Rational choice meets the new politics: choosing the Scottish Parliament’s electoral system

Although there has been extensive research about electoral system choice at the national level, we know relatively little about the dynamics of deciding the rules of the game for sub-state institutions. This article examines the factors that influenced the choice of a proportional electoral system for the new Scottish Parliament in 1999. Through the use of archival sources and interviews with key participants, we challenge the conventional rational choice explanation for the adoption of the mixed-member proportional (MMP) system. Although rational considerations on the part of the Labour Party were involved in the choice of MMP, our findings suggest that, as at the national level, theories of electoral system choice need to consider normative values as well

Rational choice meets the new politics:Choosing the Scottish Parliament’s electoral system

Although there has been extensive research about electoral system choice at the national level, we know relatively little about the dynamics of deciding the rules of the game for sub-state institutions. This article examines the factors that influenced the choice of a proportional electoral system for the new Scottish Parliament in 1999. Through the use of archival sources and interviews with key participants, we challenge the conventional rational choice explanation for the adoption of the mixed-member proportional (MMP) system. Although rational considerations on the part of the Labour Party were involved in the choice of MMP, our findings suggest that, as at the national level, theories of electoral system choice need to consider normative values as well

Modulation of GSK-3β activity in Venezuelan equine encephalitis virus infection

Alphaviruses, including Venezuelan Equine Encephalitis Virus (VEEV), cause disease in both equine and humans that exhibit overt encephalitis in a significant percentage of cases. Features of the host immune response and tissue-specific responses may contribute to fatal outcomes as well as the development of encephalitis. It has previously been shown that VEEV infection of mice induces transcription of pro-inflammatory cytokines genes (e.g., IFN-γ, IL-6, IL-12, iNOS and TNF-α) within 6 h. GSK-3β is a host protein that is known to modulate pro-inflammatory gene expression and has been a therapeutic target in neurodegenerative disorders such as Alzheimer\u27s. Hence inhibition of GSK-3β in the context of encephalitic viral infections has been useful in a neuroprotective capacity. Small molecule GSK-3β inhibitors and GSK-3β siRNA experiments indicated that GSK-3β was important for VEEV replication. Thirty-eight second generation BIO derivatives were tested and BIOder was found to be the most potent inhibitor, with an IC50 of ~0.5 µM and a CC50 of \u3e100 µM. BIOder was a more potent inhibitor of GSK-3β than BIO, as demonstrated through in vitro kinase assays from uninfected and infected cells. Size exclusion chromatography experiments demonstrated that GSK-3β is found in three distinct complexes in VEEV infected cells, whereas GSK-3β is only present in one complex in uninfected cells. Cells treated with BIOder demonstrated an increase in the anti-apoptotic gene, survivin, and a decrease in the pro-apoptotic gene, BID, suggesting that modulation of pro- and anti-apoptotic genes contributes to the protective effect of BIOder treatment. Finally, BIOder partially protected mice from VEEV induced mortality. Our studies demonstrate the utility of GSK-3β inhibitors for modulating VEEV infection

Venezuelan Equine Encephalitis Virus Capsid Implicated in Infection-Induced Cell Cycle Delay in vitro

Venezuelan equine encephalitis virus (VEEV) is a positive sense, single-stranded RNA virus and member of the New World alphaviruses. It causes a biphasic febrile illness that can be accompanied by central nervous system involvement and moderate morbidity in humans and severe mortality in equines. The virus has a history of weaponization, lacks FDA-approved therapeutics and vaccines in humans, and is considered a select agent. Like other RNA viruses, VEEV replicates in the cytoplasm of infected cells and eventually induces apoptosis. The capsid protein, which contains a nuclear localization and a nuclear export sequence, induces a shutdown of host transcription and nucleocytoplasmic trafficking. Here we show that infection with VEEV causes a dysregulation of cell cycling and a delay in the G0/G1 phase in Vero cells and U87MG astrocytes. Cells infected with VEEV encoding a capsid NLS mutant or treated with the capsid-importin α interaction inhibitor G281-1485 were partially rescued from this cell cycle dysregulation. Pathway analysis of previously published RNA-sequencing data from VEEV infected U87MG astrocytes identified alterations of canonical pathways involving cell cycle, checkpoint regulation, and proliferation. Multiple cyclins including cyclin D1, cyclin A2 and cyclin E2 and other regulators of the cell cycle were downregulated in infected cells in a capsid NLS dependent manner. Loss of Rb phosphorylation, which is a substrate for cyclin/cdk complexes was also observed. These data demonstrate the importance of capsid nuclear localization and/or importin α binding for inducing cell cycle arrest and transcriptional downregulation of key cell cycle regulators

Exploring Transduction Mechanisms of Protein Transduction Domains (PTDs) in Living Cells Utilizing Single-Quantum Dot Tracking (SQT) Technology

Specific protein domains known as protein transduction domains (PTDs) can permeate cell membranes and deliver proteins or bioactive materials into living cells. Various approaches have been applied for improving their transduction efficacy. It is, therefore, crucial to clarify the entry mechanisms and to identify the rate-limiting steps. Because of technical limitations for imaging PTD behavior on cells with conventional fluorescent-dyes, how PTDs enter the cells has been a topic of much debate. Utilizing quantum dots (QDs), we recently tracked the behavior of PTD that was derived from HIV-1 Tat (TatP) in living cells at the single-molecule level with 7-nm special precision. In this review article, we initially summarize the controversy on TatP entry mechanisms; thereafter, we will focus on our recent findings on single-TatP-QD tracking (SQT), to identify the major sequential steps of intracellular delivery in living cells and to discuss how SQT can easily provide direct information on TatP entry mechanisms. As a primer for SQT study, we also discuss the latest findings on single particle tracking of various molecules on the plasma membrane. Finally, we discuss the problems of QDs and the challenges for the future in utilizing currently available QD probes for SQT. In conclusion, direct identification of the rate-limiting steps of PTD entry with SQT should dramatically improve the methods for enhancing transduction efficiency

Expected Performance of the ATLAS Experiment - Detector, Trigger and Physics

A detailed study is presented of the expected performance of the ATLAS detector. The reconstruction of tracks, leptons, photons, missing energy and jets is investigated, together with the performance of b-tagging and the trigger. The physics potential for a variety of interesting physics processes, within the Standard Model and beyond, is examined. The study comprises a series of notes based on simulations of the detector and physics processes, with particular emphasis given to the data expected from the first years of operation of the LHC at CERN

Inverse estimates of the oceanic sources and sinks of natural CO2 and the implied oceanic carbon transport

Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 21 (2007): , doi:10.1029/2006GB002751.We use an inverse method to estimate the global-scale pattern of the air-sea flux of natural CO2, i.e., the component of the CO2 flux due to the natural carbon cycle that already existed in preindustrial times, on the basis of ocean interior observations of dissolved inorganic carbon (DIC) and other tracers, from which we estimate ΔC gasex , i.e., the component of the observed DIC that is due to the gas exchange of natural CO2. We employ a suite of 10 different Ocean General Circulation Models (OGCMs) to quantify the error arising from uncertainties in the modeled transport required to link the interior ocean observations to the surface fluxes. The results from the contributing OGCMs are weighted using a model skill score based on a comparison of each model's simulated natural radiocarbon with observations. We find a pattern of air-sea flux of natural CO2 characterized by outgassing in the Southern Ocean between 44°S and 59°S, vigorous uptake at midlatitudes of both hemispheres, and strong outgassing in the tropics. In the Northern Hemisphere and the tropics, the inverse estimates generally agree closely with the natural CO2 flux results from forward simulations of coupled OGCM-biogeochemistry models undertaken as part of the second phase of the Ocean Carbon Model Intercomparison Project (OCMIP-2). The OCMIP-2 simulations find far less air-sea exchange than the inversion south of 20°S, but more recent forward OGCM studies are in better agreement with the inverse estimates in the Southern Hemisphere. The strong source and sink pattern south of 20°S was not apparent in an earlier inversion study, because the choice of region boundaries led to a partial cancellation of the sources and sinks. We show that the inversely estimated flux pattern is clearly traceable to gradients in the observed ΔC gasex , and that it is relatively insensitive to the choice of OGCM or potential biases in ΔC gasex . Our inverse estimates imply a southward interhemispheric transport of 0.31 ± 0.02 Pg C yr−1, most of which occurs in the Atlantic. This is considerably smaller than the 1 Pg C yr−1 of Northern Hemisphere uptake that has been inferred from atmospheric CO2 observations during the 1980s and 1990s, which supports the hypothesis of a Northern Hemisphere terrestrial sink.This research was financially supported by the National Aeronautics and Space Administration under grant NAG5-12528. N. G. also acknowledges support by the National Science Foundation (OCE-0137274). Climate and Environmental Physics, Bern, acknowledges support by the European Union through the Integrated Project CarboOcean and the Swiss National Science Foundation

Metabolism during anaesthesia and recovery in colic and healthy horses: a microdialysis study

<p>Abstract</p> <p>Background</p> <p>Muscle metabolism in horses has been studied mainly by analysis of substances in blood or plasma and muscle biopsy specimens. By using microdialysis, real-time monitoring of the metabolic events in local tissue with a minimum of trauma is possible. There is limited information about muscle metabolism in the early recovery period after anaesthesia in horses and especially in the colic horse. The aims were to evaluate the microdialysis technique as a complement to plasma analysis and to study the concentration changes in lactate, pyruvate, glucose, glycerol, and urea during anaesthesia and in the recovery period in colic horses undergoing abdominal surgery and in healthy horses not subjected to surgery.</p> <p>Methods</p> <p>Ten healthy university-owned horses given anaesthesia alone and ten client-owned colic horses subjected to emergency abdominal surgery were anaesthetised for a mean (range) of 230 min (193–273) and 208 min (145–300) respectively. Venous blood samples were taken before anaesthesia. Venous blood sampling and microdialysis in the gluteal muscle were performed during anaesthesia and until 24 h after anaesthesia. Temporal changes and differences between groups were analysed with an ANOVA for repeated measures followed by Tukey Post Hoc test or Planned Comparisons.</p> <p>Results</p> <p>Lactate, glucose and urea, in both dialysate and plasma, were higher in the colic horses than in the healthy horses for several hours after recovery to standing. In the colic horses, lactate, glucose, and urea in dialysate, and lactate in plasma increased during the attempts to stand. The lactate-to-pyruvate ratio was initially high in sampled colic horses but decreased over time. In the colic horses, dialysate glycerol concentrations varied considerably whereas in the healthy horses, dialysate glycerol was elevated during anaesthesia but decreased after standing. In both groups, lactate concentration was higher in dialysate than in plasma. The correspondence between dialysate and plasma concentrations of glucose, urea and glycerol varied.</p> <p>Conclusion</p> <p>Microdialysis proved to be suitable in the clinical setting for monitoring of the metabolic events during anaesthesia and recovery. It was possible with this technique to show greater muscle metabolic alterations in the colic horses compared to the healthy horses in response to regaining the standing position.</p

p53 Activation following Rift Valley Fever Virus Infection Contributes to Cell Death and Viral Production

Rift Valley fever virus (RVFV) is an emerging viral zoonosis that is responsible for devastating outbreaks among livestock and is capable of causing potentially fatal disease in humans. Studies have shown that upon infection, certain viruses have the capability of utilizing particular cellular signaling pathways to propagate viral infection. Activation of p53 is important for the DNA damage signaling cascade, initiation of apoptosis, cell cycle arrest and transcriptional regulation of multiple genes. The current study focuses on the role of p53 signaling in RVFV infection and viral replication. These results show an up-regulation of p53 phosphorylation at several serine sites after RVFV MP-12 infection that is highly dependent on the viral protein NSs. qRT-PCR data showed a transcriptional up-regulation of several p53 targeted genes involved in cell cycle and apoptosis regulation following RVFV infection. Cell viability assays demonstrate that loss of p53 results in less RVFV induced cell death. Furthermore, decreased viral titers in p53 null cells indicate that RVFV utilizes p53 to enhance viral production. Collectively, these experiments indicate that the p53 signaling pathway is utilized during RVFV infection to induce cell death and increase viral production

Exercise and bone health across the lifespan

With ageing, bone tissue undergoes significant compositional, architectural and metabolic alterations potentially leading to osteoporosis. Osteoporosis is the most prevalent bone disorder, which is characterised by progressive bone weakening and an increased risk of fragility fractures. Although this metabolic disease is conventionally associated with ageing and menopause, the predisposing factors are thought to be established during childhood and adolescence. In light of this, exercise interventions implemented during maturation are likely to be highly beneficial as part of a long-term strategy to maximise peak bone mass and hence delay the onset of age- or menopause-related osteoporosis. This notion is supported by data on exercise interventions implemented during childhood and adolescence, which confirmed that weight-bearing activity, particularly if undertaken during peripubertal development, is capable of generating a significant osteogenic response leading to bone anabolism. Recent work on human ageing and epigenetics suggests that undertaking exercise after the fourth decade of life is still important, given the anti-ageing effect and health benefits provided, potentially occurring via a delay in telomere shortening and modification of DNA methylation patterns associated with ageing. Exercise is among the primary modifiable factors capable of influencing bone health by preserving bone mass and strength, preventing the death of bone cells and anti-ageing action provided