between the host plant and its pathogen is not well characterized. To better understand the response of oil palm to G. boninense, transcript profiles of eleven putative defence-related genes from oil palm were measured by quantitative reverse-transcription (qRT)-PCR in the roots of oil palms treated with G. boninense from 3 to 12 weeks post infection (wpi). These transcripts encode putative Bowman-Birk serine protease inhibitors (EgBBI1 and 2), defensin (EgDFS), dehydrin (EgDHN), early methionine-labeled polypeptides (EgEMLP1 and 2), glycine-rich RNA binding protein (EgGRRBP), isoflavone reductase (EgIFR), metallothionein-like protein (EgMT), pathogenesis-related-1 protein (EgPRP), and type 2 ribosome-inactivating protein (EgT2RIP). The transcript abundance of EgBBI2 increased in G. boninense-treated roots at 3 and 6wpi compared to those of controls; while the transcript abundance of EgBBI1, EgDFS, EgEMLP1, EgMT, and EgT2RIP increased in G. boninense-treated roots at 6 or 12wpi. Meanwhile, the gene expression of EgDHN was up-regulated at all three time points in G. boninense-treated roots. The expression profiles of the eleven transcripts were also studied in leaf samples upon inoculation of G. boninense and Trichoderma harzianum to identify potential biomarkers for early detection of BSR. Two candidate genes (EgEMLP1 and EgMT) that have different profiles in G. boninense-treated leaves compared to those infected by T. harzianum may have the potential to be developed as biomarkers for early detection of G. boninense infection. Copyright © 2013 Elsevier GmbH. All rights reserved.

Nucleotide-Binding Oligomerization Domain-1 and -2 Play No Role in Controlling Brucella abortus Infection in Mice

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Fernanda S. Oliveira

2012-01-01

Full Text Available Nucleotide-binding oligomerization domain proteins (NODs are modular cytoplasmic proteins implicated in the recognition of peptidoglycan-derived molecules. Further, several in vivo studies have demonstrated a role for Nod1 and Nod2 in host defense against bacterial pathogens. Here, we demonstrated that macrophages from NOD1-, NOD2-, and Rip2-deficient mice produced lower levels of TNF-α following infection with live Brucella abortus compared to wild-type mice. Similar reduction on cytokine synthesis was not observed for IL-12 and IL-6. However, NOD1, NOD2, and Rip2 knockout mice were no more susceptible to infection with virulent B. abortus than wild-type mice. Additionally, spleen cells from NOD1-, NOD2-, and Rip2-deficient mice showed unaltered production of IFN-γ compared to C57BL/6 mice. Taken together, this study demonstrates that NOD1, NOD2 and Rip2 are dispensable for the control of B. abortus during in vivo infection.

Assessment of volcanic and tectonic hazards to high level radioactive waste repositories

International Nuclear Information System (INIS)

Wallmann, P.C.; Miller, I.; Kossik, R.

1993-01-01

Golder Associates Inc. (GAI) has developed a computer program (RIP) for performing probabilistic total system performance assessment and site characterization strategy evaluation which can be applied in an iterative manner to evaluate repository site suitability and to guide characterization activities. The performance assessment model incorporated in RIP has three basic component models: (1) waste package behavior, (2) radionuclide transport pathways, and (3) disruptive events. Classes of disruptive events are specified in RIP by (1) a disruption rate (events/yr.), (2) open-quotes event descriptorsclose quotes which describe event characteristics and magnitude, and (3) the consequences associated with an event. One of the strengths of RIP is its flexibility, which allows it to evaluate different sites and conceptual models. Examples of seismic and volcanic disruptive event models constructed by GAI for Yucca Mountain are presented. Analysis of the results of these models indicates that for the simulated models, neither of these event classes significantly impacts the performance of the proposed repository over a 10,000 year time span

Polimorfismo molecular em Lonchocarpus cultratus (Fabaceae de áreas ripárias de reflorestamento natural no alto rio Paraná, Brasil - DOI: 10.4025/actascibiolsci.v26i3.1596 Molecular polymorphism in Lonchocarpus cultratus (Fabaceae from riparian areas of natural reforesting in Upper Paraná River, Brazil - DOI: 10.4025/actascibiolsci.v26i3.1596

Directory of Open Access Journals (Sweden)

Léia Carolina Lucio

2004-04-01

Full Text Available No Sul e Sudeste do Brasil, Lonchocarpus cultratus (Vell. A.M.G. Azevedo e H.C. Lima é uma espécie arbórea importante para o reflorestamento natural, incluindo áreas ripárias. Em florestas regeneradas, diferentemente de florestas não perturbadas, esta espécie tem sido observada como agregados de plantas semelhantes entre si, ao ponto de ter sido formulada a hipótese de serem clones. Em um estudo prévio, brotamento de raízes foi observado em L. cultratus, em uma floresta afetada pelo fogo. No presente estudo, análises de polimorfismo de RAPD revelaram alta diversidade genética entre as plantas de agregados de L. cultratus, em uma floresta ripária afetada pelo fogo, no alto rio Paraná. Os dados permitem sugerir que reprodução sexual tem sido a usual estratégia reprodutiva de colonização de L. cultratus, nesta área de reflorestamento naturalLonchocarpus cultratus (Vell. A.M.G. Azevedo and H.C. Lima is an important plant species in areas of natural reforesting in South and Southeastern Brazil, including riparian areas. This arboreous species seems to reproduce by seeds in undisturbed forests. In regenerating forests, however, L. cultratus has been observed mostly as patches of aggregates, consisting of highly similar plants, resembling clones. Sprouting from root buds had been previously observed in L. cultratus in a forest affected by fire. In the present study, RAPD polymorphism revealed high genetic diversity among plants from L. cultratus aggregates in a natural restoring riparian forest affected by fires, in the Upper Paraná River, Brazil. These data allow the suggestion that sexual reproduction has been the L. cultratus usual reproductive strategy to colonize the reforesting riparian area

Gene expression and gene therapy imaging

International Nuclear Information System (INIS)

Rome, Claire; Couillaud, Franck; Moonen, Chrit T.W.

2007-01-01

The fast growing field of molecular imaging has achieved major advances in imaging gene expression, an important element of gene therapy. Gene expression imaging is based on specific probes or contrast agents that allow either direct or indirect spatio-temporal evaluation of gene expression. Direct evaluation is possible with, for example, contrast agents that bind directly to a specific target (e.g., receptor). Indirect evaluation may be achieved by using specific substrate probes for a target enzyme. The use of marker genes, also called reporter genes, is an essential element of MI approaches for gene expression in gene therapy. The marker gene may not have a therapeutic role itself, but by coupling the marker gene to a therapeutic gene, expression of the marker gene reports on the expression of the therapeutic gene. Nuclear medicine and optical approaches are highly sensitive (detection of probes in the picomolar range), whereas MRI and ultrasound imaging are less sensitive and require amplification techniques and/or accumulation of contrast agents in enlarged contrast particles. Recently developed MI techniques are particularly relevant for gene therapy. Amongst these are the possibility to track gene therapy vectors such as stem cells, and the techniques that allow spatiotemporal control of gene expression by non-invasive heating (with MRI guided focused ultrasound) and the use of temperature sensitive promoters. (orig.)

Mapping bathymetry in an active surf zone with the WorldView2 multispectral satellite

Science.gov (United States)

Trimble, S. M.; Houser, C.; Brander, R.; Chirico, P.

2015-12-01

Rip currents are strong, narrow seaward flows of water that originate in the surf zones of many global beaches. They are related to hundreds of international drownings each year, but exact numbers are difficult to calculate due to logistical difficulties in obtaining accurate incident reports. Annual average rip current fatalities are estimated to be ~100, 53 and 21 in the United States (US), Costa Rica, and Australia respectively. Current warning systems (e.g. National Weather Service) do not account for fine resolution nearshore bathymetry because it is difficult to capture. The method shown here could provide frequent, high resolution maps of nearshore bathymetry at a scale required for improved rip prediction and warning. This study demonstrates a method for mapping bathymetry in the surf zone (20m deep and less), specifically within rip channels, because rips form at topographically low spots in the bathymetry as a result of feedback amongst waves, substrate, and antecedent bathymetry. The methods employ the Digital Globe WorldView2 (WV2) multispectral satellite and field measurements of depth to generate maps of the changing bathymetry at two embayed, rip-prone beaches: Playa Cocles, Puerto Viejo de Talamanca, Costa Rica, and Bondi Beach, Sydney, Australia. WV2 has a 1.1 day pass-over rate with 1.84m ground pixel resolution of 8 bands, including 'yellow' (585-625 nm) and 'coastal blue' (400-450 nm). The data is used to classify bottom type and to map depth to the return in multiple bands. The methodology is tested at each site for algorithm consistency between dates, and again for applicability between sites.

Climatology and interannual variability of dynamic variables in multiple reanalyses evaluated by the SPARC Reanalysis Intercomparison Project (S-RIP

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C. S. Long

2017-12-01

Full Text Available Two of the most basic parameters generated from a reanalysis are temperature and winds. Temperatures in the reanalyses are derived from conventional (surface and balloon, aircraft, and satellite observations. Winds are observed by conventional systems, cloud tracked, and derived from height fields, which are in turn derived from the vertical temperature structure. In this paper we evaluate as part of the SPARC Reanalysis Intercomparison Project (S-RIP the temperature and wind structure of all the recent and past reanalyses. This evaluation is mainly among the reanalyses themselves, but comparisons against independent observations, such as HIRDLS and COSMIC temperatures, are also presented. This evaluation uses monthly mean and 2.5° zonal mean data sets and spans the satellite era from 1979–2014. There is very good agreement in temperature seasonally and latitudinally among the more recent reanalyses (CFSR, MERRA, ERA-Interim, JRA-55, and MERRA-2 between the surface and 10 hPa. At lower pressures there is increased variance among these reanalyses that changes with season and latitude. This variance also changes during the time span of these reanalyses with greater variance during the TOVS period (1979–1998 and less variance afterward in the ATOVS period (1999–2014. There is a distinct change in the temperature structure in the middle and upper stratosphere during this transition from TOVS to ATOVS systems. Zonal winds are in greater agreement than temperatures and this agreement extends to lower pressures than the temperatures. Older reanalyses (NCEP/NCAR, NCEP/DOE, ERA-40, JRA-25 have larger temperature and zonal wind disagreement from the more recent reanalyses. All reanalyses to date have issues analysing the quasi-biennial oscillation (QBO winds. Comparisons with Singapore QBO winds show disagreement in the amplitude of the westerly and easterly anomalies. The disagreement with Singapore winds improves with the transition from

Rapid Inhibition Profiling in Bacillus subtilis to Identify the Mechanism of Action of New Antimicrobials.

Science.gov (United States)

Lamsa, Anne; Lopez-Garrido, Javier; Quach, Diana; Riley, Eammon P; Pogliano, Joe; Pogliano, Kit

2016-08-19

Increasing antimicrobial resistance has become a major public health crisis. New antimicrobials with novel mechanisms of action (MOA) are desperately needed. We previously developed a method, bacterial cytological profiling (BCP), which utilizes fluorescence microscopy to rapidly identify the MOA of antimicrobial compounds. BCP is based upon our discovery that cells treated with antibiotics affecting different metabolic pathways generate different cytological signatures, providing quantitative information that can be used to determine a compound's MOA. Here, we describe a system, rapid inhibition profiling (RIP), for creating cytological profiles of new antibiotic targets for which there are currently no chemical inhibitors. RIP consists of the fast, inducible degradation of a target protein followed by BCP. We demonstrate that degrading essential proteins in the major metabolic pathways for DNA replication, transcription, fatty acid biosynthesis, and peptidoglycan biogenesis in Bacillus subtilis rapidly produces cytological profiles closely matching that of antimicrobials targeting the same pathways. Additionally, RIP and antibiotics targeting different steps in fatty acid biosynthesis can be differentiated from each other. We utilize RIP and BCP to show that the antibacterial MOA of four nonsteroidal anti-inflammatory antibiotics differs from that proposed based on in vitro data. RIP is a versatile method that will extend our knowledge of phenotypes associated with inactivating essential bacterial enzymes and thereby allow for screening for molecules that inhibit novel essential targets.

Necrosome core machinery: MLKL.

Science.gov (United States)

Zhang, Jing; Yang, Yu; He, Wenyan; Sun, Liming

2016-06-01

In the study of regulated cell death, the rapidly expanding field of regulated necrosis, in particular necroptosis, has been drawing much attention. The signaling of necroptosis represents a sophisticated form of a death pathway. Anti-caspase mechanisms (e.g., using inhibitors of caspases, or genetic ablation of caspase-8) switch cell fate from apoptosis to necroptosis. The initial extracellular death signals regulate RIP1 and RIP3 kinase activation. The RIP3-associated death complex assembly is necessary and sufficient to initiate necroptosis. MLKL was initially identified as an essential mediator of RIP1/RIP3 kinase-initiated necroptosis. Recent studies on the signal transduction using chemical tools and biomarkers support the idea that MLKL is able to make more functional sense for the core machinery of the necroptosis death complex, called the necrosome, to connect to the necroptosis execution. The experimental data available now have pointed that the activated MLKL forms membrane-disrupting pores causing membrane leakage, which extends the prototypical concept of morphological and biochemical events following necroptosis happening in vivo. The key role of MLKL in necroptosis signaling thus sheds light on the logic underlying this unique "membrane-explosive" cell death pathway. In this review, we provide the general concepts and strategies that underlie signal transduction of this form of cell death, and then focus specifically on the role of MLKL in necroptosis.

Imaging gene expression in gene therapy

International Nuclear Information System (INIS)

Wiebe, Leonard I.

1997-01-01

Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on 'suicide gene therapy' of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k + ) has been use for 'suicide' in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k + gene expression where the H S V-1 t k + gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([ 18 F]F H P G; [ 18 F]-A C V), and pyrimidine- ([ 123 / 131 I]I V R F U; [ 124 / 131I ]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [ 123 / 131I ]I V R F U imaging with the H S V-1 t k + reporter gene will be presented

Ravimiuuringutes keerlevad miljonid / Sten-Aleks Pihlak

Index Scriptorium Estoniae

Pihlak, Sten-Aleks

2008-01-01

Ilmunud ka: Äripäev 5. sept. lk. 12-15, Delovõje Vedomosti 10. sept. lk. 6-7. Autor uuris ravimiuuringutes osalevate arstide tasustamist. Diagramm: Kliinilised uuringud Eestis. Tabel: Uuringuarstide TOP. Kommenteerib ravimiameti peadirektori asetäitja Alar Irs. Ajal. Äripäev ka intervjuu Ravimitootjate liidu juhatuse esimehe Akshay Modyga

Võrdne kohtlemine / Mati Heidmets

Index Scriptorium Estoniae

Heidmets, Mati

2004-01-01

Tallinna Pedagoogikaülikooli (TPÜ) rektori sõnul on valitsuse heakskiidetud riiklike investeeringute programmis (RIP) aastateks 2004-2007 kirjas valitsuse plaan rahastada TPÜ ja Eesti Humanitaarinstituudi uue õppehoone ehitust 82 miljoni krooni ulatuses, kuid sama valitsus on otsustanud selle RIP-ist maha tõmmata. Võrreldud Tallinna ja Tartu kõrgkoolidele eraldatud investeeringuid

Imaging gene expression in gene therapy

Energy Technology Data Exchange (ETDEWEB)

Wiebe, Leonard I. [Alberta Univ., Edmonton (Canada). Noujaim Institute for Pharmaceutical Oncology Research

1997-12-31

Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on `suicide gene therapy` of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k{sup +}) has been use for `suicide` in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k{sup +} gene expression where the H S V-1 t k{sup +} gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([{sup 18} F]F H P G; [{sup 18} F]-A C V), and pyrimidine- ([{sup 123}/{sup 131} I]I V R F U; [{sup 124}/{sup 131I}]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [{sup 123}/{sup 131I}]I V R F U imaging with the H S V-1 t k{sup +} reporter gene will be presented

Dihydrotanshinone I, a natural product, ameliorates DSS-induced experimental ulcerative colitis in mice.

Science.gov (United States)

Guo, Yanling; Wu, Xiaxia; Wu, Qin; Lu, Yuanfu; Shi, Jingshan; Chen, Xiuping

2018-04-01

Ulcerative colitis (UC) is a chronic and relapsing inflammatory disorder of the colon and rectum with increasing morbidity in recent years. 15,16-dihydrotanshinone Ӏ (DHT) is a natural product with multiple bioactivities. In this study, we aimed to investigate the protective effect and potential mechanisms of DHT on UC. Dextran sulfate sodium salt (DSS) was administrated in drinking water for 7 days to induce UC in mice. DHT (10 and 25 mg/kg) significantly alleviated DSS-induced body weight loss, disease activity index (DAI) scores, and improved histological alterations of colon tissues. DHT inhibited the myeloperoxidase (MPO) activity, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in colon tissues and decreased serum levels of TNF-α, IL-1β, IL-6, and high-mobility group box 1 (HMGB1). Furthermore, increased expression of kinases receptor-interacting protein 1 (RIP1), RIP3, mixed lineage kinase domain-like protein (MLKL) and decreased expression of caspase-8 in colon tissues were partially restored by DHT. In LPS-stimulated RAW264.7 macrophages, DHT significantly inhibited generation of nitric oxide, IL-6, TNF-α and protein expression of iNOS, COX-2. In addition, increased expression of iNOS, COX-2, and phosphorylated RIP1, RIP3, MLKL in response to LPS plus Z-VAD (LZ) were also suppressed by DHT. DHT had no effect on TNF-α + BV6 + Z-VAD (TBZ) induced phosphorylation of RIPs and MLKL in HT29 cells. Especially, DHT showed no effect on LZ and TBZ-induced necroptosis in RAW264.7 and HT29 cells, respectively. In summary, DHT alleviated DSS-induced UC in mice by suppressing pro-inflammatory mediators and regulating RIPs-MLKL-caspase-8 axis. Copyright © 2018 Elsevier Inc. All rights reserved.

2005 Department of Defense Survey of Health Related Behaviors among Active Duty Military Personnel

Science.gov (United States)

2006-12-01

Fentanyl Cannabis , THC, "pot", "weed", "chronic" LSD ("acid"), Phencyclidine (PCP) ("angel dust"), Mescaline, Peyote, Psilocybin, "mushrooms" (or...Palmetto) . . . . . . . . . . . . Weight loss products (such as Chromium Picolinate, Ripped Fuel, caffeine , Dexatrim, Acutrim, Metabolife, Metabolite...Echinacea, Ginseng, Saw Palmetto) . . . . . . . . . . . . . . Weight loss products (such as Chromium Picolinate, Ripped Fuel, caffeine , Dexatrim

The Tumor Suppressor Hace1 Is a Critical Regulator of TNFR1-Mediated Cell Fate

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Luigi Tortola

2016-05-01

Full Text Available Summary: The HECT domain E3 ligase HACE1 has been identified as a tumor suppressor in multiple cancers. Here, we report that HACE1 is a central gatekeeper of TNFR1-induced cell fate. Genetic inactivation of HACE1 inhibits TNF-stimulated NF-κB activation and TNFR1-NF-κB-dependent pathogen clearance in vivo. Moreover, TNF-induced apoptosis was impaired in hace1 mutant cells and knockout mice in vivo. Mechanistically, HACE1 is essential for the ubiquitylation of the adaptor protein TRAF2 and formation of the apoptotic caspase-8 effector complex. Intriguingly, loss of HACE1 does not impair TNFR1-mediated necroptotic cell fate via RIP1 and RIP3 kinases. Loss of HACE1 predisposes animals to colonic inflammation and carcinogenesis in vivo, which is markedly alleviated by genetic inactivation of RIP3 kinase and TNFR1. Thus, HACE1 controls TNF-elicited cell fate decisions and exerts tumor suppressor and anti-inflammatory activities via a TNFR1-RIP3 kinase-necroptosis pathway. : Tortola et al. report that the E3 ubiquitin ligase HACE1 is a gatekeeper of TNFR1-mediated cell fate. Hace1 deficiency impairs TNF-driven NF-κB activation and apoptosis and predisposes cells to necroptosis. Consequently, hace1–/– mice show enhanced colitis and colon cancer, which can be reverted by inactivation of pro-necroptotic kinase RIP3 and TNFR1.

Resident intruder paradigm-induced aggression relieves depressive-like behaviors in male rats subjected to chronic mild stress

Science.gov (United States)

Wei, Sheng; Ji, Xiao-wei; Wu, Chun-ling; Li, Zi-fa; Sun, Peng; Wang, Jie-qiong; Zhao, Qi-tao; Gao, Jie; Guo, Ying-hui; Sun, Shi-guang; Qiao, Ming-qi

2014-01-01

Background Accumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that the resident intruder paradigm (RIP) results in aggressive behavior in male rats. However, it is not known how resident intruder paradigm-induced aggression affects depressive-like behavior in isolated male rats subjected to chronic mild stress (CMS), which is an animal model of depression. Material/Methods Male Wistar rats were divided into 3 groups: non-stressed controls, isolated rats subjected to the CMS protocol, and resident intruder paradigm-exposed rats subjected to the CMS protocol. Results In the sucrose intake test, ingestion of a 1% sucrose solution by rats in the CMS group was significantly lower than in control and CMS+RIP rats after 3 weeks of stress. In the open-field test, CMS rats had significantly lower open-field scores compared to control rats. Furthermore, the total scores given the CMS group were significantly lower than in the CMS+RIP rats. In the forced swimming test (FST), the immobility times of CMS rats were significantly longer than those of the control or CMS+RIP rats. However, no differences were observed between controls and CMS+RIP rats. Conclusions Our data show that aggressive behavior evoked by the resident intruder paradigm could relieve broad-spectrum depressive-like behaviors in isolated adult male rats subjected to CMS. PMID:24911067

GoGene: gene annotation in the fast lane.

Science.gov (United States)

Plake, Conrad; Royer, Loic; Winnenburg, Rainer; Hakenberg, Jörg; Schroeder, Michael

2009-07-01

High-throughput screens such as microarrays and RNAi screens produce huge amounts of data. They typically result in hundreds of genes, which are often further explored and clustered via enriched GeneOntology terms. The strength of such analyses is that they build on high-quality manual annotations provided with the GeneOntology. However, the weakness is that annotations are restricted to process, function and location and that they do not cover all known genes in model organisms. GoGene addresses this weakness by complementing high-quality manual annotation with high-throughput text mining extracting co-occurrences of genes and ontology terms from literature. GoGene contains over 4,000,000 associations between genes and gene-related terms for 10 model organisms extracted from more than 18,000,000 PubMed entries. It does not cover only process, function and location of genes, but also biomedical categories such as diseases, compounds, techniques and mutations. By bringing it all together, GoGene provides the most recent and most complete facts about genes and can rank them according to novelty and importance. GoGene accepts keywords, gene lists, gene sequences and protein sequences as input and supports search for genes in PubMed, EntrezGene and via BLAST. Since all associations of genes to terms are supported by evidence in the literature, the results are transparent and can be verified by the user. GoGene is available at http://gopubmed.org/gogene.

Rod internal pressure quantification and distribution analysis using Frapcon

Energy Technology Data Exchange (ETDEWEB)

Jessee, Matthew Anderson [ORNL; Wieselquist, William A [ORNL; Ivanov, Kostadin [Pennsylvania State University, University Park

2015-09-01

This report documents work performed supporting the Department of Energy (DOE) Office of Nuclear Energy (NE) Fuel Cycle Technologies Used Fuel Disposition Campaign (UFDC) under work breakdown structure element 1.02.08.10, ST Analysis. In particular, this report fulfills the M4 milestone M4FT- 15OR0810036, Quantify effects of power uncertainty on fuel assembly characteristics, within work package FT-15OR081003 ST Analysis-ORNL. This research was also supported by the Consortium for Advanced Simulation of Light Water Reactors (http://www.casl.gov), an Energy Innovation Hub (http://www.energy.gov/hubs) for Modeling and Simulation of Nuclear Reactors under U.S. Department of Energy Contract No. DE-AC05-00OR22725. The discharge rod internal pressure (RIP) and cladding hoop stress (CHS) distributions are quantified for Watts Bar Nuclear Unit 1 (WBN1) fuel rods by modeling core cycle design data, operation data (including modeling significant trips and downpowers), and as-built fuel enrichments and densities of each fuel rod in FRAPCON-3.5. A methodology is developed which tracks inter-cycle assembly movements and assembly batch fabrication information to build individual FRAPCON inputs for each evaluated WBN1 fuel rod. An alternate model for the amount of helium released from the zirconium diboride (ZrB2) integral fuel burnable absorber (IFBA) layer is derived and applied to FRAPCON output data to quantify the RIP and CHS for these types of fuel rods. SCALE/Polaris is used to quantify fuel rodspecific spectral quantities and the amount of gaseous fission products produced in the fuel for use in FRAPCON inputs. Fuel rods with ZrB2 IFBA layers (i.e., IFBA rods) are determined to have RIP predictions that are elevated when compared to fuel rod without IFBA layers (i.e., standard rods) despite the fact that IFBA rods often have reduced fill pressures and annular fuel pellets. The primary contributor to elevated RIP predictions at burnups less than and greater than 30 GWd

Radionuclide reporter gene imaging for cardiac gene therapy

International Nuclear Information System (INIS)

Inubushi, Masayuki; Tamaki, Nagara

2007-01-01

In the field of cardiac gene therapy, angiogenic gene therapy has been most extensively investigated. The first clinical trial of cardiac angiogenic gene therapy was reported in 1998, and at the peak, more than 20 clinical trial protocols were under evaluation. However, most trials have ceased owing to the lack of decisive proof of therapeutic effects and the potential risks of viral vectors. In order to further advance cardiac angiogenic gene therapy, remaining open issues need to be resolved: there needs to be improvement of gene transfer methods, regulation of gene expression, development of much safer vectors and optimisation of therapeutic genes. For these purposes, imaging of gene expression in living organisms is of great importance. In radionuclide reporter gene imaging, ''reporter genes'' transferred into cell nuclei encode for a protein that retains a complementary ''reporter probe'' of a positron or single-photon emitter; thus expression of the reporter genes can be imaged with positron emission tomography or single-photon emission computed tomography. Accordingly, in the setting of gene therapy, the location, magnitude and duration of the therapeutic gene co-expression with the reporter genes can be monitored non-invasively. In the near future, gene therapy may evolve into combination therapy with stem/progenitor cell transplantation, so-called cell-based gene therapy or gene-modified cell therapy. Radionuclide reporter gene imaging is now expected to contribute in providing evidence on the usefulness of this novel therapeutic approach, as well as in investigating the molecular mechanisms underlying neovascularisation and safety issues relevant to further progress in conventional gene therapy. (orig.)

Avaliação do enraizamento, desenvolvimento de raízes e parte aérea de porta-enxertos de videira em condições de campo Evaluation of rooting, development of roots and shoot biomass from rootstock of grapevine, in field conditions

Directory of Open Access Journals (Sweden)

Marco Antonio Tecchio

2007-12-01

Full Text Available Objetivou-se neste trabalho avaliar o enraizamento, a brotação e o desenvolvimento de raízes de diferentes porta-enxertos de videira em condições de campo. Estacas lenhosas dos porta-enxertos '420 A', 'Golia', '5C', '8B', 'RR101-14', 'SO4', '99R', 'Kober 5BB', 'IAC 766', 'IAC 572', 'IAC 571-6', 'Ripária do Traviú' e 'Rupestris du Lot' foram colocadas em canteiro de terra, sem tratamento prévio. O delineamento foi em blocos ao acaso, com cinco repetições e vinte estacas por parcela, com as estacas dispostas em espaçamento de 12 x 5cm. As estacas foram colocadas para enraizar no início de julho e removidas no final de setembro para as avaliações. A porcentagem de estacas enraizadas variou de 79% para 'Ripária do Traviú' a 99% para o 'RR101-14'. Quanto à brotação, o 'Ripária do Traviú' apresentou 47%, 'IAC 571-6', 'IAC 572', '420 A', 'Rupestris du Lot', 'Kober', 'IAC 766', '8B', '5C', apresentaram de 76 a 89% e 'Golia', 'SO4', '99R' e 'RR 101-14' mais de 90%. 'IAC 572' e 'IAC 571-6' apresentaram o menor número de raízes por estaca, no entanto, foram as que apresentaram raízes mais desenvolvidas, seguidas pelo '5C' e 'Rupestris du Lot'. 'Kober 5BB' e 'Ripária do Traviú' apresentaram as raízes menos desenvolvidas. As demais variedades apresentaram valores intermediários. Concluiu-se que, entre todos os porta-enxertos, o 'Ripária do Traviú' apresentou os menores índices de enraizamento e brotação das estacas, nas condições de campo.The goals of this investigation was to evaluate the rooting, budding and development of roots from different rootstock of grapevine, in field conditions. Ligneous cutting of rootstock '420 A', 'Golia', '5C', '8B', 'RR101-14', 'SO4', '99R', 'Kober 5BB', 'IAC 766', 'IAC 572', 'IAC 571-6', 'Ripária do Traviú' and 'Rupestris du Lot' were planted in soil, without previous preparation. The experimental design was done in randomized blocks, with five repetitions and twenty cutting per plot

Neuroprotective Strategies for the Treatment of Blast-Induced Optic Neuropathy

Science.gov (United States)

2016-09-01

caspase 1 pro-IL-1β pro-IL-18 IL-1β IL-18 TRAF6 NFkB Rac Calpain RIP 1 pro-IL-1α RIP 3 necroptosis TXNIP NLRP eATP K + DNA P2X4...and Sleep Medicine Program. That meeting was critical for the development of a relationship between me and the clinicians and researchers at Ft

"Gorjatshaja desjatka" industrianogo regiona / Jevgeni Ashihmin

Index Scriptorium Estoniae

Ashihmin, Jevgeni

2005-01-01

Narva-Jõesuus toimunud ajalehe Äripäev Ida-Virumaa arengukonverentsil anti üle auhinnad edukamatele Ida-Virumaa ettevõtetele. Ajakirja Äripäev Ida-Virumaa TOP-i esikolmikusse kuuluvad Kohtla-Järve ettevõtted AS Nitrofert ja AS Viru Keemia Grupp ning Jõhvis asuv OÜ T.R.Tamme Auto. Ülevaade konverentsist ja Ida-Virumaa maavanema Ago Silde esinemisest

ROMI 4.0: Rough mill simulator 4.0 users manual

Science.gov (United States)

R. Edward Thomas; Timo Grueneberg; Urs. Buehlmann

2015-01-01

The Rough MIll simulator (ROMI Version 4.0) is a computer software package for personal computers (PCs) that simulates current industrial practices for rip-first, chop-first, and rip and chop-first lumber processing. This guide shows how to set up the software; design, implement, and execute simulations; and examine the results. ROMI 4.0 accepts cutting bills with as...

Gene cluster statistics with gene families.

Science.gov (United States)

Raghupathy, Narayanan; Durand, Dannie

2009-05-01

Identifying genomic regions that descended from a common ancestor is important for understanding the function and evolution of genomes. In distantly related genomes, clusters of homologous gene pairs are evidence of candidate homologous regions. Demonstrating the statistical significance of such "gene clusters" is an essential component of comparative genomic analyses. However, currently there are no practical statistical tests for gene clusters that model the influence of the number of homologs in each gene family on cluster significance. In this work, we demonstrate empirically that failure to incorporate gene family size in gene cluster statistics results in overestimation of significance, leading to incorrect conclusions. We further present novel analytical methods for estimating gene cluster significance that take gene family size into account. Our methods do not require complete genome data and are suitable for testing individual clusters found in local regions, such as contigs in an unfinished assembly. We consider pairs of regions drawn from the same genome (paralogous clusters), as well as regions drawn from two different genomes (orthologous clusters). Determining cluster significance under general models of gene family size is computationally intractable. By assuming that all gene families are of equal size, we obtain analytical expressions that allow fast approximation of cluster probabilities. We evaluate the accuracy of this approximation by comparing the resulting gene cluster probabilities with cluster probabilities obtained by simulating a realistic, power-law distributed model of gene family size, with parameters inferred from genomic data. Surprisingly, despite the simplicity of the underlying assumption, our method accurately approximates the true cluster probabilities. It slightly overestimates these probabilities, yielding a conservative test. We present additional simulation results indicating the best choice of parameter values for data

Influence of fertilizing on the 137Cs soil-plant transfer in a spruce forest of Southern Germany

International Nuclear Information System (INIS)

Zibold, G.; Klemt, E.; Konopleva, I.; Konoplev, A.

2009-01-01

Fertilization with 2.5 t/ha limestone: (83% CaCO 3 , 8% MgO, 6% K 2 O, 3% P 2 O 5 ) reduces the 137 Cs transfer from spruce forest soil into plants like fern (Dryopteris carthusiana) and blackberry (Rubus fruticosus) by a factor of 2-5 during at least 11 years as measured by the aggregated transfer factor T ag . In 1997 and 2006 these results were confirmed by additional measurements of the 137 Cs transfer factor TF, related to the root zone (O h horizon), which were explained by the selective sorption of 137 Cs in the root zone by measurements of the Radiocaesium Interception Potential (RIP) in fertilized (RIP > 179 meq/kg) and non-fertilized soils (RIP < 74 meq/kg).

Crystallization and preliminary X-ray studies of a galactose-specific lectin from the seeds of bitter gourd (Momordica charantia)

International Nuclear Information System (INIS)

Chandran, Thyageshwar; Sharma, Alok; Vijayan, M.

2010-01-01

A galactose-specific lectin purified from the seeds of bitter gourd (M. charantia) has been crystallized and preliminary X-ray study of the crystals has been carried out. A galactose-specific lectin from the seeds of bitter gourd (Momordica charantia) is a four-chain type II ribosome-inactivating protein (RIP) resulting from covalent association through a disulfide bridge between two identical copies of a two-chain unit. The available structural information on such four-chain RIPs is meagre. The bitter gourd lectin was therefore crystallized for structural investigation and the crystals have been characterized. It is anticipated that the structure of the orthorhombic crystals will be analysed using molecular replacement by taking advantage of its sequence, and presumably structural, homology to normal two-chain type II RIPs

Gene therapy prospects--intranasal delivery of therapeutic genes.

Science.gov (United States)

Podolska, Karolina; Stachurska, Anna; Hajdukiewicz, Karolina; Małecki, Maciej

2012-01-01

Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.

Gene-gene interactions and gene polymorphisms of VEGFA and EG-VEGF gene systems in recurrent pregnancy loss.

Science.gov (United States)

Su, Mei-Tsz; Lin, Sheng-Hsiang; Chen, Yi-Chi; Kuo, Pao-Lin

2014-06-01

Both vascular endothelial growth factor A (VEGFA) and endocrine gland-derived vascular endothelial growth factor (EG-VEGF) systems play major roles in angiogenesis. A body of evidence suggests VEGFs regulate critical processes during pregnancy and have been associated with recurrent pregnancy loss (RPL). However, little information is available regarding the interaction of these two major major angiogenesis-related systems in early human pregnancy. This study was conducted to investigate the association of gene polymorphisms and gene-gene interaction among genes in VEGFA and EG-VEGF systems and idiopathic RPL. A total of 98 women with history of idiopathic RPL and 142 controls were included, and 5 functional SNPs selected from VEGFA, KDR, EG-VEGF (PROK1), PROKR1 and PROKR2 were genotyped. We used multifactor dimensionality reduction (MDR) analysis to choose a best model and evaluate gene-gene interactions. Ingenuity pathways analysis (IPA) was introduced to explore possible complex interactions. Two receptor gene polymorphisms [KDR (Q472H) and PROKR2 (V331M)] were significantly associated with idiopathic RPL (P<0.01). The MDR test revealed that the KDR (Q472H) polymorphism was the best loci to be associated with RPL (P=0.02). IPA revealed EG-VEGF and VEGFA systems shared several canonical signaling pathways that may contribute to gene-gene interactions, including the Akt, IL-8, EGFR, MAPK, SRC, VHL, HIF-1A and STAT3 signaling pathways. Two receptor gene polymorphisms [KDR (Q472H) and PROKR2 (V331M)] were significantly associated with idiopathic RPL. EG-VEGF and VEGFA systems shared several canonical signaling pathways that may contribute to gene-gene interactions, including the Akt, IL-8, EGFR, MAPK, SRC, VHL, HIF-1A and STAT3.

Gene doping: gene delivery for olympic victory

OpenAIRE

Gould, David

2012-01-01

With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so called ‘gene doping’. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted...

FunGene: the functional gene pipeline and repository.

Science.gov (United States)

Fish, Jordan A; Chai, Benli; Wang, Qiong; Sun, Yanni; Brown, C Titus; Tiedje, James M; Cole, James R

2013-01-01

Ribosomal RNA genes have become the standard molecular markers for microbial community analysis for good reasons, including universal occurrence in cellular organisms, availability of large databases, and ease of rRNA gene region amplification and analysis. As markers, however, rRNA genes have some significant limitations. The rRNA genes are often present in multiple copies, unlike most protein-coding genes. The slow rate of change in rRNA genes means that multiple species sometimes share identical 16S rRNA gene sequences, while many more species share identical sequences in the short 16S rRNA regions commonly analyzed. In addition, the genes involved in many important processes are not distributed in a phylogenetically coherent manner, potentially due to gene loss or horizontal gene transfer. While rRNA genes remain the most commonly used markers, key genes in ecologically important pathways, e.g., those involved in carbon and nitrogen cycling, can provide important insights into community composition and function not obtainable through rRNA analysis. However, working with ecofunctional gene data requires some tools beyond those required for rRNA analysis. To address this, our Functional Gene Pipeline and Repository (FunGene; http://fungene.cme.msu.edu/) offers databases of many common ecofunctional genes and proteins, as well as integrated tools that allow researchers to browse these collections and choose subsets for further analysis, build phylogenetic trees, test primers and probes for coverage, and download aligned sequences. Additional FunGene tools are specialized to process coding gene amplicon data. For example, FrameBot produces frameshift-corrected protein and DNA sequences from raw reads while finding the most closely related protein reference sequence. These tools can help provide better insight into microbial communities by directly studying key genes involved in important ecological processes.

FunGene: the Functional Gene Pipeline and Repository

Directory of Open Access Journals (Sweden)

Jordan A. Fish

2013-10-01

Full Text Available Ribosomal RNA genes have become the standard molecular markers for microbial community analysis for good reasons, including universal occurrence in cellular organisms, availability of large databases, and ease of rRNA gene region amplification and analysis. As markers, however, rRNA genes have some significant limitations. The rRNA genes are often present in multiple copies, unlike most protein-coding genes. The slow rate of change in rRNA genes means that multiple species sometimes share identical 16S rRNA gene sequences, while many more species share identical sequences in the short 16S rRNA regions commonly analyzed. In addition, the genes involved in many important processes are not distributed in a phylogenetically coherent manner, potentially due to gene loss or horizontal gene transfer.While rRNA genes remain the most commonly used markers, key genes in ecologically important pathways, e.g., those involved in carbon and nitrogen cycling, can provide important insights into community composition and function not obtainable through rRNA analysis. However, working with ecofunctional gene data requires some tools beyond those required for rRNA analysis. To address this, our Functional Gene Pipeline and Repository (FunGene; http://fungene.cme.msu.edu/ offers databases of many common ecofunctional genes and proteins, as well as integrated tools that allow researchers to browse these collections and choose subsets for further analysis, build phylogenetic trees, test primers and probes for coverage, and download aligned sequences. Additional FunGene tools are specialized to process coding gene amplicon data. For example, FrameBot produces frameshift-corrected protein and DNA sequences from raw reads while finding the most closely related protein reference sequence. These tools can help provide better insight into microbial communities by directly studying key genes involved in important ecological processes.

Mining disease genes using integrated protein-protein interaction and gene-gene co-regulation information.

Science.gov (United States)

Li, Jin; Wang, Limei; Guo, Maozu; Zhang, Ruijie; Dai, Qiguo; Liu, Xiaoyan; Wang, Chunyu; Teng, Zhixia; Xuan, Ping; Zhang, Mingming

2015-01-01

In humans, despite the rapid increase in disease-associated gene discovery, a large proportion of disease-associated genes are still unknown. Many network-based approaches have been used to prioritize disease genes. Many networks, such as the protein-protein interaction (PPI), KEGG, and gene co-expression networks, have been used. Expression quantitative trait loci (eQTLs) have been successfully applied for the determination of genes associated with several diseases. In this study, we constructed an eQTL-based gene-gene co-regulation network (GGCRN) and used it to mine for disease genes. We adopted the random walk with restart (RWR) algorithm to mine for genes associated with Alzheimer disease. Compared to the Human Protein Reference Database (HPRD) PPI network alone, the integrated HPRD PPI and GGCRN networks provided faster convergence and revealed new disease-related genes. Therefore, using the RWR algorithm for integrated PPI and GGCRN is an effective method for disease-associated gene mining.

Gene-gene, gene-environment, gene-nutrient interactions and single nucleotide polymorphisms of inflammatory cytokines.

Science.gov (United States)

Nadeem, Amina; Mumtaz, Sadaf; Naveed, Abdul Khaliq; Aslam, Muhammad; Siddiqui, Arif; Lodhi, Ghulam Mustafa; Ahmad, Tausif

2015-05-15

Inflammation plays a significant role in the etiology of type 2 diabetes mellitus (T2DM). The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury, oxidative stress and beta cell apoptosis in T2DM. Among the recognized markers are interleukin (IL)-6, IL-1, IL-10, IL-18, tissue necrosis factor-alpha (TNF-α), C-reactive protein, resistin, adiponectin, tissue plasminogen activator, fibrinogen and heptoglobins. Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance. Many single nucleotide polymorphisms (SNPs) in various genes including those of pro and anti-inflammatory cytokines have been reported as a risk for T2DM. Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups. The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene, gene-environment and gene-nutrient interactions. This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6, TNF-α, resistin and adiponectin in pathogenesis of T2DM.

Identification of PaPKS1, a polyketide synthase involved in melanin formation and its use as a genetic tool in Podospora anserina.

Science.gov (United States)

Coppin, Evelyne; Silar, Philippe

2007-08-01

In the filamentous fungus Podospora anserina, many pigmentation mutations map to the median region of the complex locus '14', called segment '29'. The data presented in this paper show that segment 29 corresponds to a gene encoding a polyketide synthase, designated PaPKS1, and identifies two mutations that completely or partially abolish the activity of the PaPKS1 polypeptide. We present evidence that the P. anserina green pigment is a (DHN)-melanin. Using the powerful genetic system of PaPKS1 cloning, we demonstrate that in P. anserina trans-duplicated sequences are subject to the RIP process as previously demonstrated for the cis-duplicated regions.

MultiSimplex optimization of chromatographic separation and dansyl derivatization conditions in the ultra performance liquid chromatography-tandem mass spectrometry analysis of risperidone, 9-hydroxyrisperidone, monoamine and amino acid neurotransmitters in human urine.

Science.gov (United States)

Cai, Hua-Lin; Zhu, Rong-Hua; Li, Huan-De; Zhang, Jun; Li, Lan-Fang

2011-07-01

A pre-column dansylated ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-MS/MS) method for simultaneous determination of risperidone (RIP), 9-hydroxyrisperidone (9-OH-RIP), monoamine and amino acid neurotransmitters in human urine was developed with the aim of providing data on how neurotransmitters may influence each other or change simultaneously in response to risperidone treatment. MultiSimplex based on the simplex algorithm and the fuzzy set theory was applied to the optimization of chromatographic separation and dansyl derivatization conditions during method development. This method exhibited excellent linearity for all the analytes with regression coefficients higher than 0.997. The lower limit of quantification (LLOQ) values for 9-OH-RIP and RIP were 0.11 and 0.06 ng/ml, respectively, and for neurotrasmitters ranged from 0.31 to 12.8 nM. The mean accuracy ranged from 94.7% to 108.5%. The mean recovery varied between 81.6% and 97.5%. All the RSD of precision and stability were below 9.7%. Finally, the optimized method was applied to analyze the first morning urine samples of schizophrenic patients treated with risperidone and healthy volunteers. Copyright © 2011 Elsevier B.V. All rights reserved.

Genome-wide RIP-Chip analysis of translational repressor-bound mRNAs in the Plasmodium gametocyte

KAUST Repository

Guerreiro, Ana

2014-11-03

Background Following fertilization, the early proteomes of metazoans are defined by the translation of stored but repressed transcripts; further embryonic development relies on de novo transcription of the zygotic genome. During sexual development of Plasmodium berghei, a rodent model for human malaria species including P. falciparum, the stability of repressed mRNAs requires the translational repressors DOZI and CITH. When these repressors are absent, Plasmodium zygote development and transmission to the mosquito vector is halted, as hundreds of transcripts become destabilized. However, which mRNAs are direct targets of these RNA binding proteins, and thus subject to translational repression, is unknown. Results We identify the maternal mRNA contribution to post-fertilization development of P. berghei using RNA immunoprecipitation and microarray analysis. We find that 731 mRNAs, approximately 50% of the transcriptome, are associated with DOZI and CITH, allowing zygote development to proceed in the absence of RNA polymerase II transcription. Using GFP-tagging, we validate the repression phenotype of selected genes and identify mRNAs relying on the 5′ untranslated region for translational control. Gene deletion reveals a novel protein located in the ookinete crystalloid with an essential function for sporozoite development. Conclusions Our study details for the first time the P. berghei maternal repressome. This mRNA population provides the developing ookinete with coding potential for key molecules required for life-cycle progression, and that are likely to be critical for the transmission of the malaria parasite from the rodent and the human host to the mosquito vector.

Suicide genes or p53 gene and p53 target genes as targets for cancer gene therapy by ionizing radiation

International Nuclear Information System (INIS)

Liu Bing; Chinese Academy of Sciences, Beijing; Zhang Hong

2005-01-01

Radiotherapy has some disadvantages due to the severe side-effect on the normal tissues at a curative dose of ionizing radiation (IR). Similarly, as a new developing approach, gene therapy also has some disadvantages, such as lack of specificity for tumors, limited expression of therapeutic gene, potential biological risk. To certain extent, above problems would be solved by the suicide genes or p53 gene and its target genes therapies targeted by ionizing radiation. This strategy not only makes up the disadvantage from radiotherapy or gene therapy alone, but also promotes success rate on the base of lower dose. By present, there have been several vectors measuring up to be reaching clinical trials. This review focused on the development of the cancer gene therapy through suicide genes or p53 and its target genes mediated by IR. (authors)

Neighboring Genes Show Correlated Evolution in Gene Expression

Science.gov (United States)

Ghanbarian, Avazeh T.; Hurst, Laurence D.

2015-01-01

When considering the evolution of a gene’s expression profile, we commonly assume that this is unaffected by its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between neighboring genes in gene expression profiles in extant taxa. Indeed, in all eukaryotic genomes genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their expression or is gene expression evolution autonomous? To address this here we consider evolution of human gene expression since the human-chimp common ancestor, allowing for both variation in estimation of current expression level and error in Bayesian estimation of the ancestral state. We find that in all tissues and both sexes, the change in gene expression of a focal gene on average predicts the change in gene expression of neighbors. The effect is highly pronounced in the immediate vicinity (genes increasing their expression in humans tend to avoid nuclear lamina domains and be enriched for the gene activator 5-hydroxymethylcytosine, we conclude that, most probably owing to chromatin level control of gene expression, a change in gene expression of one gene likely affects the expression evolution of neighbors, what we term expression piggybacking, an analog of hitchhiking. PMID:25743543

Towards a theoretical determination of the geographical probability distribution of meteoroid impacts on Earth

Science.gov (United States)

Zuluaga, Jorge I.; Sucerquia, Mario

2018-06-01

Tunguska and Chelyabinsk impact events occurred inside a geographical area of only 3.4 per cent of the Earth's surface. Although two events hardly constitute a statistically significant demonstration of a geographical pattern of impacts, their spatial coincidence is at least tantalizing. To understand if this concurrence reflects an underlying geographical and/or temporal pattern, we must aim at predicting the spatio-temporal distribution of meteoroid impacts on Earth. For this purpose we designed, implemented, and tested a novel numerical technique, the `Gravitational Ray Tracing' (GRT) designed to compute the relative impact probability (RIP) on the surface of any planet. GRT is inspired by the so-called ray-casting techniques used to render realistic images of complex 3D scenes. In this paper we describe the method and the results of testing it at the time of large impact events. Our findings suggest a non-trivial pattern of impact probabilities at any given time on the Earth. Locations at 60-90° from the apex are more prone to impacts, especially at midnight. Counterintuitively, sites close to apex direction have the lowest RIP, while in the antapex RIP are slightly larger than average. We present here preliminary maps of RIP at the time of Tunguska and Chelyabinsk events and found no evidence of a spatial or temporal pattern, suggesting that their coincidence was fortuitous. We apply the GRT method to compute theoretical RIP at the location and time of 394 large fireballs. Although the predicted spatio-temporal impact distribution matches marginally the observed events, we successfully predict their impact speed distribution.

Real price and affordability as challenges for effective tobacco control policies: an analysis for Argentina.

Science.gov (United States)

Rodríguez-Iglesias, Germán; González-Rozada, Martín; Champagne, Beatriz Marcet; Schoj, Verónica

2015-02-01

To describe the evolution of cigarettes' real price and affordability during the last decade in Argentina. To analyze the real price of cigarettes, the weighted average monthly price of a pack of 20 cigarettes was divided by the consumer price index (CPI) from 2004 to 2014. The relative income price (RIP) was evaluated for the same period, defining RIP as the percentage of the income required to buy 100 packs of 20-per-pack cigarettes. The RIP was calculated for first-quartile, median, and third-quartile income groups. The lower the RIP, the higher the affordability. The nominal price of a pack of 20 cigarettes sold in Argentina increased from AR$ 2.24 in March 2004 to AR$ 14.36 in June 2014 (nominal price increase of about 19.7% per year). The real price fell from AR$ 2.24 in March 2004 to AR$ 2.11 in June 2014 (real price drop of about 0.6% per year). Between June 2004 and June 2014, the RIP decreased about 39% for the 3rd quartile income group (from 31.3% to 19.2%), about 42% for the median (from 55.7% to 32.0%), and about 50% for the 1st quartile (from 104.4% to 51.8%). In Argentina, inflation and rising income were greater than growth in cigarette prices. Cigarette affordability increased for each income group, with the highest shifts occurring among the poorest and most vulnerable income earners. The increased affordability of cigarettes might reduce the impact of implemented tobacco control policies.

Suppressing Receptor-Interacting Protein 140: a New Sight for Salidroside to Treat Cerebral Ischemia.

Science.gov (United States)

Chen, Tong; Ma, Zhanqiang; Zhu, Lingpeng; Jiang, Wenjiao; Wei, Tingting; Zhou, Rui; Luo, Fen; Zhang, Kai; Fu, Qiang; Ma, Chunhua; Yan, Tianhua

2016-11-01

The purpose of the current study was to detect the effect of salidroside (Sal) on cerebral ischemia and explore its potential mechanism. Middle cerebral artery occlusion (MCAO) was performed to investigate the effects of Sal on cerebral ischemia. The rats were randomly divided into five groups: sham group, vehicle group, clopidogrel (7.5 mg/kg) group, Sal (20 mg/kg) group, and Sal (40 mg/kg) group. SH-SY5Y cells were exposed to ischemia-reperfusion (I/R) injury to verify the protective effect of Sal in vitro. We also built the stable receptor-interacting protein 140 (RIP140)-overexpressing SH-SY5Y cells. The results showed that Sal significantly reduces brain infarct size and cerebral edema. Sal could effectively decrease the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in serum of the MCAO rats and supernatant of I/R-induced SH-SY5Y cells. Immunohistochemical and Western blot results demonstrated that Sal inhibited RIP140-mediated inflammation and apoptosis in the MCAO rats and SH-SY5Y cells. In addition, we further confirmed that RIP140/NF-κB signaling plays a crucial role by evaluating the protein expression in RIP140-overexpressing SH-SY5Y cells. Our findings suggested that Sal could be used as an effective neuroprotective agent for cerebral ischemia due to its significant effect on preventing neuronal cell injury after cerebral ischemia both in vivo and in vitro by the inhibitions of RIP140-mediated inflammation and apoptosis.

Multifunctional fluorescent sensing of chemical and physical stimuli using smart riboflavin-5'-phosphate/Eu3+ coordination polymers.

Science.gov (United States)

Xue, Shi-Fan; Zhang, Jing-Fei; Chen, Zi-Han; Han, Xin-Yue; Zhang, Min; Shi, Guoyue

2018-07-05

A novel type of stimuli-responsive fluorescent polymers has been developed via the self-assembly of riboflavin-5'-phosphate (RiP) as ligand and europium (III) (Eu 3+ ) as central metal ion coordinated with the ligand. The as-prepared RiP/Eu 3+ coordination polymers (RiP/Eu 3+ CPs) are smart and multifunctional for respectively responding to chemical and physical stimuli, in which RiP acts as the stimuli-responsive fluorescent signal indicator. For sensing chemical stimuli, 2,6-pyridinedicarboxylic acid (DPA, an anthrax biomarker) having higher bonding force towards Eu 3+ can grab it from smart RiP/Eu 3+ CPs through competition reaction, resulting in the release of RiP for highly sensitive and selective DPA monitoring in a mix-and-read fluorescent enhancement format, and the detection limit is as low as 41.5 nM. Density functional theory (DFT) calculations has been also performed to verify the DPA sensing principle. For sensing physical stimuli, the smart RiP/Eu 3+ CPs can be acting as a novel sensory probe for the determination of temperature from 10 °C to 40 °C based on the thermal-induced disruption of the binding between Eu 3+ and RiP and the disassembly of the smart RiP/Eu 3+ CPs accompanying with the recovery of the fluorescence of RiP. This work establishes an effective platform for multifunctional sensing of chemical and physical stimuli utilizing both smart lanthanide nanoscale coordination polymers (LNCPs) and novel sensing strategies. Copyright © 2018 Elsevier B.V. All rights reserved.

Real price and affordability as challenges for effective tobacco control policies: an analysis for Argentina

Directory of Open Access Journals (Sweden)

Germán Rodríguez-Iglesias

2015-02-01

Full Text Available Objective. To describe the evolution of cigarettes' real price and affordability during the last decade in Argentina. Methods. To analyze the real price of cigarettes, the weighted average monthly price of a pack of 20 cigarettes was divided by the consumer price index (CPI from 2004 to 2014. The relative income price (RIP was evaluated for the same period, defining RIP as the percentage of the income required to buy 100 packs of 20-per-pack cigarettes. The RIP was calculated for first-quartile, median, and third-quartile income groups. The lower the RIP, the higher the affordability. Results. The nominal price of a pack of 20 cigarettes sold in Argentina increased from AR$ 2.24 in March 2004 to AR$ 14.36 in June 2014 (nominal price increase of about 19.7% per year. The real price fell from AR$ 2.24 in March 2004 to AR$ 2.11 in June 2014 (real price drop of about 0.6% per year. Between June 2004 and June 2014, the RIP decreased about 39% for the 3rd quartile income group (from 31.3% to 19.2%, about 42% for the median (from 55.7% to 32.0%, and about 50% for the 1st quartile (from 104.4% to 51.8%. Conclusions. In Argentina, inflation and rising income were greater than growth in cigarette prices. Cigarette affordability increased for each income group, with the highest shifts occurring among the poorest and most vulnerable income earners. The increased affordability of cigarettes might reduce the impact of implemented tobacco control policies.

Ground-breaking virtual research in product development

DEFF Research Database (Denmark)

Søndergaard, Helle Alsted; Jespersen, Kristina Risom; Buck, Nuka

2008-01-01

MAPP also focuses on virtual reality. In the research project RIPS - the Role of Information Processing in NPD Strategy - a simulation of a product development process was used as a data collection instrument.......MAPP also focuses on virtual reality. In the research project RIPS - the Role of Information Processing in NPD Strategy - a simulation of a product development process was used as a data collection instrument....

Unge bliver ofre for kortsigtet rekruttering

DEFF Research Database (Denmark)

Nielsen, Rikke Kristine

2013-01-01

Rip-Rap-Rup-effekt: Det er fristende at hyre en kandidat med 10-20-30 års ballast fra arbejdsmarkedet. Men er det langsigtet at se bort fra de unge og mindre erfarne?......Rip-Rap-Rup-effekt: Det er fristende at hyre en kandidat med 10-20-30 års ballast fra arbejdsmarkedet. Men er det langsigtet at se bort fra de unge og mindre erfarne?...

Eesti Päevaleht korjas kolm pressipreemiat / Mari Rebane

Index Scriptorium Estoniae

Rebane, Mari

2006-01-01

Eile jagas Eesti Ajalehtede Liit 2005. aasta ajakirjandussaavutuste eest preemiaid. Eesti Päevaleht sai kujundusauhinna esikaane ja uudiskülgede eest ning arvamusloo preemia. Esikülje kujundusauhinna sai "Eesti Päevalehe" peakunstnik Merike Pinn. Parimateks uudisfoto autoriteks tunnistati Andras Kralla "Äripäevast" ja Margus Ansu "Tartu Postimehest", parimateks olemusfoto autoriteks Raul Mee "Äripäevast" ja Sille Annuk "Tartu Postimehest"

Gene Therapy

Science.gov (United States)

Gene therapy Overview Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease. Genes contain your ... that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds a new ...

Imaging reporter gene for monitoring gene therapy

International Nuclear Information System (INIS)

Beco, V. de; Baillet, G.; Tamgac, F.; Tofighi, M.; Weinmann, P.; Vergote, J.; Moretti, J.L.; Tamgac, G.

2002-01-01

Scintigraphic images can be obtained to document gene function at cellular level. This approach is presented here and the use of a reporter gene to monitor gene therapy is described. Two main ways are presented: either the use of a reporter gene coding for an enzyme the action of which will be monitored by radiolabeled pro-drug, or a cellular receptor gene, the action of which is documented by a radio labeled cognate receptor ligand. (author)

Gene-Gene and Gene-Environment Interactions in the Etiology of Breast Cancer

National Research Council Canada - National Science Library

Adegoke, Olufemi

2003-01-01

The objective of this CDA is to evaluate the gene-gene and gene-environment interactions in the etiology of breast cancer in two ongoing case-control studies, the Shanghai Breast Cancer Study (SBCS...

Gene doping: gene delivery for olympic victory.

Science.gov (United States)

Gould, David

2013-08-01

With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so called 'gene doping'. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted from the engineered cells or is retained locally to, or inside engineered cells will, to some extent, determine the likelihood of detection. It is clear that effective gene delivery technologies now exist and it is important that detection and prevention plans are in place. © 2012 The Author. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Genes2FANs: connecting genes through functional association networks

Science.gov (United States)

2012-01-01

Background Protein-protein, cell signaling, metabolic, and transcriptional interaction networks are useful for identifying connections between lists of experimentally identified genes/proteins. However, besides physical or co-expression interactions there are many ways in which pairs of genes, or their protein products, can be associated. By systematically incorporating knowledge on shared properties of genes from diverse sources to build functional association networks (FANs), researchers may be able to identify additional functional interactions between groups of genes that are not readily apparent. Results Genes2FANs is a web based tool and a database that utilizes 14 carefully constructed FANs and a large-scale protein-protein interaction (PPI) network to build subnetworks that connect lists of human and mouse genes. The FANs are created from mammalian gene set libraries where mouse genes are converted to their human orthologs. The tool takes as input a list of human or mouse Entrez gene symbols to produce a subnetwork and a ranked list of intermediate genes that are used to connect the query input list. In addition, users can enter any PubMed search term and then the system automatically converts the returned results to gene lists using GeneRIF. This gene list is then used as input to generate a subnetwork from the user’s PubMed query. As a case study, we applied Genes2FANs to connect disease genes from 90 well-studied disorders. We find an inverse correlation between the counts of links connecting disease genes through PPI and links connecting diseases genes through FANs, separating diseases into two categories. Conclusions Genes2FANs is a useful tool for interpreting the relationships between gene/protein lists in the context of their various functions and networks. Combining functional association interactions with physical PPIs can be useful for revealing new biology and help form hypotheses for further experimentation. Our finding that disease genes in

Inactivation of rifampin by Nocardia brasiliensis.

OpenAIRE

Yazawa, K; Mikami, Y; Maeda, A; Akao, M; Morisaki, N; Iwasaki, S

1993-01-01

Rifampin was glycosylated by a pathogenic species of Nocardia, i.e., Nocardia brasiliensis. The structures of two glycosylated compounds (RIP-1 and RIP-2) isolated from the culture broth of the bacterium were determined to be 3-formyl-23-(O-[beta-D-glucopyranosyl])rifamycin SV and 23-(O-[beta-D-glucopyranosyl])rifampin, respectively. Both compounds lacked antimicrobial activity against other gram-positive bacteria as well as the Nocardia species.

Classifying genes to the correct Gene Ontology Slim term in Saccharomyces cerevisiae using neighbouring genes with classification learning

Directory of Open Access Journals (Sweden)

Tsatsoulis Costas

2010-05-01

Full Text Available Abstract Background There is increasing evidence that gene location and surrounding genes influence the functionality of genes in the eukaryotic genome. Knowing the Gene Ontology Slim terms associated with a gene gives us insight into a gene's functionality by informing us how its gene product behaves in a cellular context using three different ontologies: molecular function, biological process, and cellular component. In this study, we analyzed if we could classify a gene in Saccharomyces cerevisiae to its correct Gene Ontology Slim term using information about its location in the genome and information from its nearest-neighbouring genes using classification learning. Results We performed experiments to establish that the MultiBoostAB algorithm using the J48 classifier could correctly classify Gene Ontology Slim terms of a gene given information regarding the gene's location and information from its nearest-neighbouring genes for training. Different neighbourhood sizes were examined to determine how many nearest neighbours should be included around each gene to provide better classification rules. Our results show that by just incorporating neighbour information from each gene's two-nearest neighbours, the percentage of correctly classified genes to their correct Gene Ontology Slim term for each ontology reaches over 80% with high accuracy (reflected in F-measures over 0.80 of the classification rules produced. Conclusions We confirmed that in classifying genes to their correct Gene Ontology Slim term, the inclusion of neighbour information from those genes is beneficial. Knowing the location of a gene and the Gene Ontology Slim information from neighbouring genes gives us insight into that gene's functionality. This benefit is seen by just including information from a gene's two-nearest neighbouring genes.

CLIP-seq analysis of multi-mapped reads discovers novel functional RNA regulatory sites in the human transcriptome.

Science.gov (United States)

Zhang, Zijun; Xing, Yi

2017-09-19

Crosslinking or RNA immunoprecipitation followed by sequencing (CLIP-seq or RIP-seq) allows transcriptome-wide discovery of RNA regulatory sites. As CLIP-seq/RIP-seq reads are short, existing computational tools focus on uniquely mapped reads, while reads mapped to multiple loci are discarded. We present CLAM (CLIP-seq Analysis of Multi-mapped reads). CLAM uses an expectation-maximization algorithm to assign multi-mapped reads and calls peaks combining uniquely and multi-mapped reads. To demonstrate the utility of CLAM, we applied it to a wide range of public CLIP-seq/RIP-seq datasets involving numerous splicing factors, microRNAs and m6A RNA methylation. CLAM recovered a large number of novel RNA regulatory sites inaccessible by uniquely mapped reads. The functional significance of these sites was demonstrated by consensus motif patterns and association with alternative splicing (splicing factors), transcript abundance (AGO2) and mRNA half-life (m6A). CLAM provides a useful tool to discover novel protein-RNA interactions and RNA modification sites from CLIP-seq and RIP-seq data, and reveals the significant contribution of repetitive elements to the RNA regulatory landscape of the human transcriptome. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

The Lncrna-TUG1/EZH2 Axis Promotes Pancreatic Cancer Cell Proliferation, Migration and EMT Phenotype Formation Through Sponging Mir-382.

Science.gov (United States)

Zhao, Liang; Sun, Hongwei; Kong, Hongru; Chen, Zongjing; Chen, Bicheng; Zhou, Mengtao

2017-01-01

Pancreatic carcinoma (PC) is the one of the most common and malignant cancers worldwide. LncRNA taurine upregulated gene 1 (TUG1) was initially identified as a transcript upregulated by taurine, and the abnormal expression of TUG1 has been reported in many cancers. However, the biological role and molecular mechanism of TUG1 in PC still needs further investigation. Quantitative real-time PCR (qRT-PCR) was performed to measure the expression of TUG1 in PC cell lines and tissues. MTT and colony formation assays were used to measure the effect of TUG1 on cell proliferation. A wound healing assay, transwell assay and western blot assay were employed to determine the effect of TUG1 on cell migration and the epithelial mesenchymal transition (EMT) phenotype. RNA-binding protein immunoprecipitation (RIP) and a biotin-avidin pulldown system were performed to confirm the interaction between miR-328 and TUG1. A gene expression array analysis using clinical samples and RT-qPCR suggested that enhancer of zeste homolog 2 (EZH2) was a target of miR-382 in PC. In this study, we reported that TUG1 was overexpressed in PC tissues and cell lines, and high expression of TUG1 predicted poor prognosis. Further experiments revealed that overexpressed TUG1 promoted cell proliferation, migration and contributed to EMT formation, whereas silenced TUG1 led to opposing results. Additionally, luciferase reporter assays, an RIP assay and an RNA-pulldown assay demonstrated that TUG1 could competitively sponge miR-382 and thereby regulate EZH2. Collectively, these findings revealed that TUG1 functions as an oncogenic lncRNA that promotes tumor progression, at least partially, by functioning as an endogenous 'sponge' and competing for miR-382 binding to the miRNA target EZH2. © 2017 The Author(s). Published by S. Karger AG, Basel.

The Lncrna-TUG1/EZH2 Axis Promotes Pancreatic Cancer Cell Proliferation, Migration and EMT Phenotype Formation Through Sponging Mir-382

Directory of Open Access Journals (Sweden)

Liang Zhao

2017-08-01

Full Text Available Background/Aims: Pancreatic carcinoma (PC is the one of the most common and malignant cancers worldwide. LncRNA taurine upregulated gene 1 (TUG1 was initially identified as a transcript upregulated by taurine, and the abnormal expression of TUG1 has been reported in many cancers. However, the biological role and molecular mechanism of TUG1 in PC still needs further investigation. Methods: Quantitative real-time PCR (qRT-PCR was performed to measure the expression of TUG1 in PC cell lines and tissues. MTT and colony formation assays were used to measure the effect of TUG1 on cell proliferation. A wound healing assay, transwell assay and western blot assay were employed to determine the effect of TUG1 on cell migration and the epithelial mesenchymal transition (EMT phenotype. RNA-binding protein immunoprecipitation (RIP and a biotin-avidin pulldown system were performed to confirm the interaction between miR-328 and TUG1. A gene expression array analysis using clinical samples and RT-qPCR suggested that enhancer of zeste homolog 2 (EZH2 was a target of miR-382 in PC. Results: In this study, we reported that TUG1 was overexpressed in PC tissues and cell lines, and high expression of TUG1 predicted poor prognosis. Further experiments revealed that overexpressed TUG1 promoted cell proliferation, migration and contributed to EMT formation, whereas silenced TUG1 led to opposing results. Additionally, luciferase reporter assays, an RIP assay and an RNA-pulldown assay demonstrated that TUG1 could competitively sponge miR-382 and thereby regulate EZH2. Conclusion: Collectively, these findings revealed that TUG1 functions as an oncogenic lncRNA that promotes tumor progression, at least partially, by functioning as an endogenous ‘sponge’ and competing for miR-382 binding to the miRNA target EZH2.

Sexy gene conversions: locating gene conversions on the X-chromosome.

Science.gov (United States)

Lawson, Mark J; Zhang, Liqing

2009-08-01

Gene conversion can have a profound impact on both the short- and long-term evolution of genes and genomes. Here, we examined the gene families that are located on the X-chromosomes of human (Homo sapiens), chimpanzee (Pan troglodytes), mouse (Mus musculus) and rat (Rattus norvegicus) for evidence of gene conversion. We identified seven gene families (WD repeat protein family, Ferritin Heavy Chain family, RAS-related Protein RAB-40 family, Diphosphoinositol polyphosphate phosphohydrolase family, Transcription Elongation Factor A family, LDOC1-related family, Zinc Finger Protein ZIC, and GLI family) that show evidence of gene conversion. Through phylogenetic analyses and synteny evidence, we show that gene conversion has played an important role in the evolution of these gene families and that gene conversion has occurred independently in both primates and rodents. Comparing the results with those of two gene conversion prediction programs (GENECONV and Partimatrix), we found that both GENECONV and Partimatrix have very high false negative rates (i.e. failed to predict gene conversions), which leads to many undetected gene conversions. The combination of phylogenetic analyses with physical synteny evidence exhibits high resolution in the detection of gene conversions.

Optimal Reference Genes for Gene Expression Normalization in Trichomonas vaginalis

Science.gov (United States)

dos Santos, Odelta; de Vargas Rigo, Graziela; Frasson, Amanda Piccoli; Macedo, Alexandre José; Tasca, Tiana

2015-01-01

Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR), one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis. PMID:26393928

Patenting human genes: Chinese academic articles' portrayal of gene patents.

Science.gov (United States)

Du, Li

2018-04-24

The patenting of human genes has been the subject of debate for decades. While China has gradually come to play an important role in the global genomics-based testing and treatment market, little is known about Chinese scholars' perspectives on patent protection for human genes. A content analysis of academic literature was conducted to identify Chinese scholars' concerns regarding gene patents, including benefits and risks of patenting human genes, attitudes that researchers hold towards gene patenting, and any legal and policy recommendations offered for the gene patent regime in China. 57.2% of articles were written by law professors, but scholars from health sciences, liberal arts, and ethics also participated in discussions on gene patent issues. While discussions of benefits and risks were relatively balanced in the articles, 63.5% of the articles favored gene patenting in general and, of the articles (n = 41) that explored gene patents in the Chinese context, 90.2% supported patent protections for human genes in China. The patentability of human genes was discussed in 33 articles, and 75.8% of these articles reached the conclusion that human genes are patentable. Chinese scholars view the patent regime as an important legal tool to protect the interests of inventors and inventions as well as the genetic resources of China. As such, many scholars support a gene patent system in China. These attitudes towards gene patents remain unchanged following the court ruling in the Myriad case in 2013, but arguments have been raised about the scope of gene patents, in particular that the increasing numbers of gene patents may negatively impact public health in China.

Analysis of the rendering services individual register of phonoaudiology program of the Cauca University, Colombia

OpenAIRE

Ángela Eugenia Zúñiga-Pino; Isabel Muñoz-Zambrano; Augusto Muñoz-Caicedo

2010-01-01

The program of Phonoaudiology of the University of Cauca has included the systematization of RIPS in their practices: Integrated I, Integrated II and Community VII, VIII and IX semester. The systematization uses the communicative pathologies codes stipulated in the procedure manual for the practice of audiology MPPF-II of the Colombian Association of Audiology and Technical Annex 2 of the agreement 008, 2009. The aim of this study was to analyze the information available in the RIPS, about th...

Long-term impact of reduced tillage and residue management on soil carbon stabilization: Implications for conservation agriculture on contrasting soils

OpenAIRE

Chivenge, P.P.; Murwira, H.K.; Giller, K.E.; Mapfumo, P.; Six, J.

2007-01-01

Metadata only record The long-term effects of tillage system and residue management on soil organic carbon stabilization are studied in two tropical soils in Zimbabwe, a red clay and a sandy soil. The four tillage systems evaluated were conventional tillage (CT), mulch ripping (MR), clean ripping (CR) and tied ridging (TR). Soil organic carbon (SOC) content was measured for each size fraction as well as total SOC. Based on the findings, the authors conclude that residue management - mainta...

Research progress in machine learning methods for gene-gene interaction detection.

Science.gov (United States)

Peng, Zhe-Ye; Tang, Zi-Jun; Xie, Min-Zhu

2018-03-20

Complex diseases are results of gene-gene and gene-environment interactions. However, the detection of high-dimensional gene-gene interactions is computationally challenging. In the last two decades, machine-learning approaches have been developed to detect gene-gene interactions with some successes. In this review, we summarize the progress in research on machine learning methods, as applied to gene-gene interaction detection. It systematically examines the principles and limitations of the current machine learning methods used in genome wide association studies (GWAS) to detect gene-gene interactions, such as neural networks (NN), random forest (RF), support vector machines (SVM) and multifactor dimensionality reduction (MDR), and provides some insights on the future research directions in the field.

Uranium recovery from acid leach liquors: Ix or Sx?

International Nuclear Information System (INIS)

Van Tonder, D.; Kotze, M.

2007-01-01

Various technologies for uranium recovery from sulphuric acid leach solutions were compared. Although the main consideration was the economics (Capex, recovery and Opex) of the various technologies and associated unit operations, other factors, such as flexibility, reliability, ease of operation, fire risk, stability with regards to feed flow variations, and feed solids content, would also need to be considered in the overall analysis. The design basis used for the comparison was a production rate or 200 kg/h U 3 O8 over a solution concentration range of 40 to 1500 mg/L U 3 O8. The technologies to be compared included Resin-in-pulp (RIP), Fixed-bed Ion Exchange (FBIX), Continuous Countercurrent Ion Exchange (CCIX, e.g. NIMCIX), and Solvent Extraction (Sx) using Bateman Pulsed Columns (BPC) and Bateman Settlers. Countercurrent Decantation (CCD) and clarification would be required for the Sx and FBIX technologies. The preliminary economic evaluation indicated that a flowsheet, comprising RIP for bulk uranium extraction and upgrade, followed by Sx, employing the BPC for purification of the RIP eluate stream, was the most economic option at leach liquor concentrations below 900 mg/L. Above 900 mg/L the economic evaluation suggested that CCDs followed by Sx in the BPC was the most economical processing option. For applications where the ore is abrasive and not amenable to RIP, due to the rate of resin consumption, Paste Thickeners to remove the bulk of the solids, followed by RIP, was found to be the most economic processing option at leach liquor concentrations below 200 mg/L. However, for leach liquor concentrations above 200 mg/L, a CCD-circuit followed by Sx using BPC was again the most economic favourable route

The Opening of ATP-Sensitive K+ Channels Protects H9c2 Cardiac Cells Against the High Glucose-Induced Injury and Inflammation by Inhibiting the ROS-TLR4-Necroptosis Pathway

Directory of Open Access Journals (Sweden)

Weijie Liang

2017-02-01

Full Text Available Background/Aims: Hyperglycemia activates multiple signaling molecules, including reactive oxygen species (ROS, toll-like receptor 4 (TLR4, receptor-interacting protein 3 (RIP3, a kinase promoting necroptosis, which mediate hyperglycemia-induced cardiac injury. This study explored whether inhibition of ROS-TLR4-necroptosis pathway contributed to the protection of ATP-sensitive K+ (KATP channel opening against high glucose-induced cardiac injury and inflammation. Methods: H9c2 cardiac cells were treated with 35 mM glucose (HG to establish a model of HG-induced insults. The expression of RIP3 and TLR4 were tested by western blot. Generation of ROS, cell viability, mitochondrial membrane potential (MMP and secretion of inflammatory cytokines were measured as injury indexes. Results: HG increased the expression of TLR4 and RIP3. Necrostatin-1 (Nec-1, an inhibitor of necroptosis or TAK-242 (an inhibitor of TLR4 co-treatment attenuated HG-induced up-regulation of RIP3. Diazoxide (DZ, a mitochondrial KATP channel opener or pinacidil (Pin, a non-selective KATP channel opener or N-acetyl-L-cysteine (NAC, a ROS scavenger pre-treatment blocked the up-regulation of TLR4 and RIP3. Furthermore, pre-treatment with DZ or Pin or NAC, or co-treatment with TAK-242 or Nec-1 attenuated HG-induced a decrease in cell viability, and increases in ROS generation, MMP loss and inflammatory cytokines secretion. However, 5-hydroxy decanoic acid (5-HD, a mitochondrial KATP channel blocker or glibenclamide (Gli, a non-selective KATP channel blocker pre-treatment did not aggravate HG-induced injury and inflammation. Conclusion: KATP channel opening protects H9c2 cells against HG-induced injury and inflammation by inhibiting ROS-TLR4-necroptosis pathway.

Trace analysis of loss of feedwater flow event in Lungmen ABWR

International Nuclear Information System (INIS)

Wang Jongrong; Lin Haotzu; Wang Weichen; Yang Shuming; Shih Chunkuan

2009-01-01

TRACE (TRAC/RELAP Advanced Computational Engine) model of Lungmen Nuclear Power Plant was used to analyze the Loss of Feedwater Flow transient as defined in Lungmen FSAR Chapter 15. The results were compared with those from FSAR and RETRAN02. Lungmen TRACE model will have two models: In model A, vessel is divided into 11 axial levels, 4 radial rings and 1 azimuthal sectors; In model B, vessel is divided into 11 axial levels, 4 radial rings, and 6 azimuthal sectors. The above models include feedwater control system, narrow range water level control system, and wide range water level control system. The loss of feedwater flow (LOFW) transient began with the trip of two operating feedwater pumps either from the pump mechanical/electric failure, or the operator human error, or high water level signal. Feedwater flow was assumed to descend to 0 in 5 seconds and led to the decrease of reactor water level. At L3 low water level setpoint, the system actuated reactor scram signal and RIP trip signal for RIPs not connected to the M/G set. At L2 low-low water level setpoint, the system would trip the other six RIPs. This paper compares those important thermal parameters at steady state, such as the dome pressure and temperature of reactor vessel, steam flow, feedwater flow, core flow, and RIP flow, etc.. It also compares system parameters under transient conditions, such as core thermal power, core flow, steam flow, feedwater flow, Narrow Range Water Level (NRWL), Wide Range Water Level (WRWL) and RIP flow, etc.. It was concluded that the steady state and transient results of TRACE calculations are in good agreement with those from RETRAN02. In summary, our studies concluded that Lungmen TRACE model is correct and accurate enough for future safety analysis applications. (author)

Yield and water use efficiencies of maize and cowpea as affected by tillage and cropping systems in semi-arid Eastern Kenya

International Nuclear Information System (INIS)

Miriti, M.J; Kironchi, G; Gachene, K.K.C; Esilaba, O.A.; Mwangi, M.D; Heng, K.L

2012-01-01

Soil water conservation through tillage is widely accepted as one of the ways of improving crop yields in rainfed agriculture. Field experiments were conducted between 2007 and 2009 to evaluate the effects of conservation tillage on the yields and crop water use efficiency of maize (Zea mays L.) and cowpea (Vigna unguiculata L.) in eastern Kenya. Experimental treatments were a combination of three tillage practices and four cropping systems. Tillage practices were tied-ridges, subsoiling-ripping and ox-ploughing. The cropping systems were single crop maize, single crop cowpea, intercropped maize.cowpea and single crop maize with manure. The treatments were arranged in split plots with tillage practices as the main plots and cropping systems as the sub-plots in a Randomized Complete Block Design (RCBD). The results showed that tied-ridge tillage had the greatest plant available water content while subsoiling-ripping tillage had the least in all seasons. Averaged across seasons and cropping season, tillage did not have a significant effects on maize grain yield but it did have a significant effect on crop grain and dry matter water use efficiency (WUE). Nevertheless, maize grain yields and WUE values were generally greater under tied-ridge tillage than under subsoiling-ripping and ox-plough tillages. The yields and WUE of cowpea under subsoiling-ripping tillage were less than those of ox-plough tillage. When averaged across the seasons and tillage systems, the cropping system with the manure treatment increased (P.0.05) maize grain yield, grain WUE and dry matter WUE by 36%, 30%, 26% respectively, compared to treatments without manure. Maize and cowpea when intercropped under ox-plough and ripping tillage systems did not have any yield advantage over the single crop

Gene Circuit Analysis of the Terminal Gap Gene huckebein

Science.gov (United States)

Ashyraliyev, Maksat; Siggens, Ken; Janssens, Hilde; Blom, Joke; Akam, Michael; Jaeger, Johannes

2009-01-01

The early embryo of Drosophila melanogaster provides a powerful model system to study the role of genes in pattern formation. The gap gene network constitutes the first zygotic regulatory tier in the hierarchy of the segmentation genes involved in specifying the position of body segments. Here, we use an integrative, systems-level approach to investigate the regulatory effect of the terminal gap gene huckebein (hkb) on gap gene expression. We present quantitative expression data for the Hkb protein, which enable us to include hkb in gap gene circuit models. Gap gene circuits are mathematical models of gene networks used as computational tools to extract regulatory information from spatial expression data. This is achieved by fitting the model to gap gene expression patterns, in order to obtain estimates for regulatory parameters which predict a specific network topology. We show how considering variability in the data combined with analysis of parameter determinability significantly improves the biological relevance and consistency of the approach. Our models are in agreement with earlier results, which they extend in two important respects: First, we show that Hkb is involved in the regulation of the posterior hunchback (hb) domain, but does not have any other essential function. Specifically, Hkb is required for the anterior shift in the posterior border of this domain, which is now reproduced correctly in our models. Second, gap gene circuits presented here are able to reproduce mutants of terminal gap genes, while previously published models were unable to reproduce any null mutants correctly. As a consequence, our models now capture the expression dynamics of all posterior gap genes and some variational properties of the system correctly. This is an important step towards a better, quantitative understanding of the developmental and evolutionary dynamics of the gap gene network. PMID:19876378

Gene expression

International Nuclear Information System (INIS)

Hildebrand, C.E.; Crawford, B.D.; Walters, R.A.; Enger, M.D.

1983-01-01

We prepared probes for isolating functional pieces of the metallothionein locus. The probes enabled a variety of experiments, eventually revealing two mechanisms for metallothionein gene expression, the order of the DNA coding units at the locus, and the location of the gene site in its chromosome. Once the switch regulating metallothionein synthesis was located, it could be joined by recombinant DNA methods to other, unrelated genes, then reintroduced into cells by gene-transfer techniques. The expression of these recombinant genes could then be induced by exposing the cells to Zn 2+ or Cd 2+ . We would thus take advantage of the clearly defined switching properties of the metallothionein gene to manipulate the expression of other, perhaps normally constitutive, genes. Already, despite an incomplete understanding of how the regulatory switch of the metallothionein locus operates, such experiments have been performed successfully

Genes from scratch--the evolutionary fate of de novo genes.

Science.gov (United States)

Schlötterer, Christian

2015-04-01

Although considered an extremely unlikely event, many genes emerge from previously noncoding genomic regions. This review covers the entire life cycle of such de novo genes. Two competing hypotheses about the process of de novo gene birth are discussed as well as the high death rate of de novo genes. Despite the high death rate, some de novo genes are retained and remain functional, even in distantly related species, through their integration into gene networks. Further studies combining gene expression with ribosome profiling in multiple populations across different species will be instrumental for an improved understanding of the evolutionary processes operating on de novo genes. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

Gene Duplicability of Core Genes Is Highly Consistent across All Angiosperms.

Science.gov (United States)

Li, Zhen; Defoort, Jonas; Tasdighian, Setareh; Maere, Steven; Van de Peer, Yves; De Smet, Riet

2016-02-01

Gene duplication is an important mechanism for adding to genomic novelty. Hence, which genes undergo duplication and are preserved following duplication is an important question. It has been observed that gene duplicability, or the ability of genes to be retained following duplication, is a nonrandom process, with certain genes being more amenable to survive duplication events than others. Primarily, gene essentiality and the type of duplication (small-scale versus large-scale) have been shown in different species to influence the (long-term) survival of novel genes. However, an overarching view of "gene duplicability" is lacking, mainly due to the fact that previous studies usually focused on individual species and did not account for the influence of genomic context and the time of duplication. Here, we present a large-scale study in which we investigated duplicate retention for 9178 gene families shared between 37 flowering plant species, referred to as angiosperm core gene families. For most gene families, we observe a strikingly consistent pattern of gene duplicability across species, with gene families being either primarily single-copy or multicopy in all species. An intermediate class contains gene families that are often retained in duplicate for periods extending to tens of millions of years after whole-genome duplication, but ultimately appear to be largely restored to singleton status, suggesting that these genes may be dosage balance sensitive. The distinction between single-copy and multicopy gene families is reflected in their functional annotation, with single-copy genes being mainly involved in the maintenance of genome stability and organelle function and multicopy genes in signaling, transport, and metabolism. The intermediate class was overrepresented in regulatory genes, further suggesting that these represent putative dosage-balance-sensitive genes. © 2016 American Society of Plant Biologists. All rights reserved.

Advances in study of reporter gene imaging for monitoring gene therapy

International Nuclear Information System (INIS)

Mu Chuanjie; Zhou Jiwen

2003-01-01

To evaluate the efficiency of gene therapy, it is requisite to monitor localization and expression of the therapeutic gene in vivo. Monitoring expression of reporter gene using radionuclide reporter gene technique is the best method. Adenoviral vectors expressing reporter gene are constructed using gene fusion, bicistronic, double promoter or bidirectional transcriptional recombination techniques, and transferred into target cells and tissues, then injected radiolabeled reporter probes which couple to the reporter genes. The reporter genes can be imaged invasively, repeatedly, quantitatively with γ-camera, PET and SPECT. Recently, several reporter gene and reporter probe systems have been used in studies of gene therapy. The part of them has been used for clinic trials

Anchorage strength models for end-debonding predictions in RC beams strengthened with FRP composites

Science.gov (United States)

Nardini, V.; Guadagnini, M.; Valluzzi, M. R.

2008-05-01

The increase in the flexural capacity of RC beams obtained by externally bonding FRP composites to their tension side is often limited by the premature and brittle debonding of the external reinforcement. An in-depth understanding of this complex failure mechanism, however, has not yet been achieved. With specific regard to end-debonding failure modes, extensive experimental observations reported in the literature highlight the important distinction, often neglected in strength models proposed by researchers, between the peel-off and rip-off end-debonding types of failure. The peel-off failure is generally characterized by a failure plane located within the first few millimetres of the concrete cover, whilst the rip-off failure penetrates deeper into the concrete cover and propagates along the tensile steel reinforcement. A new rip-off strength model is described in this paper. The model proposed is based on the Chen and Teng peel-off model and relies upon additional theoretical considerations. The influence of the amount of the internal tensile steel reinforcement and the effective anchorage length of FRP are considered and discussed. The validity of the new model is analyzed further through comparisons with test results, findings of a numerical investigation, and a parametric study. The new rip-off strength model is assessed against a database comprising results from 62 beams tested by various researchers and is shown to yield less conservative results.

Mono-PEGylation of Alpha-MMC and MAP30 from Momordica charantia L.: Production, Identification and Anti-Tumor Activity.

Science.gov (United States)

Sun, Yun; Sun, Fenghui; Li, Jianlong; Wu, Minlu; Fan, Xiang; Meng, Yanfa; Meng, Yao

2016-10-31

PEGylation is a well-established and effective strategy to decrease immunogenicity, which can increase the stability and in vivo half-life time. However, the generation of multi-site modified products is inevitable due to the lysine chemistry, which will bring difficulties in subsequent research, such as purification and quantification. Site-specific modification by mPEG-succinimidyl carbonate (mPEG-SC) is a widely used method for N -terminal conjugation. In this study, we used it for site-directed modification on two ribosome-inactivating proteins (RIPs), alpha-momorcharin (α-MMC) and momordica anti-HIV protein (MAP30), from Momordica charantia L. According to the optimization of previous modification conditions, we compared Macro-Cap SP with SP-Sepharose FF chromatography for separating the final mPEGylated RIPs. Two kinds of methods both can obtain homogenous mPEGylated RIPs which were identified by sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing electrophoresis (IEF), and matrix-assisted laser desorption ionization-time of flight/time of flight (MALDI-TOF/TOF) analysis. We also used iodine staining method to detect the amount of unmodified PEG. Furthermore, the inhibition activity of both mPEGylated and non-PEGylated RIPs against human lung adenocarcinoma epithelial A549 cells was detected. All of the results suggested that the mPEGylated α-MMC/MAP30 might be potentially developed as new anti-tumor drugs.

Detection of nitro-based and peroxide-based explosives by fast polarity-switchable ion mobility spectrometer with ion focusing in vicinity of Faraday detector.

Science.gov (United States)

Zhou, Qinghua; Peng, Liying; Jiang, Dandan; Wang, Xin; Wang, Haiyan; Li, Haiyang

2015-05-29

Ion mobility spectrometer (IMS) has been widely deployed for on-site detection of explosives. The common nitro-based explosives are usually detected by negative IMS while the emerging peroxide-based explosives are better detected by positive IMS. In this study, a fast polarity-switchable IMS was constructed to detect these two explosive species in a single measurement. As the large traditional Faraday detector would cause a trailing reactant ion peak (RIP), a Faraday detector with ion focusing in vicinity was developed by reducing the detector radius to 3.3 mm and increasing the voltage difference between aperture grid and its front guard ring to 591 V, which could remove trailing peaks from RIP without loss of signal intensity. This fast polarity-switchable IMS with ion focusing in vicinity of Faraday detector was employed to detect a mixture of 10 ng 2,4,6-trinitrotoluene (TNT) and 50 ng hexamethylene triperoxide diamine (HMTD) by polarity-switching, and the result suggested that [TNT-H](-) and [HMTD+H](+) could be detected in a single measurement. Furthermore, the removal of trailing peaks from RIP by the Faraday detector with ion focusing in vicinity also promised the accurate identification of KClO4, KNO3 and S in common inorganic explosives, whose product ion peaks were fairly adjacent to RIP.

Down-Regulation of Gene Expression by RNA-Induced Gene Silencing

Science.gov (United States)

Travella, Silvia; Keller, Beat

Down-regulation of endogenous genes via post-transcriptional gene silencing (PTGS) is a key to the characterization of gene function in plants. Many RNA-based silencing mechanisms such as post-transcriptional gene silencing, co-suppression, quelling, and RNA interference (RNAi) have been discovered among species of different kingdoms (plants, fungi, and animals). One of the most interesting discoveries was RNAi, a sequence-specific gene-silencing mechanism initiated by the introduction of double-stranded RNA (dsRNA), homologous in sequence to the silenced gene, which triggers degradation of mRNA. Infection of plants with modified viruses can also induce RNA silencing and is referred to as virus-induced gene silencing (VIGS). In contrast to insertional mutagenesis, these emerging new reverse genetic approaches represent a powerful tool for exploring gene function and for manipulating gene expression experimentally in cereal species such as barley and wheat. We examined how RNAi and VIGS have been used to assess gene function in barley and wheat, including molecular mechanisms involved in the process and available methodological elements, such as vectors, inoculation procedures, and analysis of silenced phenotypes.

Therapeutic genes for anti-HIV/AIDS gene therapy.

Science.gov (United States)

Bovolenta, Chiara; Porcellini, Simona; Alberici, Luca

2013-01-01

The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the treatment of monogenic immunodeficiensies, where permanent gene modification of host cells is sufficient to correct the defect for life-time. No doubt, a similar concept is not applicable for gene therapy of infectious immunodeficiensies as AIDS, where there is not a single gene to be corrected; rather engineered cells must gain immunotherapeutic or antiviral features to grant either short- or long-term efficacy mostly by acquisition of antiviral genes or payloads. Anti-HIV/AIDS gene therapy is one of the most promising strategy, although challenging, to eradicate HIV-1 infection. In fact, genetic modification of hematopoietic stem cells with one or multiple therapeutic genes is expected to originate blood cell progenies resistant to viral infection and thereby able to prevail on infected unprotected cells. Ultimately, protected cells will re-establish a functional immune system able to control HIV-1 replication. More than hundred gene therapy clinical trials against AIDS employing different viral vectors and transgenes have been approved or are currently ongoing worldwide. This review will overview anti-HIV-1 infection gene therapy field evaluating strength and weakness of the transgenes and payloads used in the past and of those potentially exploitable in the future.

Discovering implicit entity relation with the gene-citation-gene network.

Directory of Open Access Journals (Sweden)

Min Song

Full Text Available In this paper, we apply the entitymetrics model to our constructed Gene-Citation-Gene (GCG network. Based on the premise there is a hidden, but plausible, relationship between an entity in one article and an entity in its citing article, we constructed a GCG network of gene pairs implicitly connected through citation. We compare the performance of this GCG network to a gene-gene (GG network constructed over the same corpus but which uses gene pairs explicitly connected through traditional co-occurrence. Using 331,411 MEDLINE abstracts collected from 18,323 seed articles and their references, we identify 25 gene pairs. A comparison of these pairs with interactions found in BioGRID reveal that 96% of the gene pairs in the GCG network have known interactions. We measure network performance using degree, weighted degree, closeness, betweenness centrality and PageRank. Combining all measures, we find the GCG network has more gene pairs, but a lower matching rate than the GG network. However, combining top ranked genes in both networks produces a matching rate of 35.53%. By visualizing both the GG and GCG networks, we find that cancer is the most dominant disease associated with the genes in both networks. Overall, the study indicates that the GCG network can be useful for detecting gene interaction in an implicit manner.

Reduced rates of gene loss, gene silencing, and gene mutation in Dnmt1-deficient embryonic stem cells

NARCIS (Netherlands)

Chan, M.F.; van Amerongen, R.; Nijjar, T.; Cuppen, E.; Jones, P.A.; Laird, P.W.

2001-01-01

Tumor suppressor gene inactivation is a crucial event in oncogenesis. Gene inactivation mechanisms include events resulting in loss of heterozygosity (LOH), gene mutation, and transcriptional silencing. The contribution of each of these different pathways varies among tumor suppressor genes and by

A Comparison of the OSHA Modified NIOSH Physical and Chemical Analytical Method (P and CAM) 304 and the Dust Trak Photometric Aerosol Sampler for 0-Chlorobenzylidine Malonitrile

Science.gov (United States)

2013-04-02

Paper is ripped up and placed inside the coffee can, followed by the opening of CS capsules where granules of the CS are dispersed into the paper... coffee can was placed on top of the hot plate. Paper is ripped up and placed inside the coffee can to assist in the burning of the capsules , capsules ...be re-aerosolized as dried aerosol- particulates. Additionally, the outer casings of the CS capsules and paper were often added to the coffee can to

Recipes for stable linear embeddings from Hilbert spaces to R^m

OpenAIRE

Puy, Gilles; Davies, Michael; Gribonval, Remi

2017-01-01

We consider the problem of constructing a linear map from a Hilbert space H (possibly infinite dimensional) to Rm that satisfies a restricted isometry property (RIP) on an arbitrary signal model, i.e., a subset of H. We present a generic framework that handles a large class of low-dimensional subsets but also unstructured and structured linear maps. We provide a simple recipe to prove that a random linear map satisfies a general RIP with high probability. We also describe a generic technique ...

Recipes for stable linear embeddings from Hilbert spaces to R^m

OpenAIRE

Puy, Gilles; Davies, Mike; Gribonval, Rémi

2015-01-01

We consider the problem of constructing a linear map from a Hilbert space $\\mathcal{H}$ (possibly infinite dimensional) to $\\mathbb{R}^m$ that satisfies a restricted isometry property (RIP) on an arbitrary signal model $\\mathcal{S} \\subset \\mathcal{H}$. We present a generic framework that handles a large class of low-dimensional subsets but also unstructured and structured linear maps. We provide a simple recipe to prove that a random linear map satisfies a general RIP on $\\mathcal{S}$ with h...

A hybrid approach of gene sets and single genes for the prediction of survival risks with gene expression data.

Science.gov (United States)

Seok, Junhee; Davis, Ronald W; Xiao, Wenzhong

2015-01-01

Accumulated biological knowledge is often encoded as gene sets, collections of genes associated with similar biological functions or pathways. The use of gene sets in the analyses of high-throughput gene expression data has been intensively studied and applied in clinical research. However, the main interest remains in finding modules of biological knowledge, or corresponding gene sets, significantly associated with disease conditions. Risk prediction from censored survival times using gene sets hasn't been well studied. In this work, we propose a hybrid method that uses both single gene and gene set information together to predict patient survival risks from gene expression profiles. In the proposed method, gene sets provide context-level information that is poorly reflected by single genes. Complementarily, single genes help to supplement incomplete information of gene sets due to our imperfect biomedical knowledge. Through the tests over multiple data sets of cancer and trauma injury, the proposed method showed robust and improved performance compared with the conventional approaches with only single genes or gene sets solely. Additionally, we examined the prediction result in the trauma injury data, and showed that the modules of biological knowledge used in the prediction by the proposed method were highly interpretable in biology. A wide range of survival prediction problems in clinical genomics is expected to benefit from the use of biological knowledge.

Time-Course Gene Set Analysis for Longitudinal Gene Expression Data.

Directory of Open Access Journals (Sweden)

Boris P Hejblum

2015-06-01

Full Text Available Gene set analysis methods, which consider predefined groups of genes in the analysis of genomic data, have been successfully applied for analyzing gene expression data in cross-sectional studies. The time-course gene set analysis (TcGSA introduced here is an extension of gene set analysis to longitudinal data. The proposed method relies on random effects modeling with maximum likelihood estimates. It allows to use all available repeated measurements while dealing with unbalanced data due to missing at random (MAR measurements. TcGSA is a hypothesis driven method that identifies a priori defined gene sets with significant expression variations over time, taking into account the potential heterogeneity of expression within gene sets. When biological conditions are compared, the method indicates if the time patterns of gene sets significantly differ according to these conditions. The interest of the method is illustrated by its application to two real life datasets: an HIV therapeutic vaccine trial (DALIA-1 trial, and data from a recent study on influenza and pneumococcal vaccines. In the DALIA-1 trial TcGSA revealed a significant change in gene expression over time within 69 gene sets during vaccination, while a standard univariate individual gene analysis corrected for multiple testing as well as a standard a Gene Set Enrichment Analysis (GSEA for time series both failed to detect any significant pattern change over time. When applied to the second illustrative data set, TcGSA allowed the identification of 4 gene sets finally found to be linked with the influenza vaccine too although they were found to be associated to the pneumococcal vaccine only in previous analyses. In our simulation study TcGSA exhibits good statistical properties, and an increased power compared to other approaches for analyzing time-course expression patterns of gene sets. The method is made available for the community through an R package.

Norrie disease gene is distinct from the monoamine oxidase genes

OpenAIRE

Sims, Katherine B.; Ozelius, Laurie; Corey, Timothy; Rinehart, William B.; Liberfarb, Ruth; Haines, Jonathan; Chen, Wei Jane; Norio, Reijo; Sankila, Eeva; de la Chapelle, Albert; Murphy, Dennis L.; Gusella, James; Breakefield, Xandra O.

1989-01-01

The genes for MAO-A and MAO-B appear to be very close to the Norrie disease gene, on the basis of loss and /or disruption of the MAO genes and activities in atypical Norrie disease patients deleted for the DXS7 locus; linkage among the MAO genes, the Norrie disease gene, and the DXS7 locus; and mapping of all these loci to the chromosomal region Xp11. The present study provides evidence that the MAO genes are not disrupted in “classic” Norrie disease patients. Genomic DNA from these “nondelet...

Early and rapid development of insulin resistance, islet dysfunction and glucose intolerance after high-fat feeding in mice overexpressing phosphodiesterase 3B

DEFF Research Database (Denmark)

Walz, Helena A; Härndahl, Linda; Wierup, Nils

2006-01-01

Inadequate islet adaptation to insulin resistance leads to glucose intolerance and type 2 diabetes. Here we investigate whether beta-cell cAMP is crucial for islet adaptation and prevention of glucose intolerance in mice. Mice with a beta-cell-specific, 2-fold overexpression of the c......AMP-degrading enzyme phosphodiesterase 3B (RIP-PDE3B/2 mice) were metabolically challenged with a high-fat diet. We found that RIP-PDE3B/2 mice early and rapidly develop glucose intolerance and insulin resistance, as compared with wild-type littermates, after 2 months of high-fat feeding. This was evident from...... did not reveal reduced insulin sensitivity in these tissues. Significant steatosis was noted in livers from high-fat-fed wild-type and RIP-PDE3B/2 mice and liver triacyl-glycerol content was 3-fold higher than in wild-type mice fed a control diet. Histochemical analysis revealed severe islet...

Complete conformal classification of the Friedmann–Lemaître–Robertson–Walker solutions with a linear equation of state

Science.gov (United States)

Harada, Tomohiro; Carr, B. J.; Igata, Takahisa

2018-05-01

We completely classify Friedmann–Lemaître–Robertson–Walker solutions with spatial curvature and equation of state , according to their conformal structure, singularities and trapping horizons. We do not assume any energy conditions and allow , thereby going beyond the usual well-known solutions. For each spatial curvature, there is an initial spacelike big-bang singularity for w  >  ‑1/3 and , while there is no big-bang singularity for w  big-bang singularity. For each spatial curvature, there is a final spacelike future big-rip singularity for w  big-rip singularity, then bounces and blows up at a final spacelike future big-rip singularity. For w    ‑1/3, the universe contracts from infinity, then bounces and expands to infinity; for  ‑1  big-bang singularity and contracts to a big-crunch singularity; for w  <  ‑1, it expands from a regular null hypersurface and contracts to another regular null hypersurface.

PAISAGEM RIPÁRIA FLUVIAL DOS RIOS PITANGUI E JOTUVA NO PRIMEIRO PLANALTO PARANAENSE, PONTA GROSSA, PR

Directory of Open Access Journals (Sweden)

Tiaro Katu Pereira

2012-08-01

Full Text Available Esta análise quantitativa de 3.739,7 ha de paisagens ripárias fluviais dos rios Pitangui e Jotuva considerou áreas de floresta higrófila (FH e de vegetação hidrófila (VH, delimitadas mediante interpretação de ortofotos de 2001. O Pitangui apresentou 3.180 ha de áreas ripárias em 35 polígonos de FH (13,8% e 168 de VH (86,2%. O Jotuva, com 559 ha, apresentou 19 poligonos de FH (42% e 47 de VH (58%. Demonstrou-se a importância de incluir a VH nas análises das zonas ripárias destes rios, notável no Pitangui, que para efeitos de conservação, parece reunir condições mais favoráveis à manutenção da biodiversidade do que no Jotuva. Foram observados distintos padrões de paisagem em função do relevo nos rios.

Dark energy cosmology with generalized linear equation of state

International Nuclear Information System (INIS)

Babichev, E; Dokuchaev, V; Eroshenko, Yu

2005-01-01

Dark energy with the usually used equation of state p = wρ, where w const 0 ), where the constants α and ρ 0 are free parameters. This non-homogeneous linear equation of state provides the description of both hydrodynamically stable (α > 0) and unstable (α < 0) fluids. In particular, the considered cosmological model describes the hydrodynamically stable dark (and phantom) energy. The possible types of cosmological scenarios in this model are determined and classified in terms of attractors and unstable points by using phase trajectories analysis. For the dark energy case, some distinctive types of cosmological scenarios are possible: (i) the universe with the de Sitter attractor at late times, (ii) the bouncing universe, (iii) the universe with the big rip and with the anti-big rip. In the framework of a linear equation of state the universe filled with a phantom energy, w < -1, may have either the de Sitter attractor or the big rip

A genetic ensemble approach for gene-gene interaction identification

Directory of Open Access Journals (Sweden)

Ho Joshua WK

2010-10-01

Full Text Available Abstract Background It has now become clear that gene-gene interactions and gene-environment interactions are ubiquitous and fundamental mechanisms for the development of complex diseases. Though a considerable effort has been put into developing statistical models and algorithmic strategies for identifying such interactions, the accurate identification of those genetic interactions has been proven to be very challenging. Methods In this paper, we propose a new approach for identifying such gene-gene and gene-environment interactions underlying complex diseases. This is a hybrid algorithm and it combines genetic algorithm (GA and an ensemble of classifiers (called genetic ensemble. Using this approach, the original problem of SNP interaction identification is converted into a data mining problem of combinatorial feature selection. By collecting various single nucleotide polymorphisms (SNP subsets as well as environmental factors generated in multiple GA runs, patterns of gene-gene and gene-environment interactions can be extracted using a simple combinatorial ranking method. Also considered in this study is the idea of combining identification results obtained from multiple algorithms. A novel formula based on pairwise double fault is designed to quantify the degree of complementarity. Conclusions Our simulation study demonstrates that the proposed genetic ensemble algorithm has comparable identification power to Multifactor Dimensionality Reduction (MDR and is slightly better than Polymorphism Interaction Analysis (PIA, which are the two most popular methods for gene-gene interaction identification. More importantly, the identification results generated by using our genetic ensemble algorithm are highly complementary to those obtained by PIA and MDR. Experimental results from our simulation studies and real world data application also confirm the effectiveness of the proposed genetic ensemble algorithm, as well as the potential benefits of

The Mycoplasma hominis vaa gene displays a mosaic gene structure

DEFF Research Database (Denmark)

Boesen, Thomas; Emmersen, Jeppe M. G.; Jensen, Lise T.

1998-01-01

Mycoplasma hominis contains a variable adherence-associated (vaa) gene. To classify variants of the vaa genes, we examined 42 M. hominis isolated by PCR, DNA sequencing and immunoblotting. This uncovered the existence of five gene categories. Comparison of the gene types revealed a modular...

Transgenic overexpression of active calcineurin in beta-cells results in decreased beta-cell mass and hyperglycemia.

Directory of Open Access Journals (Sweden)

Ernesto Bernal-Mizrachi

2010-08-01

Full Text Available Glucose modulates beta-cell mass and function through an initial depolarization and Ca(2+ influx, which then triggers a number of growth regulating signaling pathways. One of the most important downstream effectors in Ca(2+ signaling is the calcium/Calmodulin activated serine threonine phosphatase, calcineurin. Recent evidence suggests that calcineurin/NFAT is essential for beta-cell proliferation, and that in its absence loss of beta-cells results in diabetes. We hypothesized that in contrast, activation of calcineurin might result in expansion of beta-cell mass and resistance to diabetes.To determine the role of activation of calcineurin signaling in the regulation of pancreatic beta-cell mass and proliferation, we created mice that expressed a constitutively active form of calcineurin under the insulin gene promoter (caCn(RIP. To our surprise, these mice exhibited glucose intolerance. In vitro studies demonstrated that while the second phase of Insulin secretion is enhanced, the overall insulin secretory response was conserved. Islet morphometric studies demonstrated decreased beta-cell mass suggesting that this was a major component responsible for altered Insulin secretion and glucose intolerance in caCn(RIP mice. The reduced beta-cell mass was accompanied by decreased proliferation and enhanced apoptosis.Our studies identify calcineurin as an important factor in controlling glucose homeostasis and indicate that chronic depolarization leading to increased calcineurin activity may contribute, along with other genetic and environmental factors, to beta-cell dysfunction and diabetes.

Identification of Hematopoietic Stem Cell Engraftment Genes in Gene Therapy Studies.

Science.gov (United States)

Powers, John M; Trobridge, Grant D

2013-09-01

Hematopoietic stem cell (HSC) therapy using replication-incompetent retroviral vectors is a promising approach to provide life-long correction for genetic defects. HSC gene therapy clinical studies have resulted in functional cures for several diseases, but in some studies clonal expansion or leukemia has occurred. This is due to the dyregulation of endogenous host gene expression from vector provirus insertional mutagenesis. Insertional mutagenesis screens using replicating retroviruses have been used extensively to identify genes that influence oncogenesis. However, retroviral mutagenesis screens can also be used to determine the role of genes in biological processes such as stem cell engraftment. The aim of this review is to describe the potential for vector insertion site data from gene therapy studies to provide novel insights into mechanisms of HSC engraftment. In HSC gene therapy studies dysregulation of host genes by replication-incompetent vector proviruses may lead to enrichment of repopulating clones with vector integrants near genes that influence engraftment. Thus, data from HSC gene therapy studies can be used to identify novel candidate engraftment genes. As HSC gene therapy use continues to expand, the vector insertion site data collected will be of great interest to help identify novel engraftment genes and may ultimately lead to new therapies to improve engraftment.

Gene Duplicability of Core Genes Is Highly Consistent across All Angiosperms[OPEN

Science.gov (United States)

Li, Zhen; Van de Peer, Yves; De Smet, Riet

2016-01-01

Gene duplication is an important mechanism for adding to genomic novelty. Hence, which genes undergo duplication and are preserved following duplication is an important question. It has been observed that gene duplicability, or the ability of genes to be retained following duplication, is a nonrandom process, with certain genes being more amenable to survive duplication events than others. Primarily, gene essentiality and the type of duplication (small-scale versus large-scale) have been shown in different species to influence the (long-term) survival of novel genes. However, an overarching view of “gene duplicability” is lacking, mainly due to the fact that previous studies usually focused on individual species and did not account for the influence of genomic context and the time of duplication. Here, we present a large-scale study in which we investigated duplicate retention for 9178 gene families shared between 37 flowering plant species, referred to as angiosperm core gene families. For most gene families, we observe a strikingly consistent pattern of gene duplicability across species, with gene families being either primarily single-copy or multicopy in all species. An intermediate class contains gene families that are often retained in duplicate for periods extending to tens of millions of years after whole-genome duplication, but ultimately appear to be largely restored to singleton status, suggesting that these genes may be dosage balance sensitive. The distinction between single-copy and multicopy gene families is reflected in their functional annotation, with single-copy genes being mainly involved in the maintenance of genome stability and organelle function and multicopy genes in signaling, transport, and metabolism. The intermediate class was overrepresented in regulatory genes, further suggesting that these represent putative dosage-balance-sensitive genes. PMID:26744215

Effect of the absolute statistic on gene-sampling gene-set analysis methods.

Science.gov (United States)

Nam, Dougu

2017-06-01

Gene-set enrichment analysis and its modified versions have commonly been used for identifying altered functions or pathways in disease from microarray data. In particular, the simple gene-sampling gene-set analysis methods have been heavily used for datasets with only a few sample replicates. The biggest problem with this approach is the highly inflated false-positive rate. In this paper, the effect of absolute gene statistic on gene-sampling gene-set analysis methods is systematically investigated. Thus far, the absolute gene statistic has merely been regarded as a supplementary method for capturing the bidirectional changes in each gene set. Here, it is shown that incorporating the absolute gene statistic in gene-sampling gene-set analysis substantially reduces the false-positive rate and improves the overall discriminatory ability. Its effect was investigated by power, false-positive rate, and receiver operating curve for a number of simulated and real datasets. The performances of gene-set analysis methods in one-tailed (genome-wide association study) and two-tailed (gene expression data) tests were also compared and discussed.

Human Gene Therapy: Genes without Frontiers?

Science.gov (United States)

Simon, Eric J.

2002-01-01

Describes the latest advancements and setbacks in human gene therapy to provide reference material for biology teachers to use in their science classes. Focuses on basic concepts such as recombinant DNA technology, and provides examples of human gene therapy such as severe combined immunodeficiency syndrome, familial hypercholesterolemia, and…

Gene function prediction based on Gene Ontology Hierarchy Preserving Hashing.

Science.gov (United States)

Zhao, Yingwen; Fu, Guangyuan; Wang, Jun; Guo, Maozu; Yu, Guoxian

2018-02-23

Gene Ontology (GO) uses structured vocabularies (or terms) to describe the molecular functions, biological roles, and cellular locations of gene products in a hierarchical ontology. GO annotations associate genes with GO terms and indicate the given gene products carrying out the biological functions described by the relevant terms. However, predicting correct GO annotations for genes from a massive set of GO terms as defined by GO is a difficult challenge. To combat with this challenge, we introduce a Gene Ontology Hierarchy Preserving Hashing (HPHash) based semantic method for gene function prediction. HPHash firstly measures the taxonomic similarity between GO terms. It then uses a hierarchy preserving hashing technique to keep the hierarchical order between GO terms, and to optimize a series of hashing functions to encode massive GO terms via compact binary codes. After that, HPHash utilizes these hashing functions to project the gene-term association matrix into a low-dimensional one and performs semantic similarity based gene function prediction in the low-dimensional space. Experimental results on three model species (Homo sapiens, Mus musculus and Rattus norvegicus) for interspecies gene function prediction show that HPHash performs better than other related approaches and it is robust to the number of hash functions. In addition, we also take HPHash as a plugin for BLAST based gene function prediction. From the experimental results, HPHash again significantly improves the prediction performance. The codes of HPHash are available at: http://mlda.swu.edu.cn/codes.php?name=HPHash. Copyright © 2018 Elsevier Inc. All rights reserved.

A Nonlinear Model for Gene-Based Gene-Environment Interaction

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Jian Sa

2016-06-01

Full Text Available A vast amount of literature has confirmed the role of gene-environment (G×E interaction in the etiology of complex human diseases. Traditional methods are predominantly focused on the analysis of interaction between a single nucleotide polymorphism (SNP and an environmental variable. Given that genes are the functional units, it is crucial to understand how gene effects (rather than single SNP effects are influenced by an environmental variable to affect disease risk. Motivated by the increasing awareness of the power of gene-based association analysis over single variant based approach, in this work, we proposed a sparse principle component regression (sPCR model to understand the gene-based G×E interaction effect on complex disease. We first extracted the sparse principal components for SNPs in a gene, then the effect of each principal component was modeled by a varying-coefficient (VC model. The model can jointly model variants in a gene in which their effects are nonlinearly influenced by an environmental variable. In addition, the varying-coefficient sPCR (VC-sPCR model has nice interpretation property since the sparsity on the principal component loadings can tell the relative importance of the corresponding SNPs in each component. We applied our method to a human birth weight dataset in Thai population. We analyzed 12,005 genes across 22 chromosomes and found one significant interaction effect using the Bonferroni correction method and one suggestive interaction. The model performance was further evaluated through simulation studies. Our model provides a system approach to evaluate gene-based G×E interaction.

Diverse Lifestyles and Strategies of Plant Pathogenesis Encoded in the Genomes of Eighteen Dothideomycetes Fungi

Energy Technology Data Exchange (ETDEWEB)

Ohm, Robin A.; Feau, Nicolas; Henrissat, Bernard; Schoch, Conrad L.; Horwitz, Benjamin A.; Barry, Kerrie W.; Condon, Bradford J.; Copeland, Alex C.; Dhillon, Braham; Glaser, Fabian; Hesse, Cedar N.; Kosti, Idit; LaButti, Kurt; Lindquist, Erika A.; Lucas, Susan; Salamov, Asaf A.; Bradshaw, Rosie E.; Ciuffetti, Lynda; Hamelin, Richard C.; Kema, Gert H. J.; Lawrence, Christopher; Scott, James A.; Spatafora, Joseph W.; Turgeon, B. Gillian; Wit, Pierre J. G. M. de; Zhong, Shaobin; Goodwin, Stephen B.; Grigoriev, Igor V.

2012-02-29

The class Dothideomycetes is one of the largest groups of fungi with a high level of ecological diversity including many plant pathogens infecting a broad range of hosts. Here, we compare genome features of 18 members of this class, including 6 necrotrophs, 9 (hemi)biotrophs and 3 saprotrophs, to analyze genome structure, evolution, and the diverse strategies of pathogenesis. The Dothideomycetes most likely evolved from a common ancestor more than 280 million years ago. The 18 genome sequences differ dramatically in size due to variation in repetitive content, but show much less variation in number of (core) genes. Gene order appears to have been rearranged mostly within chromosomal boundaries by multiple inversions, in extant genomes frequently demarcated by adjacent simple repeats. Several Dothideomycetes contain one or more gene-poor, transposable element (TE)-rich putatively dispensable chromosomes of unknown function. The 18 Dothideomycetes offer an extensive catalogue of genes involved in cellulose degradation, proteolysis, secondary metabolism, and cysteine-rich small secreted proteins. Ancestors of the two major orders of plant pathogens in the Dothideomycetes, the Capnodiales and Pleosporales, may have had different modes of pathogenesis, with the former having fewer of these genes than the latter. Many of these genes are enriched in proximity to transposable elements, suggesting faster evolution because of the effects of repeat induced point (RIP) mutations. A syntenic block of genes, including oxidoreductases, is conserved in most Dothideomycetes and upregulated during infection in L. maculans, suggesting a possible function in response to oxidative stress.

Vertebrate gene predictions and the problem of large genes

DEFF Research Database (Denmark)

Wang, Jun; Li, ShengTing; Zhang, Yong

2003-01-01

To find unknown protein-coding genes, annotation pipelines use a combination of ab initio gene prediction and similarity to experimentally confirmed genes or proteins. Here, we show that although the ab initio predictions have an intrinsically high false-positive rate, they also have a consistent...

Abundance, distribution and potential impact of transposable elements in the genome of Mycosphaerella fijiensis.

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Santana, Mateus F; Silva, José C F; Batista, Aline D; Ribeiro, Lílian E; da Silva, Gilvan F; de Araújo, Elza F; de Queiroz, Marisa V

2012-12-22

Mycosphaerella fijiensis is a ascomycete that causes Black Sigatoka in bananas. Recently, the M. fijiensis genome was sequenced. Repetitive sequences are ubiquitous components of fungal genomes. In most genomic analyses, repetitive sequences are associated with transposable elements (TEs). TEs are dispersed repetitive DNA sequences found in a host genome. These elements have the ability to move from one location to another within the genome, and their insertion can cause a wide spectrum of mutations in their hosts. Some of the deleterious effects of TEs may be due to ectopic recombination among TEs of the same family. In addition, some transposons are physically linked to genes and can control their expression. To prevent possible damage caused by the presence of TEs in the genome, some fungi possess TE-silencing mechanisms, such as RIP (Repeat Induced Point mutation). In this study, the abundance, distribution and potential impact of TEs in the genome of M. fijiensis were investigated. A total of 613 LTR-Gypsy and 27 LTR-Copia complete elements of the class I were detected. Among the class II elements, a total of 28 Mariner, five Mutator and one Harbinger complete elements were identified. The results of this study indicate that transposons were and are important ectopic recombination sites. A distribution analysis of a transposable element from each class of the M. fijiensis isolates revealed variable hybridization profiles, indicating the activity of these elements. Several genes encoding proteins involved in important metabolic pathways and with potential correlation to pathogenicity systems were identified upstream and downstream of transposable elements. A comparison of the sequences from different transposon groups suggested the action of the RIP silencing mechanism in the genome of this microorganism. The analysis of TEs in M. fijiensis suggests that TEs play an important role in the evolution of this organism because the activity of these elements, as well

Abundance, distribution and potential impact of transposable elements in the genome of Mycosphaerella fijiensis

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Santana Mateus F

2012-12-01

Full Text Available Abstract Background Mycosphaerella fijiensis is a ascomycete that causes Black Sigatoka in bananas. Recently, the M. fijiensis genome was sequenced. Repetitive sequences are ubiquitous components of fungal genomes. In most genomic analyses, repetitive sequences are associated with transposable elements (TEs. TEs are dispersed repetitive DNA sequences found in a host genome. These elements have the ability to move from one location to another within the genome, and their insertion can cause a wide spectrum of mutations in their hosts. Some of the deleterious effects of TEs may be due to ectopic recombination among TEs of the same family. In addition, some transposons are physically linked to genes and can control their expression. To prevent possible damage caused by the presence of TEs in the genome, some fungi possess TE-silencing mechanisms, such as RIP (Repeat Induced Point mutation. In this study, the abundance, distribution and potential impact of TEs in the genome of M. fijiensis were investigated. Results A total of 613 LTR-Gypsy and 27 LTR-Copia complete elements of the class I were detected. Among the class II elements, a total of 28 Mariner, five Mutator and one Harbinger complete elements were identified. The results of this study indicate that transposons were and are important ectopic recombination sites. A distribution analysis of a transposable element from each class of the M. fijiensis isolates revealed variable hybridization profiles, indicating the activity of these elements. Several genes encoding proteins involved in important metabolic pathways and with potential correlation to pathogenicity systems were identified upstream and downstream of transposable elements. A comparison of the sequences from different transposon groups suggested the action of the RIP silencing mechanism in the genome of this microorganism. Conclusions The analysis of TEs in M. fijiensis suggests that TEs play an important role in the evolution of

Reranking candidate gene models with cross-species comparison for improved gene prediction

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Pereira Fernando CN

2008-10-01

Full Text Available Abstract Background Most gene finders score candidate gene models with state-based methods, typically HMMs, by combining local properties (coding potential, splice donor and acceptor patterns, etc. Competing models with similar state-based scores may be distinguishable with additional information. In particular, functional and comparative genomics datasets may help to select among competing models of comparable probability by exploiting features likely to be associated with the correct gene models, such as conserved exon/intron structure or protein sequence features. Results We have investigated the utility of a simple post-processing step for selecting among a set of alternative gene models, using global scoring rules to rerank competing models for more accurate prediction. For each gene locus, we first generate the K best candidate gene models using the gene finder Evigan, and then rerank these models using comparisons with putative orthologous genes from closely-related species. Candidate gene models with lower scores in the original gene finder may be selected if they exhibit strong similarity to probable orthologs in coding sequence, splice site location, or signal peptide occurrence. Experiments on Drosophila melanogaster demonstrate that reranking based on cross-species comparison outperforms the best gene models identified by Evigan alone, and also outperforms the comparative gene finders GeneWise and Augustus+. Conclusion Reranking gene models with cross-species comparison improves gene prediction accuracy. This straightforward method can be readily adapted to incorporate additional lines of evidence, as it requires only a ranked source of candidate gene models.

Water stress, CO2 and photoperiod influence hormone levels in wheat

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Nan, Rubin; Carman, John G.; Salisbury, Frank B.; Campbell, W. F. (Principal Investigator)

2002-01-01

'Super Dwarf' wheat (Triticum aestivum L.) plants have been grown from seed to maturity in the Mir space station where they were periodically exposed, because of microgravity and other constraints, to water deficit, waterlogging, high CO2 levels, and low light intensities. The plants produced many tillers, but none of them produced viable seed. Studies have been initiated to determine why the plants responded in these ways. In the present study, effects of the listed stresses on abscisic acid (ABA), indole-3-acetic acid (IAA) and isopentenyl adenosine ([9R]iP) levels in roots and leaves of plants grown under otherwise near optimal conditions on earth were measured. Hormones were extracted, purified by HPLC, and quantified by noncompetitive indirect ELISA. In response to water deficit, ABA levels increased in roots and leaves, IAA levels decreased in roots and leaves, and [9R]iP levels increased in leaves but decreased in roots. In response to waterlogging, ABA, IAA and [9R]iP levels briefly increased in roots and leaves and then decreased. When portions of the root system were exposed to waterlogging and/or water deficit, ABA levels in leaves increased while [9R]iP and IAA levels decreased. These responses were correlated with the percentage of the root system stressed. At a low photosynthetic photon flux (100 micromoles m-2 s-1), plants grown in continuous light had higher leaf ABA levels than plants grown using an 18 or 21 h photoperiod.

Expression of a Recombinant Anti-HIV and Anti-Tumor Protein, MAP30, in Nicotiana tobacum Hairy Roots: A pH-Stable and Thermophilic Antimicrobial Protein.

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Ali Moghadam

Full Text Available In contrast to conventional antibiotics, which microorganisms can readily evade, it is nearly impossible for a microbial strain that is sensitive to antimicrobial proteins to convert to a resistant strain. Therefore, antimicrobial proteins and peptides that are promising alternative candidates for the control of bacterial infections are under investigation. The MAP30 protein of Momordica charantia is a valuable type I ribosome-inactivating protein (RIP with anti-HIV and anti-tumor activities. Whereas the antimicrobial activity of some type I RIPs has been confirmed, less attention has been paid to the antimicrobial activity of MAP30 produced in a stable, easily handled, and extremely cost-effective protein-expression system. rMAP30-KDEL was expressed in Nicotiana tobacum hairy roots, and its effect on different microorganisms was investigated. Analysis of the extracted total proteins of transgenic hairy roots showed that rMAP30-KDEL was expressed effectively and that this protein exhibited significant antibacterial activity in a dose-dependent manner. rMAP30-KDEL also possessed thermal and pH stability. Bioinformatic analysis of MAP30 and other RIPs regarding their conserved motifs, amino-acid contents, charge, aliphatic index, GRAVY value, and secondary structures demonstrated that these factors accounted for their thermophilicity. Therefore, RIPs such as MAP30 and its derived peptides might have promising applications as food preservatives, and their analysis might provide useful insights into designing clinically applicable antibiotic agents.

Programmed Necrosis: A Prominent Mechanism of Cell Death following Neonatal Brain Injury

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Raul Chavez-Valdez

2012-01-01

Full Text Available Despite the introduction of therapeutic hypothermia, neonatal hypoxic ischemic (HI brain injury remains a common cause of developmental disability. Development of rational adjuvant therapies to hypothermia requires understanding of the pathways of cell death and survival modulated by HI. The conceptualization of the apoptosis-necrosis “continuum” in neonatal brain injury predicts mechanistic interactions between cell death and hydrid forms of cell death such as programmed or regulated necrosis. Many of the components of the signaling pathway regulating programmed necrosis have been studied previously in models of neonatal HI. In some of these investigations, they participate as part of the apoptotic pathways demonstrating clear overlap of programmed death pathways. Receptor interacting protein (RIP-1 is at the crossroads between types of cellular death and survival and RIP-1 kinase activity triggers formation of the necrosome (in complex with RIP-3 leading to programmed necrosis. Neuroprotection afforded by the blockade of RIP-1 kinase following neonatal HI suggests a role for programmed necrosis in the HI injury to the developing brain. Here, we briefly review the state of the knowledge about the mechanisms behind programmed necrosis in neonatal brain injury recognizing that a significant proportion of these data derive from experiments in cultured cell and some from in vivo adult animal models. There are still more questions than answers, yet the fascinating new perspectives provided by the understanding of programmed necrosis in the developing brain may lay the foundation for new therapies for neonatal HI.

Evolution of homeobox genes.

Science.gov (United States)

Holland, Peter W H

2013-01-01

Many homeobox genes encode transcription factors with regulatory roles in animal and plant development. Homeobox genes are found in almost all eukaryotes, and have diversified into 11 gene classes and over 100 gene families in animal evolution, and 10 to 14 gene classes in plants. The largest group in animals is the ANTP class which includes the well-known Hox genes, plus other genes implicated in development including ParaHox (Cdx, Xlox, Gsx), Evx, Dlx, En, NK4, NK3, Msx, and Nanog. Genomic data suggest that the ANTP class diversified by extensive tandem duplication to generate a large array of genes, including an NK gene cluster and a hypothetical ProtoHox gene cluster that duplicated to generate Hox and ParaHox genes. Expression and functional data suggest that NK, Hox, and ParaHox gene clusters acquired distinct roles in patterning the mesoderm, nervous system, and gut. The PRD class is also diverse and includes Pax2/5/8, Pax3/7, Pax4/6, Gsc, Hesx, Otx, Otp, and Pitx genes. PRD genes are not generally arranged in ancient genomic clusters, although the Dux, Obox, and Rhox gene clusters arose in mammalian evolution as did several non-clustered PRD genes. Tandem duplication and genome duplication expanded the number of homeobox genes, possibly contributing to the evolution of developmental complexity, but homeobox gene loss must not be ignored. Evolutionary changes to homeobox gene expression have also been documented, including Hox gene expression patterns shifting in concert with segmental diversification in vertebrates and crustaceans, and deletion of a Pitx1 gene enhancer in pelvic-reduced sticklebacks. WIREs Dev Biol 2013, 2:31-45. doi: 10.1002/wdev.78 For further resources related to this article, please visit the WIREs website. The author declares that he has no conflicts of interest. Copyright © 2012 Wiley Periodicals, Inc.

Horizontal acquisition of multiple mitochondrial genes from a parasitic plant followed by gene conversion with host mitochondrial genes

Science.gov (United States)

2010-01-01

Background Horizontal gene transfer (HGT) is relatively common in plant mitochondrial genomes but the mechanisms, extent and consequences of transfer remain largely unknown. Previous results indicate that parasitic plants are often involved as either transfer donors or recipients, suggesting that direct contact between parasite and host facilitates genetic transfer among plants. Results In order to uncover the mechanistic details of plant-to-plant HGT, the extent and evolutionary fate of transfer was investigated between two groups: the parasitic genus Cuscuta and a small clade of Plantago species. A broad polymerase chain reaction (PCR) survey of mitochondrial genes revealed that at least three genes (atp1, atp6 and matR) were recently transferred from Cuscuta to Plantago. Quantitative PCR assays show that these three genes have a mitochondrial location in the one species line of Plantago examined. Patterns of sequence evolution suggest that these foreign genes degraded into pseudogenes shortly after transfer and reverse transcription (RT)-PCR analyses demonstrate that none are detectably transcribed. Three cases of gene conversion were detected between native and foreign copies of the atp1 gene. The identical phylogenetic distribution of the three foreign genes within Plantago and the retention of cytidines at ancestral positions of RNA editing indicate that these genes were probably acquired via a single, DNA-mediated transfer event. However, samplings of multiple individuals from two of the three species in the recipient Plantago clade revealed complex and perplexing phylogenetic discrepancies and patterns of sequence divergence for all three of the foreign genes. Conclusions This study reports the best evidence to date that multiple mitochondrial genes can be transferred via a single HGT event and that transfer occurred via a strictly DNA-level intermediate. The discovery of gene conversion between co-resident foreign and native mitochondrial copies suggests

Horizontal acquisition of multiple mitochondrial genes from a parasitic plant followed by gene conversion with host mitochondrial genes

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Hao Weilong

2010-12-01

Full Text Available Abstract Background Horizontal gene transfer (HGT is relatively common in plant mitochondrial genomes but the mechanisms, extent and consequences of transfer remain largely unknown. Previous results indicate that parasitic plants are often involved as either transfer donors or recipients, suggesting that direct contact between parasite and host facilitates genetic transfer among plants. Results In order to uncover the mechanistic details of plant-to-plant HGT, the extent and evolutionary fate of transfer was investigated between two groups: the parasitic genus Cuscuta and a small clade of Plantago species. A broad polymerase chain reaction (PCR survey of mitochondrial genes revealed that at least three genes (atp1, atp6 and matR were recently transferred from Cuscuta to Plantago. Quantitative PCR assays show that these three genes have a mitochondrial location in the one species line of Plantago examined. Patterns of sequence evolution suggest that these foreign genes degraded into pseudogenes shortly after transfer and reverse transcription (RT-PCR analyses demonstrate that none are detectably transcribed. Three cases of gene conversion were detected between native and foreign copies of the atp1 gene. The identical phylogenetic distribution of the three foreign genes within Plantago and the retention of cytidines at ancestral positions of RNA editing indicate that these genes were probably acquired via a single, DNA-mediated transfer event. However, samplings of multiple individuals from two of the three species in the recipient Plantago clade revealed complex and perplexing phylogenetic discrepancies and patterns of sequence divergence for all three of the foreign genes. Conclusions This study reports the best evidence to date that multiple mitochondrial genes can be transferred via a single HGT event and that transfer occurred via a strictly DNA-level intermediate. The discovery of gene conversion between co-resident foreign and native

Gene coexpression network analysis as a source of functional annotation for rice genes.

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Kevin L Childs

Full Text Available With the existence of large publicly available plant gene expression data sets, many groups have undertaken data analyses to construct gene coexpression networks and functionally annotate genes. Often, a large compendium of unrelated or condition-independent expression data is used to construct gene networks. Condition-dependent expression experiments consisting of well-defined conditions/treatments have also been used to create coexpression networks to help examine particular biological processes. Gene networks derived from either condition-dependent or condition-independent data can be difficult to interpret if a large number of genes and connections are present. However, algorithms exist to identify modules of highly connected and biologically relevant genes within coexpression networks. In this study, we have used publicly available rice (Oryza sativa gene expression data to create gene coexpression networks using both condition-dependent and condition-independent data and have identified gene modules within these networks using the Weighted Gene Coexpression Network Analysis method. We compared the number of genes assigned to modules and the biological interpretability of gene coexpression modules to assess the utility of condition-dependent and condition-independent gene coexpression networks. For the purpose of providing functional annotation to rice genes, we found that gene modules identified by coexpression analysis of condition-dependent gene expression experiments to be more useful than gene modules identified by analysis of a condition-independent data set. We have incorporated our results into the MSU Rice Genome Annotation Project database as additional expression-based annotation for 13,537 genes, 2,980 of which lack a functional annotation description. These results provide two new types of functional annotation for our database. Genes in modules are now associated with groups of genes that constitute a collective functional

The drug target genes show higher evolutionary conservation than non-target genes.

Science.gov (United States)

Lv, Wenhua; Xu, Yongdeng; Guo, Yiying; Yu, Ziqi; Feng, Guanglong; Liu, Panpan; Luan, Meiwei; Zhu, Hongjie; Liu, Guiyou; Zhang, Mingming; Lv, Hongchao; Duan, Lian; Shang, Zhenwei; Li, Jin; Jiang, Yongshuai; Zhang, Ruijie

2016-01-26

Although evidence indicates that drug target genes share some common evolutionary features, there have been few studies analyzing evolutionary features of drug targets from an overall level. Therefore, we conducted an analysis which aimed to investigate the evolutionary characteristics of drug target genes. We compared the evolutionary conservation between human drug target genes and non-target genes by combining both the evolutionary features and network topological properties in human protein-protein interaction network. The evolution rate, conservation score and the percentage of orthologous genes of 21 species were included in our study. Meanwhile, four topological features including the average shortest path length, betweenness centrality, clustering coefficient and degree were considered for comparison analysis. Then we got four results as following: compared with non-drug target genes, 1) drug target genes had lower evolutionary rates; 2) drug target genes had higher conservation scores; 3) drug target genes had higher percentages of orthologous genes and 4) drug target genes had a tighter network structure including higher degrees, betweenness centrality, clustering coefficients and lower average shortest path lengths. These results demonstrate that drug target genes are more evolutionarily conserved than non-drug target genes. We hope that our study will provide valuable information for other researchers who are interested in evolutionary conservation of drug targets.

Identifying potential maternal genes of Bombyx mori using digital gene expression profiling

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Xu, Pingzhen

2018-01-01

Maternal genes present in mature oocytes play a crucial role in the early development of silkworm. Although maternal genes have been widely studied in many other species, there has been limited research in Bombyx mori. High-throughput next generation sequencing provides a practical method for gene discovery on a genome-wide level. Herein, a transcriptome study was used to identify maternal-related genes from silkworm eggs. Unfertilized eggs from five different stages of early development were used to detect the changing situation of gene expression. The expressed genes showed different patterns over time. Seventy-six maternal genes were annotated according to homology analysis with Drosophila melanogaster. More than half of the differentially expressed maternal genes fell into four expression patterns, while the expression patterns showed a downward trend over time. The functional annotation of these material genes was mainly related to transcription factor activity, growth factor activity, nucleic acid binding, RNA binding, ATP binding, and ion binding. Additionally, twenty-two gene clusters including maternal genes were identified from 18 scaffolds. Altogether, we plotted a profile for the maternal genes of Bombyx mori using a digital gene expression profiling method. This will provide the basis for maternal-specific signature research and improve the understanding of the early development of silkworm. PMID:29462160

Novel gene sets improve set-level classification of prokaryotic gene expression data.

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Holec, Matěj; Kuželka, Ondřej; Železný, Filip

2015-10-28

Set-level classification of gene expression data has received significant attention recently. In this setting, high-dimensional vectors of features corresponding to genes are converted into lower-dimensional vectors of features corresponding to biologically interpretable gene sets. The dimensionality reduction brings the promise of a decreased risk of overfitting, potentially resulting in improved accuracy of the learned classifiers. However, recent empirical research has not confirmed this expectation. Here we hypothesize that the reported unfavorable classification results in the set-level framework were due to the adoption of unsuitable gene sets defined typically on the basis of the Gene ontology and the KEGG database of metabolic networks. We explore an alternative approach to defining gene sets, based on regulatory interactions, which we expect to collect genes with more correlated expression. We hypothesize that such more correlated gene sets will enable to learn more accurate classifiers. We define two families of gene sets using information on regulatory interactions, and evaluate them on phenotype-classification tasks using public prokaryotic gene expression data sets. From each of the two gene-set families, we first select the best-performing subtype. The two selected subtypes are then evaluated on independent (testing) data sets against state-of-the-art gene sets and against the conventional gene-level approach. The novel gene sets are indeed more correlated than the conventional ones, and lead to significantly more accurate classifiers. The novel gene sets are indeed more correlated than the conventional ones, and lead to significantly more accurate classifiers. Novel gene sets defined on the basis of regulatory interactions improve set-level classification of gene expression data. The experimental scripts and other material needed to reproduce the experiments are available at http://ida.felk.cvut.cz/novelgenesets.tar.gz.

[Gene doping: gene transfer and possible molecular detection].

Science.gov (United States)

Argüelles, Carlos Francisco; Hernández-Zamora, Edgar

2007-01-01

The use of illegal substances in sports to enhance athletic performance during competition has caused international sports organizations such as the COI and WADA to take anti doping measures. A new doping method know as gene doping is defined as "the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance". However, gene doping in sports is not easily identified and can cause serious consequences. Molecular biology techniques are needed in order to distinguish the difference between a "normal" and an "altered" genome. Further, we need to develop new analytic methods and biological molecular techniques in anti-doping laboratories, and design programs that avoid the non therapeutic use of genes.

Spectroscopy on neutron-rich nuclei at RIKEN. Present and future

International Nuclear Information System (INIS)

Sakurai, H.

2003-01-01

Recent studies on nuclear structure by using radioactive isotope beams available at the RIKEN projectile-fragment separator (RIPS) are introduced. Special emphasis is given to experiments selected from the recent programs that highlight studies at N=20-28; on the large deformation of 30 Ne and 34 Mg via the in-beam gamma spectroscopy, and on the particle stability of very neutron-rich nuclei, 34 Ne, 37 Na and 43 Si. The RI Beam Factory (RIBF) project is illustrated through review of such present research activities at RIPS. (author)

A new methodology for repository site suitability evaluation

International Nuclear Information System (INIS)

Miller, I.; Kossik, R.; Cunnane, M.

1992-01-01

Golder Associates Inc. (GAI) has developed a probabilistic total system performance assessment and strategy evaluation model (RIP) which can be applied in an iterative manner to evaluate repository site suitability and guide site characterization. The major portion of the software is the performance assessment model, which consists of a series of coupled component models for radionuclide transfer. The performance model itself is embedded within a decision analysis model which allows the user to evaluate alternative site characterization strategies. This paper provides an overview of the methodology, and summarizes the basic concepts of RIP

Delimiting Coalescence Genes (C-Genes) in Phylogenomic Data Sets.

Science.gov (United States)

Springer, Mark S; Gatesy, John

2018-02-26

coalescence methods have emerged as a popular alternative for inferring species trees with large genomic datasets, because these methods explicitly account for incomplete lineage sorting. However, statistical consistency of summary coalescence methods is not guaranteed unless several model assumptions are true, including the critical assumption that recombination occurs freely among but not within coalescence genes (c-genes), which are the fundamental units of analysis for these methods. Each c-gene has a single branching history, and large sets of these independent gene histories should be the input for genome-scale coalescence estimates of phylogeny. By contrast, numerous studies have reported the results of coalescence analyses in which complete protein-coding sequences are treated as c-genes even though exons for these loci can span more than a megabase of DNA. Empirical estimates of recombination breakpoints suggest that c-genes may be much shorter, especially when large clades with many species are the focus of analysis. Although this idea has been challenged recently in the literature, the inverse relationship between c-gene size and increased taxon sampling in a dataset-the 'recombination ratchet'-is a fundamental property of c-genes. For taxonomic groups characterized by genes with long intron sequences, complete protein-coding sequences are likely not valid c-genes and are inappropriate units of analysis for summary coalescence methods unless they occur in recombination deserts that are devoid of incomplete lineage sorting (ILS). Finally, it has been argued that coalescence methods are robust when the no-recombination within loci assumption is violated, but recombination must matter at some scale because ILS, a by-product of recombination, is the raison d'etre for coalescence methods. That is, extensive recombination is required to yield the large number of independently segregating c-genes used to infer a species tree. If coalescent methods are powerful

Gene therapy of cancer and development of therapeutic target gene

Energy Technology Data Exchange (ETDEWEB)

Kim, Chang Min; Kwon, Hee Chung

1998-04-01

We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene.

Gene therapy of cancer and development of therapeutic target gene

International Nuclear Information System (INIS)

Kim, Chang Min; Kwon, Hee Chung

1998-04-01

We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene

DAVID Knowledgebase: a gene-centered database integrating heterogeneous gene annotation resources to facilitate high-throughput gene functional analysis

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Baseler Michael W

2007-11-01

Full Text Available Abstract Background Due to the complex and distributed nature of biological research, our current biological knowledge is spread over many redundant annotation databases maintained by many independent groups. Analysts usually need to visit many of these bioinformatics databases in order to integrate comprehensive annotation information for their genes, which becomes one of the bottlenecks, particularly for the analytic task associated with a large gene list. Thus, a highly centralized and ready-to-use gene-annotation knowledgebase is in demand for high throughput gene functional analysis. Description The DAVID Knowledgebase is built around the DAVID Gene Concept, a single-linkage method to agglomerate tens of millions of gene/protein identifiers from a variety of public genomic resources into DAVID gene clusters. The grouping of such identifiers improves the cross-reference capability, particularly across NCBI and UniProt systems, enabling more than 40 publicly available functional annotation sources to be comprehensively integrated and centralized by the DAVID gene clusters. The simple, pair-wise, text format files which make up the DAVID Knowledgebase are freely downloadable for various data analysis uses. In addition, a well organized web interface allows users to query different types of heterogeneous annotations in a high-throughput manner. Conclusion The DAVID Knowledgebase is designed to facilitate high throughput gene functional analysis. For a given gene list, it not only provides the quick accessibility to a wide range of heterogeneous annotation data in a centralized location, but also enriches the level of biological information for an individual gene. Moreover, the entire DAVID Knowledgebase is freely downloadable or searchable at http://david.abcc.ncifcrf.gov/knowledgebase/.

Estimating actigraphy from motion artifacts in ECG and respiratory effort signals.

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Fonseca, Pedro; Aarts, Ronald M; Long, Xi; Rolink, Jérôme; Leonhardt, Steffen

2016-01-01

Recent work in unobtrusive sleep/wake classification has shown that cardiac and respiratory features can help improve classification performance. Nevertheless, actigraphy remains the single most discriminative modality for this task. Unfortunately, it requires the use of dedicated devices in addition to the sensors used to measure electrocardiogram (ECG) or respiratory effort. This paper proposes a method to estimate actigraphy from the body movement artifacts present in the ECG and respiratory inductance plethysmography (RIP) based on the time-frequency analysis of those signals. Using a continuous wavelet transform to analyze RIP, and ECG and RIP combined, it provides a surrogate measure of actigraphy with moderate correlation (for ECG+RIP, ρ = 0.74, p  <  0.001) and agreement (mean bias ratio of 0.94 and 95% agreement ratios of 0.11 and 8.45) with reference actigraphy. More important, it can be used as a replacement of actigraphy in sleep/wake classification: after cross-validation with a data set comprising polysomnographic (PSG) recordings of 15 healthy subjects and 25 insomniacs annotated by an external sleep technician, it achieves a statistically non-inferior classification performance when used together with respiratory features (average κ of 0.64 for 15 healthy subjects, and 0.50 for a dataset with 40 healthy and insomniac subjects), and when used together with respiratory and cardiac features (average κ of 0.66 for 15 healthy subjects, and 0.56 for 40 healthy and insomniac subjects). Since this method eliminates the need for a dedicated actigraphy device, it reduces the number of sensors needed for sleep/wake classification to a single sensor when using respiratory features, and to two sensors when using respiratory and cardiac features without any loss in performance. It offers a major benefit in terms of comfort for long-term home monitoring and is immediately applicable for legacy ECG and RIP monitoring devices already used in clinical

Evolutionary dynamics of human autoimmune disease genes and malfunctioned immunological genes

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Podder Soumita

2012-01-01

Full Text Available Abstract Background One of the main issues of molecular evolution is to divulge the principles in dictating the evolutionary rate differences among various gene classes. Immunological genes have received considerable attention in evolutionary biology as candidates for local adaptation and for studying functionally important polymorphisms. The normal structure and function of immunological genes will be distorted when they experience mutations leading to immunological dysfunctions. Results Here, we examined the fundamental differences between the genes which on mutation give rise to autoimmune or other immune system related diseases and the immunological genes that do not cause any disease phenotypes. Although the disease genes examined are analogous to non-disease genes in product, expression, function, and pathway affiliation, a statistically significant decrease in evolutionary rate has been found in autoimmune disease genes relative to all other immune related diseases and non-disease genes. Possible ways of accumulation of mutation in the three steps of the central dogma (DNA-mRNA-Protein have been studied to trace the mutational effects predisposed to disease consequence and acquiring higher selection pressure. Principal Component Analysis and Multivariate Regression Analysis have established the predominant role of single nucleotide polymorphisms in guiding the evolutionary rate of immunological disease and non-disease genes followed by m-RNA abundance, paralogs number, fraction of phosphorylation residue, alternatively spliced exon, protein residue burial and protein disorder. Conclusions Our study provides an empirical insight into the etiology of autoimmune disease genes and other immunological diseases. The immediate utility of our study is to help in disease gene identification and may also help in medicinal improvement of immune related disease.

Carboxylesterase 1 genes

DEFF Research Database (Denmark)

Rasmussen, Henrik Berg; Madsen, Majbritt Busk

2018-01-01

The carboxylesterase 1 gene (CES1) encodes a hydrolase that metabolizes commonly used drugs. The CES1-related pseudogene, carboxylesterase 1 pseudogene 1 (CES1P1), has been implicated in gene exchange with CES1 and in the formation of hybrid genes including the carboxylesterase 1A2 gene (CES1A2...

Bayesian assignment of gene ontology terms to gene expression experiments

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Sykacek, P.

2012-01-01

Motivation: Gene expression assays allow for genome scale analyses of molecular biological mechanisms. State-of-the-art data analysis provides lists of involved genes, either by calculating significance levels of mRNA abundance or by Bayesian assessments of gene activity. A common problem of such approaches is the difficulty of interpreting the biological implication of the resulting gene lists. This lead to an increased interest in methods for inferring high-level biological information. A common approach for representing high level information is by inferring gene ontology (GO) terms which may be attributed to the expression data experiment. Results: This article proposes a probabilistic model for GO term inference. Modelling assumes that gene annotations to GO terms are available and gene involvement in an experiment is represented by a posterior probabilities over gene-specific indicator variables. Such probability measures result from many Bayesian approaches for expression data analysis. The proposed model combines these indicator probabilities in a probabilistic fashion and provides a probabilistic GO term assignment as a result. Experiments on synthetic and microarray data suggest that advantages of the proposed probabilistic GO term inference over statistical test-based approaches are in particular evident for sparsely annotated GO terms and in situations of large uncertainty about gene activity. Provided that appropriate annotations exist, the proposed approach is easily applied to inferring other high level assignments like pathways. Availability: Source code under GPL license is available from the author. Contact: peter.sykacek@boku.ac.at PMID:22962488

Bayesian assignment of gene ontology terms to gene expression experiments.

Science.gov (United States)

Sykacek, P

2012-09-15

Gene expression assays allow for genome scale analyses of molecular biological mechanisms. State-of-the-art data analysis provides lists of involved genes, either by calculating significance levels of mRNA abundance or by Bayesian assessments of gene activity. A common problem of such approaches is the difficulty of interpreting the biological implication of the resulting gene lists. This lead to an increased interest in methods for inferring high-level biological information. A common approach for representing high level information is by inferring gene ontology (GO) terms which may be attributed to the expression data experiment. This article proposes a probabilistic model for GO term inference. Modelling assumes that gene annotations to GO terms are available and gene involvement in an experiment is represented by a posterior probabilities over gene-specific indicator variables. Such probability measures result from many Bayesian approaches for expression data analysis. The proposed model combines these indicator probabilities in a probabilistic fashion and provides a probabilistic GO term assignment as a result. Experiments on synthetic and microarray data suggest that advantages of the proposed probabilistic GO term inference over statistical test-based approaches are in particular evident for sparsely annotated GO terms and in situations of large uncertainty about gene activity. Provided that appropriate annotations exist, the proposed approach is easily applied to inferring other high level assignments like pathways. Source code under GPL license is available from the author. peter.sykacek@boku.ac.at.

Targeting the human lysozyme gene on bovine αs1- casein gene ...

African Journals Online (AJOL)

Targeting an exogenous gene into a favorable gene locus and for expression under endogenous regulators is an ideal method in mammary gland bioreactor research. For this purpose, a gene targeting vector was constructed to targeting the human lysozyme gene on bovine αs1-casein gene locus. In this case, the ...

A powerful score-based test statistic for detecting gene-gene co-association.

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Xu, Jing; Yuan, Zhongshang; Ji, Jiadong; Zhang, Xiaoshuai; Li, Hongkai; Wu, Xuesen; Xue, Fuzhong; Liu, Yanxun

2016-01-29

The genetic variants identified by Genome-wide association study (GWAS) can only account for a small proportion of the total heritability for complex disease. The existence of gene-gene joint effects which contains the main effects and their co-association is one of the possible explanations for the "missing heritability" problems. Gene-gene co-association refers to the extent to which the joint effects of two genes differ from the main effects, not only due to the traditional interaction under nearly independent condition but the correlation between genes. Generally, genes tend to work collaboratively within specific pathway or network contributing to the disease and the specific disease-associated locus will often be highly correlated (e.g. single nucleotide polymorphisms (SNPs) in linkage disequilibrium). Therefore, we proposed a novel score-based statistic (SBS) as a gene-based method for detecting gene-gene co-association. Various simulations illustrate that, under different sample sizes, marginal effects of causal SNPs and co-association levels, the proposed SBS has the better performance than other existed methods including single SNP-based and principle component analysis (PCA)-based logistic regression model, the statistics based on canonical correlations (CCU), kernel canonical correlation analysis (KCCU), partial least squares path modeling (PLSPM) and delta-square (δ (2)) statistic. The real data analysis of rheumatoid arthritis (RA) further confirmed its advantages in practice. SBS is a powerful and efficient gene-based method for detecting gene-gene co-association.

Prediction of regulatory gene pairs using dynamic time warping and gene ontology.

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Yang, Andy C; Hsu, Hui-Huang; Lu, Ming-Da; Tseng, Vincent S; Shih, Timothy K

2014-01-01

Selecting informative genes is the most important task for data analysis on microarray gene expression data. In this work, we aim at identifying regulatory gene pairs from microarray gene expression data. However, microarray data often contain multiple missing expression values. Missing value imputation is thus needed before further processing for regulatory gene pairs becomes possible. We develop a novel approach to first impute missing values in microarray time series data by combining k-Nearest Neighbour (KNN), Dynamic Time Warping (DTW) and Gene Ontology (GO). After missing values are imputed, we then perform gene regulation prediction based on our proposed DTW-GO distance measurement of gene pairs. Experimental results show that our approach is more accurate when compared with existing missing value imputation methods on real microarray data sets. Furthermore, our approach can also discover more regulatory gene pairs that are known in the literature than other methods.

The Drosophila melanogaster methuselah gene: a novel gene with ancient functions.

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Ana Rita Araújo

Full Text Available The Drosophila melanogaster G protein-coupled receptor gene, methuselah (mth, has been described as a novel gene that is less than 10 million years old. Nevertheless, it shows a highly specific expression pattern in embryos, larvae, and adults, and has been implicated in larval development, stress resistance, and in the setting of adult lifespan, among others. Although mth belongs to a gene subfamily with 16 members in D. melanogaster, there is no evidence for functional redundancy in this subfamily. Therefore, it is surprising that a novel gene influences so many traits. Here, we explore the alternative hypothesis that mth is an old gene. Under this hypothesis, in species distantly related to D. melanogaster, there should be a gene with features similar to those of mth. By performing detailed phylogenetic, synteny, protein structure, and gene expression analyses we show that the D. virilis GJ12490 gene is the orthologous of mth in species distantly related to D. melanogaster. We also show that, in D. americana (a species of the virilis group of Drosophila, a common amino acid polymorphism at the GJ12490 orthologous gene is significantly associated with developmental time, size, and lifespan differences. Our results imply that GJ12490 orthologous genes are candidates for developmental time and lifespan differences in Drosophila in general.

Constructing an integrated gene similarity network for the identification of disease genes.

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Tian, Zhen; Guo, Maozu; Wang, Chunyu; Xing, LinLin; Wang, Lei; Zhang, Yin

2017-09-20

Discovering novel genes that are involved human diseases is a challenging task in biomedical research. In recent years, several computational approaches have been proposed to prioritize candidate disease genes. Most of these methods are mainly based on protein-protein interaction (PPI) networks. However, since these PPI networks contain false positives and only cover less half of known human genes, their reliability and coverage are very low. Therefore, it is highly necessary to fuse multiple genomic data to construct a credible gene similarity network and then infer disease genes on the whole genomic scale. We proposed a novel method, named RWRB, to infer causal genes of interested diseases. First, we construct five individual gene (protein) similarity networks based on multiple genomic data of human genes. Then, an integrated gene similarity network (IGSN) is reconstructed based on similarity network fusion (SNF) method. Finally, we employee the random walk with restart algorithm on the phenotype-gene bilayer network, which combines phenotype similarity network, IGSN as well as phenotype-gene association network, to prioritize candidate disease genes. We investigate the effectiveness of RWRB through leave-one-out cross-validation methods in inferring phenotype-gene relationships. Results show that RWRB is more accurate than state-of-the-art methods on most evaluation metrics. Further analysis shows that the success of RWRB is benefited from IGSN which has a wider coverage and higher reliability comparing with current PPI networks. Moreover, we conduct a comprehensive case study for Alzheimer's disease and predict some novel disease genes that supported by literature. RWRB is an effective and reliable algorithm in prioritizing candidate disease genes on the genomic scale. Software and supplementary information are available at http://nclab.hit.edu.cn/~tianzhen/RWRB/ .

Evolutionary signatures amongst disease genes permit novel methods for gene prioritization and construction of informative gene-based networks.

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Nolan Priedigkeit

2015-02-01

Full Text Available Genes involved in the same function tend to have similar evolutionary histories, in that their rates of evolution covary over time. This coevolutionary signature, termed Evolutionary Rate Covariation (ERC, is calculated using only gene sequences from a set of closely related species and has demonstrated potential as a computational tool for inferring functional relationships between genes. To further define applications of ERC, we first established that roughly 55% of genetic diseases posses an ERC signature between their contributing genes. At a false discovery rate of 5% we report 40 such diseases including cancers, developmental disorders and mitochondrial diseases. Given these coevolutionary signatures between disease genes, we then assessed ERC's ability to prioritize known disease genes out of a list of unrelated candidates. We found that in the presence of an ERC signature, the true disease gene is effectively prioritized to the top 6% of candidates on average. We then apply this strategy to a melanoma-associated region on chromosome 1 and identify MCL1 as a potential causative gene. Furthermore, to gain global insight into disease mechanisms, we used ERC to predict molecular connections between 310 nominally distinct diseases. The resulting "disease map" network associates several diseases with related pathogenic mechanisms and unveils many novel relationships between clinically distinct diseases, such as between Hirschsprung's disease and melanoma. Taken together, these results demonstrate the utility of molecular evolution as a gene discovery platform and show that evolutionary signatures can be used to build informative gene-based networks.

Models of gene gain and gene loss for probabilistic reconstruction of gene content in the last universal common ancestor of life.

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Kannan, Lavanya; Li, Hua; Rubinstein, Boris; Mushegian, Arcady

2013-12-19

The problem of probabilistic inference of gene content in the last common ancestor of several extant species with completely sequenced genomes is: for each gene that is conserved in all or some of the genomes, assign the probability that its ancestral gene was present in the genome of their last common ancestor. We have developed a family of models of gene gain and gene loss in evolution, and applied the maximum-likelihood approach that uses phylogenetic tree of prokaryotes and the record of orthologous relationships between their genes to infer the gene content of LUCA, the Last Universal Common Ancestor of all currently living cellular organisms. The crucial parameter, the ratio of gene losses and gene gains, was estimated from the data and was higher in models that take account of the number of in-paralogs in genomes than in models that treat gene presences and absences as a binary trait. While the numbers of genes that are placed confidently into LUCA are similar in the ML methods and in previously published methods that use various parsimony-based approaches, the identities of genes themselves are different. Most of the models of either kind treat the genes found in many existing genomes in a similar way, assigning to them high probabilities of being ancestral ("high ancestrality"). The ML models are more likely than others to assign high ancestrality to the genes that are relatively rare in the present-day genomes.

Visual gene developer: a fully programmable bioinformatics software for synthetic gene optimization

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McDonald Karen

2011-08-01

Full Text Available Abstract Background Direct gene synthesis is becoming more popular owing to decreases in gene synthesis pricing. Compared with using natural genes, gene synthesis provides a good opportunity to optimize gene sequence for specific applications. In order to facilitate gene optimization, we have developed a stand-alone software called Visual Gene Developer. Results The software not only provides general functions for gene analysis and optimization along with an interactive user-friendly interface, but also includes unique features such as programming capability, dedicated mRNA secondary structure prediction, artificial neural network modeling, network & multi-threaded computing, and user-accessible programming modules. The software allows a user to analyze and optimize a sequence using main menu functions or specialized module windows. Alternatively, gene optimization can be initiated by designing a gene construct and configuring an optimization strategy. A user can choose several predefined or user-defined algorithms to design a complicated strategy. The software provides expandable functionality as platform software supporting module development using popular script languages such as VBScript and JScript in the software programming environment. Conclusion Visual Gene Developer is useful for both researchers who want to quickly analyze and optimize genes, and those who are interested in developing and testing new algorithms in bioinformatics. The software is available for free download at http://www.visualgenedeveloper.net.

Gene delivery to the lungs: pulmonary gene therapy for cystic fibrosis.

Science.gov (United States)

Villate-Beitia, Ilia; Zarate, Jon; Puras, Gustavo; Pedraz, José Luis

2017-07-01

Cystic fibrosis (CF) is a monogenic autosomal recessive disorder where the defective gene, the cystic fibrosis transmembrane conductance regulator (CFTR), is well identified. Moreover, the respiratory tract can be targeted through noninvasive aerosolized formulations for inhalation. Therefore, gene therapy is considered a plausible strategy to address this disease. Conventional gene therapy strategies rely on the addition of a correct copy of the CFTR gene into affected cells in order to restore the channel activity. In recent years, genome correction strategies have emerged, such as zinc-finger nucleases, transcription activator-like effector nucleases and clustered regularly interspaced short palindromic repeats associated to Cas9 nucleases. These gene editing tools aim to repair the mutated gene at its original genomic locus with high specificity. Besides, the success of gene therapy critically depends on the nucleic acids carriers. To date, several clinical studies have been carried out to add corrected copies of the CFTR gene into target cells using viral and non-viral vectors, some of them with encouraging results. Regarding genome editing systems, preliminary in vitro studies have been performed in order to repair the CFTR gene. In this review, after briefly introducing the basis of CF, we discuss the up-to-date gene therapy strategies to address the disease. The review focuses on the main factors to take into consideration when developing gene delivery strategies, such as the design of vectors and plasmid DNA, in vitro/in vivo tests, translation to human use, administration methods, manufacturing conditions and regulatory issues.

Iron homeostasis in Arabidopsis thaliana: transcriptomic analyses reveal novel FIT-regulated genes, iron deficiency marker genes and functional gene networks.

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Mai, Hans-Jörg; Pateyron, Stéphanie; Bauer, Petra

2016-10-03

FIT (FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR) is the central regulator of iron uptake in Arabidopsis thaliana roots. We performed transcriptome analyses of six day-old seedlings and roots of six week-old plants using wild type, a fit knock-out mutant and a FIT over-expression line grown under iron-sufficient or iron-deficient conditions. We compared genes regulated in a FIT-dependent manner depending on the developmental stage of the plants. We assembled a high likelihood dataset which we used to perform co-expression and functional analysis of the most stably iron deficiency-induced genes. 448 genes were found FIT-regulated. Out of these, 34 genes were robustly FIT-regulated in root and seedling samples and included 13 novel FIT-dependent genes. Three hundred thirty-one genes showed differential regulation in response to the presence and absence of FIT only in the root samples, while this was the case for 83 genes in the seedling samples. We assembled a virtual dataset of iron-regulated genes based on a total of 14 transcriptomic analyses of iron-deficient and iron-sufficient wild-type plants to pinpoint the best marker genes for iron deficiency and analyzed this dataset in depth. Co-expression analysis of this dataset revealed 13 distinct regulons part of which predominantly contained functionally related genes. We could enlarge the list of FIT-dependent genes and discriminate between genes that are robustly FIT-regulated in roots and seedlings or only in one of those. FIT-regulated genes were mostly induced, few of them were repressed by FIT. With the analysis of a virtual dataset we could filter out and pinpoint new candidates among the most reliable marker genes for iron deficiency. Moreover, co-expression and functional analysis of this virtual dataset revealed iron deficiency-induced and functionally distinct regulons.

Intracellular delivery of potential therapeutic genes: prospects in cancer gene therapy.

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Bakhtiar, Athirah; Sayyad, Mustak; Rosli, Rozita; Maruyama, Atsushi; Chowdhury, Ezharul H

2014-01-01

Conventional therapies for malignant cancer such as chemotherapy and radiotherapy are associated with poor survival rates owing to the development of cellular resistance to cancer drugs and the lack of targetability, resulting in unwanted adverse effects on healthy cells and necessitating the lowering of therapeutic dose with consequential lower efficacy of the treatment. Gene therapy employing different types of viral and non-viral carriers to transport gene(s) of interest and facilitating production of the desirable therapeutic protein(s) has tremendous prospects in cancer treatments due to the high-level of specificity in therapeutic action of the expressed protein(s) with diminished off-target effects, although cancer cell-specific delivery of transgene(s) still poses some challenges to be addressed. Depending on the potential therapeutic target genes, cancer gene therapy could be categorized into tumor suppressor gene replacement therapy, immune gene therapy and enzyme- or prodrug-based therapy. This review would shed light on the current progress of delivery of potentially therapeutic genes into various cancer cells in vitro and animal models utilizing a variety of viral and non-viral vectors.

Divergence of gene body DNA methylation and evolution of plant duplicate genes.

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Jun Wang

Full Text Available It has been shown that gene body DNA methylation is associated with gene expression. However, whether and how deviation of gene body DNA methylation between duplicate genes can influence their divergence remains largely unexplored. Here, we aim to elucidate the potential role of gene body DNA methylation in the fate of duplicate genes. We identified paralogous gene pairs from Arabidopsis and rice (Oryza sativa ssp. japonica genomes and reprocessed their single-base resolution methylome data. We show that methylation in paralogous genes nonlinearly correlates with several gene properties including exon number/gene length, expression level and mutation rate. Further, we demonstrated that divergence of methylation level and pattern in paralogs indeed positively correlate with their sequence and expression divergences. This result held even after controlling for other confounding factors known to influence the divergence of paralogs. We observed that methylation level divergence might be more relevant to the expression divergence of paralogs than methylation pattern divergence. Finally, we explored the mechanisms that might give rise to the divergence of gene body methylation in paralogs. We found that exonic methylation divergence more closely correlates with expression divergence than intronic methylation divergence. We show that genomic environments (e.g., flanked by transposable elements and repetitive sequences of paralogs generated by various duplication mechanisms are associated with the methylation divergence of paralogs. Overall, our results suggest that the changes in gene body DNA methylation could provide another avenue for duplicate genes to develop differential expression patterns and undergo different evolutionary fates in plant genomes.

Giant black hole rips star apart

Science.gov (United States)

2004-02-01

Astronomers believe that a doomed star came too close to a giant black hole after a close encounter with another star threw it off course. As it neared the enormous gravity of the black hole, the star was stretched by tidal forces until it was torn apart. This discovery provides crucial information on how these black holes grow and affect the surrounding stars and gas. "Stars can survive being stretched a small amount, as they are in binary star systems, but this star was stretched beyond its breaking point," said Dr Stefanie Komossa of the Max Planck Institute for Extraterrestrial Physics (MPE) in Germany, who led the international team of researchers. "This unlucky star just wandered into the wrong neighbourhood." While other observations have hinted that stars are destroyed by black holes (events known as ‘stellar tidal disruptions’), these new results are the first strong evidence. Observations with XMM-Newton and Chandra, combined with earlier images from the German Roentgensatellite (ROSAT), detected a powerful X-ray outburst from the centre of the galaxy RXJ1242-11. This outburst, one of the most extreme ever detected in a galaxy, was caused by gas from the destroyed star that was heated to millions of degrees before being swallowed by the black hole. The energy liberated in this process is equivalent to that of a supernova. "Now, with all of the data in hand, we have the smoking gun proof that this spectacular event has occurred," said co-author Prof. Guenther Hasinger, also of MPE. The black hole in the centre of RX J1242-11 is estimated to have a mass about 100 million times that of the Sun. By contrast, the destroyed star probably had a mass about equal to that of the Sun, making it a lopsided battle of gravity. "This is the ultimate ‘David versus Goliath’ battle, but here David loses," said Hasinger. The astronomers estimated that about one hundredth of the mass of the star was ultimately consumed, or accreted, by the black hole. This small amount is consistent with predictions that the momentum and energy of the accretion process will cause most of the destroyed star's gas to be flung away from the black hole. The force that disrupted the star in RXJ1242-11 is an extreme example of the tidal force caused by differences in gravity acting on the front and back of an object. The tidal force from the Moon causes tides in the oceans on Earth, and tidal force from Jupiter pulled Comet Shoemaker-Levy apart before it plunged into the giant planet. The odds that stellar tidal disruption will happen in a typical galaxy are long, about one in ten thousand. If it happened at the centre of the Milky Way, the resulting X-ray source would be about 50 000 times more powerful than the strongest X-ray source in our galaxy. However, such an event would not pose a threat to Earth because of the intervening distance of 25 000 light years. Other dramatic flares have been seen from galaxies, but this is the first to have been studied with the high spectral resolution of XMM-Newton and the high spatial resolution of Chandra. Both instruments have made a critical advance. Chandra showed that the RXJ1242-11 event occurred in the centre of a galaxy, where the black hole lurks. The XMM-Newton spectrum revealed the fingerprints expected for the surroundings of a black hole, and allowed other possible astronomical explanations to be ruled out. Evidence already exists for super-massive black holes in many galaxies, but looking for tidal disruptions represents a completely independent way to search for black holes. Observations like these are urgently needed to determine how quickly black holes can grow by swallowing neighbouring stars. Notes to editors This discovery was announced today at a press conference at NASA Headquarters in Washington DC, USA. A paper describing these results, by Stefanie Komossa and others, will be published in The Astrophysical Journal. ESA’s XMM-Newton can detect more X-ray sources than any previous satellite and is helping to solve many cosmic mysteries of the violent Universe, from black holes to the formation of galaxies. It was launched on 10 December 1999, using an Ariane-5 rocket, from French Guiana. It is expected to return data for a decade. XMM-Newton's high-tech design uses over 170 wafer-thin cylindrical mirrors spread over three telescopes. Its orbit takes it almost a third of the way to the Moon, so that astronomers can enjoy long, uninterrupted views of celestial objects. NASA's Marshall Space Flight Center, Huntsville, Alabama, manages the Chandra programme for the Office of Space Science, NASA Headquarters, Washington DC, USA. Northrop Grumman of Redondo Beach, California, formerly TRW Inc., was the prime development contractor for the observatory. The Smithsonian Astrophysical Observatory controls science and flight operations from the Chandra X-ray Center in Cambridge, Massachusetts.

GeneTopics - interpretation of gene sets via literature-driven topic models

Science.gov (United States)

2013-01-01

Background Annotation of a set of genes is often accomplished through comparison to a library of labelled gene sets such as biological processes or canonical pathways. However, this approach might fail if the employed libraries are not up to date with the latest research, don't capture relevant biological themes or are curated at a different level of granularity than is required to appropriately analyze the input gene set. At the same time, the vast biomedical literature offers an unstructured repository of the latest research findings that can be tapped to provide thematic sub-groupings for any input gene set. Methods Our proposed method relies on a gene-specific text corpus and extracts commonalities between documents in an unsupervised manner using a topic model approach. We automatically determine the number of topics summarizing the corpus and calculate a gene relevancy score for each topic allowing us to eliminate non-specific topics. As a result we obtain a set of literature topics in which each topic is associated with a subset of the input genes providing directly interpretable keywords and corresponding documents for literature research. Results We validate our method based on labelled gene sets from the KEGG metabolic pathway collection and the genetic association database (GAD) and show that the approach is able to detect topics consistent with the labelled annotation. Furthermore, we discuss the results on three different types of experimentally derived gene sets, (1) differentially expressed genes from a cardiac hypertrophy experiment in mice, (2) altered transcript abundance in human pancreatic beta cells, and (3) genes implicated by GWA studies to be associated with metabolite levels in a healthy population. In all three cases, we are able to replicate findings from the original papers in a quick and semi-automated manner. Conclusions Our approach provides a novel way of automatically generating meaningful annotations for gene sets that are directly

Models of gene gain and gene loss for probabilistic reconstruction of gene content in the last universal common ancestor of life

Science.gov (United States)

2013-01-01

Background The problem of probabilistic inference of gene content in the last common ancestor of several extant species with completely sequenced genomes is: for each gene that is conserved in all or some of the genomes, assign the probability that its ancestral gene was present in the genome of their last common ancestor. Results We have developed a family of models of gene gain and gene loss in evolution, and applied the maximum-likelihood approach that uses phylogenetic tree of prokaryotes and the record of orthologous relationships between their genes to infer the gene content of LUCA, the Last Universal Common Ancestor of all currently living cellular organisms. The crucial parameter, the ratio of gene losses and gene gains, was estimated from the data and was higher in models that take account of the number of in-paralogs in genomes than in models that treat gene presences and absences as a binary trait. Conclusion While the numbers of genes that are placed confidently into LUCA are similar in the ML methods and in previously published methods that use various parsimony-based approaches, the identities of genes themselves are different. Most of the models of either kind treat the genes found in many existing genomes in a similar way, assigning to them high probabilities of being ancestral (“high ancestrality”). The ML models are more likely than others to assign high ancestrality to the genes that are relatively rare in the present-day genomes. Reviewers This article was reviewed by Martijn A Huynen, Toni Gabaldón and Fyodor Kondrashov. PMID:24354654

Nuclear reactor system for ABWR

International Nuclear Information System (INIS)

Miyano, Hiroshi; Kitagawa, Koji

1997-01-01

Various tests and measurements were performed during the pre-operational test run of Unit No. 6 of The Tokyo Electric Power Co., Inc.'s Kashiwazaki-Kariwa Nuclear Power Station, the first advanced boiling water reactor (ABWR) unit in the world, and the design and performance adequacy of the ABWR were confirmed. The realization of the ABWR in Japan took about 20 years. It was decided that technologies for the reactor internal pump (RIP) and the fine-motion control rod drive (FMCRD), which had been applied in Europe, would be incorporated in the ABWR aiming at simplification of its structure and operation. These main components were evaluated, modified and verified in consideration of the unique Japanese environment, such as seismic conditions, through a joint study program with Japanese utilities as well as an improvement and standardization program in cooperation with the government. In addition to incorporating RIP and FMCRD technologies, the ABWR also has improved features in terms of the design of the reactor pressure vessel and internals, as well as automated servicing equipment for the RIP, FMCRD, and primary containment vessel. (author)

RIKEN RI Beam Factory and recent research activities

International Nuclear Information System (INIS)

Ueno, H.

2014-01-01

RIKEN has started the operation of the new facility for the Radioactive-Isotope Beam Factory (RIBF) project since 2006. In this project, intense primary beams are delivered at the energy E/A = 345 MeV over the whole range of the atomic number under the cyclotron-cascade acceleration scheme. The current, stability and sustainability in beam delivery have been increased significantly by recent improvement of the accelerator system. A high-current primary beam is then used to produce radioactive-isotope beams at the world's highest current utilizing the superconducting in-flight RI separator BigRIPS. Following the BigRIPS separator, several large-scale experimental key devices have been / will be installed, in order to fully capitalize the RIBF project. Owing to these progresses, nuclear structure information on far-unstable nuclei, which cannot be obtained by conventional technology, are now capable of being measured. Furthermore, in addition to such BigRIPS-related devices, other original experimental devices have been also newly installed at the lower energy experimental sites. Unique research opportunities are now available at the RIBF facility. (author)

Numerical modelling of the flow in the resin infusion process on the REV scale: A feasibility study

Energy Technology Data Exchange (ETDEWEB)

Jabbari, M.; Spangenberg, J.; Hattel, J. H. [Process Modelling Group, Department of Mechanical Engineering, Technical University of Denmark, Nils Koppels Allé, 2800 Kgs. Lyngby (Denmark); Jambhekar, V. A.; Helmig, R. [Department of Hydromechanics and Modelling of Hydrosystems, Institute for Modelling Hydraulic and Environmental Systems, Universität Stuttgart, Stuttgart (Germany); Gersborg, A. R. [SCION DTU, Diplomvej 373N, DK-2800 Lyngby (Denmark)

2016-06-08

The resin infusion process (RIP) has developed as a low cost method for manufacturing large fibre reinforced plastic parts. However, the process still presents some challenges to industry with regards to reliability and repeatability, resulting in expensive and inefficient trial and error development. In this paper, we show the implementation of 2D numerical models for the RIP using the open source simulator DuMu{sup X}. The idea of this study is to present a model which accounts for the interfacial forces coming from the capillary pressure on the so-called representative elementary volume (REV) scale. The model is described in detail and three different test cases — a constant and a tensorial permeability as well as a preform/Balsa domain — are investigated. The results show that the developed model is very applicable for the RIP for manufacturing of composite parts. The idea behind this study is to test the developed model for later use in a real application, in which the preform medium has numerous layers with different material properties.

Gene therapy: An overview

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Sudip Indu

2013-01-01

Full Text Available Gene therapy "the use of genes as medicine" involves the transfer of a therapeutic or working copy of a gene into specific cells of an individual in order to repair a faulty gene copy. The technique may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. The objective of gene therapy is to introduce new genetic material into target cells while causing no damage to the surrounding healthy cells and tissues, hence the treatment related morbidity is decreased. The delivery system includes a vector that delivers a therapeutic gene into the patient′s target cell. Functional proteins are created from the therapeutic gene causing the cell to return to a normal stage. The vectors used in gene therapy can be viral and non-viral. Gene therapy, an emerging field of biomedicine, is still at infancy and much research remains to be done before this approach to the treatment of condition will realize its full potential.

Gene doping in sports.

Science.gov (United States)

Unal, Mehmet; Ozer Unal, Durisehvar

2004-01-01

Gene or cell doping is defined by the World Anti-Doping Agency (WADA) as "the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance". New research in genetics and genomics will be used not only to diagnose and treat disease, but also to attempt to enhance human performance. In recent years, gene therapy has shown progress and positive results that have highlighted the potential misuse of this technology and the debate of 'gene doping'. Gene therapies developed for the treatment of diseases such as anaemia (the gene for erythropoietin), muscular dystrophy (the gene for insulin-like growth factor-1) and peripheral vascular diseases (the gene for vascular endothelial growth factor) are potential doping methods. With progress in gene technology, many other genes with this potential will be discovered. For this reason, it is important to develop timely legal regulations and to research the field of gene doping in order to develop methods of detection. To protect the health of athletes and to ensure equal competitive conditions, the International Olympic Committee, WADA and International Sports Federations have accepted performance-enhancing substances and methods as being doping, and have forbidden them. Nevertheless, the desire to win causes athletes to misuse these drugs and methods. This paper reviews the current status of gene doping and candidate performance enhancement genes, and also the use of gene therapy in sports medicine and ethics of genetic enhancement. Copyright 2004 Adis Data Information BV

Identifying key genes in rheumatoid arthritis by weighted gene co-expression network analysis.

Science.gov (United States)

Ma, Chunhui; Lv, Qi; Teng, Songsong; Yu, Yinxian; Niu, Kerun; Yi, Chengqin

2017-08-01

This study aimed to identify rheumatoid arthritis (RA) related genes based on microarray data using the WGCNA (weighted gene co-expression network analysis) method. Two gene expression profile datasets GSE55235 (10 RA samples and 10 healthy controls) and GSE77298 (16 RA samples and seven healthy controls) were downloaded from Gene Expression Omnibus database. Characteristic genes were identified using metaDE package. WGCNA was used to find disease-related networks based on gene expression correlation coefficients, and module significance was defined as the average gene significance of all genes used to assess the correlation between the module and RA status. Genes in the disease-related gene co-expression network were subject to functional annotation and pathway enrichment analysis using Database for Annotation Visualization and Integrated Discovery. Characteristic genes were also mapped to the Connectivity Map to screen small molecules. A total of 599 characteristic genes were identified. For each dataset, characteristic genes in the green, red and turquoise modules were most closely associated with RA, with gene numbers of 54, 43 and 79, respectively. These genes were enriched in totally enriched in 17 Gene Ontology terms, mainly related to immune response (CD97, FYB, CXCL1, IKBKE, CCR1, etc.), inflammatory response (CD97, CXCL1, C3AR1, CCR1, LYZ, etc.) and homeostasis (C3AR1, CCR1, PLN, CCL19, PPT1, etc.). Two small-molecule drugs sanguinarine and papaverine were predicted to have a therapeutic effect against RA. Genes related to immune response, inflammatory response and homeostasis presumably have critical roles in RA pathogenesis. Sanguinarine and papaverine have a potential therapeutic effect against RA. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Identification of suitable reference genes for gene expression studies of shoulder instability.

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Mariana Ferreira Leal

Full Text Available Shoulder instability is a common shoulder injury, and patients present with plastic deformation of the glenohumeral capsule. Gene expression analysis may be a useful tool for increasing the general understanding of capsule deformation, and reverse-transcription quantitative polymerase chain reaction (RT-qPCR has become an effective method for such studies. Although RT-qPCR is highly sensitive and specific, it requires the use of suitable reference genes for data normalization to guarantee meaningful and reproducible results. In the present study, we evaluated the suitability of a set of reference genes using samples from the glenohumeral capsules of individuals with and without shoulder instability. We analyzed the expression of six commonly used reference genes (ACTB, B2M, GAPDH, HPRT1, TBP and TFRC in the antero-inferior, antero-superior and posterior portions of the glenohumeral capsules of cases and controls. The stability of the candidate reference gene expression was determined using four software packages: NormFinder, geNorm, BestKeeper and DataAssist. Overall, HPRT1 was the best single reference gene, and HPRT1 and B2M composed the best pair of reference genes from different analysis groups, including simultaneous analysis of all tissue samples. GenEx software was used to identify the optimal number of reference genes to be used for normalization and demonstrated that the accumulated standard deviation resulting from the use of 2 reference genes was similar to that resulting from the use of 3 or more reference genes. To identify the optimal combination of reference genes, we evaluated the expression of COL1A1. Although the use of different reference gene combinations yielded variable normalized quantities, the relative quantities within sample groups were similar and confirmed that no obvious differences were observed when using 2, 3 or 4 reference genes. Consequently, the use of 2 stable reference genes for normalization, especially

The Pathway From Genes to Gene Therapy in Glaucoma: A Review of Possibilities for Using Genes as Glaucoma Drugs.

Science.gov (United States)

Borrás, Teresa

2017-01-01

Treatment of diseases with gene therapy is advancing rapidly. The use of gene therapy has expanded from the original concept of re-placing the mutated gene causing the disease to the use of genes to con-trol nonphysiological levels of expression or to modify pathways known to affect the disease. Genes offer numerous advantages over conventional drugs. They have longer duration of action and are more specific. Genes can be delivered to the target site by naked DNA, cells, nonviral, and viral vectors. The enormous progress of the past decade in molecular bi-ology and delivery systems has provided ways for targeting genes to the intended cell/tissue and safe, long-term vectors. The eye is an ideal organ for gene therapy. It is easily accessible and it is an immune-privileged site. Currently, there are clinical trials for diseases affecting practically every tissue of the eye, including those to restore vision in patients with Leber congenital amaurosis. However, the number of eye trials compared with those for systemic diseases is quite low (1.8%). Nevertheless, judg-ing by the vast amount of ongoing preclinical studies, it is expected that such number will increase considerably in the near future. One area of great need for eye gene therapy is glaucoma, where a long-term gene drug would eliminate daily applications and compliance issues. Here, we review the current state of gene therapy for glaucoma and the possibilities for treating the trabecular meshwork to lower intraocular pressure and the retinal ganglion cells to protect them from neurodegeneration. Copyright© 2017 Asia-Pacific Academy of Ophthalmology.

Integrating Ontological Knowledge and Textual Evidence in Estimating Gene and Gene Product Similarity

Energy Technology Data Exchange (ETDEWEB)

Sanfilippo, Antonio P.; Posse, Christian; Gopalan, Banu; Tratz, Stephen C.; Gregory, Michelle L.

2006-06-08

With the rising influence of the Gene On-tology, new approaches have emerged where the similarity between genes or gene products is obtained by comparing Gene Ontology code annotations associ-ated with them. So far, these approaches have solely relied on the knowledge en-coded in the Gene Ontology and the gene annotations associated with the Gene On-tology database. The goal of this paper is to demonstrate that improvements to these approaches can be obtained by integrating textual evidence extracted from relevant biomedical literature.

UniGene Tabulator: a full parser for the UniGene format.

Science.gov (United States)

Lenzi, Luca; Frabetti, Flavia; Facchin, Federica; Casadei, Raffaella; Vitale, Lorenza; Canaider, Silvia; Carinci, Paolo; Zannotti, Maria; Strippoli, Pierluigi

2006-10-15

UniGene Tabulator 1.0 provides a solution for full parsing of UniGene flat file format; it implements a structured graphical representation of each data field present in UniGene following import into a common database managing system usable in a personal computer. This database includes related tables for sequence, protein similarity, sequence-tagged site (STS) and transcript map interval (TXMAP) data, plus a summary table where each record represents a UniGene cluster. UniGene Tabulator enables full local management of UniGene data, allowing parsing, querying, indexing, retrieving, exporting and analysis of UniGene data in a relational database form, usable on Macintosh (OS X 10.3.9 or later) and Windows (2000, with service pack 4, XP, with service pack 2 or later) operating systems-based computers. The current release, including both the FileMaker runtime applications, is freely available at http://apollo11.isto.unibo.it/software/

Automated Identification of Core Regulatory Genes in Human Gene Regulatory Networks.

Directory of Open Access Journals (Sweden)

Vipin Narang

Full Text Available Human gene regulatory networks (GRN can be difficult to interpret due to a tangle of edges interconnecting thousands of genes. We constructed a general human GRN from extensive transcription factor and microRNA target data obtained from public databases. In a subnetwork of this GRN that is active during estrogen stimulation of MCF-7 breast cancer cells, we benchmarked automated algorithms for identifying core regulatory genes (transcription factors and microRNAs. Among these algorithms, we identified K-core decomposition, pagerank and betweenness centrality algorithms as the most effective for discovering core regulatory genes in the network evaluated based on previously known roles of these genes in MCF-7 biology as well as in their ability to explain the up or down expression status of up to 70% of the remaining genes. Finally, we validated the use of K-core algorithm for organizing the GRN in an easier to interpret layered hierarchy where more influential regulatory genes percolate towards the inner layers. The integrated human gene and miRNA network and software used in this study are provided as supplementary materials (S1 Data accompanying this manuscript.

Maximum Gene-Support Tree

Directory of Open Access Journals (Sweden)

Yunfeng Shan

2008-01-01

Full Text Available Genomes and genes diversify during evolution; however, it is unclear to what extent genes still retain the relationship among species. Model species for molecular phylogenetic studies include yeasts and viruses whose genomes were sequenced as well as plants that have the fossil-supported true phylogenetic trees available. In this study, we generated single gene trees of seven yeast species as well as single gene trees of nine baculovirus species using all the orthologous genes among the species compared. Homologous genes among seven known plants were used for validation of the finding. Four algorithms—maximum parsimony (MP, minimum evolution (ME, maximum likelihood (ML, and neighbor-joining (NJ—were used. Trees were reconstructed before and after weighting the DNA and protein sequence lengths among genes. Rarely a gene can always generate the “true tree” by all the four algorithms. However, the most frequent gene tree, termed “maximum gene-support tree” (MGS tree, or WMGS tree for the weighted one, in yeasts, baculoviruses, or plants was consistently found to be the “true tree” among the species. The results provide insights into the overall degree of divergence of orthologous genes of the genomes analyzed and suggest the following: 1 The true tree relationship among the species studied is still maintained by the largest group of orthologous genes; 2 There are usually more orthologous genes with higher similarities between genetically closer species than between genetically more distant ones; and 3 The maximum gene-support tree reflects the phylogenetic relationship among species in comparison.

Interactive visualization of gene regulatory networks with associated gene expression time series data

NARCIS (Netherlands)

Westenberg, M.A.; Hijum, van S.A.F.T.; Lulko, A.T.; Kuipers, O.P.; Roerdink, J.B.T.M.; Linsen, L.; Hagen, H.; Hamann, B.

2008-01-01

We present GENeVis, an application to visualize gene expression time series data in a gene regulatory network context. This is a network of regulator proteins that regulate the expression of their respective target genes. The networks are represented as graphs, in which the nodes represent genes,

Using gene expression noise to understand gene regulation

NARCIS (Netherlands)

Munsky, B.; Neuert, G.; van Oudenaarden, A.

2012-01-01

Phenotypic variation is ubiquitous in biology and is often traceable to underlying genetic and environmental variation. However, even genetically identical cells in identical environments display variable phenotypes. Stochastic gene expression, or gene expression "noise," has been suggested as a

Gene Conversion in Angiosperm Genomes with an Emphasis on Genes Duplicated by Polyploidization

Directory of Open Access Journals (Sweden)

Xi-Yin Wang

2011-01-01

Full Text Available Angiosperm genomes differ from those of mammals by extensive and recursive polyploidizations. The resulting gene duplication provides opportunities both for genetic innovation, and for concerted evolution. Though most genes may escape conversion by their homologs, concerted evolution of duplicated genes can last for millions of years or longer after their origin. Indeed, paralogous genes on two rice chromosomes duplicated an estimated 60–70 million years ago have experienced gene conversion in the past 400,000 years. Gene conversion preserves similarity of paralogous genes, but appears to accelerate their divergence from orthologous genes in other species. The mutagenic nature of recombination coupled with the buffering effect provided by gene redundancy, may facilitate the evolution of novel alleles that confer functional innovations while insulating biological fitness of affected plants. A mixed evolutionary model, characterized by a primary birth-and-death process and occasional homoeologous recombination and gene conversion, may best explain the evolution of multigene families.

Determining potential pregnancy status differences based on a new method of yearling heifer prebreeding examination.

Science.gov (United States)

Monday, Jessica D; Larson, Robert L; Laflin, Shelie; White, Brad J; Theurer, Miles E

2018-01-01

The study objective was to evaluate the Ready-Intermediate-Problem (RIP) replacement heifer evaluation matrix's ability to classify heifers into groups with differing reproductive outcomes. Beef heifers (n = 341) from six Kansas herds were classified according to RIP matrix guidelines and then exposed to AI breeding, bull breeding, or a combination of both as per the management plans for each participating herd. Following the breeding season the heifers were evaluated to determine pregnancy status, AI pregnancy status, days bred, and the number of 21 day cycles needed during the breeding season to become pregnant. After the breeding season, 298 (87%) of the heifers were pregnant, 204 (68%) of which became pregnant in the first 21 days of the breeding season. There was a significant interaction (P = 0.01) in RIP classification and pregnancy by 21 day cycle. Ready classified heifers had a significantly greater risk of becoming pregnant after a single AI exposure (P = 0.03) and in the first 21-day cycle (P = 0.02) compared to Problem classified heifers, and significantly less risk of being non-pregnant at the end of the breeding season (P < 0.01) compared to Problem classified heifers. The RIP matrix can be useful for classifying heifers prior to the onset of the breeding season. Further research is needed to evaluate the matrix in other settings and populations of U.S. beef heifers as well as at different intervals between evaluation and the start of breeding season. Copyright © 2017 Elsevier Inc. All rights reserved.

Necrosulfonamide Attenuates Spinal Cord Injury via Necroptosis Inhibition.

Science.gov (United States)

Wang, Yongxiang; Wang, Jingcheng; Wang, Hua; Feng, Xinmin; Tao, Yuping; Yang, Jiandong; Cai, Jun

2018-03-31

Spinal cord injury (SCI) is a serious trauma without efficient treatment currently. Necroptosis can be blocked post injury by special inhibitors. This study is to investigate the effects, mechanism, and potential benefit of necrosulfonamide (NSA) for SCI therapy. Pathologic condition was detected using hematoxylin-eosin staining on injured spinal cord and other major organs. Necroptosis-related factors-RIP1, RIP3, and MLKL-were detected using Western blot. Detections on mitochondrial functions such as adenosine triphosphate generation and activities of superoxide dismutase and caspase-3 were also performed. Finally, ethologic performance was detected using a 21-point open-field locomotion test. Reduced lesions and protected neurons were found in the injured spinal cord after treatment with NSA using hematoxylin-eosin staining for pathologic detection. No obvious toxicity on rat liver, kidney, heart, and spleen was detected. Rather than RIP1 and RIP3, MLKL was significantly inhibited by the NSA using Western blot detection. Adenosine triphosphate generation was obviously decreased post injury but slightly increased after the NSA treatment, especially 24 hours post injury. No significant changes were found on activities of superoxide dismutase and caspase-3 after the treatment of NSA. Ethologic performance was significantly improved using a 21-point, open-field locomotion test. Our research indicates NSA attenuates the spinal cord injury via necroptosis inhibition. It might be a potential and safe chemical benefit for SCI therapy. To our knowledge, this is the first study on the effects of NSA as treatment of traumatic SCI. Copyright © 2018 Elsevier Inc. All rights reserved.

Enalapril and ASS inhibit tumor growth in a transgenic mouse model of islet cell tumors.

Science.gov (United States)

Fendrich, V; Lopez, C L; Manoharan, J; Maschuw, K; Wichmann, S; Baier, A; Holler, J P; Ramaswamy, A; Bartsch, D K; Waldmann, J

2014-10-01

Accumulating evidence suggests a role for angiotensin-converting enzymes involving the angiotensin II-receptor 1 (AT1-R) and the cyclooxygenase pathway in carcinogenesis. The effects of ASS and enalapril were assessed in vitro and in a transgenic mouse model of pancreatic neuroendocrine neoplasms (pNENs). The effects of enalapril and ASS on proliferation and expression of the AGTR1A and its target gene vascular endothelial growth factor (Vegfa) were assessed in the neuroendocrine cell line BON1. Rip1-Tag2 mice were treated daily with either 0.6 mg/kg bodyweight of enalapril i.p., 20 mg/kg bodyweight of ASS i.p., or a vehicle in a prevention (weeks 5-12) and a survival group (week 5 till death). Tumor surface, weight of pancreatic glands, immunostaining for AT1-R and nuclear factor kappa beta (NFKB), and mice survival were analyzed. In addition, sections from human specimens of 20 insulinomas, ten gastrinomas, and 12 non-functional pNENs were evaluated for AT1-R and NFKB (NFKB1) expression and grouped according to the current WHO classification. Proliferation was significantly inhibited by enalapril and ASS in BON1 cells, with the combination being the most effective. Treatment with enalapril and ASS led to significant downregulation of known target genes Vegf and Rela at RNA level. Tumor growth was significantly inhibited by enalapril and ASS in the prevention group displayed by a reduction of tumor size (84%/67%) and number (30%/45%). Furthermore, daily treatment with enalapril and ASS prolonged the overall median survival compared with vehicle-treated Rip1-Tag2 (107 days) mice by 9 and 17 days (P=0.016 and P=0.013). The AT1-R and the inflammatory transcription factor NFKB were abolished completely upon enalapril and ASS treatment. AT1-R and NFKB expressions were observed in 80% of human pNENs. Enalapril and ASS may provide an approach for chemoprevention and treatment of pNENs. © 2014 Society for Endocrinology.

G-NEST: a gene neighborhood scoring tool to identify co-conserved, co-expressed genes

Directory of Open Access Journals (Sweden)

Lemay Danielle G

2012-09-01

Full Text Available Abstract Background In previous studies, gene neighborhoods—spatial clusters of co-expressed genes in the genome—have been defined using arbitrary rules such as requiring adjacency, a minimum number of genes, a fixed window size, or a minimum expression level. In the current study, we developed a Gene Neighborhood Scoring Tool (G-NEST which combines genomic location, gene expression, and evolutionary sequence conservation data to score putative gene neighborhoods across all possible window sizes simultaneously. Results Using G-NEST on atlases of mouse and human tissue expression data, we found that large neighborhoods of ten or more genes are extremely rare in mammalian genomes. When they do occur, neighborhoods are typically composed of families of related genes. Both the highest scoring and the largest neighborhoods in mammalian genomes are formed by tandem gene duplication. Mammalian gene neighborhoods contain highly and variably expressed genes. Co-localized noisy gene pairs exhibit lower evolutionary conservation of their adjacent genome locations, suggesting that their shared transcriptional background may be disadvantageous. Genes that are essential to mammalian survival and reproduction are less likely to occur in neighborhoods, although neighborhoods are enriched with genes that function in mitosis. We also found that gene orientation and protein-protein interactions are partially responsible for maintenance of gene neighborhoods. Conclusions Our experiments using G-NEST confirm that tandem gene duplication is the primary driver of non-random gene order in mammalian genomes. Non-essentiality, co-functionality, gene orientation, and protein-protein interactions are additional forces that maintain gene neighborhoods, especially those formed by tandem duplicates. We expect G-NEST to be useful for other applications such as the identification of core regulatory modules, common transcriptional backgrounds, and chromatin domains. The

The Cumulative Effect of Gene-Gene and Gene-Environment Interactions on the Risk of Prostate Cancer in Chinese Men

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Ming Liu

2016-01-01

Full Text Available Prostate cancer (PCa is a multifactorial disease involving complex genetic and environmental factors interactions. Gene-gene and gene-environment interactions associated with PCa in Chinese men are less studied. We explored the association between 36 SNPs and PCa in 574 subjects from northern China. Body mass index (BMI, smoking, and alcohol consumption were determined through self-administered questionnaires in 134 PCa patients. Then gene-gene and gene-environment interactions among the PCa-associated SNPs were analyzed using the generalized multifactor dimensionality reduction (GMDR and logistic regression methods. Allelic and genotypic association analyses showed that six variants were associated with PCa and the cumulative effect suggested men who carried any combination of 1, 2, or ≥3 risk genotypes had a gradually increased PCa risk (odds ratios (ORs = 1.79–4.41. GMDR analysis identified the best gene-gene interaction model with scores of 10 for both the cross-validation consistency and sign tests. For gene-environment interactions, rs6983561 CC and rs16901966 GG in individuals with a BMI ≥ 28 had ORs of 7.66 (p = 0.032 and 5.33 (p = 0.046, respectively. rs7679673 CC + CA and rs12653946 TT in individuals that smoked had ORs of 2.77 (p = 0.007 and 3.11 (p = 0.024, respectively. rs7679673 CC in individuals that consumed alcohol had an OR of 4.37 (p = 0.041. These results suggest that polymorphisms, either individually or by interacting with other genes or environmental factors, contribute to an increased risk of PCa.

Primetime for Learning Genes.

Science.gov (United States)

Keifer, Joyce

2017-02-11

Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene ( BDNF ), by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be "poised" for rapid response to activate or repress gene expression depending on environmental stimuli.

Characterization of Genes for Beef Marbling Based on Applying Gene Coexpression Network

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Dajeong Lim

2014-01-01

Full Text Available Marbling is an important trait in characterization beef quality and a major factor for determining the price of beef in the Korean beef market. In particular, marbling is a complex trait and needs a system-level approach for identifying candidate genes related to the trait. To find the candidate gene associated with marbling, we used a weighted gene coexpression network analysis from the expression value of bovine genes. Hub genes were identified; they were topologically centered with large degree and BC values in the global network. We performed gene expression analysis to detect candidate genes in M. longissimus with divergent marbling phenotype (marbling scores 2 to 7 using qRT-PCR. The results demonstrate that transmembrane protein 60 (TMEM60 and dihydropyrimidine dehydrogenase (DPYD are associated with increasing marbling fat. We suggest that the network-based approach in livestock may be an important method for analyzing the complex effects of candidate genes associated with complex traits like marbling or tenderness.

Simple Comparative Analyses of Differentially Expressed Gene Lists May Overestimate Gene Overlap.

Science.gov (United States)

Lawhorn, Chelsea M; Schomaker, Rachel; Rowell, Jonathan T; Rueppell, Olav

2018-04-16

Comparing the overlap between sets of differentially expressed genes (DEGs) within or between transcriptome studies is regularly used to infer similarities between biological processes. Significant overlap between two sets of DEGs is usually determined by a simple test. The number of potentially overlapping genes is compared to the number of genes that actually occur in both lists, treating every gene as equal. However, gene expression is controlled by transcription factors that bind to a variable number of transcription factor binding sites, leading to variation among genes in general variability of their expression. Neglecting this variability could therefore lead to inflated estimates of significant overlap between DEG lists. With computer simulations, we demonstrate that such biases arise from variation in the control of gene expression. Significant overlap commonly arises between two lists of DEGs that are randomly generated, assuming that the control of gene expression is variable among genes but consistent between corresponding experiments. More overlap is observed when transcription factors are specific to their binding sites and when the number of genes is considerably higher than the number of different transcription factors. In contrast, overlap between two DEG lists is always lower than expected when the genetic architecture of expression is independent between the two experiments. Thus, the current methods for determining significant overlap between DEGs are potentially confounding biologically meaningful overlap with overlap that arises due to variability in control of expression among genes, and more sophisticated approaches are needed.

Comparative genome analysis of PHB gene family reveals deep evolutionary origins and diverse gene function.

Science.gov (United States)

Di, Chao; Xu, Wenying; Su, Zhen; Yuan, Joshua S

2010-10-07

PHB (Prohibitin) gene family is involved in a variety of functions important for different biological processes. PHB genes are ubiquitously present in divergent species from prokaryotes to eukaryotes. Human PHB genes have been found to be associated with various diseases. Recent studies by our group and others have shown diverse function of PHB genes in plants for development, senescence, defence, and others. Despite the importance of the PHB gene family, no comprehensive gene family analysis has been carried to evaluate the relatedness of PHB genes across different species. In order to better guide the gene function analysis and understand the evolution of the PHB gene family, we therefore carried out the comparative genome analysis of the PHB genes across different kingdoms. The relatedness, motif distribution, and intron/exon distribution all indicated that PHB genes is a relatively conserved gene family. The PHB genes can be classified into 5 classes and each class have a very deep evolutionary origin. The PHB genes within the class maintained the same motif patterns during the evolution. With Arabidopsis as the model species, we found that PHB gene intron/exon structure and domains are also conserved during the evolution. Despite being a conserved gene family, various gene duplication events led to the expansion of the PHB genes. Both segmental and tandem gene duplication were involved in Arabidopsis PHB gene family expansion. However, segmental duplication is predominant in Arabidopsis. Moreover, most of the duplicated genes experienced neofunctionalization. The results highlighted that PHB genes might be involved in important functions so that the duplicated genes are under the evolutionary pressure to derive new function. PHB gene family is a conserved gene family and accounts for diverse but important biological functions based on the similar molecular mechanisms. The highly diverse biological function indicated that more research needs to be carried out

Genes and Hearing Loss

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... ENTCareers Marketplace Find an ENT Doctor Near You Genes and Hearing Loss Genes and Hearing Loss Patient ... mutation may only have dystopia canthorum. How Do Genes Work? Genes are a road map for the ...

Neurospora crassa female development requires the PACC and other signal transduction pathways, transcription factors, chromatin remodeling, cell-to-cell fusion, and autophagy.

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Jennifer L Chinnici

Full Text Available Using a screening protocol we have identified 68 genes that are required for female development in the filamentous fungus Neurospora crassa. We find that we can divide these genes into five general groups: 1 Genes encoding components of the PACC signal transduction pathway, 2 Other signal transduction pathway genes, including genes from the three N. crassa MAP kinase pathways, 3 Transcriptional factor genes, 4 Autophagy genes, and 5 Other miscellaneous genes. Complementation and RIP studies verified that these genes are needed for the formation of the female mating structure, the protoperithecium, and for the maturation of a fertilized protoperithecium into a perithecium. Perithecia grafting experiments demonstrate that the autophagy genes and the cell-to-cell fusion genes (the MAK-1 and MAK-2 pathway genes are needed for the mobilization and movement of nutrients from an established vegetative hyphal network into the developing protoperithecium. Deletion mutants for the PACC pathway genes palA, palB, palC, palF, palH, and pacC were found to be defective in two aspects of female development. First, they were unable to initiate female development on synthetic crossing medium. However, they could form protoperithecia when grown on cellophane, on corn meal agar, or in response to the presence of nearby perithecia. Second, fertilized perithecia from PACC pathway mutants were unable to produce asci and complete female development. Protein localization experiments with a GFP-tagged PALA construct showed that PALA was localized in a peripheral punctate pattern, consistent with a signaling center associated with the ESCRT complex. The N. crassa PACC signal transduction pathway appears to be similar to the PacC/Rim101 pathway previously characterized in Aspergillus nidulans and Saccharomyces cerevisiae. In N. crassa the pathway plays a key role in regulating female development.

Neurospora crassa female development requires the PACC and other signal transduction pathways, transcription factors, chromatin remodeling, cell-to-cell fusion, and autophagy.

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Chinnici, Jennifer L; Fu, Ci; Caccamise, Lauren M; Arnold, Jason W; Free, Stephen J

2014-01-01

Using a screening protocol we have identified 68 genes that are required for female development in the filamentous fungus Neurospora crassa. We find that we can divide these genes into five general groups: 1) Genes encoding components of the PACC signal transduction pathway, 2) Other signal transduction pathway genes, including genes from the three N. crassa MAP kinase pathways, 3) Transcriptional factor genes, 4) Autophagy genes, and 5) Other miscellaneous genes. Complementation and RIP studies verified that these genes are needed for the formation of the female mating structure, the protoperithecium, and for the maturation of a fertilized protoperithecium into a perithecium. Perithecia grafting experiments demonstrate that the autophagy genes and the cell-to-cell fusion genes (the MAK-1 and MAK-2 pathway genes) are needed for the mobilization and movement of nutrients from an established vegetative hyphal network into the developing protoperithecium. Deletion mutants for the PACC pathway genes palA, palB, palC, palF, palH, and pacC were found to be defective in two aspects of female development. First, they were unable to initiate female development on synthetic crossing medium. However, they could form protoperithecia when grown on cellophane, on corn meal agar, or in response to the presence of nearby perithecia. Second, fertilized perithecia from PACC pathway mutants were unable to produce asci and complete female development. Protein localization experiments with a GFP-tagged PALA construct showed that PALA was localized in a peripheral punctate pattern, consistent with a signaling center associated with the ESCRT complex. The N. crassa PACC signal transduction pathway appears to be similar to the PacC/Rim101 pathway previously characterized in Aspergillus nidulans and Saccharomyces cerevisiae. In N. crassa the pathway plays a key role in regulating female development.

Establishing gene models from the Pinus pinaster genome using gene capture and BAC sequencing.

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Seoane-Zonjic, Pedro; Cañas, Rafael A; Bautista, Rocío; Gómez-Maldonado, Josefa; Arrillaga, Isabel; Fernández-Pozo, Noé; Claros, M Gonzalo; Cánovas, Francisco M; Ávila, Concepción

2016-02-27

In the era of DNA throughput sequencing, assembling and understanding gymnosperm mega-genomes remains a challenge. Although drafts of three conifer genomes have recently been published, this number is too low to understand the full complexity of conifer genomes. Using techniques focused on specific genes, gene models can be established that can aid in the assembly of gene-rich regions, and this information can be used to compare genomes and understand functional evolution. In this study, gene capture technology combined with BAC isolation and sequencing was used as an experimental approach to establish de novo gene structures without a reference genome. Probes were designed for 866 maritime pine transcripts to sequence genes captured from genomic DNA. The gene models were constructed using GeneAssembler, a new bioinformatic pipeline, which reconstructed over 82% of the gene structures, and a high proportion (85%) of the captured gene models contained sequences from the promoter regulatory region. In a parallel experiment, the P. pinaster BAC library was screened to isolate clones containing genes whose cDNA sequence were already available. BAC clones containing the asparagine synthetase, sucrose synthase and xyloglucan endotransglycosylase gene sequences were isolated and used in this study. The gene models derived from the gene capture approach were compared with the genomic sequences derived from the BAC clones. This combined approach is a particularly efficient way to capture the genomic structures of gene families with a small number of members. The experimental approach used in this study is a valuable combined technique to study genomic gene structures in species for which a reference genome is unavailable. It can be used to establish exon/intron boundaries in unknown gene structures, to reconstruct incomplete genes and to obtain promoter sequences that can be used for transcriptional studies. A bioinformatics algorithm (GeneAssembler) is also provided as a

Mining tissue specificity, gene connectivity and disease association to reveal a set of genes that modify the action of disease causing genes

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Reverter Antonio

2008-09-01

Full Text Available Abstract Background The tissue specificity of gene expression has been linked to a number of significant outcomes including level of expression, and differential rates of polymorphism, evolution and disease association. Recent studies have also shown the importance of exploring differential gene connectivity and sequence conservation in the identification of disease-associated genes. However, no study relates gene interactions with tissue specificity and disease association. Methods We adopted an a priori approach making as few assumptions as possible to analyse the interplay among gene-gene interactions with tissue specificity and its subsequent likelihood of association with disease. We mined three large datasets comprising expression data drawn from massively parallel signature sequencing across 32 tissues, describing a set of 55,606 true positive interactions for 7,197 genes, and microarray expression results generated during the profiling of systemic inflammation, from which 126,543 interactions among 7,090 genes were reported. Results Amongst the myriad of complex relationships identified between expression, disease, connectivity and tissue specificity, some interesting patterns emerged. These include elevated rates of expression and network connectivity in housekeeping and disease-associated tissue-specific genes. We found that disease-associated genes are more likely to show tissue specific expression and most frequently interact with other disease genes. Using the thresholds defined in these observations, we develop a guilt-by-association algorithm and discover a group of 112 non-disease annotated genes that predominantly interact with disease-associated genes, impacting on disease outcomes. Conclusion We conclude that parameters such as tissue specificity and network connectivity can be used in combination to identify a group of genes, not previously confirmed as disease causing, that are involved in interactions with disease causing

AffyMiner: mining differentially expressed genes and biological knowledge in GeneChip microarray data

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Xia Yuannan

2006-12-01

Full Text Available Abstract Background DNA microarrays are a powerful tool for monitoring the expression of tens of thousands of genes simultaneously. With the advance of microarray technology, the challenge issue becomes how to analyze a large amount of microarray data and make biological sense of them. Affymetrix GeneChips are widely used microarrays, where a variety of statistical algorithms have been explored and used for detecting significant genes in the experiment. These methods rely solely on the quantitative data, i.e., signal intensity; however, qualitative data are also important parameters in detecting differentially expressed genes. Results AffyMiner is a tool developed for detecting differentially expressed genes in Affymetrix GeneChip microarray data and for associating gene annotation and gene ontology information with the genes detected. AffyMiner consists of the functional modules, GeneFinder for detecting significant genes in a treatment versus control experiment and GOTree for mapping genes of interest onto the Gene Ontology (GO space; and interfaces to run Cluster, a program for clustering analysis, and GenMAPP, a program for pathway analysis. AffyMiner has been used for analyzing the GeneChip data and the results were presented in several publications. Conclusion AffyMiner fills an important gap in finding differentially expressed genes in Affymetrix GeneChip microarray data. AffyMiner effectively deals with multiple replicates in the experiment and takes into account both quantitative and qualitative data in identifying significant genes. AffyMiner reduces the time and effort needed to compare data from multiple arrays and to interpret the possible biological implications associated with significant changes in a gene's expression.

Gene therapy in periodontics.

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Chatterjee, Anirban; Singh, Nidhi; Saluja, Mini

2013-03-01

GENES are made of DNA - the code of life. They are made up of two types of base pair from different number of hydrogen bonds AT, GC which can be turned into instruction. Everyone inherits genes from their parents and passes them on in turn to their children. Every person's genes are different, and the changes in sequence determine the inherited differences between each of us. Some changes, usually in a single gene, may cause serious diseases. Gene therapy is 'the use of genes as medicine'. It involves the transfer of a therapeutic or working gene copy into specific cells of an individual in order to repair a faulty gene copy. Thus it may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. It has a promising era in the field of periodontics. Gene therapy has been used as a mode of tissue engineering in periodontics. The tissue engineering approach reconstructs the natural target tissue by combining four elements namely: Scaffold, signaling molecules, cells and blood supply and thus can help in the reconstruction of damaged periodontium including cementum, gingival, periodontal ligament and bone.

Norrie disease gene is distinct from the monoamine oxidase genes.

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Sims, K B; Ozelius, L; Corey, T; Rinehart, W B; Liberfarb, R; Haines, J; Chen, W J; Norio, R; Sankila, E; de la Chapelle, A

1989-09-01

The genes for MAO-A and MAO-B appear to be very close to the Norrie disease gene, on the basis of loss and/or disruption of the MAO genes and activities in atypical Norrie disease patients deleted for the DXS7 locus; linkage among the MAO genes, the Norrie disease gene, and the DXS7 locus; and mapping of all these loci to the chromosomal region Xp11. The present study provides evidence that the MAO genes are not disrupted in "classic" Norrie disease patients. Genomic DNA from these "nondeletion" Norrie disease patients did not show rearrangements at the MAOA or DXS7 loci. Normal levels of MAO-A activities, as well as normal amounts and size of the MAO-A mRNA, were observed in cultured skin fibroblasts from these patients, and MAO-B activity in their platelets was normal. Catecholamine metabolites evaluated in plasma and urine were in the control range. Thus, although some atypical Norrie disease patients lack both MAO-A and MAO-B activities, MAO does not appear to be an etiologic factor in classic Norrie disease.

Energy resources integrated planning as instrument for clean development; Planejamento integrado de recursos energeticos como instrumento de desenvolvimento limpo

Energy Technology Data Exchange (ETDEWEB)

Galvao, Luis Claudio Ribeiro; Kanayama, Paulo Helio [Universidade de Sao Paulo (EPUSP), SP (Brazil). Escola Politecnica; Grimoni, Jose Aquiles Baeso; Udaeta, Miguel Edgar Morales [Universidade de Sao Paulo (IEE/USP), SP (Brazil). Inst. de Eletrotecnica e Energia

2008-07-01

This paper presents the RIP - Resources Integrated Planning, viewing the sustainable development. In the RIP the regional energy resource utilization are a prioritization and the regional economic talent is viewing as a competitive advantage for improvement of the social indexes, and the environmental limitations are considered, including the effects of global heating. Also, the political forces are respected, the involved and interested participates in the planning, and the most important the systemic approaching for obtaining the sustainable, rational and efficient use of the energy are obtained in advance which allows to predict the development consequences before the implantation of projects.

Quasi-three-dimensional modelling of the morphology of longshore bars

DEFF Research Database (Denmark)

Dronen, N.; Deigaard, Rolf

2007-01-01

-forming processes associated with the undertow and the horizontal wave-driven circulation currents, which may cause instabilities of the bar and the formation of rip channels. Situations with normal and oblique wave incidence are considered. Compared to the depth integrated approach the Q3D model produces less...... pronounced alongshore irregularities for obliquely incident waves. For normal incident waves the Q3D model produces a crescentic bar while the depth integrated model predicts almost straight sections of the bar interrupted by rip channels. The sensitivity to variation of wave angle and beach slope is further...

Gene profile analysis of osteoblast genes differentially regulated by histone deacetylase inhibitors

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Lamblin Anne-Francoise

2007-10-01

Full Text Available Abstract Background Osteoblast differentiation requires the coordinated stepwise expression of multiple genes. Histone deacetylase inhibitors (HDIs accelerate the osteoblast differentiation process by blocking the activity of histone deacetylases (HDACs, which alter gene expression by modifying chromatin structure. We previously demonstrated that HDIs and HDAC3 shRNAs accelerate matrix mineralization and the expression of osteoblast maturation genes (e.g. alkaline phosphatase, osteocalcin. Identifying other genes that are differentially regulated by HDIs might identify new pathways that contribute to osteoblast differentiation. Results To identify other osteoblast genes that are altered early by HDIs, we incubated MC3T3-E1 preosteoblasts with HDIs (trichostatin A, MS-275, or valproic acid for 18 hours in osteogenic conditions. The promotion of osteoblast differentiation by HDIs in this experiment was confirmed by osteogenic assays. Gene expression profiles relative to vehicle-treated cells were assessed by microarray analysis with Affymetrix GeneChip 430 2.0 arrays. The regulation of several genes by HDIs in MC3T3-E1 cells and primary osteoblasts was verified by quantitative real-time PCR. Nine genes were differentially regulated by at least two-fold after exposure to each of the three HDIs and six were verified by PCR in osteoblasts. Four of the verified genes (solute carrier family 9 isoform 3 regulator 1 (Slc9a3r1, sorbitol dehydrogenase 1, a kinase anchor protein, and glutathione S-transferase alpha 4 were induced. Two genes (proteasome subunit, beta type 10 and adaptor-related protein complex AP-4 sigma 1 were suppressed. We also identified eight growth factors and growth factor receptor genes that are significantly altered by each of the HDIs, including Frizzled related proteins 1 and 4, which modulate the Wnt signaling pathway. Conclusion This study identifies osteoblast genes that are regulated early by HDIs and indicates pathways that

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

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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.

Determining Physical Mechanisms of Gene Expression Regulation from Single Cell Gene Expression Data

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Ezer, Daphne; Moignard, Victoria; G?ttgens, Berthold; Adryan, Boris

2016-01-01

Many genes are expressed in bursts, which can contribute to cell-to-cell heterogeneity. It is now possible to measure this heterogeneity with high throughput single cell gene expression assays (single cell qPCR and RNA-seq). These experimental approaches generate gene expression distributions which can be used to estimate the kinetic parameters of gene expression bursting, namely the rate that genes turn on, the rate that genes turn off, and the rate of transcription. We construct a complete ...

Enhanced resistance to blast fungus in rice (Oryza sativa L.) by expressing the ribosome-inactivating protein α-momorcharin.

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Qian, Qian; Huang, Lin; Yi, Rong; Wang, Shuzhen; Ding, Yi

2014-03-01

Rice blast caused by Magnaporthe grisea is one of the three major diseases that seriously affect the rice production. Alpha-momorcharin (α-MC), a ribosome-inactivating protein (RIP) isolated from Momordica charantia seeds, has antifungal effects in vitro. In this study, the α-MC gene was constitutively expressed under the control of the 2×35S promoter in transgenic rice (Oryza sativa L.) using an Agrobacterium tumefaciens-mediated method. The nine transgenic plants were obtained and confirmed by PCR and RT-PCR, and the four (B2, B4, B7 and B9) of them whose copy numbers were 1, 2, 3 and 3, respectively, were shown to express the α-MC protein by Western blot. The molecular weight of α-MC in transgenic plants was approximately 38 kDa larger than the purified α-MC protein (28 kDa) in vitro. When the confirmed T1 generations were inoculated with a suspension of M. grisea spores for ten days, the lesions on leaves of transgenic plants were much lesser than those found on wild type (WT). According to the criteria of International Rice Research Institute standard, the mean values for morbidity and disease index numbers were 29.8% and 14.9%, respectively, which were lower than for WT. It is unclear whether RIPs could impact plant fitness and however our results suggest that the α-MC protein is an effective antifungal protein preventing rice blast in transgenic rice. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Discovering genes underlying QTL

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Vanavichit, Apichart [Kasetsart University, Kamphaengsaen, Nakorn Pathom (Thailand)

2002-02-01

A map-based approach has allowed scientists to discover few genes at a time. In addition, the reproductive barrier between cultivated rice and wild relatives has prevented us from utilizing the germ plasm by a map-based approach. Most genetic traits important to agriculture or human diseases are manifested as observable, quantitative phenotypes called Quantitative Trait Loci (QTL). In many instances, the complexity of the phenotype/genotype interaction and the general lack of clearly identifiable gene products render the direct molecular cloning approach ineffective, thus additional strategies like genome mapping are required to identify the QTL in question. Genome mapping requires no prior knowledge of the gene function, but utilizes statistical methods to identify the most likely gene location. To completely characterize genes of interest, the initially mapped region of a gene location will have to be narrowed down to a size that is suitable for cloning and sequencing. Strategies for gene identification within the critical region have to be applied after the sequencing of a potentially large clone or set of clones that contains this gene(s). Tremendous success of positional cloning has been shown for cloning many genes responsible for human diseases, including cystic fibrosis and muscular dystrophy as well as plant disease resistance genes. Genome and QTL mapping, positional cloning: the pre-genomics era, comparative approaches to gene identification, and positional cloning: the genomics era are discussed in the report. (M. Suetake)

GSEH: A Novel Approach to Select Prostate Cancer-Associated Genes Using Gene Expression Heterogeneity.

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Kim, Hyunjin; Choi, Sang-Min; Park, Sanghyun

2018-01-01

When a gene shows varying levels of expression among normal people but similar levels in disease patients or shows similar levels of expression among normal people but different levels in disease patients, we can assume that the gene is associated with the disease. By utilizing this gene expression heterogeneity, we can obtain additional information that abets discovery of disease-associated genes. In this study, we used collaborative filtering to calculate the degree of gene expression heterogeneity between classes and then scored the genes on the basis of the degree of gene expression heterogeneity to find "differentially predicted" genes. Through the proposed method, we discovered more prostate cancer-associated genes than 10 comparable methods. The genes prioritized by the proposed method are potentially significant to biological processes of a disease and can provide insight into them.

Validation of reference genes for quantifying changes in gene expression in virus-infected tobacco.

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Baek, Eseul; Yoon, Ju-Yeon; Palukaitis, Peter

2017-10-01

To facilitate quantification of gene expression changes in virus-infected tobacco plants, eight housekeeping genes were evaluated for their stability of expression during infection by one of three systemically-infecting viruses (cucumber mosaic virus, potato virus X, potato virus Y) or a hypersensitive-response-inducing virus (tobacco mosaic virus; TMV) limited to the inoculated leaf. Five reference-gene validation programs were used to establish the order of the most stable genes for the systemically-infecting viruses as ribosomal protein L25 > β-Tubulin > Actin, and the least stable genes Ubiquitin-conjugating enzyme (UCE) genes were EF1α > Cysteine protease > Actin, and the least stable genes were GAPDH genes, three defense responsive genes were examined to compare their relative changes in gene expression caused by each virus. Copyright © 2017 Elsevier Inc. All rights reserved.

Human gene therapy: novel approaches to improve the current gene delivery systems.

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Cucchiarini, Magali

2016-06-01

Even though gene therapy made its way through the clinics to treat a number of human pathologies since the early years of experimental research and despite the recent approval of the first gene-based product (Glybera) in Europe, the safe and effective use of gene transfer vectors remains a challenge in human gene therapy due to the existence of barriers in the host organism. While work is under active investigation to improve the gene transfer systems themselves, the use of controlled release approaches may offer alternative, convenient tools of vector delivery to achieve a performant gene transfer in vivo while overcoming the various physiological barriers that preclude its wide use in patients. This article provides an overview of the most significant contributions showing how the principles of controlled release strategies may be adapted for human gene therapy.

From gene engineering to gene modulation and manipulation: can we prevent or detect gene doping in sports?

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Fischetto, Giuseppe; Bermon, Stéphane

2013-10-01

During the last 2 decades, progress in deciphering the human gene map as well as the discovery of specific defective genes encoding particular proteins in some serious human diseases have resulted in attempts to treat sick patients with gene therapy. There has been considerable focus on human recombinant proteins which were gene-engineered and produced in vitro (insulin, growth hormone, insulin-like growth factor-1, erythropoietin). Unfortunately, these substances and methods also became improper tools for unscrupulous athletes. Biomedical research has focused on the possible direct insertion of gene material into the body, in order to replace some defective genes in vivo and/or to promote long-lasting endogenous synthesis of deficient proteins. Theoretically, diabetes, anaemia, muscular dystrophies, immune deficiency, cardiovascular diseases and numerous other illnesses could benefit from such innovative biomedical research, though much work remains to be done. Considering recent findings linking specific genotypes and physical performance, it is tempting to submit the young athletic population to genetic screening or, alternatively, to artificial gene expression modulation. Much research is already being conducted in order to achieve a safe transfer of genetic material to humans. This is of critical importance since uncontrolled production of the specifically coded protein, with serious secondary adverse effects (polycythaemia, acute cardiovascular problems, cancer, etc.), could occur. Other unpredictable reactions (immunogenicity of vectors or DNA-vector complex, autoimmune anaemia, production of wild genetic material) also remain possible at the individual level. Some new substances (myostatin blockers or anti-myostatin antibodies), although not gene material, might represent a useful and well-tolerated treatment to prevent progression of muscular dystrophies. Similarly, other molecules, in the roles of gene or metabolic activators [5-aminoimidazole-4

A model of gene-gene and gene-environment interactions and its implications for targeting environmental interventions by genotype

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Wallace Helen M

2006-10-01

Full Text Available Abstract Background The potential public health benefits of targeting environmental interventions by genotype depend on the environmental and genetic contributions to the variance of common diseases, and the magnitude of any gene-environment interaction. In the absence of prior knowledge of all risk factors, twin, family and environmental data may help to define the potential limits of these benefits in a given population. However, a general methodology to analyze twin data is required because of the potential importance of gene-gene interactions (epistasis, gene-environment interactions, and conditions that break the 'equal environments' assumption for monozygotic and dizygotic twins. Method A new model for gene-gene and gene-environment interactions is developed that abandons the assumptions of the classical twin study, including Fisher's (1918 assumption that genes act as risk factors for common traits in a manner necessarily dominated by an additive polygenic term. Provided there are no confounders, the model can be used to implement a top-down approach to quantifying the potential utility of genetic prediction and prevention, using twin, family and environmental data. The results describe a solution space for each disease or trait, which may or may not include the classical twin study result. Each point in the solution space corresponds to a different model of genotypic risk and gene-environment interaction. Conclusion The results show that the potential for reducing the incidence of common diseases using environmental interventions targeted by genotype may be limited, except in special cases. The model also confirms that the importance of an individual's genotype in determining their risk of complex diseases tends to be exaggerated by the classical twin studies method, owing to the 'equal environments' assumption and the assumption of no gene-environment interaction. In addition, if phenotypes are genetically robust, because of epistasis

Characteristics of functional enrichment and gene expression level of human putative transcriptional target genes.

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Osato, Naoki

2018-01-19

Transcriptional target genes show functional enrichment of genes. However, how many and how significantly transcriptional target genes include functional enrichments are still unclear. To address these issues, I predicted human transcriptional target genes using open chromatin regions, ChIP-seq data and DNA binding sequences of transcription factors in databases, and examined functional enrichment and gene expression level of putative transcriptional target genes. Gene Ontology annotations showed four times larger numbers of functional enrichments in putative transcriptional target genes than gene expression information alone, independent of transcriptional target genes. To compare the number of functional enrichments of putative transcriptional target genes between cells or search conditions, I normalized the number of functional enrichment by calculating its ratios in the total number of transcriptional target genes. With this analysis, native putative transcriptional target genes showed the largest normalized number of functional enrichments, compared with target genes including 5-60% of randomly selected genes. The normalized number of functional enrichments was changed according to the criteria of enhancer-promoter interactions such as distance from transcriptional start sites and orientation of CTCF-binding sites. Forward-reverse orientation of CTCF-binding sites showed significantly higher normalized number of functional enrichments than the other orientations. Journal papers showed that the top five frequent functional enrichments were related to the cellular functions in the three cell types. The median expression level of transcriptional target genes changed according to the criteria of enhancer-promoter assignments (i.e. interactions) and was correlated with the changes of the normalized number of functional enrichments of transcriptional target genes. Human putative transcriptional target genes showed significant functional enrichments. Functional

Conditional gene expression in the mouse using a Sleeping Beauty gene-trap transposon

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Hackett Perry B

2006-06-01

Full Text Available Abstract Background Insertional mutagenesis techniques with transposable elements have been popular among geneticists studying model organisms from E. coli to Drosophila and, more recently, the mouse. One such element is the Sleeping Beauty (SB transposon that has been shown in several studies to be an effective insertional mutagen in the mouse germline. SB transposon vector studies have employed different functional elements and reporter molecules to disrupt and report the expression of endogenous mouse genes. We sought to generate a transposon system that would be capable of reporting the expression pattern of a mouse gene while allowing for conditional expression of a gene of interest in a tissue- or temporal-specific pattern. Results Here we report the systematic development and testing of a transposon-based gene-trap system incorporating the doxycycline-repressible Tet-Off (tTA system that is capable of activating the expression of genes under control of a Tet response element (TRE promoter. We demonstrate that the gene trap system is fully functional in vitro by introducing the "gene-trap tTA" vector into human cells by transposition and identifying clones that activate expression of a TRE-luciferase transgene in a doxycycline-dependent manner. In transgenic mice, we mobilize gene-trap tTA vectors, discover parameters that can affect germline mobilization rates, and identify candidate gene insertions to demonstrate the in vivo functionality of the vector system. We further demonstrate that the gene-trap can act as a reporter of endogenous gene expression and it can be coupled with bioluminescent imaging to identify genes with tissue-specific expression patterns. Conclusion Akin to the GAL4/UAS system used in the fly, we have made progress developing a tool for mutating and revealing the expression of mouse genes by generating the tTA transactivator in the presence of a secondary TRE-regulated reporter molecule. A vector like the gene

Diverse lifestyles and strategies of plant pathogenesis encoded in the genomes of eighteen Dothideomycetes fungi.

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Robin A Ohm

Full Text Available The class Dothideomycetes is one of the largest groups of fungi with a high level of ecological diversity including many plant pathogens infecting a broad range of hosts. Here, we compare genome features of 18 members of this class, including 6 necrotrophs, 9 (hemibiotrophs and 3 saprotrophs, to analyze genome structure, evolution, and the diverse strategies of pathogenesis. The Dothideomycetes most likely evolved from a common ancestor more than 280 million years ago. The 18 genome sequences differ dramatically in size due to variation in repetitive content, but show much less variation in number of (core genes. Gene order appears to have been rearranged mostly within chromosomal boundaries by multiple inversions, in extant genomes frequently demarcated by adjacent simple repeats. Several Dothideomycetes contain one or more gene-poor, transposable element (TE-rich putatively dispensable chromosomes of unknown function. The 18 Dothideomycetes offer an extensive catalogue of genes involved in cellulose degradation, proteolysis, secondary metabolism, and cysteine-rich small secreted proteins. Ancestors of the two major orders of plant pathogens in the Dothideomycetes, the Capnodiales and Pleosporales, may have had different modes of pathogenesis, with the former having fewer of these genes than the latter. Many of these genes are enriched in proximity to transposable elements, suggesting faster evolution because of the effects of repeat induced point (RIP mutations. A syntenic block of genes, including oxidoreductases, is conserved in most Dothideomycetes and upregulated during infection in L. maculans, suggesting a possible function in response to oxidative stress.

Essential Bacillus subtilis genes

DEFF Research Database (Denmark)

Kobayashi, K.; Ehrlich, S.D.; Albertini, A.

2003-01-01

To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximate to4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were...... predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related...... to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from...

Integrative characterization of germ cell-specific genes from mouse spermatocyte UniGene library

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Eddy Edward M

2007-07-01

Full Text Available Abstract Background The primary regulator of spermatogenesis, a highly ordered and tightly regulated developmental process, is an intrinsic genetic program involving male germ cell-specific genes. Results We analyzed the mouse spermatocyte UniGene library containing 2155 gene-oriented transcript clusters. We predict that 11% of these genes are testis-specific and systematically identified 24 authentic genes specifically and abundantly expressed in the testis via in silico and in vitro approaches. Northern blot analysis disclosed various transcript characteristics, such as expression level, size and the presence of isoform. Expression analysis revealed developmentally regulated and stage-specific expression patterns in all of the genes. We further analyzed the genes at the protein and cellular levels. Transfection assays performed using GC-2 cells provided information on the cellular characteristics of the gene products. In addition, antibodies were generated against proteins encoded by some of the genes to facilitate their identification and characterization in spermatogenic cells and sperm. Our data suggest that a number of the gene products are implicated in transcriptional regulation, nuclear integrity, sperm structure and motility, and fertilization. In particular, we found for the first time that Mm.333010, predicted to contain a trypsin-like serine protease domain, is a sperm acrosomal protein. Conclusion We identify 24 authentic genes with spermatogenic cell-specific expression, and provide comprehensive information about the genes. Our findings establish a new basis for future investigation into molecular mechanisms underlying male reproduction.

Genome-wide identification of key modulators of gene-gene interaction networks in breast cancer.

Science.gov (United States)

Chiu, Yu-Chiao; Wang, Li-Ju; Hsiao, Tzu-Hung; Chuang, Eric Y; Chen, Yidong

2017-10-03

With the advances in high-throughput gene profiling technologies, a large volume of gene interaction maps has been constructed. A higher-level layer of gene-gene interaction, namely modulate gene interaction, is composed of gene pairs of which interaction strengths are modulated by (i.e., dependent on) the expression level of a key modulator gene. Systematic investigations into the modulation by estrogen receptor (ER), the best-known modulator gene, have revealed the functional and prognostic significance in breast cancer. However, a genome-wide identification of key modulator genes that may further unveil the landscape of modulated gene interaction is still lacking. We proposed a systematic workflow to screen for key modulators based on genome-wide gene expression profiles. We designed four modularity parameters to measure the ability of a putative modulator to perturb gene interaction networks. Applying the method to a dataset of 286 breast tumors, we comprehensively characterized the modularity parameters and identified a total of 973 key modulator genes. The modularity of these modulators was verified in three independent breast cancer datasets. ESR1, the encoding gene of ER, appeared in the list, and abundant novel modulators were illuminated. For instance, a prognostic predictor of breast cancer, SFRP1, was found the second modulator. Functional annotation analysis of the 973 modulators revealed involvements in ER-related cellular processes as well as immune- and tumor-associated functions. Here we present, as far as we know, the first comprehensive analysis of key modulator genes on a genome-wide scale. The validity of filtering parameters as well as the conservativity of modulators among cohorts were corroborated. Our data bring new insights into the modulated layer of gene-gene interaction and provide candidates for further biological investigations.

A new type of gene-disruption cassette with a rescue gene for Pichia pastoris.

Science.gov (United States)

Shibui, Tatsuro; Hara, Hiroyoshi

2017-09-01

Pichia pastoris has been used for the production of many recombinant proteins, and many useful mutant strains have been created. However, the efficiency of mutant isolation by gene-targeting is usually low and the procedure is difficult for those inexperienced in yeast genetics. In order to overcome these issues, we developed a new gene-disruption system with a rescue gene using an inducible Cre/mutant-loxP system. With only short homology regions, the gene-disruption cassette of the system replaces its target-gene locus containing a mutation with a compensatory rescue gene. As the cassette contains the AOX1 promoter-driven Cre gene, when targeted strains are grown on media containing methanol, the DNA fragment, i.e., the marker, rescue and Cre genes, between the mutant-loxP sequences in the cassette is excised, leaving only the remaining mutant-loxP sequence in the genome, and consequently a target gene-disrupted mutant can be isolated. The system was initially validated on ADE2 gene disruption, where the disruption can easily be detected by color-change of the colonies. Then, the system was applied for knocking-out URA3 and OCH1 genes, reported to be difficult to accomplish by conventional gene-targeting methods. All three gene-disruption cassettes with their rescue genes replaced their target genes, and the Cre/mutant-loxP system worked well to successfully isolate their knock-out mutants. This study identified a new gene-disruption system that could be used to effectively and strategically knock out genes of interest, especially whose deletion is detrimental to growth, without using special strains, e.g., deficient in nonhomologous end-joining, in P. pastoris. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1201-1208, 2017. © 2017 American Institute of Chemical Engineers.