bluuebunny/crossref_metadata_2025 huggingface dataset:
An investigation on the effects of side assisting gas flow and metallic vapour jet on the stability of keyhole and molten pool during laser full-penetration welding
Authors: Zhang Linjie , Zhang Jianxun , Zhang Guifeng , Bo Wu , Gong Shuili
Published: March 2011

This paper reports on a study aiming at separating the effects of side assisting gas flow from a metallic vapour jet on the transient behaviour of a molten pool and a keyhole during laser full-penetration welding. To achieve the research purpose, laser welding process was simulated under three different conditions: in the presence of both side gas flow and metallic vapour jet, in the presence of side gas flow alone and in the presence of metallic vapour jet alone. It was found that the side gas flow not only pushed the molten melt to flow towards the rear part of the molten pool but also formed, on the molten pool surface, a proper pressure distribution which helped maintain both the humping in the rear part of the molten pool and the concave around the upper exit of the keyhole. Under the condition with side gas flow, the swelling formed around the keyhole blocked the side gas flow and on the other hand the side gas flow pushed them to flow backwards to the rear part of the molten pool more effectively, thereby enlarging and stabilizing the keyhole exit. Furthermore, the peak value of the average pressure in the region composed of the molten pool and keyhole decreased step by step with the growth of the concave. Finally, the interaction between the metallic vapour and molten melt was well controlled using the side gas flow, which led to an improvement in the stability of the molten pool and a reduction in spatters and pores.
On the Waring problem with Dickson polynomials in finite fields
Authors: Ostafe Alina , Shparlinski Igor
Published: March 2011

We improve recent results of D. Gomez and A. Winterhof on the Waring problem with Dickson polynomials in finite fields. Our approach is based on recent advances in arithmetic combinatorics in arbitrary finite fields due to A. Glibichuk and M. Rudnev.
Growth-phase dependence of susceptibility to antimicrobial peptides in Staphylococcus aureus
Authors: Matsuo Miki , Oogai Yuichi , Kato Fuminori , Sugai Motoyuki , Komatsuzawa Hitoshi
Published: March 2011

Bacterial cell surface charge is responsible for susceptibility to cationic antimicrobial peptides. Previously, Staphylococcus aureus dlt and mprF were identified as factors conferring a positive charge upon cell surfaces. In this study, we investigated the regulation of cell surface charge during growth. Using a group of S. aureus MW2 mutants, which are gene-inactivated in 15 types of two-component systems (TCSs), we tested dltC and mprF expression and found that two TCSs, aps and agr, were associated with dltC and mprF expression in a growth phase-dependent manner. The first of these, aps, which had already been identified as a sensor of antimicrobial peptides and a positive regulator of dlt and mprF expression, was expressed strongly in the exponential phase, while its expression was significantly suppressed by agr in the stationary phase, resulting in higher expression of dltC and mprF in the exponential phase and lower expression in the stationary phase. Since both types of expression affected the cell surface charge, the susceptibility to antimicrobial peptides and cationic antibiotics was changed during growth. Furthermore, we found that the ability to sense antimicrobial peptides only functioned in the exponential phase. These results suggest that cell surface charge is tightly regulated during growth in S. aureus.
The peptide transport system Opt is involved in both nutrition and environmental sensing during growth of Lactococcus lactis in milk
Authors: Lamarque Mauld , Aubel Dominique , Piard Jean-Christophe , Gilbert Christophe , Juillard Vincent , Atlan Danièle
Published: March 2011

Lactococcus lactis is known to take up extracellular peptides via at least three distinct peptide transporters. The well-described oligopeptide transporter Opp alone is able to ensure the growth of L. lactis in milk, while the di- and tripeptide transporter DtpT is involved in a peptide-dependent signalling mechanism. The oligopeptide Opt transporter displays two peptide-binding proteins, OptA and OptS. We previously demonstrated that OptA-dependent transport is dedicated to nutritional peptides, as an optABCDF mutant (of a strain devoid of Opp) has an impaired capacity to grow in milk. Using isogenic peptide transport mutants, this study shows that biosynthesis of the Opt transporter is much less sensitive to downregulation that is dependent on extracellular peptides taken up by DtpT than is Opp biosynthesis; this peptide-dependent regulation relies on the transcriptional repressor CodY. We demonstrate the dual function of the Opt system; while OptA contributes to the bacterial nutrition during growth in milk, OptS is involved in the transport of signalling peptides derived from milk and controlling opp expression. So, these results shed new light on the peptide-dependent regulation relying on two peptide transporters with different specificities: DtpT and Opt (via OptS).
RAFgene fusion breakpoints in pediatric brain tumors are characterized by significant enrichment of sequence microhomology
Authors: Lawson Andrew R.J. , Hindley Guy F.L. , Forshew Tim , Tatevossian Ruth G. , Jamie Gabriel A. , Kelly Gavin P. , Neale Geoffrey A. , Ma Jing , Jones Tania A. , Ellison David W. , Sheer Denise
Published: March 2011

Gene fusions involving members of the RAF family of protein kinases have recently been identified as characteristic aberrations of low-grade astrocytomas, the most common tumors of the central nervous system in children. While it has been shown that these fusions cause constitutive activation of the ERK/MAPK pathway, very little is known about their formation. Here, we present a detailed analysis ofRAFgene fusion breakpoints from a well-characterized cohort of 43 low-grade astrocytomas. Our findings show that the rearrangements that generate theseRAFgene fusions may be simple or complex and that both inserted nucleotides and microhomology are common at the DNA breakpoints. Furthermore, we identify novel enrichment of microhomologous sequences in the regions immediately flanking the breakpoints. We thus provide evidence that the tandem duplications responsible for these fusions are generated by microhomology-mediated break-induced replication (MMBIR). Although MMBIR has previously been implicated in the pathogenesis of other diseases and the evolution of eukaryotic genomes, we demonstrate here that the proposed details of MMBIR are consistent with a recurrent rearrangement in cancer. Our analysis of repetitive elements, Z-DNA and sequence motifs in the fusion partners identified significant enrichment of the human minisatellite conserved sequence/χ-like element at one side of the breakpoint. Therefore, in addition to furthering our understanding of low-grade astrocytomas, this study provides insights into the molecular mechanistic details of MMBIR and the sequence of events that occur in the formation of genomic rearrangements.
High sensitivity to aligner and high rate of false positives in the estimates of positive selection in the 12 Drosophila genomes
Authors: Markova-Raina Penka , Petrov Dmitri
Published: March 2011

We investigate the effect of aligner choice on inferences of positive selection using site-specific models of molecular evolution. We find that independently of the choice of aligner, the rate of false positives is unacceptably high. Our study is a whole-genome analysis of all protein-coding genes in 12 Drosophila genomes annotated in either all 12 species (∼6690 genes) or in the six melanogaster group species. We compare six popular aligners: PRANK, T-Coffee, ClustalW, ProbCons, AMAP, and MUSCLE, and find that the aligner choice strongly influences the estimates of positive selection. Differences persist when we use (1) different stringency cutoffs, (2) different selection inference models, (3) alignments with or without gaps, and/or additional masking, (4) per-site versus per-gene statistics, (5) closely related melanogaster group species versus more distant 12 Drosophila genomes. Furthermore, we find that these differences are consequential for downstream analyses such as determination of over/under-represented GO terms associated with positive selection. Visual analysis indicates that most sites inferred as positively selected are, in fact, misaligned at the codon level, resulting in false positive rates of 48%–82%. PRANK, which has been reported to outperform other aligners in simulations, performed best in our empirical study as well. Unfortunately, PRANK still had a high, and unacceptable for most applications, false positives rate of 50%–55%. We identify misannotations and indels, many of which appear to be located in disordered protein regions, as primary culprits for the high misalignment-related error levels and discuss possible workaround approaches to this apparently pervasive problem in genome-wide evolutionary analyses.
The AP2/ERF Transcription Factor AtERF73/HRE1 Modulates Ethylene Responses during Hypoxia in Arabidopsis
Authors: Yang Chin-Ying , Hsu Fu-Chiun , Li Jin-Ping , Wang Ning-Ning , Shih Ming-Che
Published: March 2011

A number of APETALA2 (AP2)/ETHYLENE RESPONSE FACTOR (ERF) genes have been shown to function in abiotic and biotic stress responses, and these genes are often induced by multiple stresses. We report here the characterization of an AP2/ERF gene in Arabidopsis (Arabidopsis thaliana) that is specifically induced during hypoxia. We show that under normoxic conditions, the expression of AtERF73/HRE1 can be induced by exogenous addition of 1-aminocyclopropane-1-carboxylic acid and that a combination of hypoxia and 1-aminocyclopropane-1-carboxylic acid results in hyperinduction of AtERF73/HRE1 expression. In addition, hypoxic induction of AtERF73/HRE1 is reduced but not completely abolished in ethylene-insensitive mutants and in the presence of inhibitors of ethylene biosynthesis and responses. These results suggest that, in addition to ethylene, an ethylene-independent signal is also required to mediate hypoxic induction of AtERF73/HRE1. To assess the role of AtERF73/HRE1, we generated three independent RNA interference (RNAi) knockdown lines of AtERF73/HRE1. Under normoxic conditions, the AtERF73/HRE1-RNAi seedlings displayed increased ethylene sensitivity and exaggerated triple responses, indicating that AtERF73/HRE1 might play a negative regulatory role in modulating ethylene responses. Gas chromatography analyses showed that the production of ethylene was similar between wild-type and RNAi lines under hypoxia. Quantitative reverse transcription-polymerase chain reaction analyses showed that hypoxia-inducible genes could be affected by AtERF73/HRE1-RNAi lines in two different ways: hypoxic induction of glycolytic and fermentative genes was reduced, whereas induction of a number of peroxidase and cytochrome P450 genes was increased. Taken together, our results show that AtERF73/HRE1 is involved in modulating ethylene responses under both normoxia and hypoxia.
Alcohol‐related negative consequences among drinkers around the world
Authors: Graham Kathryn , Bernards Sharon , Knibbe Ronald , Kairouz Sylvia , Kuntsche Sandra , Wilsnack Sharon C. , Greenfield Thomas K. , Dietze Paul , Obot Isidore , Gmel Gerhard
Published: March 2011

Aims This paper examines (i) gender and country differences in negative consequences related to drinking; (ii) relative rates of different consequences; and (iii) country‐level predictors of consequences.

Design, setting and participants Multi‐level analyses used survey data from the Gender, Alcohol, and Culture: An International Study (GENACIS) collaboration.

Measurements Measures included 17 negative consequences grouped into (i) high endorsement acute, (ii) personal and (iii) social. Country‐level measures included average frequency and quantity of drinking, percentage who were current drinkers, gross domestic product (GDP) and Human Development Index (HDI).

Findings Overall, the three groupings of consequences were reported by 44%, 12% and 7% of men and by 31%, 6% and 3% of women, respectively. More men than women endorsed all consequences, but gender differences were greatest for consequences associated with chronic drinking and social consequences related to male roles. The highest prevalence of consequences was in Uganda and lowest in Uruguay. Personal and social consequences were more likely in countries with higher usual quantity, fewer current drinkers and lower scores on GDP and HDI. However, significant interactions with individual‐level quantity indicated a stronger relationship between consequences and usual quantity among drinkers in countries with lower quantity, more current drinkers and higher scores on GDP and HDI.

Conclusions Both gender and country need to be taken into consideration when assessing adverse drinking consequences. Individual measures of alcohol consumption and country‐level variables are associated with experiencing such consequences. Additionally, country‐level variables affect the strength of the relationship between usual quantity consumed by individuals and adverse consequences.
Prescribing of smoking cessation medication in England since the introduction of varenicline
Authors: Langley Tessa E. , Huang Yue , McNeill Ann , Coleman Tim , Szatkowski Lisa , Lewis Sarah
Published: March 2011

Aims  To estimate the effect of the introduction of a new smoking cessation medication, varenicline, and the publication of guidance related to its use, on trends in prescribing of smoking cessation medications in England.

Design  Interrupted time series analysis of primary care data on prescribing of smoking cessation medication using autoregressive integrated moving average (ARIMA) modelling.

Setting  A total of 446 general practices included in The Health Improvement Network (THIN), a database of UK electronic primary care records.

Participants  All primary care patients registered with a THIN practice in England.

Measurements  Monthly rates of prescribing of varenicline, nicotine replacement therapy (NRT) and bupropion per 100 000 patients registered with a THIN practice between June 2000 and June 2009.

Findings  NRT was the most commonly prescribed stop smoking medication, and bupropion the least frequently prescribed. After its introduction in December 2006 varenicline rapidly became the second most commonly prescribed drug. There was no statistically significant change in overall prescribing for smoking cessation medications after its introduction (P = 0.760), or after the publication of the related guidance in July 2007 (P = 0.134).

Conclusions  Soon after being introduced in England, varenicline was widely prescribed; after nicotine replacement therapy it was the most commonly prescribed cessation medication. However, this does not appear to have increased overall rates of prescribing for smoking cessation medication.
Professional background and the comprehension of family‐centredness of rehabilitation for children with cerebral palsy
Authors: Jeglinsky I. , Autti‐Rämö I. , Brogren Carlberg E.
Published: March 2011

Background  Children with cerebral palsy have difficulties in several areas of functioning, and they need long‐lasting rehabilitation with a clear focus on the individual's needs. Finnish guidelines emphasize family‐centred service. The values of family‐centred service are widely known, but how the principles of family‐centred service are adopted in clinical practice is not well documented. The objective of this study was to analyse the family‐centred behaviour of professionals working with children and adolescents with cerebral palsy.

Methods  A translated version of the Measure of Processes of Care for Service Providers (MPOC‐SP) questionnaire was used to evaluate the family‐centred service. The questionnaire was sent to all the professionals in the multidisciplinary rehabilitation teams at all the hospitals and governmental special schools treating children and adolescents with cerebral palsy in Finland (n= 327). Furthermore, 438 physiotherapy service providers working in the children's home region were invited to participate.

Results  A total of 201 multidisciplinary team members and 311 physiotherapy service providers completed the questionnaire. Both the team members and the service providers generally rated their family‐centred behaviour positively. There was statistically significant difference in how the team members in the multidisciplinary teams self‐assessed their family‐centred service. Physiotherapists working in multidisciplinary teams rated their family‐centred service higher than physiotherapy service providers. The professional's apprehension of family‐centred service increased with work experience.

Conclusions  Professional background and professional context seem to affect the apprehension of family‐centred service. Also work experience and being part of a multidisciplinary team have an influence on how the professionals embrace the family‐centred service delivered. The MPOC‐SP can be used to identify areas for improvement.
Management of drooling in children: a survey of UK paediatricians' clinical practice
Authors: Parr J. R. , Buswell C. A. , Banerjee K. , Fairhurst C. , Williams J. , O'Hare A. , Pennington L. ,   on behalf of the British Academy of Childhood Disability Drooling Study Development Group
Published: March 2011

Background  Drooling is common in children with disordered oral‐motor control. There is little evidence about the comparative effectiveness of different interventions used to reduce the impact of drooling. Anecdotal reports suggest clinicians' management of drooling varies widely. The aims of this survey were to establish which drooling interventions are currently used, how their effectiveness is monitored and how frequently adverse effects are reported.

Methods  151 UK paediatricians completed a questionnaire about their management of drooling.

Results  Paediatricians saw one new child with problematic drooling and three follow‐up children per month. The most common prescribing pattern was hyoscine first line (84.7%) followed by glycopyrronium bromide second line. The reported rate of adverse effects of medications was lower than expected (median 10% for hyoscine). Very few paediatricians used standardized methods of measuring the medication's effectiveness or adverse effects.

Conclusion  Paediatricians regularly see small numbers of children with problematic drooling. Their clinical management of drooling varies; this is most likely because of a lack of evidence about the most effective approach. Comparative trials of interventions and the development of evidence‐based clinical guidelines would improve the management of children's drooling.
A single case study of a family‐centred intervention with a young girl with cerebral palsy who is a multimodal communicator
Authors: Wadnerkar M. B. , Pirinen T. , Haines‐Bazrafshan R. , Rodgers J. , James D.
Published: March 2011

Background  This paper describes the impact of a family‐centred intervention that used video to enhance communication in a young girl with cerebral palsy. This single case study describes how the video‐based intervention worked in the context of multimodal communication, which included high‐tech augmentative and alternative communication (AAC) device use. This paper includes the family's perspective of the video intervention and they describe the impact of it on their family.

Methods  This single case study was based on the premise that the video interaction guidance intervention would increase attentiveness between participants during communication. It tests a hypothesis that eye gaze is a fundamental prerequisite for all communicative initiatives, regardless of modality in the child. Multimodality is described as the range of communicative behaviours used by the child and these are coded as AAC communication, vocalizations (intelligible and unintelligible), sign communication, nodding and pointing. Change was analysed over time with multiple testing both pre and post intervention. Data were analysed within INTERACT, a computer software to analyse behaviourally observed data. Behaviours were analysed for frequency and duration, contingency and co‐occurrence.

Results  Results indicated increased duration of mother's and girl's eye gaze, increased frequency and duration in AAC communication by the girl and significant change in frequency [χ2 (5, n = 1) = 13.25, P < 0.05] and duration [χ2 (5, n = 1) = 12.57, P < 0.05] of the girl's multimodal communicative behaviours. Contingency and co‐occurrence analysis indicated that mother's eye gaze followed by AAC communication was the most prominent change between the pre‐ and post‐intervention assessments.

Conclusions  There was a trend for increased eye gaze in both mum and girl and AAC communication in the girl following the video intervention. The family's perspective concurs with the results.
Association between filaggrin null mutations and concomitant atopic dermatitis and contact allergy
Authors: Carlsen B. C. , Thyssen J. P. , Menné T. , Meldgaard M. , Linneberg A. , Nielsen N. H. , Szecsi P. B. , Stender S. , Johansen J. D.
Published: March 2011

Background. The phenotypic traits of people with the filaggrin mutation (FLG) genotype and atopic dermatitis (AD) are still under elucidation, and the association with concomitant AD and contact allergy (CA) has not previously been examined.

Aim. To assess FLG status in a subset of patients with AD and a minimum of one positive patch-test reaction.

Methods. In total, 430 people from a hospital population and 3335 people from the general population were tested for FLG mutations by DNA hybridization to paramagnetic polystyrene beads and analysis on a multiplex analysis system. All of the individuals in the hospital population had a minimum of one CA. AD was diagnosed according to the UK Working Party Criteria, (questions-only version). Individuals from the hospital population who had both AD and CA were considered as cases, and comparison of mutation carrier frequency was estimated (χ2 test) against individuals without AD but with CA from the hospital population, individuals from the general population, and individuals with AD from the general population.

Results. The mutation frequency in patients with AD and CA in the hospital population was significantly less than that of people with AD from the general population (OR = 0.54; 95% CI 0.30–0.98). No difference in mutation frequency was found between individuals with and without AD in the hospital population (OR = 1.40; 95% CI 0.70–2.79), or between individuals with AD and CA in the hospital population and in the overall general population (OR = 1.29; 95% CI 0.76–2.20).

Conclusions. The spectrum of observable traits characteristic for the FLG mutation genotype in patients with AD is at present not defined. Our results indicate that the subset of patients with both AD and CA represent a phenotype of AD that is not associated with FLG mutations.
A survey of the availability of sunscreen filters in the UK
Authors: Kerr A. C.
Published: March 2011

The frequency, and thus availability to patients, of ultraviolet (UV) filters contained within sunscreens changes over time. Obtaining current data on filter availability is necessary when considering which agents to include in sunscreen series for patch and photopatch testing of patients. A survey of sunscreen products was undertaken in Dundee, UK, in 2010. In total, 337 products were identified, with a median sun-protection factor of 30 (range 2–50+). In these products, 19 UV filters were identified, of which the most common was butyl methoxydibenzoylmethane. Compared with data from 2005, most filters had an increase in frequency of inclusion, with a trend towards broader spectrum protection. This information should be of use to clinicians considering investigation of contact and photocontact allergy. It also aids determination of the allergenic potential of these filters when reports of allergy and photocontact allergy arise in the literature.
Association between effective dose of prednisolone, alone or in conjunction with other immunosuppressants, and titre of anti-bullous pemphigoid 180 antibody: a retrospective study of 42 cases
Authors: Miida H. , Fujiwara H. , Ito M.
Published: March 2011

Background. Corticosteroids, especially prednisolone or prednisone, are the most commonly used drugs for the treatment of bullous pemphigoid (BP). However, the appropriate initial effective prednisolone dose has not been established. Recently, a highly sensitive and specific ELISA for detection of autoantibodies to the non-collagenous extracellular domain (NC16A) of the 180 kDa transmembrane hemidesmosome component [bullous pemphigoid (BP)180] was developed, and the titre of anti-BP180 antibody was found to be closely related to disease activity.

Aim. To investigate the relationship between anti-BP180 antibody titre and effective prednisolone dose alone or in conjunction with other immunosuppressants.

Methods. Anti-BP180 antibody titres were measured by ELISA for the NC16A domain of BP180 in the sera of patients with BP (n = 42) at the start of treatment. The effective prednisolone dose was calculated from the patients’ records.

Results. Higher anti-BP180 antibody titres correlated with a higher effective prednisolone dose. In particular, patients with antibody titres > 200 required a significantly higher effective prednisolone dose than did those with antibody titres ≤ 200.

Conclusions. A higher effective prednisolone dose may be necessary for patients who have both a high titre of anti-BP180 antibody and severe clinical disease.
Wnt10b promotes growth of hair follicles via a canonical Wnt signalling pathway
Authors: Li Y.-H. , Zhang K. , Ye J.-X. , Lian X.-H. , Yang T.
Published: March 2011

Background. Wnt10b (wingless-related mouse mammary tumour virus integration site 10b) plays various roles in a wide range of biological actions, including hair-follicle development.

Aim. To assess the roles that Wnt10b plays in postnatal hair-follicle growth.

Methods. Adenovirus vectors AdWnt10b, AdGFP, AdGFP plus AdRFP, AdWnt10b plus AdFrzB, and AdWnt10b plus AdSimBC were co-cultured separately with vibrissae. In situ protein expression of Wnt10b, β-catenin and Lef1 was determined by immunohistochemistry, and the proliferation status of the hair follicle was detected by 5-bromo-2-deoxyuridine (BrdU) labelling. The presence of Wnt signalling molecules in the three stages of hair-follicle growth was detected by PCR-based microarray.

Results. AdWnt10b-infected cells were able to secrete bioactive Wnt10b, and when this was added into the basal medium, the vibrissae grew faster than in control medium or in medium containing canonical Wnt signalling antagonists. The in situ protein expression of Wnt10b was consistent with that of β-catenin and Lef1. The expression locus of Wnt10b was almost the same as the proliferating cells labelled by BrdU in the anagen hair follicle.

Conclusions. Wnt10b may promote hair-follicle growth by inducing the switch from telogen to anagen via a canonical Wnt signalling pathway to promote the proliferation of matrix cells.
Changes in satellite‐derived vegetation growth trend in temperate and boreal Eurasia from 1982 to 2006
Authors: PIAO SHILONG , WANG XUHUI , CIAIS PHILIPPE , ZHU BIAO , WANG TAO , LIU JIE
Published: March 2011

Monitoring changes in vegetation growth has been the subject of considerable research during the past several decades, because of the important role of vegetation in regulating the terrestrial carbon cycle and the climate system. In this study, we combined datasets of satellite‐derived Normalized Difference Vegetation Index (NDVI) and climatic factors to analyze spatio‐temporal patterns of changes in vegetation growth and their linkage with changes in temperature and precipitation in temperate and boreal regions of Eurasia (> 23.5°N) from 1982 to 2006. At the continental scale, although a statistically significant positive trend of average growing season NDVI is observed (0.5 × 10−3 year−1, P = 0.03) during the entire study period, there are two distinct periods with opposite trends in growing season NDVI. Growing season NDVI has first significantly increased from 1982 to 1997 (1.8 × 10−3 year−1, P < 0.001), and then decreased from 1997 to 2006 (−1.3 × 10−3 year−1, P = 0.055). This reversal in the growing season NDVI trends over Eurasia are largely contributed by spring and summer NDVI changes. Both spring and summer NDVI significantly increased from 1982 to 1997 (2.1 × 10−3 year−1, P = 0.01; 1.6 × 10−3 year−1P < 0.001, respectively), but then decreased from 1997 to 2006, particularly summer NDVI which may be related to the remarkable decrease in summer precipitation (−2.7 mm yr−1, P = 0.009). Further spatial analyses supports the idea that the vegetation greening trend in spring and summer that occurred during the earlier study period 1982–1997 was either stalled or reversed during the following study period 1997–2006. But the turning point of vegetation NDVI is found to vary across different regions.
Evaluating the effects of 14‐day oral vedaprofen and tolfenamic acid treatment on renal function, hematological and biochemical profiles in healthy cats
Authors: KHWANJAI V. , CHUTHATEP S. , DURONGPHONGTORN S. , YIBCHOK‐ANUN S.
Published: March 2011

Khwanjai, V., Chuthatep, S., Durongphongtorn, S., Yibchok‐Anun, S. Evaluating the effects of 14‐day oral vedaprofen and tolfenamic acid treatment on renal function, hematological and biochemical profiles in healthy cats.J. vet. Pharmacol. Therap. 35, 13–18.

The objective of this study was to evaluate the effects of the nonsteroidal anti‐inflammatory drugs vedaprofen and tolfenamic acid on renal function after oral administration for 2 weeks in healthy cats. Experiments were performed using nineteen domestic short‐haired cats randomly divided into one control (n = 6) and two treatment groups. All cats in the first (n = 6) and second treatment groups (n = 7) received vedaprofen (0.5 mg/kg/day) and tolfenamic acid (4 mg/kg/day), respectively. During the experiment, renal function was evaluated using percent renal uptakes of99mTechnetium‐diethylenetriamine‐pentaacetic acid (99mTc‐DTPA) collected from renal scintigraphy and blood samples used to determine complete blood count and biochemical profiles. Renal scintigraphy and blood collections were performed at days 0, 5, 11, 15, and 45. The percent of renal uptake after the administration of vedaprofen and tolfenamic acid were not significantly different compared to pretreatment (day 0) and control group levels. In addition, significant changes were not observed in hematological and biochemical profiles within or between groups, with the exception of slightly lower numbers in red blood cell counts compared to the normal value on day 45 in the tolfenamic acid‐treated group. Taken together, we conclude 14‐day administration of vedaprofen and tolfenamic acid might not cause any adverse effects on renal function, hematological and serum biochemical variables.
Pharmacokinetics of intravenous and intramuscular buprenorphine in the horse
Authors: DAVIS J. L. , MESSENGER K. M. , LaFEVERS D. H. , BARLOW B. M. , POSNER L. P.
Published: March 2011

Davis, J. L., Messenger, K. M., LaFevers, D. H., Barlow, B. M., Posner, L. P. Pharmacokinetics of intravenous and intramuscular buprenorphine in the horse.J. vet. Pharmacol. Therap. 35, 52–58.

The purpose of this study was to determine the pharmacokinetics of buprenorphine following intravenous (i.v.) and intramuscular (i.m.) administration in horses. Six horses received i.v. or i.m. buprenorphine (0.005 mg/kg) in a randomized, crossover design. Plasma samples were collected at predetermined times and horses were monitored for adverse reactions. Buprenorphine concentrations were measured using ultra‐performance liquid chromatography with electrospray ionization mass spectrometry. Following i.v. administration, clearance was 7.97 ± 5.16 mL/kg/min, and half‐life (T1/2) was 3.58 h (harmonic mean). Volume of distribution was 3.01 ± 1.69 L/kg. Following i.m. administration, maximum concentration (Cmax) was 1.74 ± 0.09 ng/mL, which was significantly lower than the highest measured concentration (4.34 ± 1.22 ng/mL) after i.v. administration (P < 0.001). Time to Cmaxwas 0.9 ± 0.69 h andT1/2was 4.24 h. Bioavailability was variable (51–88%). Several horses showed signs of excitement. Gut sounds were decreased 10 ± 2.19 and 8.67 ± 1.63 h in the i.v. and i.m. group, respectively. Buprenorphine has a moderateT1/2in the horse and was detected at concentrations expected to be therapeutic in other species after i.v. and i.m. administration of 0.005 mg/kg. Signs of excitement and gastrointestinal stasis may be noted.
Interesting twists on small RNA themes in Pseudomonas aeruginosa
Authors: Sharma Cynthia Mira , Storz Gisela
Published: March 2011

While many of the initial studies of regulatory small RNA (sRNA) function focused on Escherichia coli and Salmonella, there is expanding characterization of sRNAs in other bacteria. These studies are revealing unique permutations of the themes found in E. coli and Salmonella. This point is nicely illustrated by the Pseudomonas aeruginosa Hfq‐binding RNA, PhrS, which activates the synthesis of the key quorum sensing transcription regulator PqsR as described by Sonnleitner et al. in the current issue of Molecular Microbiology. The PhrS RNA combines features of several previously characterized sRNAs; its expression is induced by low oxygen, it encodes a small protein, and it modulates the expression of a quorum sensing regulator by preventing the formation of an inhibitory secondary structure. However, in contrast to other base pairing sRNAs that activate translation, PhrS does not act directly on pqsR but rather increases the translation of a small upstream open reading frame (uof) whose translation is coupled to pqsR.
Cerebral small vessel endothelial structural changes predate hypertension in stroke‐prone spontaneously hypertensive rats: a blinded, controlled immunohistochemical study of 5‐ to 21‐week‐old rats
Authors: Bailey E. L. , Wardlaw J. M. , Graham D. , Dominiczak A. F. , Sudlow C. L. M. , Smith C.
Published: March 2011

E. L. Bailey, J. M. Wardlaw, D. Graham, A. F. Dominiczak, C. L. M. Sudlow and C. Smith (2011) Neuropathology and Applied Neurobiology37, 711–726

Cerebral small vessel endothelial structural changes predate hypertension in stroke‐prone spontaneously hypertensive rats: a blinded, controlled immunohistochemical study of 5‐ to 21‐week‐old rats

Aims: The spontaneously hypertensive stroke‐prone rat (SHRSP) is a potential animal model of human lacunar stroke, but there is little information on SHRSP small vessel pathology, especially in young rats. We investigated the structural changes that occur in cortical and subcortical vessels and adjacent tissue in SHRSP before, during and after the onset of hypertension. Methods: We examined brains from SHRSP and Wistar Kyoto rats (WKY) at 5, 16 and 21 weeks of age. Structural changes in small arterioles and adjacent tissue were studied using antibodies to investigate different components of the neurovascular unit. We quantified staining in three standard regions, at two coronal levels. Results: Immunostaining for claudin‐5, a marker of endothelial tight junctions, was reduced in SHRSP at all ages compared to age‐matched WKY controls. Smooth muscle actin, glial fibrillary acidic protein and ionized calcium‐binding adaptor molecule 1 were increased in SHRSP vs. WKY by 16 weeks. Additionally, 21‐week‐old WKY and SHRSP rats fed a high‐salt diet showed differences in claudin‐5, glial fibrillary acidic protein and matrix metalloproteinase 9 staining compared to those fed a normal diet. Conclusion: Endothelial tight junction alterations of SHRSP rats from the earliest ages point towards increased susceptibility to blood–brain barrier dysfunction and stroke, which is exacerbated by salt loading. Salt loading may also damage the neurovascular unit in WKY controls.
Chronic food restriction augments the reinstatement of extinguished heroin‐seeking behavior in rats
Authors: Shalev Uri
Published: March 2011

Currently, there are no existing procedures that model in animals the situation where exposure to prolonged mild food restriction results in relapse to drug abuse. Here, reinstatement of extinguished heroin‐seeking behavior was assessed in rats under extinction conditions. Ten, but not 7, days of food restriction (∼80% of sated body weight) induced reinstatement of heroin seeking, over and above the spontaneous recovery of the behavior. It is suggested that chronic, mild, food restriction following extinction of drug seeking behavior might serve as a useful model to study the increased risk for relapse to drug abuse due to dietary challenges.
Identification of genes regulated in the mouse extended amygdala by excessive ethanol drinking associated with dependence
Authors: Contet Candice , Gardon Olivier , Filliol Dominique , Becker Jérôme A. J. , Koob George F. , Kieffer Brigitte L.
Published: March 2011

Alcoholism is characterized by a progressive loss of control over ethanol intake. The purpose of this study was to identify transcriptional changes selectively associated with excessive ethanol drinking in dependent mice, as opposed to non‐dependent mice maintaining a stable voluntary consumption or mice solely undergoing forced intoxication. We measured expression levels of 106 candidate genes in the extended amygdala, a key brain structure for the development of drug addiction. Cluster analysis identified 17 and 15 genes selectively induced or repressed, respectively, under conditions of excessive drinking. These genes belong to signaling pathways involved in neurotransmission and transcriptional regulation.
Best friends and alcohol use in adolescence: the role of the dopamine D4 receptor gene
Authors: van der Zwaluw Carmen S. , Larsen Helle , Engels Rutger C. M. E.
Published: March 2011

The influence of friends and peers is theoretically one of the most consistent and important factors explaining adolescent alcohol use. However, not all adolescents are equally likely to be influenced by their friends' drinking behaviors. Genetic factors may underlie these inter‐individual differences in susceptibility to the drinking behavior of friends. Because the long allele (≥ 7 repeats) of the dopamine D4 receptor (DRD4) gene has been associated with susceptibility to alcohol and alcohol‐related cues, we tested whether associations between best friend's and adolescent's alcohol use differed for DRD4 genotypes. A Dutch nationwide sample of 308 adolescents (age 13 at baseline) participated in a prospective, community‐based study with five annual waves. A cross‐lagged path analysis was carried out in Mplus to examine bi‐directional relations between friends' and adolescents' weekly alcohol use (number of drinks). A multi‐group approach was applied to test for moderation effects of a 48‐base pair variable number of tandem repeats polymorphism in exon 3 of the DRD4 gene. Additionally, with latent growth curve models, it was examined whether the interaction between friends' drinking and DRD4 genotype predicted the development of adolescents' alcohol use. Results showed that both cross‐sectionally and longitudinally higher levels of friends' alcohol use resulted in higher levels of adolescents' alcohol consumption over time (and vice versa). No significant moderation of DRD4 genotype was found: Associations between adolescents' and friends' drinking did not differ for adolescent carriers of the DRD4 long allele, when compared with adolescents without the DRD4 long allele. Because this is the first study to examine DRD4 × friends' drinking effects prospectively, replication is essential. Future longitudinal studies, possibly with observational or diary designs, are needed to increase our understanding of the interplay between genetic and environmental risk factors for adolescent alcohol use.
Epigenetic down regulation of nerve growth factor during alcohol withdrawal
Authors: Heberlein Annemarie , Muschler Marc , Frieling Helge , Behr Michael , Eberlein Christian , Wilhelm Julia , Gröschl Michael , Kornhuber Johannes , Bleich Stefan , Hillemacher Thomas
Published: March 2011

We investigated the Cytosin‐phosphatidyl‐Guanin (CpG) island promoter methylation (mean and methylation of individual CpG‐sites) of the nerve growth factor (NGF) gene in the blood of alcohol‐dependent patients (57 male patients) during withdrawal (days 1, 7 and 14). Methylation and NGF serum levels did not change significantly from days 1–7. From days 7–14, mean methylation increased (F = 30.55, P < 0.001), whereas the NGF serum levels decreased significantly (days 7–14: F = 17.95, P < 0.001). The NGF serum levels were significantly associated with the mean methylation of the investigated CpG‐sites (F = 1.55, P < 0.001). These results imply an epigenetic regulation of the NGF gene during alcohol withdrawal.
Pharmacological modulation of mGluR7 with AMN082 and MMPIP exerts specific influences on alcohol consumption and preference in rats
Authors: Bahi Amine , Fizia Katharina , Dietz Monika , Gasparini Fabrizio , Flor Peter J.
Published: March 2011

Growing evidence supports a role for the central nervous system (CNS) neurotransmitter L‐glutamate and its metabotropic receptors (mGluRs) in drug addiction in general and alcohol‐use disorders in particular. Alcohol dependence, for instance, has a genetic component, and the recent discovery that variations in the gene coding for mGluR7 modulate alcohol consumption further validates involvement of the L‐glutamate system. Consequently, increasing interest emerges in developing L‐glutamatergic therapies for the treatment of alcohol abuse and dependence. To this end, we performed a detailed behavioral pharmacology study to investigate the regulation of alcohol consumption and preference following administration of the mGluR7‐selective drugs N,N′‐dibenzyhydryl‐ethane‐1,2‐diamine dihydrochloride (AMN082) and 6‐(4‐Methoxyphenyl)‐5‐methyl‐3‐(4‐pyridinyl)‐isoxazolo[4,5‐c]pyridin‐4(5H)‐one hydrochloride (MMPIP). Upon administration of the allosteric agonist AMN082 (10 mg/kg, i.p.) in rats, there was a significant decrease in ethanol consumption and preference, without affecting ethanol blood metabolism. In contrast, mGluR7 blockade with MMPIP (10 mg/kg, i.p.) showed an increase in alcohol intake and reversed AMN082's effect on ethanol consumption and preference. Both mGluR7‐directed pharmacological tools had no effect on total fluid intake, taste preference, or on spontaneous locomotor activity. In conclusion, these findings support a specific regulatory role for mGluR7 on alcohol drinking and preference and provide evidence for the use of AMN082‐type drugs as potential new treatments for alcohol‐use disorders in man.
Rapamycin attenuates the expression of cocaine‐induced place preference and behavioral sensitization
Authors: Bailey Jeffrey , Ma Dzwokai , Szumlinski Karen K.
Published: March 2011

The mammalian target of rapamycin (mTOR) is a serine‐threonine kinase that controls global protein synthesis, in part, by modulating translation initiation, a rate‐limiting step for many mRNAs. Previous studies implicate mTOR in regulating stimulant‐induced sensitization and antidepressive‐like behavior in rodents, as well as drug craving in abstinent heroin addicts. To determine if signaling downstream of mTOR is affected by repeated cocaine administration in reward‐associated brain regions, and if inhibition of mTOR alters cocaine‐induced behavioral plasticity, C57BL/6J mice received four intraperitoneal (i.p.) injections of 15 mg/kg cocaine and levels of phosphorylated P70S6 kinase and ribosomal S6 protein—two translational regulators directly downstream of mTOR—were analyzed by immunoblotting across several brain regions. Cocaine place preference and locomotor sensitization were elicited by four pairings of cocaine with a distinct environment and the effects of mTOR inhibition were assessed by pre‐treating the mice with 10 mg/kg rapamycin, 1 hour prior to: (1) each saline/cocaine conditioning session; (2) a post‐conditioning test; or (3) a test for locomotor sensitization conducted at 3 weeks withdrawal. While systemic pre‐treatment with 10 mg/kg rapamycin during conditioning failed to alter the development of a cocaine place preference or locomotor sensitization, pre‐treatment prior to the post‐conditioning test attenuated the expression of the place preference. Additionally, rapamycin pre‐treatment prior to a cocaine challenge 3 weeks post‐conditioning blocked the expression of the sensitized locomotor response. These findings suggest a role for mTOR activity, and perhaps translational control, in the expression of cocaine‐induced place preference and locomotor sensitization.
Spanish MYH7 founder mutation of Italian ancestry causing a large cluster of Laing myopathy patients
Authors: Muelas N , Hackman P , Luque H , Suominen T , Espinós C , Garcés‐Sánchez M , Sevilla T , Azorín I , Millán JM , Udd B , Vílchez JJ
Published: March 2011

Muelas N, Hackman P, Luque H, Suominen T, Espinós C, Garcés‐Sánchez M, Sevilla T, Azorín I, Millán JM, Udd B, Vílchez JJ. Spanish MYH7 founder mutation of Italian ancestry causing a large cluster of Laing myopathy patients.

Laing myopathy is a distal myopathy caused by mutations in the tail of the slow beta‐myosin heavy chain gene MYH7. A large cluster of patients belonging to different families, with Laing myopathy due to p.K1729del mutation, was found in the Safor region, Spain. The same mutation was previously reported in an American family with Italian ancestry. The possibility that p.K1729del in MYH7 might be a founder mutation in the Safor patients and the chance of a common origin with the Italian‐American family mutation was investigated by haplotype analyses, mutation data origin estimation and historical inquiry. Our results show that the p.K1729del in MYH7 harboured by patients from the Safor indeed is a founder mutation. A common ancestral origin of this mutation in the Spanish and Italian families is also suggested because they all share a core SNP haplotype at locus MYH7. Data estimation yields the origin of the mutation in the Safor at the beginning of the XVII century, when the Moorish were spelt and the region was resettled with Italian families.
Die chemischen und physikalisch‐chemischen Eigenschaften des Blutes beim Rinde, ihre Schwankungen und individuellen Unterschiede
Authors: Awdejewa M. S. , Gerasimowitsch W. W. , Iwanowa E. J. , Messinewa N. A. , Prowatorowa E. L. , Sawitsch N. G.
Published: March 2011

Aus unserer Arbeit, in der wir folgende Blutwerte untersuchten: Blutzucker, Hg. Eisen, Katalase, Gesamtfett des Serums, Natrium, Chlor, Calcium, Eiweiß, Reststickstoff, Kreatinin, Leitfähigkeit können wir folgende Schlüsse ziehen: Unter den starken Änderungen der Umweltbedingungen des Versuches (verschiedene Temperatur und Fütterung), denen die Tiere unterworfen waren, können wir doch 1. von einer Konstanz der Schwankungsgrenzen einzelner Blutkomponenten (z. B. Leitfähigkeit des Serums, Natrium, Kreatinin, Eiweiß, Zucker, Katalase); 2. von den individuellen Unterschieden dieser Schwankungsgrenzen und 3. von ganz bestimmten gegenseitigen Verhältnissen der einzelnen Komponenten (Hämoglobin‐Eisen, Leitfähigkeit‐Eiweißgehalt, Natrium‐Eiweiß, Temperatur ‐ Eisen) sprechen.