bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial and spatio-temporal analysis ofSalmonellainfection in dairy herds in England and Wales
Authors: FENTON S. E. , CLOUGH H. E. , DIGGLE P. J. , EVANS S. J. , DAVISON H. C. , VINK W. D. , FRENCH N. P. 
Published: September 2008

SUMMARYUsing data from a cohort study conducted by the Veterinary Laboratories Agency (VLA), evidence of spatial clustering at distances up to 30 km was found forS. Agama andS. Dublin (Pvalues of 0·001) and borderline evidence was found for spatial clustering ofS. Typhimurium (P=0·077). The evolution of infection status of study farms over time was modelled using a Markov Chain model with transition probabilities describing changes in status at each of four visits, allowing for the effect of sampling visit. The degree of geographical clustering of infection, having allowed for temporal effects, was assessed by comparing the residual deviance from a model including a measure of recent neighbourhood infection levels with one excluding this variable. The number of cases arising within a defined distance and time period of an index case was higher than expected. This provides evidence for spatial and spatio-temporal clustering, which suggests either a contagious process (e.g. through direct or indirect farm-to-farm transmission) or geographically localized environmental and/or farm factors which increase the risk of infection. The results emphasize the different epidemiology of the threeSalmonellaserovars investigated.
Mechanism of the elevation in cardiolipin during HeLa cell entry into the S-phase of the human cell cycle
Authors: Hauff Kristin , Linda Dorota , Hatch Grant M. 
Published: September 2008

CL (cardiolipin) is a key phospholipid involved in ATP generation. Since progression through the cell cycle requires ATP we examined regulation of CL synthesis during S-phase in human cells and investigated whether CL or CL synthesis was required to support nucleotide synthesis in S-phase. HeLa cells were made quiescent by serum depletion for 24 h. Serum addition resulted in substantial stimulation of [methyl-3H]thymidine incorporation into cells compared with serum-starved cells by 8 h, confirming entry into the S-phase. CL mass was unaltered at 8 h, but increased 2-fold by 16 h post-serum addition compared with serum-starved cells. The reason for the increase in CL mass upon entry into S-phase was an increase in activity and expression of CL de novo biosynthetic and remodelling enzymes and this paralleled the increase in mitochondrial mass. CL de novo biosynthesis from D-[U-14C]glucose was elevated, and from [1,3-3H]glycerol reduced, upon serum addition to quiescent cells compared with controls and this was a result of differences in the selection of precursor pools at the level of uptake. Triascin C treatment inhibited CL synthesis from [1-14C]oleate but did not affect [methyl-3H]thymidine incorporation into HeLa cells upon serum addition to serum-starved cells. Barth Syndrome lymphoblasts, which exhibit reduced CL, showed similar [methyl-3H]thymidine incorporation into cells upon serum addition to serum-starved cells compared with cells from normal aged-matched controls. The results indicate that CL de novo biosynthesis is up-regulated via elevated activity and expression of CL biosynthetic genes and this accounted for the doubling of CL seen during S-phase; however, normal de novo CL biosynthesis or CL itself is not essential to support nucleotide synthesis during entry into S-phase of the human cell cycle.
Environmental indicators: utility in meeting regulatory needs. An overview
Authors: Rees Hubert L. , Hyland Jeffrey L. , Hylland Ketil , Mercer Clarke Colleen S. L. , Roff John C. , Ware Suzanne 
Published: September 2008

Abstract
Rees, H. L., Hyland, J. L., Hylland, K., Mercer Clarke, C. S. L., Roff, J. C., and Ware, S. 2008. Environmental indicators: utility in meeting regulatory needs. An overview. – ICES Journal of Marine Science, 65: 1381–1386. The utility of environmental indicators in meeting regulatory needs was addressed at an international symposium held in November 2007. This paper summarizes the attributes and range of uses of indicators and highlights key points from theme sessions and a workshop on unifying concepts. The symposium attracted regulators and scientists, who supported the need to promote dialogue during the construction of indicator-based management frameworks and at key stages towards operational use. Scientists expressed willingness to engage with the wider societal context for indicator applications, which is essential to the development of ecosystem-based management. For the latter to be effective, more effort is needed to combine indicators with thresholds to guide management actions and, in the process, to assess the full range of consequences of non-compliance. There are clear benefits to periodic interdisciplinary reviews of progress in this area, and a follow-up event with a regulatory emphasis is suggested.
Contribution of the activities of CYP3A, CYP2D6, CYP1A2 and other potential covariates to the disposition of methadone in patients undergoing methadone maintenance treatment
Authors: Shiran Mohammad‐Reza , Lennard Martin S. , Iqbal Mohammad‐Zafar , Lagundoye Oldwale , Seivewright Nicholas , Tucker Geoffrey T. , Rostami‐Hodjegan Amin 
Published: September 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Several cytochromes P450 (CYPs) have been implicated in the metabolism of methadone, but there is no consensus on their relative contributions to overall disposition and hence variability in response.WHAT THIS STUDY ADDS• Variability in CYP3A4 activity has statistically significant but nonetheless modest influence on the oral clearance of methadone and its enantiomers.• However, CYPs 1A2 and 2D6 appear to have no impact at all.AIMSTo investigate the influence of different cytochrome P450 (CYP) activities and other potential covariates on the disposition of methadone in patients on methadone maintenance therapy (MMT).METHODSEighty‐eight patients (58 male; 21–55 years; 84 White) on MMT were studied. CYP2D6 activity [3 h plasma metabolic ratio of dextromethorphan (DEX) to dextrorphan (DOR)] was determined in 44 patients (29 male; 24–55 years), CYP1A2 activity (salivary caffeine elimination half‐life) in 44 patients (21 male; 24–55 years) and CYP3A activity (oral clearance of midazolam) in 49 patients (33 male; 23–55 years). Data on all three CYPs were obtained from 32 subjects. Total plasma concentrations of (RS)‐methadone and total and unbound plasma concentrations of both enantiomers were measured by LC/MS. Population pharmacokinetics and subsequent multiple regression analysis were used to calculate methadone oral clearance and to identify its covariates.RESULTSBetween 61 and 68% of the overall variation in total plasma trough concentrations of (RS)‐, (R)‐ and (S)‐methadone was explained by methadone dose, duration of addiction before starting MMT, CYP3A activity and illicit morphine use. CYP3A activity explained 22, 16, 15 and 23% of the variation in unbound (R)‐, unbound (S)‐, total (RS)‐ and total (S)‐methadone clearances, respectively. Neither CYP2D6 nor CYP1A2 activity was related to methadone disposition.CONCLUSIONSCYP3A activity has a modest influence on methadone disposition. Inhibitors and inducers of this enzyme should be monitored in patients taking methadone.
Type‐B monogalactosyldiacylglycerol synthases are involved in phosphate starvation‐induced lipid remodeling, and are crucial for low‐phosphate adaptation
Authors: Kobayashi Koichi , Awai Koichiro , Nakamura Masanobu , Nagatani Akira , Masuda Tatsuru , Ohta Hiroyuki 
Published: September 2008

SummaryMono‐ and digalactosyldiacylglycerol (MGDG and DGDG, respectively) constitute the bulk of membrane lipids in plant chloroplasts. Mutant analyses in Arabidopsis have shown that these galactolipids are essential for chloroplast biogenesis and photoautotrophic growth. Moreover, these non‐phosphorous lipids are proposed to participate in low‐phosphate (Pi) adaptations. Under Pi‐limited conditions, a drastic accumulation of DGDG occurs concomitantly with a large reduction in membrane phospholipids, suggesting that plants substitute DGDG for phospholipids during Pi starvation. Previously, we reported that among the three MGDG synthase genes (MGD1, MGD2 and MGD3), the type‐B MGD2 and MGD3 are upregulated in parallel with DGDG synthase genes during Pi starvation. Here, we describe the identification and characterization of T‐DNA insertional mutants of Arabidopsis type‐B MGD genes. Under Pi‐starved conditions, the mgd3‐1 mutant showed a drastic reduction in DGDG accumulation, particularly in the root, indicating that MGD3 is the main isoform responsible for DGDG biosynthesis in Pi‐starved roots. Moreover, in the roots of mgd2 mgd3 plants, Pi stress‐induced accumulation of DGDG was almost fully abolished, showing that type‐B MGD enzymes are essential for membrane lipid remodeling in Pi‐starved roots. Reductions in fresh weight, root growth and photosynthetic performance were also observed in these mutants under Pi‐starved conditions. These results demonstrate that Pi stress‐induced membrane lipid remodeling is important in plant growth during Pi starvation. The widespread distribution of type‐B MGD genes in land plants suggests that membrane lipid remodeling mediated by type‐B MGD enzymes is a potent adaptation to Pi deficiency for land plants.
Hybrid breakdown and mitochondrial dysfunction in hybrids of Nasonia parasitoid wasps
Authors: ELLISON C. K. , NIEHUIS O. , GADAU J. 
Published: September 2008

AbstractMale F2hybrids of the waspsNasonia giraultiandNasonia vitripennissuffer increased mortality during development. Previous studies suggested that the mitochondria may play an important role in this pattern of hybrid breakdown. The mitochondrial genome encodes 13 polypeptides, which are integral subunits of the oxidative phosphorylation enzyme complexes I, III, IV and V. We show that the mitochondrial ATP production rate and the efficacy of the enzyme complexes I, III and IV, but not that of the completely nuclear‐encoded complex II, are reduced in F2hybrid males ofN. giraultiandN. vitripennis. We hypothesize that nuclear–mitochondrial protein interactions in the oxidative phosphorylation pathway are disrupted in these hybrids, reducing energy generation capacity and potentially reducing hybrid fitness. Our results suggest that dysfunctional cytonuclear interactions could represent an under‐appreciated post‐zygotic isolation mechanism that, due to elevated evolutionary rates of mitochondrial genes, evolves very early in the speciation process.
The frequency of multiple paternity predicts variation in testes size among island populations of house mice
Authors: FIRMAN R. C. , SIMMONS L. W. 
Published: September 2008

AbstractPolyandry generates selection on males through sperm competition, which has broad implications for the evolution of ejaculates and male reproductive anatomy. Comparative analyses across species and competitive mating trials within species have suggested that sperm competition can influence the evolution of testes size, sperm production and sperm form and function. Surprisingly, the intraspecific approach of comparing among population variation for investigating the selective potential of sperm competition has rarely been explored. We sampled seven island populations of house mice and determined the frequency of multiple paternity within each population. Applying the frequency of multiple paternity as an index of the risk of sperm competition, we looked for selective responses in male reproductive traits. We found that the risk of sperm competition predicted testes size across the seven island populations of house mice. However, variation in sperm traits was not explained by sperm competition risk. We discuss these findings in relation to sperm competition theory, and other intrinsic and extrinsic factors that might influence ejaculate quality.
Nice natives and mean migrants: the evolution of dispersal‐dependent social behaviour in viscous populations
Authors: EL MOUDEN C. , GARDNER A. 
Published: September 2008

AbstractThere has been much interest in the evolution of social behaviour in viscous populations. While low dispersal increases the relatedness of neighbours, which tends to promote the evolution of indiscriminate helping behaviour, it can also increase competition between neighbours, which tends to inhibit the evolution of helping and may even favour harming behaviour. In the simplest scenario, these two effects exactly cancel, so that dispersal rate has no impact on the evolution of helping or harming. Here, we show that dispersal rate does matter when individuals can adjust their social behaviour conditional on whether they have dispersed or whether they have remained close to their place of origin. We find that nondispersing individuals are weakly favoured to indiscriminately help their neighbours, whereas dispersing individuals are more readily favoured to indiscriminately harm their neighbours.
Investigating latitudinal clines for life history and stress resistance traits in Drosophila simulans from eastern Australia
Authors: ARTHUR A. L. , WEEKS A. R. , SGRÒ C. M. 
Published: September 2008

AbstractLatitudinal clines have been demonstrated for many quantitative traits in Drosophila and are assumed to be due to climatic selection. However, clinal studies are often performed in species of Drosophila that contain common cosmopolitan inversion polymorphisms that also show clinal patterns. These inversion polymorphisms may be responsible for much of the observed clinal variation. Here, we consider latitudinal clines for quantitative traits in Drosophila simulans from eastern Australia. Drosophila simulans does not contain cosmopolitan inversion polymorphisms, so allows the study of clinal selection on quantitative traits that are not confounded by associations with inversions. Body size showed a strong linear cline for both females and males. Starvation resistance exhibited a weak linear cline in females, whereas chill‐coma recovery exhibited a significant nonlinear cline in females only. No clinal pattern was evident for development time, male chill‐coma recovery, desiccation or heat resistance. We discuss these results with reference to the role inversion polymorphisms play in generating clines in quantitative traits of Drosophila.
Male sterility, fitness gain curves and the evolution of gender specialization from distyly in Erythroxylum havanense
Authors: ROSAS F. , DOMÍNGUEZ C. A. 
Published: September 2008

AbstractThe evolution of dioecy from a monomorphic hermaphroditic condition requires two mutations, one producing females and one producing males. Conversely, a single mutation sterilizing one sexual function in one morph of distylous species would result in functional dioecy because such a mutation also affects the complementary function in the other morph. In this study, we tested these ideas with Erythroxylum havanense, a distylous species with morph‐biased male sterility. Based on sex allocation theory we evaluated whether the invasion of thrum females is favoured over the maintenance of this morph cosexuals. Completely male sterile thrum plants obtained higher fitness returns than hermaphrodites or partial male sterile individuals of the same morph, thus favouring the invasion of female thrum plants. We concluded that because fruit production of pin individuals depends on the pollen produced by thrum plants, the invasion of thrum females would result on the evolution of functional dioecy.
Human ProNGF: biological effects and binding profiles at TrkA, P75NTR and sortilin
Authors: Clewes Oliver , Fahey Mark S. , Tyler Sue J. , Watson Judy J. , Seok Heon , Catania Caterina , Cho Kwangwook , Dawbarn David , Allen Shelley J. 
Published: September 2008

AbstractNerve growth factor (NGF) promotes cell survival via binding to the tyrosine kinase receptor A (TrkA). Its precursor, proNGF, binds to p75NTR and sortilin receptors to initiate apoptosis. Current disagreement exists over whether proNGF acts neurotrophically following binding to TrkA. As in Alzheimer’s disease the levels of proNGF increase and TrkA decrease, it is important to clarify the properties of proNGF. Here, wild‐type and cleavage‐resistant mutated forms (M) of proNGF were engineered and their binding characteristics determined. M‐proNGF and NGF bound to p75NTR with similar affinities, whilst M‐proNGF had a lower affinity than NGF for TrkA. M‐proNGF behaved neurotrophically, albeit less effectively than NGF. M‐proNGF addition resulted in phosphorylation of TrkA and ERK1/2, and in PC12 cells elicited neurite outgrowth and supported cell survival. Conversely, M‐proNGF addition to cultured cortical neurons initiated caspase 3 cleavage. Importantly, these biological effects were shown to be mediated by unprocessed M‐proNGF. Surprisingly, binding of the pro region alone to TrkA, at a site other than that of NGF, caused TrkA and ERK1/2 phosphorylation. Our data show that M‐proNGF stimulates TrkA to a lesser degree than NGF, suggesting that in Alzheimer brain the increased proNGF : NGF and p75NTR : TrkA ratios may permit apoptotic effects to predominate over neurotrophic effects.
Mechanisms of Zn2+ efflux in cultured cortical neurons
Authors: Qin Yan , Thomas Dustin , Fontaine Charles P. , Colvin Robert A. 
Published: September 2008

AbstractZinc dyshomeostasis in brain might be involved in the pathogenesis of brain diseases such as Alzheimer’s disease and stroke. Resting neurons tightly regulate and maintain low to subnanomolar levels of intracellular free Zn2+, but mechanisms of normal Zn2+ homeostasis are poorly understood. In this study, the mechanisms of transporter‐mediated Zn2+ extrusion across the plasma membrane of cultured cortical neurons were studied. Changes in intracellular free Zn2+ levels were tracked in individual neurons by microfluorometry using a Zn2+ selective fluorophore, FluoZin3. Unopposed Zn2+ efflux was measured by first loading cultured cortical neurons with Zn2+ then reducing extracellular Zn2+ to near zero by addition of EDTA. Studies revealed that the primary means of Zn2+ efflux in cortical neurons required both extracellular Na+ and Ca2+. The actions of either Na+ or Ca2+ on Zn2+ efflux were blunted in the absence of the other cation. Reversed Na+ gradients could induce Zn2+ uptake. The Na+ dependence of Zn2+ efflux was not affected by a small pHo shift (7.6–8); whereas an effect of Ca2+ was not observed at pHo 8. In summary, a Na+, Ca2+/Zn2+ exchanger mechanism is proposed to be the primary transport mechanism that extrudes Zn2+ when neuronal intracellular free Zn2+ levels rise.
A Manual of Guidelines to Score the Modified Cumulative Illness Rating Scale and Its Validation in Acute Hospitalized Elderly Patients
Authors: Salvi Fabio , Miller Mark D. , Grilli Annalisa , Giorgi Raffaella , Towers Adele L. , Morichi Valeria , Spazzafumo Liana , Mancinelli Lucia , Espinosa Emma , Rappelli Alessandro , Dessì‐Fulgheri Paolo 
Published: September 2008

OBJECTIVES: To update previous guidelines to score the Cumulative Illness Rating Scale (CIRS) and test their usefulness in hospitalized elderly patients.DESIGN: The CIRS was scored retrospectively in a cohort of elderly patients followed for 18 months.SETTING: An acute internal medicine ward in an academic tertiary care hospital.PARTICIPANTS: Three hundred eighty‐seven patients aged 65 and older.MEASUREMENTS: The CIRS was retrospectively scored for the enrolled patients. Intrarater and interrater reliability were calculated. Two illness severity indices (total score (TSC) and severity (SV)) and one comorbidity index (CM) were obtained. Clinical features and comprehensive geriatric assessment (CGA) variables were also used. All patients underwent an 18‐month follow‐up for mortality and rehospitalization.RESULTS: Intrarater and interrater reliability of the CIRS scored following the guidelines was good (intraclass correlation coefficients of 0.83 and 0.81, respectively). The TSC, SV, and CM correlated with clinical features (laboratory values, medication usage, and length of in‐hospital stay) and CGA variables (cognitive impairment, depression and disability). All three indices were able to predict 18‐month mortality and rehospitalization rates.CONCLUSION: This study confirmed the validity of the CIRS as an indicator of health status and demonstrated its ability to predict 18‐month mortality and rehospitalization in hospitalized elderly patients. The availability of detailed guidelines for scoring the CIRS can improve its usefulness and facilitate more‐widespread use for research and clinical aims.
Fatigue Predicts Mortality in Older Adults
Authors: Hardy Susan E. , Studenski Stephanie A 
Published: September 2008

OBJECTIVES: To determine the association between fatigue and survival over 10 years in a population of older community‐dwelling primary care patients.DESIGN: Prospective cohort study.SETTING: Medicare health maintenance organization and Veterans Affairs primary care programs.PARTICIPANTS: Older primary care patients (N=492).MEASUREMENTS: Fatigue, operationalized as feeling tired most of the time, was assessed at baseline. Mortality was ascertained from the National Death Index. Covariates included demographics, comorbidity, cognitive function, depressive symptoms, body mass index, self‐rated health, functional status, and gait speed.RESULTS: Mortality rates at 10 years were 59% (123/210) for older adults with fatigue, versus 38% (106/282) for those without fatigue (P<.001). After adjustment for multiple potential confounders, participants who were tired at baseline had a greater risk of death than those who were not (hazard ratio=1.44, 95% confidence interval=1.08–1.93).CONCLUSION: A single simple question “Do you feel tired most of the time?” identifies older adults with a higher risk of mortality. Further research is needed to identify and characterize the underlying mechanisms of fatigue, to develop and test specific treatments, and to determine whether improvement leads to decreased morbidity and mortality.
Research Opportunities in Simulation‐based Medical Education Using Deliberate Practice
Authors: McGaghie William C. 
Published: September 2008

AbstractThere are many opportunities for the academic emergency medicine (EM) community to engage in simulation‐based educational research using deliberate practice (DP). This article begins by defining and giving examples of two key concepts: deliberate practice and mastery learning. The article proceeds to report six lessons learned from a research legacy in simulation‐based medical education (SBME). It concludes by listing and amplifying 10 DP research opportunities in academic EM. A coda states that the research agenda is rich and ambitious and should focus on the goal of educating superb, expert clinicians.