G protein signaling and vein graft intimal hyperplasia: reduction of intimal hyperplasia in vein grafts by a Gbetagamma inhibitor suggests a major role of G protein signaling in lesion development.

Vein grafting results in the development of intimal hyperplasia with accompanying changes in guanine nucleotide-binding (G) protein expression and function. Several serum mitogens that act through G protein-coupled receptors, such as lysophosphatidic acid, stimulate proliferative pathways that are dependent on the G protein betagamma subunit (Gbetagamma)-mediated activation of p21ras. This study examines the role of Gbetagamma signaling in intimal hyperplasia by targeting a gene encoding a specific Gbetagamma inhibitor in an experimental rabbit vein graft model. This inhibitor, the carboxyl terminus of the beta-adrenergic receptor kinase (betaARK(CT)), contains a Gbetagamma-binding domain. Vein graft intimal hyperplasia was significantly reduced by 37% (P<0.01), and physiological studies demonstrated that the normal alterations in G protein coupling phenotypically seen in this model were blocked by betaARK(CT) treatment. Thus, it appears that Gbetagamma-mediated pathways play a major role in intimal hyperplasia and that targeting inhibitors of Gbetagamma signaling offers novel intraoperative therapeutic modalities to inhibit the development of vein graft intimal hyperplasia and subsequent vein graft failure.

Loss of a major idiotype (CRIA) after repopulation of irradiated mice.

The normal immune response of A/J mice against arsonate coupled to hemocyanin is characterized by a major recurrent cross-reactive Id, the CRIA. This Id is encoded by a single gene segment combination: VHidcr11-DFL16.1e-JH2 for the H chain and Vkidcr-Jk1 for the L chain. In this report, we show that lethal irradiation of A/J mice followed by reconstitution with autologous or syngeneic lymphoid cells results in loss of major CRIA Id expression in the response to arsonate. Different protocols were performed to repopulate the irradiated mice. First, lethally irradiated A/J mice were reconstituted by the transfer of syngeneic bone marrow cells. Second, A/J mice were lethally irradiated while their hind limbs were partially shielded. Third, lethally irradiated A/J mice received a transfer of syngeneic spleen cells. The three groups of mice produce high titers of antiarsonate antibodies completely devoid of CRIA DH-JH related idiotopes expression. Moreover, a lack of affinity maturation is observed in the secondary antiarsonate response of all irradiated and reconstituted mice. A transfer of syngeneic peritoneal cells or a transfer of primed T cells in irradiated and reconstituted A/J mice do not restore in a significant manner either the recurrent CRIA expression or the affinity maturation of the antiarsonate response. Our data suggest that the choice of this Id is not solely dictated by the Igh locus.

Dry deposition and heavy acid loading in the vicinity of Masaya Volcano, a major sulfur and chlorine source in Nicaragua

info:eu-repo/semantics/published

Analytical laboratory comparison of major and minor constituents in an active crater lake

info:eu-repo/semantics/published

Performance measurement and benchmarking of a major innovation programme

Purpose: The purpose of this paper is to describe the problems encountered and the solutions developed when using benchmarking and key performance indicators (KPIs) to monitor a major UK social house building innovation (change) programme. The innovation programme sought improvements to both the quality of the house product and the procurement process. Design/methodology/approach: Benchmarking and KPIs were used to quantify performance and in-depth case studies to identify underlying cause and effect relationships within the innovation programme. Findings: The inherent competition between consortium members; the complexity of the relationship between the consortium and its strategic partner; the lack of an authoritative management control structure; and the rapidly changing nature of the UK social housing market all proved problematic to the development of a reliable and robust monitoring system. These problems were overcome by the development of multi-dimensional benchmarking model that balanced the needs and aspirations of the individual organisations with the broader objectives of the consortium. Research limitations/implications: Whilst the research methodology provides insight into the factors that affected the performance of a major innovation programme its findings may not be representative of all projects. Practical implications: The lessons learnt should assist those developing benchmarking models for multi-client consortia. Originality/value: The work reported in this paper describes an inclusive approach to benchmarking in which a multiple client group and their strategic partner sought to work together for shared gain. Very few papers have addressed this issue.

Radiolaria: Major exporters of organic carbon to the deep ocean

Very large pulses of particulate organic matter intermittently sink to the deep waters of the open ocean in the Northeast Atlantic. These pulses, measured by moored sediment traps since 1989, can contribute up to 60% of the organic flux to 3000 m in a particular year and are thus a major cause of the variability in carbon sequestration from the atmosphere in the region. Pulses occur in the late summer and are characterized by material that is very rich in organic carbon but with low concentrations of the biominerals opal and calcite. A number of independent lines of evidence have been examined to determine the causes of these pulses: (1) Data from the Continuous Plankton Recorder (CPR) survey show that in this region, radiolarian protozoans intermittently reach high abundances in the late summer just preceding organic pulses to depth. (2) CPR data also show that the interannual variability in radiolarian abundance since 1997 mirrors very closely the variability of deep ocean organic deposition. (3) The settling material collected in the traps displays a strong correlation between fecal pellets produced by radiolaria and the measured organic carbon flux. These all suggest that the pulses are mediated by radiolarians, a group of protozoans found throughout the world’s oceans and which are widely used by paleontologists to determine past climate conditions. Changes in the upper ocean community structure (between years and on longer timescales) may have profound effects on the ability of the oceans to sequester carbon dioxide from the atmosphere.

Feeding and overwintering of Antarctic krill across its major habitats: The role of sea ice cover, water depth, and phytoplankton abundance

Antarctic krill (Euphausia superba) were sampled in contrasting habitats: a seasonally ice-covered deep ocean (Lazarev Sea), ice-free shelves at their northern range (South Georgia) and the Antarctic Peninsula (Bransfield Strait), and shelf and oceanic sites in the Scotia Sea. Across 92 stations, representing a year-round average, the food volume in krill stomachs comprised 71 +/- 29% algae, 17 +/- 21% protozoans, and 12 +/- 25% metazoans. Fatty acid trophic markers showed that copepods were consistently part of krill diet, not a switch food. In open waters, both diatom and copepod consumption increased with phytoplankton abundance. Under sea ice, ingestion of diatoms became rare, whereas feeding on copepods remained constant. During winter, larvae contained high but variable proportions of diatom markers, whereas in postlarvae the role of copepods increased with krill body length. Overwintering differed according to habitat. Krill from South Georgia had lower lipid stores than those from the Bransfield Strait or Lazarev Sea. Feeding effort was much reduced in Lazarev Sea krill, whereas most individuals from the Bransfield Strait and South Georgia contained phytoplankton and seabed detritus in their stomachs. Their retention of essential body reserves indicates that krill experienced most winter hardship in the Lazarev Sea, followed by South Georgia and then Bransfield Strait. This was reflected in the delayed development from juveniles to adults in the Lazarev Sea. Circumpolar comparisons of length frequencies suggest that krill growth conditions are more favorable in the southwest Atlantic than in the Lazarev Sea or off East Antarctica because of longer phytoplankton bloom periods and rewarding access to benthic food.

Modelling the Influence of Major Baltic Inflows on Near-Bottom Conditions at the Entrance of the Gulf of Finland

A coupled hydrodynamic-biogeochemical model was implemented in order to estimate the effects of Major Baltic Inflows on the near-bottom hydrophysical and biogeochemical conditions in the northern Baltic Proper and the western Gulf of Finland during the period 1991�2009. We compared results of a realistic reference run to the results of an experimental run where Major Baltic Inflows were suppressed. Further to the expected overall decrease in bottom salinity, this modelling experiment confirms that in the absence of strong saltwater inflows the deep areas of the Baltic Proper would become more anoxic, while in the shallower areas (western Gulf of Finland) near-bottom average conditions improve. Our experiment revealed that typical estuarine circulation results in the sporadic emergence of short-lasting events of near-bottom anoxia in the western Gulf of Finland due to transport of water masses from the Baltic Proper. Extrapolating our results beyond the modelled period, we speculate that the further deepening of the halocline in the Baltic Proper is likely to prevent inflows of anoxic water to the Gulf of Finland and in the longer term would lead to improvement in near-bottom conditions in the Baltic Proper. Our results reaffirm the importance of accurate representation of salinity dynamics in coupled Baltic Sea models serving as a basis for credible hindcast and future projection simulations of biogeochemical conditions.

Quantification of urinary excretion of ethosuximide enantiomers and their major metabolites in the rat.

A chiral gas chromatographic assay has been developed for quantitative analysis of ethosuximide and its major metabolites in rat urine. The extraction procedure was found to be precise and reproducible. Recovery was in the range of 94-98%, intraday CV(%) was 0.92% for (S)-ethosuximide (50 mug/ml) and 0.51% for (R)-ethosuximide (50 mug/ml). Interday CV(%) was 1.12% for (S)-ethosuximide and 0.72% for (R)-ethosuximide. The limit of detection was determined to be around 0.01 mug/ml for each enantiomer. Following administration of rac-ethosuximide by i.v., i.p. and oral routes, unchanged ethosuximide was detected in urine up to 72h after drug administration. The appearance of all detected metabolites occurred Within 24h of drug administration. Significantly more (S)-ethosuximide was excreted unchanged than (R)-ethosuximide with all three routes studied. A substantial amount of the drug was eliminated as the 2-(1-hydroxyethyl)-2-methylsuccinimide (2 pairs of diastereoisomers). Much less drug was eliminated as the 2-ethyl-3-hydroxy-2-methylsuccinimide with only one diastereoisomer observed. Examination of the one pair of diastereoisomers of 2-(1-hydroxyethyl)-2-methylsuccinimide that was resolved showed preferential excretion of one isomer. Comparison of both pairs of diastereoisomers showed that one pair was formed in preference to the other with a ratio of approximately 0.8:1. It is concluded that stereoselective metabolism of ethosuximide occurs. Copyright (C) 2001 John Wiley & Sons, Ltd. Author Keywords: chiral pharmacokinetics; ethosuximide enantiomers; metabolism; rat; urinary excretion; gas chromatography