bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic and environmental variability of adult size in some stocks of the edible snail, Helix aspersa
Authors: Dupont‐Nivet Mathilde , Guiller Annie , Bonnet Jean‐Claude 
Published: March 2009

This paper aims at providing a better knowledge of factors determining body size (especially the importance of heredity) in Helix aspersa Müller.A preliminary investigation of snails from Maghreb allowed us to show the importance of heredity in the variability of body size and to produce an efficient design for a subsequent reliable estimation of heritabilities. All traits measured (diameter, height and weight) were highly correlated and weight appeared to be the most convenient measure of size.The second experiment provided 4150 snails born from known individuals among 500 wild snails. Pedigrees were recorded. Weight and diameter revealed high heritabilities (>0.4), which is relevant for commercial selection since variability of both traits was important. The design also revealed a significant non‐genetic maternal effect and also that offspring from pairs where only one animal laid were bigger than offspring from pairs where both animals laid. This surprising observation has to be confirmed and its mechanisms studied.
Mortality rates of mammals
Authors: Sibly R. M. , Collett D. , Promislow D. E. L. , Peacock D. J. , Harvey P. H. 
Published: March 2009

Life‐table data of 56 natural populations of mammals were analysed, modelling mortality rate as a three‐phase step function of age (the step model) instead of using the Gompertz model. In the step model, mortality rale is constant in each phase. The phases correspond to juveniles and young and old adults. The age of transition between young and old adults is referred to as the age of senescence. This approach has the advantages that, for the first time, the age of senescence is identified objectively using a robust statistical procedure, and that young adult mortality rates are estimated without bias since no assumption is made about how adult mortality rate changes with age. A further statistical problem solved here that has previously caused difficulty is that of correctly accounting for the different levels of precision in data from different age classes.Significant changes (P < 0.05) in adult mortality rate with age were found in 27 out of 56 populations. In 23 of these 27 cases, adult mortality rate increased with age. Juvenile mortality rate differed significantly from young adult mortality rate in 21 cases; in 18 of these the rate for juveniles was higher. These results are discussed in relation to earlier analyses, in particular that of Promislow (1991).
Correlations of red (Cervus elaphus) and roe (Capreolus capreolus) deer densities in Scottish forests with environmental variables
Authors: Latham J. , Staines B. W. , Gorman M. L. 
Published: March 2009

The relationship between densities of red and roe deer and a range of environmental variables were investigated. The aim was to assess which factor, or combination of factors, was most associated with, and hence potentially responsible for, variations in densities of deer. Twenty plantation forests throughout Scotland were used as study sites and estimates of deer densities within them were based on dung‐group counts. Using ratios of cull records and local information, 10 forests were selected which were expected to give a wide range of deer densities to aid the correlation exercise. The other 10 were selected randomly from within the geographic range of both species and without expectation of density: this allowed deer densities to be used as predictors of each other in the analyses without any bias that selection on the basis of ratio may have introduced. The variables used in analyses included forest habitat structure, climate, vegetation composition, soil type, culling pressure, and the density of other deer species.Red deer densities were positively correlated with mean daily temperature (P<0.05) throughout the year and mean daily snow depth (P<0.05) for October through to March, but negatively correlated with mean daily windspeed (P<0.05) for the quarter April to June. Roe deer density was negatively correlated with mean daily rainfall (P<0.05) throughout the year. Red deer density was negatively correlated (P<0.05) with an index of culling pressure, but roe deer density was uncorrelated with this parameter. The actual influence of culling pressure on red deer population density is unclear. Proportions of structural habitats within forests (defined by tree age classes and growth form) were uncorrelated with deer densities, but were secondary predictors of deer density in regression analyses: red deer density was predicted by the proportion of open‐thicket (trees aged 15‐28 years), and roe deer density by the proportion of restocked areas (0‐8 years) and pre‐thicket (9‐14 years). Stepwise multiple regression analyses suggested that high red deer density has an important negative influence on roe deer density (P<0.05), but that the reverse did not hold.Possible mechanisms by which significantly correlated variables may influence deer densities are discussed. It is suggested that the differential variation of red and roe deer densities across Scotland may be a result of different climatic adaptations and, possibly, an interspecific influence of red deer on roe deer.
Limiting factors might obscure population regulation of moose (Cervidae:Alces alces) in unproductive boreal forests
Authors: Crête Michel , Courtois Réhaume 
Published: March 2009

(1) In the core of the moose range in North America, moose numbers are regulated at a low equilibrium density (∼ 0.4 animal x km‐2) by predation when wolves coexist with a bear species. We hypothesized that top‐down dominance of moose could also occur further north in undisturbed boreal forest where densities generally reach less than 0.1 moose x km‐2.(2) Summer forage production (leaves of shrubs and trees) averaged only 17 kg x ha‐1in our 3090 km2study area, whereas it ranged between 144 and 241 kg x ha‐1in the core of moose range in the Québec‐Labrador peninsula. Annual production of preferred winter forage (twigs of deciduous shrubs and trees) was also very low in the study area, contrary to that of the evergreen balsam fir, whose availability was comparable to that measured in southern ranges.(3) Low forage production in the study area was due to a high proportion of outcrops (17%) and open black spruce stands (20%), and to the old age of most forest stands.(4) Forage had a patchy distribution: production of leaves in the most productive habitat type, deciduous stands, exceeded by 22 times that measured in the coniferous stands. Forage distribution influenced habitat use by moose, which generally showed year‐round preferences for forage‐rich mixed and deciduous stands and resulted in large home ranges.(5) Balsam fir dominated moose diets in late winter, whereas this plant species represented only 17‐19% of forage consumed further south in the moose range. We hypothesized that heavy consumption of balsam fir negatively affected the energy balance of moose in winter.(6) Monitored females produced only 78 calves: 100 cows, during three consecutive years. This relatively low rate of calf production could be related to suboptimal nutrition in winter and in summer. We found a significant relationship between snow depth, summer temperature, and lactation rate, an index to cow:calf ratios in autumn. Lactation rate was more strongly related to weather of the preceding year than that of the current one, suggesting that weather had an immediate influence on body reserves of dams, but little impact on calf production until the next year.(7) Calves experienced high survival, particularly during their first summer of life (90%), in contrast with southern moose populations exposed to higher predation pressure. Annual survival of adult females (87%) exceeded that of males (74%) because the latter were more vulnerable to hunting. Natural mortality was similar in both sexes, 8‐10%. In adults, predation may have been lighter, and other natural mortality causes higher in the study area than in the core of the moose range.(8) Limiting factors. i.e. climate, drowning, played a greater role in the demography of the study moose population than predation, the suspected regulating factor. Our data set illustrates that regulation may be difficult to detect in unproductive environments, a common situation at the periphery of any species distribution.
Early white‐matter abnormalities of the ventral frontostriatal pathway in fragile X syndrome
Authors: HAAS BRIAN W , BARNEA‐GORALY NAAMA , LIGHTBODY AMY A , PATNAIK SWETAPADMA S , HOEFT FUMIKO , HAZLETT HEATHER , PIVEN JOSEPH , REISS ALLAN L 
Published: March 2009

Aim  Fragile X syndrome is associated with cognitive deficits in inhibitory control and with abnormal neuronal morphology and development.Method  In this study, we used a diffusion tensor imaging (DTI) tractography approach to reconstruct white‐matter fibers in the ventral frontostriatal pathway in young males with fragile X syndrome (n=17; mean age 2y 9mo, SD 7mo, range 1y 7mo–3y 10mo), and two age‐matched comparison groups: (1) typically developing (n=13; mean age 2y 3mo, SD 7mo, range 1y 7mo–3y 6mo) and (2) developmentally delayed (n=8; mean age 3y, SD 4mo, range 2y 9mo–3y 8mo).Results  We observed that young males with fragile X syndrome exhibited increased density of DTI reconstructed fibers than those in the typically developing (p=0.001) and developmentally delayed (p=0.001) groups. Aberrant white‐matter structure was localized in the left ventral frontostriatal pathway. Greater relative fiber density was found to be associated with lower IQ (Mullen composite scores) in the typically developing group (p=0.008).Interpretation  These data suggest that diminished or absent fragile X mental retardation 1 protein expression can selectively alter white‐matter anatomy during early brain development and, in particular, neural pathways. The results also point to an early neurobiological marker for an important component of cognitive dysfunction associated with fragile X syndrome.
Brain oxidative stress and selective behaviour of aluminium in specific areas of rat brain: potential effects in a 6‐OHDA‐induced model of Parkinson’s disease
Authors: Sánchez‐Iglesias Sofía , Méndez‐Álvarez Estefanía , Iglesias‐González Javier , Muñoz‐Patiño Ana , Sánchez‐Sellero Inés , Labandeira‐García José Luís , Soto‐Otero Ramón 
Published: March 2009

J. Neurochem. (2009) 109, 879–888.AbstractThe ability of aluminium to affect the oxidant status of specific areas of the brain (cerebellum, ventral midbrain, cortex, hippocampus, striatum) was investigated in rats intraperitoneally treated with aluminium chloride (10 mg Al3+/kg/day) for 10 days. The potential of aluminium to act as an etiological factor in Parkinson’s disease (PD) was assessed by studying its ability to increase oxidative stress in ventral midbrain and striatum and the striatal dopaminergic neurodegeneration induced by 6‐hydroxydopamine in an experimental model of PD. The results showed that aluminium caused an increase in oxidative stress (TBARS, protein carbonyl content, and protein thiol content) for most of the brain regions studied, which was accompanied by a decrease in the activity of some antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase). However, studies in vitro confirmed the inability of aluminium to affect the activity of those enzymes. The reported effects exhibited a regional‐selective behaviour for all the cerebral structures studied. Aluminium also enhanced the ability of 6‐hydroxydopamine to cause oxidative stress and neurodegeneration in the dopaminergic system, which confirms its potential as a risk factor in the development of PD.
RXRA gene variations influence Alzheimer's disease risk and cholesterol metabolism
Authors: Kölsch Heike , Lütjohann Dieter , Jessen Frank , Popp Julius , Hentschel Frank , Kelemen Peter , Friedrichs Silvia , Maier T.A. Wolfgang , Heun Reinhard 
Published: March 2009

AbstractCholesterol metabolism is altered in Alzheimer's disease (AD). The nuclear hormone receptor Retinoic X Receptor a (RXRa) is a member of the nuclear ligand‐activated transcription factor family. RXRs are key regulators of cholesterol synthesis and thus cholesterol metabolism. We performed a systematic screen for gene variants in the RXRA gene. The effect of these gene variants on the risk of AD was investigated in 405 AD patients (mean age: 74.27 ± 9.37 years; female 78.6%) and 347 controls (mean age: 73.26 ± 8.37 years; female 57.2%). Furthermore, the influence of RXRA gene variants on CSF and plasma levels of cholesterol, lathosterol and 24S‐hydroxycholesterol were evaluated. One of the identified seven SNPs in RXRA influenced AD risk in our single marker analysis (rs3132293: P= 0.006). Haplotype analysis identified a three‐marker haplotype (TGC) consisting of rs3118570, rs1536475 and rs3132293, which decreased the risk of AD (P= 0.009). The single marker rs3132293 (P= 0.026) and the TGC haplotype (P= 0.026) influenced CSF lathosterol levels in non‐demented controls, and cholesterol levels in the combined sample comprising AD patients and controls (Rs3132293: P= 0.050; TGC haplotype: P= 0.035). 24S‐Hydroxycholesterol CSF and plasma levels were also influenced by rs3132293 (CSF: P= 0.004; plasma: P= 0.001) and the TGC haplotype (CSF: P= 0.004; plasma: P= 0.002); this effect was most pronounced in AD patients (rs3132293: CSF: P= 0.009, plasma: P= 0.002; TGC haplotype: CSF: P= 0.019, plasma: P= 0.005). Our results suggest that RXRA gene variants might act as risk factor for AD via an influence on cerebral cholesterol metabolism.
Inner retinal ischaemia: current understanding and needs for further investigations
Authors: Bek Toke 
Published: March 2009

Abstract.Inner retinal ischaemia is involved in the pathogenesis of major vision‐threatening diseases such as retinal vein thrombosis, diabetic retinopathy and retinopathy of prematurity. However, the pathogenesis of inner retinal ischaemia has not been fully elucidated, which represents an impediment to the development and improvement of techniques to prevent and treat these diseases on a rational basis. This paper provides a comprehensive review of current knowledge of the pathophysiology of inner retinal ischaemia, including clinical, anatomical and physiological aspects of disease development. It is suggested that chronic inner retinal ischaemia caused by capillary occlusion may develop secondary to an increase in hydrostatic pressure in the vessels. Further knowledge of the pathophysiology of inner retinal ischaemia can be obtained by identifying the mechanisms that lead to increased hydrostatic pressure in the capillary bed and establishing the structural and functional basis for the different response patterns in the central and peripheral areas of the retina that develop secondary to this increased hydrostatic pressure. Further elucidation of these unknown response patterns requires both in vitro and in vivo studies of retinal vascular pathophysiology. It is conceivable that a more detailed knowledge of these response patterns may help in the design of new treatments for retinal ischaemia and its vision‐threatening consequences.
Combination Therapy in Treatment of Experimental Pulmonary Aspergillosis: In Vitro and In Vivo Correlations of the Concentration- and Dose- Dependent Interactions between Anidulafungin and Voriconazole by Bliss Independence Drug Interaction Analysis
Authors: Petraitis Vidmantas , Petraitiene Ruta , Hope William W. , Meletiadis Joseph , Mickiene Diana , Hughes Johanna E. , Cotton Margaret P. , Stergiopoulou Theodouli , Kasai Miki , Francesconi Andrea , Schaufele Robert L. , Sein Tin , Avila Nilo A. , Bacher John , Walsh Thomas J. 
Published: March 2009

ABSTRACTWe studied the antifungal activity of anidulafungin (AFG) in combination with voriconazole (VRC) against experimental invasive pulmonary aspergillosis (IPA) in persistently neutropenic rabbits and further explored the in vitro and in vivo correlations by using Bliss independence drug interaction analysis. Treatment groups consisted of those receiving AFG at 5 (AFG5 group) and 10 (AFG10 group) mg/kg of body weight/day, VRC at 10 mg/kg every 8 h (VRC group), AFG5 plus VRC (AFG5+VRC group), and AFG10 plus VRC (AFG10+VRC group) and untreated controls. Survival throughout the study was 60% for the AFG5+VRC group, 50% for the VRC group, 27% for the AFG10+VRC group, 22% for the AFG5 group, 18% for the AFG10 group, and 0% for control rabbits (P< 0.001). There was a significant reduction of organism-mediated pulmonary injury, measured by infarct scores, lung weights, residual fungal burdens, and galactomannan indexes, in AFG5+VRC-treated rabbits versus those treated with AFG5 and VRC alone (P< 0.05). In comparison, AFG10+VRC significantly lowered only infarct scores and lung weights in comparison to those of AFG10-treated animals (P< 0.05). AFG10+VRC showed no significant difference in other outcome variables. Significant Bliss synergy was found in vivo between AFG5 and VRC, with observed effects being 24 to 30% higher than expected levels if the drugs were acting independently. These synergistic interactions were also found between AFG and VRC in vitro. However, for AFG10+VRC, only independence and antagonism were observed among the outcome variables. We concluded that the combination of AFG with VRC in treatment of experimental IPA in persistently neutropenic rabbits was independent to synergistic at a dosage of 5 mg/kg/day but independent to antagonistic at 10 mg/kg/day, as assessed by Bliss independence analysis, suggesting that higher dosages of an echinocandin may be deleterious to the combination.
Population Pharmacokinetics of Ganciclovir in Solid-Organ Transplant Recipients Receiving Oral Valganciclovir
Authors: Perrottet N. , Csajka C. , Pascual M. , Manuel O. , Lamoth F. , Meylan P. , Aubert J. D. , Venetz J. P. , Soccal P. , Decosterd L. A. , Biollaz J. , Buclin T. 
Published: March 2009

ABSTRACTValganciclovir (VGC) is an oral prodrug of ganciclovir (GCV) recently introduced for prophylaxis and treatment of cytomegalovirus infection. Optimal concentration exposure for effective and safe VGC therapy would require either reproducible VGC absorption and GCV disposition or dosage adjustment based on therapeutic drug monitoring (TDM). We examined GCV population pharmacokinetics in solid organ transplant recipients receiving oral VGC, including the influence of clinical factors, the magnitude of variability, and its impact on efficacy and tolerability. Nonlinear mixed effect model (NONMEM) analysis was performed on plasma samples from 65 transplant recipients under VGC prophylaxis or treatment. A two-compartment model with first-order absorption appropriately described the data. Systemic clearance was markedly influenced by the glomerular filtration rate (GFR), patient gender, and graft type (clearance/GFR = 1.7 in kidney, 0.9 in heart, and 1.2 in lung and liver recipients) with interpatient and interoccasion variabilities of 26 and 12%, respectively. Body weight and sex influenced central volume of distribution (V1= 0.34 liter/kg in males and 0.27 liter/kg in females [20% interpatient variability]). No significant drug interaction was detected. The good prophylactic efficacy and tolerability of VGC precluded the demonstration of any relationship with GCV concentrations. In conclusion, this analysis highlights the importance of thorough adjustment of VGC dosage to renal function and body weight. Considering the good predictability and reproducibility of the GCV profile after treatment with oral VGC, routine TDM does not appear to be clinically indicated in solid-organ transplant recipients. However, GCV plasma measurement may still be helpful in specific clinical situations.
Bone Penetration of Amoxicillin and Clavulanic Acid Evaluated by Population Pharmacokinetics and Monte Carlo Simulation
Authors: Landersdorfer Cornelia B. , Kinzig Martina , Bulitta Jürgen B. , Hennig Friedrich F. , Holzgrabe Ulrike , Sörgel Fritz , Gusinde Johannes 
Published: March 2009

ABSTRACT

Amoxicillin (amoxicilline)-clavulanic acid has promising activity against pathogens that cause bone infections. We present the first evaluation of the bone penetration of a beta-lactam by population pharmacokinetics and pharmacodynamic profiling via Monte Carlo simulations. Twenty uninfected patients undergoing total hip replacement received a single intravenous infusion of 2,000 mg/200 mg amoxicillin-clavulanic acid before surgery. Blood and bone specimens were collected. Bone samples were pulverized under liquid nitrogen with a cryogenic mill, including an internal standard. The drug concentrations in serum and total bone were analyzed by liquid chromatography-tandem mass spectrometry. We used NONMEM and S-ADAPT for population pharmacokinetic analysis and a target time of the non-protein-bound drug concentration above the MIC for ≥50% of the dosing interval for near-maximal bactericidal activity in serum. The median of the ratio of the area under the curve (AUC) for bone/AUC for serum was 20% (10th to 90th percentile for between-subject variability [variability], 16 to 25%) in cortical bone and 18% (variability, 11 to 29%) in cancellous bone for amoxicillin and 15% (variability, 11 to 21%) in cortical bone and 10% (variability, 5.1 to 21%) in cancellous bone for clavulanic acid. Analysis in S-ADAPT yielded similar results. The equilibration half-lives between serum and bone were 12 min for amoxicillin and 14 min for clavulanic acid. For a 30-min infusion of 2,000 mg/200 mg amoxicillin-clavulanic acid every 4 h, amoxicillin achieved robust (≥90%) probabilities of target attainment (PTAs) for MICs of ≤12 mg/liter in serum and 2 to 3 mg/liter in bone and population PTAs above 95% against methicillin-susceptible
Staphylococcus aureus
in bone and serum. The AUC of amoxicillin-clavulanic acid was 5 to 10 times lower in bone than in serum, and amoxicillin-clavulanic acid achieved a rapid equilibrium and favorable population PTAs against pathogens commonly encountered in bone infections.