bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential regulation of Toll‐like receptor signalling in spleen and Peyer’s patch dendritic cells
Authors: Davies Julie M. , MacSharry John , Shanahan Fergus
Published: June 2010

Toll‐like receptor (TLR) signalling shapes dendritic cell (DC) responses by inducing co‐stimulatory molecule up‐regulation and cytokine secretion while TLR regulatory proteins inhibit this process. We aimed to determine if gene expression of TLRs and TLR regulatory proteins underpins the functionally different lipopolysaccharide (LPS) responses of DCs from murine Peyer’s patches (PP) and spleen and of murine bacteria‐conditioned bone‐marrow‐derived cells. Isolated spleen and PP DCs were analysed for basal expression of TLRs by flow cytometry and real time quantitative reverse transcription polymerase chain reaction (qRT‐PCR). The DCs were stimulated with LPS to determine cytokine secretion by enzyme‐linked immunosorbent assay and expression of TLR regulatory proteins by qRT‐PCR. In vitro results were confirmed following in vivo intraperitoneal LPS injection. In addition, changes in gene expression of TLR regulatory proteins were assessed in bacteria‐conditioned bone‐marrow‐derived cells. Results indicated that surface expression of TLR2 and TLR4 on PP DCs was decreased compared with spleen DCs. The PP DCs secreted a limited profile of cytokines compared with spleen DCs following LPS stimulation. In vivo LPS exposure up‐regulated sigirr, tollip and tmed1 messenger RNA in PP DCs, but not spleen DCs. Similar gene expression changes were observed in bacteria‐conditioned bone‐marrow‐derived cells. Therefore, functionally different LPS responses in PP and spleen DCs reflect their characteristic expression of TLRs and TLR regulatory proteins. Differential regulation of TLR signalling was also evident in bacteria‐conditioned bone‐marrow‐derived cells indicating that bacterial signalling may be a mechanism for inducing altered gene regulation in PP DCs.
Gqα‐linked phospholipase Cβ1 and phospholipase Cγ are essential components of the pheromone biosynthesis activating neuropeptide (PBAN) signal transduction cascade
Authors: Hull J. J. , Lee J. M. , Matsumoto S.
Published: June 2010

Sex pheromone production for most moths is regulated by pheromone biosynthesis activating neuropeptide (PBAN). In Bombyx mori, PBAN binding triggers the opening of store‐operated Ca2+ channels, suggesting the involvement of a receptor‐activated phospholipase C (PLC). In this study, we found that PLC inhibitors U73122 and compound 48/80 reduced sex pheromone production and that intracellular levels of 3H‐inositol phosphate species increased following PBAN stimulation. In addition, we amplified cDNAs from pheromone glands corresponding to PLCβ1, PLCβ4, PLCγ and two G protein α subunits, Go and Gq. In vivo RNA interference‐mediated knockdown analyses revealed that BmPLCβ1, BmGq1, and unexpectedly, BmPLCγ, are part of the PBAN signal transduction cascade.
Determinants of partial bird migration in the Amazon Basin
Authors: Jahn Alex E. , Levey Douglas J. , Hostetler Jeffrey A. , Mamani Ana María
Published: June 2010

1. Little is known about mechanisms that drive migration of birds at tropical latitudes. Because most migratory bird species in South America have populations that are present year‐round, partial migration (in which only some individuals of a given population migrate at the end of the breeding season) is likely to be common, providing an opportunity to assess proximate mechanisms of migration.

2. Two non‐mutually exclusive hypotheses explaining intraspecific variation in migratory behaviour were tested in a Tropical Kingbird Tyrannus melancholicus population in the southern Amazon Basin, where a dramatic dry season decrease in the abundance of insect food for kingbirds may promote migration of some individuals.

3. The Dominance hypothesis predicts sub‐dominant individuals migrate at the end of the breeding season and dominant individuals do not, whereas the Body Size hypothesis predicts smaller individuals migrate and larger individuals do not.

4. Based on 4 years of data on individually‐marked birds, strong support was found for occurrence of partial migration in the study population.

5. In the best model, the largest males (which are typically older and dominant to younger individuals) had the highest probability of migrating. Younger females (which are the smallest individuals in the population) were also more likely to migrate than other kingbirds, except the largest males. Thus, an individual’s probability of migrating was associated with a more complex interaction of size, age and sex than predicted by current hypotheses.

6. These results suggest that determinants of migratory behaviour differ between North temperate and tropical latitudes. Most tests of partial migration theory have been conducted on granivores (e.g. emberizids) or omnivores (e.g. turdids and icterids) at North temperate latitudes, where seasonality is primarily defined by temperature cycles. In tropical South America, however, the most common long‐distance migrants are primarily insectivorous (i.e. tyrannids), and seasonality is largely defined by rainfall cycles.

7. We propose a hypothesis based on seasonal food limitation to explain partial migration of primarily insectivorous species in seasonal tropical habitats.
Sanitary versus environmental policies: fitting together two pieces of the puzzle of European vulture conservation
Authors: Margalida Antoni , Donázar José A. , Carrete Martina , Sánchez‐Zapata José A.
Published: June 2010

1. Between 1996 and 2000 the appearance of bovine spongiform encephalopathy swiftly became one of the most serious public health and political crises concerning food safety ever experienced in the European Union (EU). Subsequent sanitary regulations led to profound changes in the management of livestock carcasses (i.e. the industrial destruction of around 80% of all animal carcasses), thereby threatening the last remaining healthy scavenger populations of the Old World and thus contradicting the long‐term environmental policies of the EU.

2. Several warning signs such as a decrease in breeding success, an apparent increase in mortality in young age classes of vultures and an increase in the number of cases of vultures attacking and killing cattle, as well as a halt in population growth, suggest that the decrease in the availability of food resources has had harmful effects on vulture populations.

3. Between 2002 and 2005, a number of dispositions to the EU regulations (2003/322/CE 2005/830/CE) enabled conservation managers to adopt rapid solutions (i.e. the creation of vulture restaurants) aimed at satisfying the food requirements of vultures. However, these conservation measures may seriously modify habitat quality and have indirect detrimental effects on avian scavenger populations and communities.

4. Synthesis and applications. Conservation managers and policy‐makers need to balance the demands of public health protection and the long‐term conservation of biodiversity. The regulations concerning carrion provisioning need to be more flexible and there needs to be greater compatibility between sanitary and environmental policies. We advocate policies that authorize the abandonment of livestock carcasses and favours populations of wild herbivores to help to maintain populations of avian scavengers. Conservation strategies should be incorporated into new European Commission regulations, which should be effective in 2011.
Management of bovine tuberculosis in brushtail possums in New Zealand: predictions from a spatially explicit, individual‐based model
Authors: Ramsey David S. L. , Efford Murray G.
Published: June 2010

1. Bovine tuberculosis Mycobacterium bovis (Tb) in brushtail possums Trichosurus vulpecula in New Zealand continues to pose a threat to the livestock industry. While significant reductions in cattle reactor rates have been achieved by widespread possum control, there is still a need for significant improvement, particularly in relation to limiting the further spread of the disease.

2. A recently developed oral Tb vaccine based on bacille Calmette–Guérin (BCG) offers a possible alternative to poison baiting for widespread disease control in possums. In addition, there is ongoing development of orally delivered fertility control vaccines (FC) as an alternative method for possum control. However, there is some doubt about whether control strategies based on oral BCG or FC can offer cost‐effective solutions for disease control in possums.

3. We developed a spatially explicit, individual‐based model (IBM) of Tb in possums to address perceived shortcomings in existing non‐spatial models, particularly their failure to model realistically the spatial scale of transmission. The spatial IBM was also used to compare the cost‐effectiveness of control strategies using BCG and combined BCG/FC to existing strategies based on lethal control. In particular, we explored the effectiveness of strategies to contain a localized outbreak.

4. Considering the cumulative cost of control to contain a localized Tb outbreak, the most cost‐effective strategy combined an initial cull of possums with both BCG and FC applied every 3 years. In addition, the combined culling/BCG/FC strategy required only a 2‐ to 3‐km control buffer around the outbreak site to achieve successful containment. By comparison, control strategies that used BCG or BCG/FC alone were not as cost‐effective as they required at least a 5‐km buffer around the outbreak site to achieve containment.

5. Synthesis and applications. Current strategies for Tb control in possums rely heavily on lethal control techniques, but there is public antipathy in New Zealand to the widespread use of toxicants for pest control. Strategies for Tb control that use oral vaccination of possums with BCG, or combined BCG/FC, in combination with a single initial cull of the population offer a cost‐effective alternative for local eradication and containing disease spread. Such strategies would greatly reduce the need for repeated application of toxicants.
Exploring temperament and character traits in nurses and nursing students in a large regional area of Australia
Authors: Eley Diann , Eley Rob , Young Louise , Rogers‐Clark Cath
Published: June 2010

Aims and objectives. To describe individual temperament and character trait profiles associated with nurses and nursing students in a large regional health district and university in Australia.

Background. Identification of personality characteristics have been undertaken in most professions; however there is little extant literature on nurses which looks at specific aspects of temperament and character.

Design. A cross‐sectional quantitative study of nurses and nursing students in a large regional health service district and university in South East Queensland, Australia.

Method. An online survey to nurses and nursing students included a demographic questionnaire and the temperament and character inventory (TCI) to identify levels of the seven basic dimensions of temperament and character. Univariate analysis made multiple and covariate comparisons between TCI scores, nurses, students, working status and age.

Results. The target number of responses was exceeded and totalled 451. Results are reported for females who comprised 90% of respondents; 53·5% students and 46·5% nurses. Significant main effects for age and student status were detected in several temperament and character inventory dimensions. Working students had significantly different temperament and character profiles compared to non‐working students.

Conclusions. Overall, this sample displays levels of temperament and character traits congruent with a profession requiring high levels of persistence, self‐directedness, cooperativeness and reward dependence. Our findings prompt further investigation of whether individuals with the requisite temperament traits are attracted to nursing, or do individuals develop certain character traits as a product of their professional experiences/training.

Relevance to clinical practice. The identification of distinct profiles of temperament and character traits among different nursing roles may provide insight into what traits are conducive to retention of nurses in these roles. The predictive potential of the temperament traits plus the modifiable component of character traits may provide scope for nursing educators and policy‐makers to assist in recruitment and retention of nurses in the workforce.
An integrative literature review of interventions to reduce violence against emergency department nurses
Authors: Anderson Linda , FitzGerald Mary , Luck Lauretta
Published: June 2010

Aim. To critique the evidence that underpins interventions intended to minimise workplace violence directed against emergency department nurses, to inform researchers and policy makers regarding the design, development, implementation and evaluation of emergency nursing anti‐violence and counter‐violence interventions.

Background. Workplace violence perpetrated against emergency department nurses is at least continuing and at worst increasing. Occupational violence has detrimental effects on job satisfaction, retention and recruitment, and the quality and cost of patient care.

Design. An integrated literature review.

Method. Searches of the Cochrane Library, CINAHL, MEDLINE and the Joanna Briggs Institute between 1986–May 2007. Included articles were appraised and then synthesised into a narrative summary.

Results. Ten primary research studies were included. Interventions were classified as environmental, practices and policies, or skills. While each study has useful information regarding the implementation of interventions, there is no strong evidence for their efficacy.

Conclusions. The weight of effort is still directed towards defining the phenomenon rather than addressing solutions. Studies that assessed the efficacy of a single intervention failed to take account of context; and participatory context‐driven studies failed to provide generalisable evidence. Concerted multi‐site and multi‐disciplinary, action‐oriented research studies are urgently needed to provide an evidence base for the prevention and mitigation of violence perpetrated against emergency department nurses.

Relevance to clinical practice. The investigation of interventions rather than repeatedly redefining the problem and directing resources into debating semantics or differentiating ‘degrees’ of violence and aggression is recommended. This review unambiguously identifies the gap in research‐based interventions.
Understanding patient satisfaction with family doctor care
Authors: Marcinowicz Ludmila , Chlabicz Slawomir , Grebowski Ryszard
Published: June 2010

Rationale, aims and objectives  Patient satisfaction is receiving increased attention in the evaluation of health care quality. However, qualitative methods have seldom been used to study patient satisfaction. The purpose of this study was to explore how satisfaction is understood from the perspective of patients receiving care from family doctors.

Method  We used a qualitative approach consisting of in‐depth interviews with 36 patients attending clinics in Poland. Interviews were audiotaped and transcribed, and content analysis performed.

Results  There was no single definition of satisfaction among study participants; however, some core characteristics of satisfaction emerged. These characteristics were: (1) good doctor–patient interaction; (2) health improvement or resolution of health problems; (3) fulfilment of prior expectations; (4) availability of health care; (5) combination of multiple characteristics; and (6) absence of dissatisfaction.

Conclusion  Because patients have differing concepts of satisfaction with health care provided by family doctors, quality assessments should focus on components of satisfaction whereas questions about satisfaction itself should be avoided.
Reporting cancer patients' experiences of care for quality improvement: analysis of 2000 and 2004 survey results for South East England
Authors: Madden Peter B. , Davies Elizabeth A.
Published: June 2010

Background  National surveys of patients' experiences of English cancer services found improvements between 2000 and 2004, particularly in the areas of information, communication and trust in professionals.

Objectives  We assessed the potential such surveys might have to stimulate service improvements by comparing their inclusion criteria, sampling and timing and by investigating how representative they were of patients registered with cancer in South East England. Where hospital trusts had data from 50 patients with the same cancer, we determined whether national improvements in six key areas held at hospital trust level.

Design  Data were extracted from the two national surveys and from the Thames Cancer Registry.

Results  The 2000 survey achieved a higher response rate, included a larger number of hospital trusts, and a wider range of cancer sites, but a lower proportion with lung cancer. Each survey sampled patients at different points following diagnosis, with a year elapsing between data collection and reporting. Compared with cancer registry data, breast cancer patients appeared most well‐represented. Only three hospital trusts had sufficiently large samples to allow comparison over time. We found no change in experience in three of the key areas, but a significant decline from previously high scores in two.

Conclusion  To provide information useful for quality improvement future surveys will need to sample larger numbers of patients from most hospital trusts, including patients with less common cancers or receiving palliative care. Surveys should also sample patients at a consistent time after diagnosis and feedback results more rapidly to services.
Osteoporosis risk assessment and management in primary care: focus on quantity and quality
Authors: Blazkova Sarka , Vytrisalova Magda , Palicka Vladimir , Stepan Jan , Byma Svatopluk , Kubena Ales A. , Hala Tomas , Vlcek Jiri
Published: June 2010

Introduction and hypothesis  Early identification of high‐risk patients by general practitioners (GPs) plays the key role in the management of osteoporosis (OP).

Methods  We conducted a postal questionnaire survey among 1500 Czech GPs to examine their behaviour related to OP.

Results  The overall questionnaire return rate was 38%. The respondents (mean age 52 years; 61.5% women) did not differ from non‐respondents. OP knowledge correlated negatively with age (P < 0.001). The most common reason for both suspicion of OP and referral for suspected OP is the patient's complaints. When the initial skeletal examination for suspected OP is conducted on the GP's initiative, it is most often X‐ray (76%) followed by osteodensitometry (61%). The respondents address five patients (median) per month about this issue. The number of referrals to a specialist for suspected OP during the last quarter was 5 (median). The most commonly reported barriers to OP management were financial limits set by the health insurance agency (71%) and lack of authorization to prescribe selected drugs (71%).

Conclusions  The GPs should pay greater attention to risk factors and be more active in the detection of at‐risk patients. It is necessary to motivate the GPs and to overcome the barriers to effective clinical practice.
Hematologic improvement in dogs with parvovirus infection treated with recombinant canine granulocyte‐colony stimulating factor
Authors: DUFFY A. , DOW S. , OGILVIE G. , RAO S. , HACKETT T.
Published: June 2010

Duffy A., Dow S., Ogilvie G., Rao S., Hackett T. Hematologic improvement in dogs with parvovirus infection treated with recombinant canine granulocyte‐colony stimulating factor.J. vet. Pharmacol. Therap.doi: 10.1111/j.1365‐2885.2009.01153.x.

Previously, dogs with canine parvovirus‐induced neutropenia have not responded to treatment with recombinant human granulocyte‐colony stimulating factor (rhG‐CSF). However, recombinant canine G‐CSF (rcG‐CSF) has not been previously evaluated for treatment of parvovirus‐induced neutropenia in dogs. We assessed the effectiveness of rcG‐CSF in dogs with parvovirus‐induced neutropenia with a prospective, open‐label, nonrandomized clinical trial. Endpoints of our study were time to recovery of WBC and neutrophil counts, and duration of hospitalization. 28 dogs with parvovirus and neutropenia were treated with rcG‐CSF and outcomes were compared to those of 34 dogs with parvovirus and neutropenia not treated with rcG‐CSF. We found that mean WBC and neutrophil counts were significantly higher (P < 0.05) in the 28 dogs treated with rcG‐CSF compared to disease‐matched dogs not treated with rcG‐CSF. In addition, the mean duration of hospitalization was reduced (P = 0.01) in rcG‐CSF treated dogs compared to untreated dogs. However, survival times were decreased in dogs treated with rcG‐CSF compared to untreated dogs. These results suggest that treatment with rcG‐CSF was effective in stimulating neutrophil recovery and shortening the duration of hospitalization in dogs with parvovirus infection, but indicate the need for additional studies to evaluate overall safety of the treatment.
Pharmacokinetics and tissue depletion of florfenicol in Leghorn and Taiwan Native chickens
Authors: CHANG S. K. , DAVIS J. L. , CHENG C. N. , SHIEN R. H. , HSIEH M. K. , KOH B. W. , CHOU C. C.
Published: June 2010

Chang, S. K., Davis, J. L., Cheng, C. N., Shien, R. H., Hsieh, M. K., Koh, B. W., Chou, C. C. Pharmacokinetics and tissue depletion of florfenicol in Leghorn and Taiwan Native chickens.J. vet. Pharmacol. Therap.33, 471–479.

Florfenicol (Ff) is a synthetic antibiotic with a broad antibacterial spectrum and high therapeutic effectiveness that was specifically developed for veterinary use. In the present study, tissue residual levels and the pharmacokinetics of Ff after oral administration of 30 mg/kg to Leghorn and Taiwan Native chicken were studied. Furthermore, differential pharmacokinetics between leg and breast muscles were compared using samples collected from an optimized microdialysis model designed for avian species. Significant differences inCmaxwere detected between the plasma and muscle microdialysates, and between the breast and leg microdialysates of the Leghorn chickens by noncompartmental pharmacokinetic analysis. After a single oral dose of Ff at 30 mg/kg, the drug was quickly absorbed and widely distributed with tissue penetration factors significantly different between leg and breast muscles. The serum protein binding of Ff was estimated to be 16.8 ± 1.2%. Significant breed differences in tissue depletion were noted and characterized by higher Ff concentration in the brain, lung, kidney and at least 12 h longer resident times in kidney, heart and spleen for Taiwan Native chicken. Results from this investigation demonstrate the practicality of usingin vivomicrodialysis in chickens for pharmacokinetic studies and reveal significant time‐dependent differences in the free concentrations of Ff in leg and breast muscles. The tissue depletion study signified breed differences in tissue residue concentration and detection times between Leghorn and Taiwan Native chickens. Therefore, currently used withdrawal times for Ff in chickens can not be assumed safe for Taiwan Native chickens.
Excretion mass balance evaluation, metabolite profile analysis and metabolite identification in plasma and excreta after oral administration of [14C]‐meloxicam to the male cat: preliminary study
Authors: GRUDE P. , GUITTARD J. , GARCIA C. , DAOULAS I. , THOULON F. , EBNER T.
Published: June 2010

Grudé, P., Guittard, J., Garcia, C., Daoulas, I., Thoulon, F., Ebner, T. Excretion mass balance evaluation, metabolite profile analysis and metabolite identification in plasma and excreta after oral administration of [14C]‐meloxicam to the male cat: preliminary study.J. vet. Pharmacol. Therap.doi: 10.1111/j.1365‐2885.2010.01157.x.

The objective of this study was to investigate the metabolic pathways and routes of excretion of oral meloxicam in the cat. [14C]‐meloxicam was administered orally to three fasted male cats. Urine, faeces, vomit and cage washes were collected over the following 144 h period. Blood was collected predosing and at 3 and 12 h postdosing. Metabolites were identified by HPLC/MS/MS. When possible a metabolic structure was proposed for each metabolite detected. Only unchanged meloxicam was identified in plasma. Five major metabolites were detected in urine and four in faeces, which were identified by HPLC/MS/MS as products of oxidative metabolism. No conjugated metabolites were detected. Elimination occurred early (61% during the first 48 h). A total of 21% of the recovered dose was eliminated in urine (2% as unchanged meloxicam, 19% as metabolites) and 79% in the faeces (49% as unchanged meloxicam, 30% as metabolites). The results indicate that after oral administration the major route of excretion of meloxicam in the cat is faecal and that the main pathway of biotransformation of meloxicam in the cat is oxidation.
Pharmacokinetics of ketamine in plasma and milk of mature Holstein cows
Authors: SELLERS G. , LIN H. C. , RIDDELL M. G. , RAVIS W. R. , LIN Y. J. , DURAN S. H. , GIVENS M. D.
Published: June 2010

Sellers, G., Lin, H. C., G. Riddell, M. G., Ravis, W. R., Lin, Y. J., Duran, S. H., Givens, M.D. Pharmacokinetics of ketamine in plasma and milk of mature Holstein cows.J. vet. Pharmacol. Therap.33, 480–484.

The purpose of this study was to evaluate the pharmacokinetics of ketamine in mature Holstein cows following administration of a single intravenous (i.v.) dose. Plasma and milk concentrations were determined using a high‐performance liquid chromatography assay. Pharmacokinetic parameters were estimated using a noncompartmental method. Following i.v. administration, plasmaTmaxwas 0.083 h and plasmaCmaxwas 18 135 ± 22 720 ng/mL. PlasmaAUCwas 4484 ± 1,398 ng·h/mL. Plasmat½βwas 1.80 ± 0.50 h and mean residence time was 0.794 ± 0.318 h with total body clearance of 1.29 ± 0.70 L/h/kg. The mean plasma steady‐state volume of distribution was calculated as 0.990 ± 0.530 L/kg and volume of distribution based on area was calculated as 3.23 ± 1.51 L/kg. The last measurable time for ketamine detection in plasma was 8.0 h with a mean concentration of 24.9 ± 11.8 ng/mL. MilkTmaxwas detected at 0.67 ± 0.26 h withCmaxof 2495 ± 904 ng/mL. MilkAUCtill the last time was 6593 ± 2617 ng·h/mL with meanAUCmilk toAUCplasma ratio of 1.99 ± 2.15. The last measurable time that ketamine was detected in milk was 44 ± 10.0 h with a mean concentration of 16.0 ± 9.0 ng/mL.
Insect nicotinic acetylcholine receptor agonists as flea adulticides in small animals
Authors: VO D. T. , HSU W H. , ABU‐BASHA E. A. , MARTIN R. J.
Published: June 2010

Vo, D. T., Hsu, W. H., Abu‐Basha, E. A., Martin, R. J. Insect nicotinic acetylcholine receptor agonists as flea adulticides in small animals.J. vet. Pharmacol. Therap.doi: 10.1111/j.1365‐2885.2010.01160.x.

Fleas are significant ectoparasites of small animals. They can be a severe irritant to animals and serve as a vector for a number of infectious diseases. In this article, we discuss the pharmacological characteristics of four insect nicotinic acetylcholine receptor (nAChR) agonists used as flea adulticides in dogs and cats, which include three neonicotinoids (imidacloprid, nitenpyram, and dinotefuran) and a macrocyclic lactone (spinosad). Insect nAChR agonists are one of the most important classes of insecticides, which are used to control sucking insects on both plants and animals. These novel compounds provide a new approach for practitioners to safely and effectively eliminate adult fleas.
Pharmacokinetic profile and behavioral effects of gabapentin in the horse
Authors: TERRY R. L. , McDONNELL S. M. , Van EPS A. W. , SOMA L. R. , LIU Y. , UBOH C. E. , MOATE P. J. , DRIESSEN B.
Published: June 2010

Terry, R. L., McDonnell, S. M., van Eps, A. W., Soma, L. R., Liu, Y., Uboh, C. E., Moate, P. J., Driessen, B. Pharmacokinetic profile and behavioral effects of gabapentin in the horse.J. vet. Pharmacol. Therap.33, 485–494.

Gabapentin is being used in horses although its pharmacokinetic (PK) profile, pharmacodynamic (PD) effects and safety in the equine are not fully investigated. Therefore, we characterized PKs and cardiovascular and behavioral effects of gabapentin in horses. Gabapentin (20 mg/kg) was administered i.v. or p.o. to six horses using a randomized crossover design. Plasma gabapentin concentrations were measured in samples collected 0–48 h postadministration employing liquid chromatography‐tandem mass spectrometry. Blood pressures, ECG, and sedation scores were recorded before and for 12 h after gabapentin dosage. Nineteen quantitative measures of behaviors were evaluated. After i.v. gabapentin, the decline in plasma drug concentration over time was best described by a 3‐compartment mammillary model. Terminal elimination half‐life (t1/2γ) was 8.5 (7.1–13.3) h. After p.o. gabapentin terminal elimination half‐life () was 7.7 (6.7–11.9) h. The mean oral bioavailability of gabapentin (±SD) was 16.2 ± 2.8% indicating relatively poor absorption of gabapentin following oral administration in horses. Gabapentin caused a significant increase in sedation scores for 1 h after i.v. dose only (P < 0.05). Among behaviors, drinking frequency was greater and standing rest duration was lower with i.v. gabapentin (P < 0.05). Horses tolerated both i.v. and p.o. gabapentin doses well. There were no significant differences inand. Oral administration yielded much lower plasma concentrations because of low bioavailability.
In vitroandex vivoinhibition of COX isoforms by robenacoxib in the cat: a comparative study
Authors: SCHMID V.B. , SEEWALD W. , LEES P. , KING J.N.
Published: June 2010

Schmid, V.B., Seewald, W., Lees, P., King, J.N.In vitroandex vivoinhibition of COX isoforms by robenacoxib in the cat: a comparative study.J. vet. Pharmacol. Therap.33, 444–452.

Robenacoxib is a novel nonsteroidal anti‐inflammatory drug (NSAID) developed for use in companion animals. Whole blood assays were used to characterize in the cat the pharmacodynamics of robenacoxib for inhibition of the cyclooxygenase (COX) isoforms, COX‐1 and COX‐2, in comparison with other NSAIDs. Based onin vitroIC50COX‐1:IC50COX‐2 ratios, robenacoxib was COX‐2 selective (ratio = 32.2), diclofenac (ratio = 3.9) and meloxicam (ratio = 2.7) were only weakly COX‐2 preferential, and ketoprofen (ratio = 0.049) was COX‐1 selective. In anin vivopharmacokineticex vivopharmacodynamic study, after both p.o. (1–2 mg/kg) and subcutaneous (2 mg/kg) dosing, robenacoxib achieved peak blood concentrations rapidly (Tmax = 1 h for both administration routes) and was cleared from blood relatively rapidly (mean residence time was 1.70 h after p.o. and 1.79 h after subcutaneous dosing). Inex vivoCOX isoform inhibition assays, orally (1–2 mg/kg) or subcutaneously (2 mg/kg) administered robenacoxib significantly inhibited COX‐2, with a relatively short duration of action in the central compartment, and had no effect on COX‐1. Therefore robenacoxib was COX‐2 selective and spared COX‐1in vivo. In contrast, meloxicam (0.3 mg/kg via subcutaneous injection) inhibited both COX‐1 and COX‐2 isoforms significantly for at least 24 h, indicating nonselectivityin vivo.
Mycobacterium tuberculosis CYP125A1, a steroid C27 monooxygenase that detoxifies intracellularly generated cholest‐4‐en‐3‐one
Authors: Ouellet Hugues , Guan Shenheng , Johnston Jonathan B. , Chow Eric D. , Kells Petrea M. , Burlingame Alma L. , Cox Jeffery S. , Podust Larissa M. , De Montellano Paul R. Ortiz
Published: June 2010

The infectivity and persistence of Mycobacterium tuberculosis requires the utilization of host cell cholesterol. We have examined the specific role of cytochrome P450 CYP125A1 in the cholesterol degradation pathway using genetic, biochemical and high‐resolution mass spectrometric approaches. The analysis of lipid profiles from cells grown on cholesterol revealed that CYP125A1 is required to incorporate the cholesterol side‐chain carbon atoms into cellular lipids, as evidenced by an increase in the mass of the methyl‐branched phthiocerol dimycocerosates. We observed that cholesterol‐exposed cells lacking CYP125A1 accumulate cholest‐4‐en‐3‐one, suggesting that this is a physiological substrate for this enzyme. Reconstitution of enzymatic activity with spinach ferredoxin and ferredoxin reductase revealed that recombinant CYP125A1 indeed binds both cholest‐4‐en‐3‐one and cholesterol, efficiently hydroxylates both of them at C‐27, and then further oxidizes 27‐hydroxycholest‐4‐en‐3‐one to cholest‐4‐en‐3‐one‐27‐oic acid. We determined the X‐ray structure of cholest‐4‐en‐3‐one‐bound CYP125A1 at a resolution of 1.58 Å. CYP125A1 is essential for growth of CDC1551 in media containing cholesterol or cholest‐4‐en‐3‐one. In its absence, the latter compound is toxic for both CDC1551 and H37Rv when added with glycerol as a second carbon source. CYP125A1 is a key enzyme in cholesterol metabolism and plays a crucial role in circumventing the deleterious effect of cholest‐4‐en‐3‐one.
LapF, the second largest Pseudomonas putida protein, contributes to plant root colonization and determines biofilm architecture
Authors: Martínez‐Gil Marta , Yousef‐Coronado Fátima , Espinosa‐Urgel Manuel
Published: June 2010

We have investigated the role of LapF, one of the two largest proteins encoded in the genome of Pseudomonas putida KT2440, in bacterial colonization of solid surfaces. LapF is 6310 amino acids long, and is localized on the cell surface. The C‐terminal region of the protein is essential for its secretion, which presumably requires the ABC transporter encoded by an operon (lapHIJ) adjacent to the lapF gene. Although the initial attachment stages are not different between the wild type and a lapF mutant, microcolony formation and subsequent development of a mature biofilm is impaired in the mutant. This is consistent with the expression pattern of lapF; activation of its promoter takes place at late stages of growth and is regulated by the alternative sigma factor RpoS. A lapF mutant is also affected in individual and competitive plant root colonization. In these assays, mixed microcolonies formed by cells of both the wild‐type and the mutant strains could be observed but microcolonies of the mutant alone were not found. These data and the localization of the protein at discrete spots in areas of contact between cells in biofilms suggest that LapF determines the establishment of cell–cell interactions during sessile growth.
A cyanobacterial serine protease of Plasmodium falciparum is targeted to the apicoplast and plays an important role in its growth and development
Authors: Rathore Sumit , Sinha Dipto , Asad Mohd , Böttcher Thomas , Afrin Farhat , Chauhan Virander S. , Gupta Dinesh , Sieber Stephan A. , Mohmmed Asif
Published: June 2010

The prokaryotic ATP‐dependent protease machineries such as ClpQY and ClpAP in the malaria parasite may represent potential drug targets. In the present study, we show that the orthologue of cyanobacterial ClpP protease in Plasmodium falciparum (PfClpP) is expressed in the asexual blood stages and possesses serine protease activity. The PfClpP was localized in the apicoplast using a GFP‐targeting approach, immunoelectron microscopy and by immunofluorescence assays. A set of cell permeable β‐lactones, which specifically bind with the active site of prokaryotic ClpP, were screened using an in vitro protease assay of PfClpP. A PfClpP‐specific protease inhibitor was identified in the screen, labelled as U1‐lactone. In vitro growth of the asexual stage parasites was significantly inhibited by U1‐lactone treatment. The U1‐treated parasites showed developmental arrest at the late‐schizont stage. We further show that the U1‐lactone treatment resulted in formation of abnormal apicoplasts which were not able to grow and segregate in the parasite progeny; these effects were also evident by blockage in the replication of the apicoplast genome. Overall, our data show that the PfClpP protease has confirmed localization in the apicoplast and it plays important role in development of functional apicoplasts.
MUTYH‐associated polyposis – variability of the clinical phenotype in patients with biallelic and monoallelic MUTYH mutations and report on novel mutations
Authors: Morak M , Laner A , Bacher U , Keiling C , Holinski‐Feder E
Published: June 2010

Morak M, Laner A, Bacher U, Keiling C, Holinski‐Feder E. MUTYH‐associated polyposis – variability of the clinical phenotype in patients with biallelic and monoallelic MUTYH mutations and report on novel mutations.

To further characterize 215 APC mutation‐negative patients with colorectal neoplasias classified in classical, attenuated, or atypical familial adenomatous polyposis (FAP) coli we performed mutation screening in the Mut Y homologue (MUTYH) gene.

The incidence was 15% for biallelic and 3.7% for monoallelic MUTYH mutations. We describe six novel MUTYH mutations in biallelic constellation and two novel monoallelic missense mutations.

Of 33 MUTYH‐associated polyposis coli (MAP) patients 57% were attenuated familial adenomatous polyposis (AFAP) patients, 10% display early‐onset classical FAP and 18% had only few adenomas at higher age. Biallelic cases had a high incidence of extracolonic polyposis in 32% and colorectal cancer (CRC) in 33% of the cases.

The clinical picture of MAP ranged from classical FAP or synchronous CRC at age 30 years to few adenomas at age 54 years without evidence of CRC, initially suspected for hereditary non‐polyposis colorectal cancer (HNPCC). The mean age of onset was 43 years, with 11 (33%) patients being younger than 40 years of age, indicating that the clinical manifestation can be earlier than so far reported. Monoallelic MUTYH mutation carriers had a positive family history in seven of eight cases allowing the hypothesis of a disease‐causing synergism of MUTYH mutations with other genes.
Reproductive decision‐making: a qualitative study among couples at increased risk of having a child with retinoblastoma
Authors: Dommering CJ , Van Den Heuvel MR , Moll AC , Imhof SM , Meijers‐Heijboer H , Henneman L
Published: June 2010

Dommering CJ, van den Heuvel MR, Moll AC, Imhof SM, Meijers‐Heijboer H, Henneman L. Reproductive decision‐making: a qualitative study among couples at increased risk of having a child with retinoblastoma.

Little is known about the reproductive decision‐making process of couples with an increased risk of having a child with retinoblastoma (Rb). A qualitative study was conducted to explore the impact of prospective risk on reproductive decisions, factors influencing these decisions, and the needs of couples with regard to reproductive counselling. Fourteen couples of childbearing age who received genetic counselling between 2002 and 2006 participated in semi‐structured interviews in 2008. The risk of having a child with Rb ranged from less than 1% to 50%. In most cases, the diagnosis of Rb influenced subsequent family planning. Prenatal diagnosis was used by two couples, while others refrained from having more children. Reproductive decisions were influenced by the burden of the disease for the patient and family members, the impact of ophthalmological screening under anaesthesia, and couples' perceived risk, which did not always relate to their actual risk. Reproductive choices with regard to the number of children wanted changed over time. Our findings indicate topics to be discussed during genetic counselling of couples at increased risk for a child with Rb. We suggest continued access to genetic counselling also after the initial diagnosis and treatment.
Spinal arteriovenous malformation presenting as spastic monoplegic cerebral palsy in a child
Authors: Flett Peter John , Baulderstone David , Russo Remo , Davies Roger Philip
Published: June 2010

A case of spinal arterio‐venous malformation (AVM) initially diagnosed as unilateral cerebral palsy (CP) is reported. The presentation was of a long‐standing spastic monoparesis of the left leg, with initial response to Botulinum toxin injections to the calf and tibialis posterior muscles. This was followed by progressive deterioration occurring over a 3‐month period before further investigation and definitive diagnosis at 7 years. Imaging demonstrated a large extra‐medullary spinal AVM compressing the mid‐thoracic cord. This was successfully managed by embolisation with a non‐adhesive polymer: ethylene‐vinyl alcohol copolymer injected into the dominant feeding vessel. This case highlights the need to consider alternative diagnoses when a child with a diagnosis of CP presents with atypical clinical features such as monoparesis and has worsening or altered clinical signs. Moreover, a normal magnetic resonance imaging brain scan and the absence of ipsilateral upper limb neurological signs or functional impairment should raise suspicion even in the context of static lower limb signs. A literature review was performed on the management of spinal AVM in children and this will be is discussed.
Predator control promotes invasive dominated ecological states
Authors: Wallach Arian D. , Johnson Christopher N. , Ritchie Euan G. , O’Neill Adam J.
Published: June 2010

Ecology Letters (2010) 13: 1008–1018

Invasive species are regarded as one of the top five drivers of the global extinction crisis. In response, extreme measures have been applied in an attempt to control or eradicate invasives, with little success overall. We tested the idea that state shifts to invasive dominance are symptomatic of losses in ecosystem resilience, due to the suppression of apex predators. This concept was investigated in Australia where the high rate of mammalian extinctions is largely attributed to the destructive influence of invasive species. Intensive pest control is widely applied across the continent, simultaneously eliminating Australia’s apex predator, the dingo (Canis lupus dingo). We show that predator management accounts for shifts between two main ecosystem states. Lethal control fractures dingo social structure and leads to bottom‐up driven increases in invasive mesopredators and herbivores. Where control is relaxed, dingoes re‐establish top–down regulation of ecosystems, allowing for the recovery of biodiversity and productivity.
Spatial mismatch and congruence between taxonomic, phylogenetic and functional diversity: the need for integrative conservation strategies in a changing world
Authors: Devictor Vincent , Mouillot David , Meynard Christine , Jiguet Frédéric , Thuiller Wilfried , Mouquet Nicolas
Published: June 2010

Ecology Letters (2010) 13: 1030–1040

Functional and phylogenetic diversity are increasingly quantified in various fields of ecology and conservation biology. The need to maintain diversity turnover among sites, so‐called beta‐diversity, has also been raised in theoretical and applied ecology. In this study, we propose the first comprehensive framework for the large‐scale mapping of taxonomic, phylogenetic and functional diversity and of their respective turnover. Using high‐resolution data on the spatial distribution and abundance of birds at a country scale, we disentangled areas of mismatches and congruencies between biodiversity components. We further revealed unequal representation of each component in protected areas: functional diversity was significantly under‐represented whereas taxonomic diversity was significantly over‐represented in protected areas. Our results challenge the use of any one diversity component as a surrogate for other components and stress the need to adopt an integrative approach to biodiversity conservation.
Nitrogen availability is a primary determinant of conifer mycorrhizas across complex environmental gradients
Authors: Cox Filipa , Barsoum Nadia , Lilleskov Erik A. , Bidartondo Martin I.
Published: June 2010

Ecology Letters (2010) 13: 1103–1113

Global environmental change has serious implications for functional biodiversity in temperate and boreal forests. Trees depend on mycorrhizal fungi for nutrient uptake, but predicted increases in nitrogen availability may alter fungal communities. To address a knowledge gap regarding the effects of nitrogen availability on mycorrhizal communities at large scales, we examine the relationship between nitrogen and ectomycorrhizas in part of a European biomonitoring network of pine forest plots. Our analyses show that increased nitrogen reduces fungal diversity and causes shifts in mycorrhizal community composition across plots, but we do not find strong evidence that within‐plot differences in nitrogen availability affect ectomycorrhizal communities. We also carry out exploratory analyses to determine the relative importance of other environmental variables in structuring mycorrhizal communities, and discuss the potential use of indicator species to predict nitrogen‐induced shifts in fungal communities.
Coexistence of perennial plants: an embarrassment of niches
Authors: Adler Peter B. , Ellner Stephen P. , Levine Jonathan M.
Published: June 2010

Ecology Letters (2010) 13: 1019–1029

Despite decades of research documenting niche differences between species, we lack a quantitative understanding of their effect on coexistence in natural communities. We perturbed an empirical sagebrush steppe community model to remove the demographic effect of niche differences and quantify their impact on coexistence. With stabilizing mechanisms operating, all species showed positive growth rates when rare, generating stable coexistence. Fluctuation‐independent mechanisms contributed more than temporal variability to coexistence and operated more strongly on recruitment than growth or survival. As expected, removal of stabilizing niche differences led to extinction of all inferior competitors. However, complete exclusion required 300–400 years, indicating small fitness differences among species. Our results show an ‘excess’ of niche differences: stabilizing mechanisms were not only strong enough to maintain diversity but were much stronger than necessary given the small fitness differences. The diversity of this community cannot be understood without consideration of niche differences.
The role of enemy release, tolerance and resistance in plant invasions: linking damage to performance
Authors: Chun Young Jin , Van Kleunen Mark , Dawson Wayne
Published: June 2010

Ecology Letters (2010) 13: 937–946

An explanation for successful invasion is that invasive alien species sustain less pressure from natural enemies than co‐occurring native species. Using meta‐analysis, we examined whether invasive species: (1) incur less damage, (2) exhibit better performance in the presence of enemies, and (3) tolerate damage more than native species. Invasive alien species did not incur less damage than native species overall. The performance of invasive alien species was reduced compared to natives in the presence of enemies, indicating the invasive alien species were less tolerant to damage than native species. However, there was no overall difference in performance of invasive alien and native species with enemies present. The damage and degree of reduction in performance of invasive alien relative to native species did not depend on relatedness to natives. Our results suggest aliens may not always experience enemy release, and enemy release may not always result in greater plant performance.