bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotypic differentiation and seeding dispersal in non-mucoid and mucoid Pseudomonas aeruginosa biofilms
Authors: Purevdorj-Gage B. , Costerton W. J. , Stoodley P.
Published: May 2005

There is growing evidence thatPseudomonas aeruginosabiofilms exhibit a multicellular developmental life cycle analogous to that of the myxobacteria. In non-mucoid PAO1 biofilms cultured in glass flow cells the phenotypic differentiation of microcolonies into a motile phenotype in the interior of the microcolony and a non-motile surrounding ‘wall phenotype’ are described. After differentiation the interior cells coordinately evacuated the microcolony from local break out points and spread over the wall of the flow cell, suggesting that the specialized microcolonies were analogous to crude fruiting bodies. A microcolony diameter of approximately 80 μm was required for differentiation, suggesting that regulation was related to cell density and mass transfer conditions. This phenomenon was termed ‘seeding dispersal’ to differentiate it from ‘erosion’ which is the passive removal of single cells by fluid shear. Using the flow cell culturing method, in which reproducible seeding phenotype in PAO1 wild-type was demonstrated, the effects of quorum sensing (QS) and rhamnolipid production (factors previously identified as important in determining biofilm structure) on seeding dispersal using knockout mutants isogenic with PAO1 was investigated. Rhamnolipid (rhlA) was not required for seeding dispersal butlas/rhlQS (PAO1-JP2) was, in our system. To assess the clinical relevance of these data, mucoidP. aeruginosacystic fibrosis isolate FRD1 was also investigated and was seeding-dispersal-negative.
Pleiotropic effect of the SCO2127 gene on the glucose uptake, glucose kinase activity and carbon catabolite repression in Streptomyces peucetius var. caesius
Authors: Guzmán Silvia , Carmona Alonso , Escalante Laura , Imriskova Iveta , López Ruth , Rodríguez-Sanoja Romina , Ruiz Beatriz , Servín-González Luis , Sánchez Sergio , Langley Elizabeth
Published: May 2005

SCO2127 and SCO2126 (glkA) are adjacent regions located in Streptomyces coelicolor DNA. glkA encodes glucose kinase (Glk), which has been implicated in carbon catabolite repression (CCR) in the genus Streptomyces. In this work, the glkA and SCO2127 genes from S. coelicolor were used, either individually or together, to transform three mutants of Streptomyces peucetius var. caesius resistant to CCR. These mutants present decreased levels of Glk, and deficiency in glucose transport. When the mutants were transformed with a plasmid containing the SCO2127 sequence, glucose uptake and Glk activity values were increased to levels similar to or higher than those of the original strain, and each strain regained sensitivity to CCR. This result was surprising considering that the putative SCO2127 amino acid sequence does not seem to encode a glucose permease or a Glk. In agreement with these results, an increase in glkA mRNA levels was observed in a CCR-resistant mutant transformed with SCO2127 compared with those of the original strain and the CCR-resistant mutant itself. As expected, recombinants containing the glkA sequence reverted Glk to normal activity values, but glucose uptake remained deficient. The data suggest that the SCO2127 gene product enhances transcription of both genes, and support the first specific role for this region in Streptomyces species. The physiological consequence of this effect is an increase in the glucose catabolites that may be involved in eliciting CCR in this genus.
Prolonged selection in aerobic, glucose-limited chemostat cultures of Saccharomyces cerevisiae causes a partial loss of glycolytic capacity
Authors: Jansen Mickel L. A. , Diderich Jasper A. , Mashego Mlawule , Hassane Adham , de Winde Johannes H. , Daran-Lapujade Pascale , Pronk Jack T.
Published: May 2005

Prolonged cultivation ofSaccharomyces cerevisiaein aerobic, glucose-limited chemostat cultures (dilution rate, 0·10 h−1) resulted in a progressive decrease of the residual glucose concentration (from 20 to 8 mg l−1after 200 generations). This increase in the affinity for glucose was accompanied by a fivefold decrease of fermentative capacity, and changes in cellular morphology. These phenotypic changes were retained when single-cell isolates from prolonged cultures were used to inoculate fresh chemostat cultures, indicating that genetic changes were involved. Kinetic analysis of glucose transport in an ‘evolved’ strain revealed a decreasedKm, whileVmaxwas slightly increased relative to the parental strain. Apparently, fermentative capacity in the evolved strain was not controlled by glucose uptake. Instead, enzyme assays in cell extracts of the evolved strain revealed strongly decreased capacities of enzymes in the lower part of glycolysis. This decrease was corroborated by genome-wide transcriptome analysis using DNA microarrays. In aerobic batch cultures on 20 g glucose l−1, the specific growth rate of the evolved strain was lower than that of the parental strain (0·28 and 0·37 h−1, respectively). Instead of the characteristic instantaneous production of ethanol that is observed when aerobic, glucose-limited cultures of wild-typeS. cerevisiaeare exposed to excess glucose, the evolved strain exhibited a delay of ∼90 min before aerobic ethanol formation set in. This study demonstrates that the effects of selection in glucose-limited chemostat cultures extend beyond glucose-transport kinetics. Although extensive physiological analysis offered insight into the underlying cellular processes, the evolutionary ‘driving force’ for several of the observed changes remains to be elucidated.
Yeast wall protein 1 of Candida albicans
Authors: Granger Bruce L. , Flenniken Michelle L. , Davis Dana A. , Mitchell Aaron P. , Cutler Jim E.
Published: May 2005

Yeast wall protein 1 (Ywp1, also called Pga24) ofCandida albicansis predicted to be a 533 aa polypeptide with an N-terminal secretion signal, a C-terminal glycosylphosphatidylinositol anchor signal and a central region rich in serine and threonine. In yeast cultures, Ywp1p appeared to be linked covalently to glucans of the wall matrix, but, as cultures approached stationary phase, Ywp1p accumulated in the medium and was extractable from cells with disulfide-reducing agents. An 11 kDa propeptide of Ywp1p was also present in these soluble fractions; it possessed the soleN-glycan of Ywp1p and served as a useful marker for Ywp1p. DNA vaccines encoding all or part of Ywp1p generated analytically useful antisera in mice, but did not increase survival times for disseminated candidiasis. Replacement of the coding sequence ofYWP1with the fluorescent reporterGFPrevealed that expression ofYWP1is greatest during yeast exponential-phase growth, but downregulated in stationary phase and upon filamentation. Expression was upregulated when the extracellular phosphate concentration was low. Disruption by homologous recombination of bothYWP1alleles resulted in no obvious change in growth, morphology or virulence, but the Ywp1p-deficient blastoconidia exhibited increased adhesiveness and biofilm formation, suggesting that Ywp1p may promote dispersal of yeast forms ofC. albicans.
The rapid assignment of ruminal fungi to presumptive genera using ITS1 and ITS2 RNA secondary structures to produce group-specific fingerprints
Authors: Tuckwell Danny S. , Nicholson Matthew J. , McSweeney Christopher S. , Theodorou Michael K. , Brookman Jayne L.
Published: May 2005

Identification of microbial community members in complex environmental samples is time consuming and repetitive. Here, ribosomal sequences and hidden Markov models are used in a novel approach to rapidly assign fungi to their presumptive genera. The ITS1 and ITS2 fragments from a range of axenic, anaerobic gut fungal cultures, including several type strains, were isolated and the RNA secondary structures predicted for these sequences were used to generate a fingerprinting program. The methodology was then tested and the algorithms improved using a collection of environmentally derived sequences, providing a rapid indicator of the fungal diversity and numbers of novel sequence groups within the environmental sample from which they were derived. While the methodology was developed to assist in investigations involving the rumen ecosystem, it has potential generic application in studying diversity and population dynamics in other microbial ecosystems.
Pseudomonas aeruginosa lectin LecB is located in the outer membrane and is involved in biofilm formation
Authors: Tielker Denis , Hacker Stephanie , Loris Remy , Strathmann Martin , Wingender Jost , Wilhelm Susanne , Rosenau Frank , Jaeger Karl-Erich
Published: May 2005

Pseudomonas aeruginosais an opportunistic pathogen which causes a variety of diseases, including respiratory tract infections in patients suffering from cystic fibrosis. Therapeutic treatment ofP. aeruginosainfections is still very difficult because the bacteria exhibit high intrinsic resistance against a variety of different antibiotics and, in addition, form stable biofilms, e.g. in the human lung. Several virulence factors are produced byP. aeruginosa, among them the two lectins LecA and LecB, which exert different cytotoxic effects on respiratory epithelial cells and presumably facilitate bacterial adhesion to the airway mucosa. Here, the physiology has been studied of the lectin LecB, which binds specifically tol-fucose. A LecB-deficientP. aeruginosamutant was shown to be impaired in biofilm formation when compared with the wild-type strain, suggesting an important role for LecB in this process. This result prompted an investigation of the subcellular localization of LecB by cell fractionation and subsequent immunoblotting. The results show that LecB is abundantly present in the bacterial outer-membrane fraction. It is further demonstrated that LecB could be released specifically by treatment of the outer-membrane fraction withp-nitrophenylα-l-fucose, whereas treatment withd-galactose had no effect. In contrast, a LecB protein carrying the mutation D104A, which results in a defective sugar-binding site, was no longer detectable in the membrane fraction, suggesting that LecB binds to specific carbohydrate ligands located at the bacterial cell surface. Staining of biofilm cells using fluorescently labelled LecB confirmed the presence of these ligands.
Analysing protein–protein interactions of the Myxococcus xanthus Dif signalling pathway using the yeast two-hybrid system
Authors: Lancero Hope L. , Castaneda Schryl , Caberoy Nora B. , Ma Xiaoyuan , Garza Anthony G. , Shi Wenyuan
Published: May 2005

Thedifoperon is essential for fruiting body formation, fibril (exopolysaccharide) production and social motility ofMyxococcus xanthus. Thediflocus contains a gene cluster homologous to chemotaxis genes such asmcp(difA),cheW(difC),cheY(difD),cheA(difE) andcheC(difF), as well as an unknown ORF calleddifB. This study used yeast two-hybrid analysis to investigate possible interactions between Dif proteins, and determined that DifA, C, D and E interact in a similar fashion to chemotaxis proteins ofEscherichia coliandBacillus subtilis. It also showed that DifF interacted with DifD, and that the novel protein DifB did not interact with Dif proteins. Furthermore, DifA–F proteins were used to determine other possible protein–protein interactions in theM. xanthusgenomic library. The authors not only confirmed the specific interactions among known Dif proteins, but also discovered two novel interactions between DifE and Nla19, and DifB and YidC, providing some new information about the Dif signalling pathway. Based on these findings, a model for the Dif signalling pathway is proposed.
Genetic identification of microcystin ecotypes in toxic cyanobacteria of the genus Planktothrix
Authors: Kurmayer Rainer , Christiansen Guntram , Gumpenberger Marlies , Fastner Jutta
Published: May 2005

Microcystins (MCs) are toxic heptapeptides which are synthesized by the filamentous cyanobacterium Planktothrix and other genera via non-ribosomal peptide synthesis. MCs share the common structure cyclo(-d-ala1-l-x2-d-erythro-β-iso-aspartic acid3-l-z4-adda5-d-Glu6-N-methyl-dehydroalanine7) [Adda; (2S, 3S, 8S, 9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid], in which numerous MC variants have been reported. In general, the variation in structure is due to different amino acid residues in positions 7, 2 and 4 within the MC molecule, which are thought to be activated by the adenylation domains mcyAAd1, mcyBAd1 and mcyCAd, respectively. It was the aim of the study (i) to identify MC ecotypes that differed in the production of specific MC variants and (ii) to correlate the genetic variation within adenylation domains with the observed MC variants among 17 Planktothrix strains. Comparison of the sequences of mcyAAd1 revealed two distinctive Ad-genotypes differing in base pair composition and the insertion of an N-methyl transferase (NMT) domain. The mcyAAd1 genotype with NMT (2854 bp) correlated with N-methyl-dehydroalanine and the mcyAAd1 genotype without NMT (1692 bp) correlated with dehydrobutyrine in position 7. Within mcyBAd1, a lower genetic variation (0–4 %) and an exclusive correlation between one Ad-genotype and homotyrosine as well as another Ad-genotype and arginine in position 2 was found. The sequences of mcyCAd were found to be highly similar (0–1 % dissimilarity) and all strains contained arginine in position 4. The results on adenylation domain polymorphism do provide insights into the evolutionary origin of adenylation domains in Planktothrix and may be combined with ecological research in order to provide clues about the abundance of genetically defined MC ecotypes in nature.
Deletion of the yiaMNO transporter genes affects the growth characteristics of Escherichia coli K-12
Authors: Plantinga Titia H. , van der Does Chris , Tomkiewicz Danuta , van Keulen Geertje , Konings Wil N. , Driessen Arnold J. M.
Published: May 2005

Binding-protein-dependent secondary transporters make up a unique transport protein family. They use a solute-binding protein in proton-motive-force-driven transport. Only a few systems have been functionally analysed. TheyiaMNOgenes ofEscherichia coliK-12 encode one family member that transports the rare pentosel-xylulose. Its physiological role is unknown, since wild-typeE. coliK-12 does not utilizel-xylulose as sole carbon source. Deletion of theyiaMNOgenes inE. coliK-12 strain MC4100 resulted in remarkable changes in the transition from exponential growth to the stationary phase, high-salt survival and biofilm formation.
Consuming Now or Later?
Authors: Malkoc Selin A. , Zauberman Gal , Ulu Canan
Published: May 2005

Decisions are often temporally separated from their outcomes. Using theories of structural alignment and temporal construal, we examined how temporal distance and the associated shift in decision processes moderate susceptibility to context effects. Specifically, in two experiments (one hypothetical, one with real outcomes), we demonstrated that people attend more to nonalignable differences when the outcome of the decision is in the distant future than when it is in the near future. This shift in decision processes was found in preference and choice data, as well as coded written protocols. We further show that this temporal shift cannot be explained by differential involvement with the decision or by the feasibility and desirability of the attributes. Our findings establish temporal distance as an important moderator of structural alignment effects and also extend the implications of temporal construal theory beyond the nature of the attributes to the structural relationships among attributes.
The quality of release habitat for reared juvenile flounder, Platichthys flesus, with respect to salinity and depth
Authors: ANDERSEN A. K. , SCHOU J. , SPARREVOHN C. R. , NICOLAJSEN H. , STØTTRUP J. G.
Published: May 2005

Abstract  One prerequisite for a successful stocking programme is the choice of an appropriate release site, which would ensure good growth, survival and recruitment to the local fishery. The influence of different salinity regimes on habitat quality for juvenile flounder, Platichthys flesus (L.), was examined in Danish inshore waters using enclosures to study growth and survival. Three locations were chosen: Virksund (V) – constant low salinity at 10‰; Harre Vig (HV) – constant high salinity at 24‰; and Hjerk Nor – variable salinity, 0–25‰. Fish movement was examined, using a diffusion model, at the first two sites. At HV the fish had unrestricted dispersal opportunity resulting in average individual movement of 45 m day−1. Fish at V were restricted in dispersal in one direction because of a dam, about which they would concentrate under certain hydrographical conditions. Growth was highest at the locations with stable salinity and mortality highest at the location with variable salinity.
Evaluation of the Personal Dental Services (Wave 1) for Lambeth, Southwark and Lewisham Primary Care Trusts – Part 2: Retrospective analyses of treatment and other dental record data
Authors: Best Helen , Newton Tim
Published: May 2005

Aim/Objective  The purpose of the study was to undertake analyses of treatment data for the Personal Dental Services (PDS) of Lambeth, Southwark and Lewisham Primary Care Trusts and relate the analyses to the PDS goals of supporting practitioners deliver appropriate quality dental care and ensuring that appropriate quality safety net services are available for all residents.

Method  Analyses of treatment data provided by the Dental Practice Board were undertaken for the post‐PDS period (February 1999–March 2003, based on data availability). Analyses of the clinic notes for 1500 patients were also undertaken for the 1 year pre‐PDS period (October 1997–September 1998) and post‐introduction of the PDS (October 1998–June 2003). Two sets of analyses were undertaken to evaluate trends in treatment claims for the Dental Practice Board data, absolute numbers of each type of treatment claimed each month and change in numbers of types of treatments claimed over time. The clinic notes were used to undertake post‐PDS, pre‐PDS comparisons of the number of treatment items and grouped treatment item categories undertaken and the number of courses and percentages of private treatment items provided. The following sociodemographic characteristics of the patients were also analysed, age, gender, exemption  status  and  attendance  status.

Results  Overall it was identified that the percentage reduction in the number of treatment items undertaken was 13% (95% CI −19%, −7%), post‐ as compared to the pre‐PDS introduction period. On an annual basis it was identified that the percentage reduction in the number of treatment items undertaken per year per patient post‐PDS was 4% (95% CI −6%, −2%). There were significant variations in the impact of the PDS on the number of treatment items undertaken for different types of patients. A limited number of treatment types changed significantly post‐ as compared to pre‐PDS. The proportion of exempt patients treated did not increase  post‐PDS.

Conclusions  It is possible that a less  invasive style of dental treatment was provided during the course of the PDS, however, there was only limited evidence to indicate that dentists practice style changed based on types of treatment categories provided. The PDS provided a limited safety net service for local residents. In setting program goals the nature of quality dental practice requires definition and evaluation should be undertaken on a prospective basis.
Measuring men's preferences for involvement in medical care: getting the question right
Authors: Gattellari Melina , Ward Jeanette E.
Published: May 2005

Rationale, aims and objectives  Now that active involvement by patients in their health care is widely endorsed, valid and reliable methods for determining preferences for involvement in treatment decision making are essential. Relatively little methodological work has been conducted to compare and contrast their reliability and validity. Available single‐item measures exist to determine preferences, ranging from ‘menu‐based’ questions to simpler Likert‐type scales.

Methods  Within a larger community survey of 514 men aged 50–70 years in Sydney, Australia, we compared two measures to assess their preferences for involvement in medical decision making. Using the ‘menu‐based’ Control Preference Scale (CPS), men were classified as preferring to be either ‘passive’ or ‘active’ during decision making or to share (‘shared’) with their doctors on an equal basis. Men also were classified as preferring to be either ‘passive’ or ‘active’ according to a Likert‐scale measure.

Results  Agreement between the two measures was ‘poor’ (kappa = 0.19). While 24.9% of participants were classified as preferring a ‘passive’ role in treatment decision making according to the CPS, almost half (47.9%) were so classified according to Arora and McHorney's measure. In the absence of a ‘shared’ response option on the Arora and McHorney measure, 45.3% of men classified as preferring a ‘shared role’ on the CPS were instead categorized as ‘passive’ using Arora and McHorney's measure. Predictors of preferring a ‘passive’ role also differed, depending on the measure employed. Only occupational skill level predicted men's preferences for a ‘passive’ role when measured by the CPS [odds ratio (OR) = 1.67; 95% CI 1.09–2.55] (P = 0.02). For the Arora and McHorney's measure of preferences for involvement, men were significantly more likely to prefer a ‘passive’ role if they were older [adjusted odds ratio (AOR) = 1.06, 95% CI 1.02–1.09] (P = 0.001), currently smoking (AOR = 1.86, 95% CI 1.09–3.17) (P = 0.02) and had higher chance health locus of control scores (AOR = 1.26; 95% CI 1.01–1.56) (P = 0.04). Having been employed or previously employed in an occupation of a lower skill level was also significantly and independently predictive of a passive role (AOR = 2.35, 95% CI 1.57–3.50)  (P < 0.001).  

Conclusions  Single‐item measures of decisional preferences have poor convergent validity. Characteristics associated with preference classifications also differ, depending upon the measures used. These results suggest that research efforts should be directed towards developing psychometrically robust measures to determine decisional preferences.
Strengthening the HIV/AIDS service delivery system in Liberia: an international research capacity‐building strategy
Authors: Johnson Knowlton , Kennedy Stephen B. , Harris Albert O. , Lincoln Adams , Neace William , Collins David
Published: May 2005

Liberia's prolonged post‐conflict transition has negatively impacted its health infrastructure, including the functioning of its health care delivery system. Considering the current national health crises, a study was conducted to identify research gaps and the need to propose changes for improving the health care delivery system in the country. The study results clearly demonstrated a lack of HIV/AIDS research infrastructure including organizational structure, linkages, leadership, champions, expertise, resources, and policies and procedures. Alignment of research needs and practice, and research use to support HIV/AIDS service delivery programmes in the country was also limited. An international research capacity‐building partnership is proposed as an effective planned change strategy to strengthen HIV/AIDS‐related research infrastructure and to inform management and practice within the Liberian HIV/AIDS service delivery system. A proposed capacity‐building planning model can also strengthen research infrastructure and the production and use of research to positively impact the HIV/AIDS epidemic in Liberia and other developing countries.
Costs and effectiveness of pre‐ and post‐operative home physiotherapy for total knee replacement: randomized controlled trial
Authors: Mitchell Caroline , Walker Jane , Walters Stephen , Morgan Anne B. , Binns Teena , Mathers Nigel
Published: May 2005

Aims and objectives  To assess the effectiveness of pre‐ and post‐operative physiotherapy at home for unilateral total knee replacement (TKR).

Methods  In this pragmatic randomized controlled trial set in participants’ homes (four primary care trust areas) and physiotherapy outpatients in a South Yorkshire teaching hospital trust, 160 osteoarthritis patients waiting for unilateral TKR were randomly allocated to intervention (home) group (n = 80) or control (hospital outpatient) group (n = 80). The intervention group had pre‐ and post‐operative home visits for assessment and treatment by a community physiotherapist. Outcome measures were health‐related quality of life (HRQoL), measured by the Western Ontario McMaster Osteoarthritis index (WOMAC) and the Short Form 36 health survey (SF‐36) pre‐operatively and at 12 weeks post‐TKR operation; patient satisfaction; and  NHS resource use.

Results  No significant differences were observed between the two treatment groups in the primary outcome measure, the WOMAC pain score, or any other HRQoL score. The home group had a significantly greater mean number of physiotherapy sessions than the hospital group [mean difference 5.2 sessions, 95% confidence interval (CI) = −6.3 to −4.1; P = 0.001]. There was no significant difference in the total NHS costs per patient between groups. However, home physiotherapy for TKR was significantly more expensive (mean difference –£136.5, 95% CI = –£160 to –£113; P = 0.001). Patients were equally satisfied with physiotherapy at home or in hospital; however, more of the home group would choose their location for physiotherapy again.

Conclusions  Although home physiotherapy was as effective and as acceptable to patients as hospital outpatient physiotherapy for unilateral TKR, it was more expensive. Additional pre‐operative home physiotherapy did not improve patient‐perceived health outcomes.
Characterization of Gonadotrophin‐Releasing Hormone Precursor cDNA in the Old World Mole‐Rat Cryptomys Hottentotus Pretoriae: High Degree of Identity with the New World Guinea Pig Sequence
Authors: Kalamatianos T. , Du Toit L. , Hrabovszky E. , Kalló I. , Marsh P. J. , Bennett N. C. , Coen C. W.
Published: May 2005

Regulation of pituitary gonadotrophins by the decapeptide gonadotrophin‐releasing hormone 1 (GnRH1) is crucial for the development and maintenance of reproductive functions. A common amino acid sequence for this decapeptide, designated as ‘mammalian’ GnRH, has been identified in all mammals thus far investigated with the exception of the guinea pig, in which there are two amino acid substitutions. Among hystricognath rodents, the members of the family Bathyergidae regulate reproduction in response to diverse cues. Thus, highveld mole‐rats (Cryptomys hottentotus pretoriae) are social bathyergids in which breeding is restricted to a particular season in the dominant female, but continuously suppressed in subordinate colony members. Elucidation of reproductive control in these animals will be facilitated by characterization of their GnRH1 gene. A partial sequence of GnRH1 precursor cDNA was isolated and characterized. Comparative analysis revealed the highest degree of identity (86%) to guinea pig GnRH1 precursor mRNA. Nevertheless, the deduced amino acid sequence of the mole‐rat decapeptide is identical to the ‘mammalian’ sequence rather than that of guinea pigs. Successful detection of GnRH1‐synthesizing neurones using either a guinea pig GnRH1 riboprobe or an antibody against the ‘mammalian’ decapeptide is consistent with the guinea pig‐like sequence for the precursor and the classic ‘mammalian’ form for the decapeptide. The high degree of identity in the GnRH1 precursor sequence between this Old World mole‐rat and the New World guinea pig is consistent with the theory that caviomorphs and phiomorphs originated from a common ancestral line in the Palaeocene to mid Eocene, some 63–45 million years ago.
Pilot study of the safety and efficacy of Myobloc™ (botulinum toxin type B) for treatment of axillary hyperhidrosis
Authors: Baumann Leslie , Slezinger Anele , Halem Monica , Vujevich Justin , Martin Lucy K. , Black Laura , Bryde Joy
Published: May 2005

Background  Botulinum toxin type B (BTX‐B, Myobloc™, San Francisco, CA, USA) was FDA‐approved for the treatment of cervical dystonia in December 2000. It has since been used off‐label for the treatment of axillary hyperhidrosis. However, there are sparse data in the medical literature evaluating the safety and efficacy of Myobloc™ (botulinum toxin type B) for this indication.

Objective  To assess the safety, efficacy and duration of action of Myobloc™ (botulinum toxin type B) in the treatment of bilateral axillary hyperhidrosis.

Methods  This study was a double‐blinded, randomized, pilot study conducted in an outpatient office setting at a private academic medical center beginning in November 2001. Twenty‐three male and female volunteers between the ages of 18 and 80 were screened for participation; 20 participants with primary axillary hyperhidrosis were enrolled. Participants were injected subcutaneously with either Myobloc™ (botulinum toxin type B) (2500 U, or 0.5 ml, per axilla) or 0.5 ml vehicle (100 mM NaCl, 10 mM succinate, and 0.5 mg/ml human albumin) into bilateral axillae. Participants who received placebo were rolled over and received Myobloc™ (botulinum toxin type B) at subsequent visits. All participants were followed until sweating returned to baseline levels. This trial was initially conceived as a placebo‐controlled study; however, owing to the insufficient size of the placebo group, the placebo arm of this trial was dropped during data analysis. The main outcome measures were safety, efficacy, and duration of effect.

Results  According to participant assessment of axillary hyperhidrosis improvement (A‐HI) and quality of life (A‐HQOL) scores and the physician assessment scores, a significant difference was observed in treatment response at Day 30 in the participants receiving Myobloc™ (botulinum toxin type B) injections. Duration of action ranged from 2.2 to 8.1 months (mean 5.0 months). The adverse event profile included bruising, flu‐like symptoms, and dry eyes.

Conclusion  Myobloc™ (botulinum toxin type B) proved to be safe and efficacious for the treatment of bilateral axillary hyperhidrosis. More studies are needed to assess the duration of response using different doses of Myobloc™ (botulinum toxin type B).
Lifestyle of Nordic people with psoriasis
Authors: Davidsson Steingrimur , Blomqvist Kirsti , Molin Lars , Mørk Cato , Sigurgeirsson Bardur , Zachariae Hugh , Zachariae Robert
Published: May 2005

Aim  The Nordic Quality of Life Study was undertaken to assess the relationship between psoriasis and the quality of life in Nordic countries. The intention was also to determine whether there was a relationship between drinking, smoking, and the use of psychotherapeutic agents on the one hand, and psoriasis severity and quality of life on the other.

Materials and methods  A questionnaire was mailed to 11,300 members of the Nordic Psoriasis Associations. Additional psoriasis patients were recruited by dermatologists (387) or admitted to dermatologic wards (385). These patients also underwent a physical examination, and their Psoriasis Area and Severity Index (PASI) was determined. The questionnaire included the Psoriasis Disability Index (PDI), Psoriasis Life Stress Inventory (PLSI), and additional questions on disease severity, treatment, and psoriasis arthritis. It also included questions regarding lifestyle issues, such as smoking, alcohol use, and the use of tranquilizers, antidepressants, and sleeping medications.

Results  The response rate for members was 50.2%. Included in the evaluation were 6497 patients. Men drank significantly more beer and liquor than women. The number of beers per day had a weak correlation with the PDI. Wine consumption, however, showed a weak, but significant, negative correlation with both PDI and PLSI. Patients admitted to dermatologic wards smoked more cigarettes and drank less wine than the other two groups. Significant differences were found between countries with regard to total alcohol consumption and cigarette smoking. The number of cigarettes and the use of tranquilizers, sleeping medications, and antidepressants showed small, but significant, positive correlations with psoriasis quality of life measures.

Conclusions  Cigarette smoking and the use of tranquilizers, sleeping medications, and antidepressants are statistically correlated with impaired psoriasis‐related quality of life.
Effect on quality of life in patients with pityriasis rosea: Is it associated with rash severity?
Authors: Chuh Antonio A. T. , Chan Henry H. L.
Published: May 2005

Background  It is unknown how the quality of life (QOL) is affected in patients with pityriasis rosea (PR), and whether it is related to rash severity.

Methods  We constructed a valid and reliable Cantonese version of the Dermatology Life Quality Index (DLQI). We recruited patients with PR, with atopic dermatitis and with acne vulgaris, and controls of the same sex and comparable age. We applied the DLQI and the Pityriasis Rosea Severity Score (PRSS) to the patients with PR, the DLQI and the SCORing Atopic Dermatitis Index (SCORAD) to the controls with atopic dermatitis, and the DLQI and the Leeds Acne Grading System (LAGS) to the controls with acne vulgaris.

Results  Total DLQI scores of the 22 patients with PR (mean: 6.36, SD: 5.79) were significantly lower than those of the 22 controls with atopic dermatitis (mean: 12.00, SD: 5.38) (P = 0.021), but were insignificantly different from those of the 22 controls with acne vulgaris (mean: 6.86, SD: 4.53) (P = 0.57). Correlation between the total DLQI and PRSS scores was weak (γs = +0.19) and insignificant (P = 0.40). All six DLQI parameters were insignificantly correlated with the PRSS scores.

In contrast, the total DLQI scores and most of the DLQI parameters were strongly correlated with the rash severity scores for the control subjects. Significantly more patients with PR have concerns regarding disease etiology and infectivity.

Conclusions  The QOL of the patients with PR was significantly less affected than that for the patients with atopic dermatitis, but was insignificantly different from the patients with acne vulgaris. Unlike atopic dermatitis and acne vulgaris, the effects on the QOL in PR are insignificantly correlated with rash severity. These results bear important implications on clinical management.
Tectonic control on development of a Frasnian–Famennian (Late Devonian) palaeokarst surface, Canning Basin reef complexes, northwestern Australia
Authors: CHOW N. , GEORGE A. D. , TRINAJSTIC K. M.
Published: May 2005

The Frasnian–Famennian boundary in the Canning Basin has long been associated with a shelf‐wide, short‐lived fall in relative sea‐level. A near‐planar palaeokarst surface, separating Frasnian proximal forereef and Famennian backreef facies, locally marks the boundary in the northwestern Lennard Shelf (Chedda Cliffs area, northern Napier Range). Surface and subsurface relationships between the Frasnian and Famennian strata suggest that a major episode of normal faulting and associated tilting in the latest Frasnian uplifted the platform margin to subaerially expose and erode all of the margin and uppermost forereef facies. Tectonic control on the development of this Frasnian–Famennian palaeokarst surface questions the interpretation of a simple, shelf‐wide eustatically driven relative sea‐level fall. Instead, a tectonic event affecting the northwestern Lennard Shelf, coupled with widespread recognition of a reduction in carbonate production at or very near the Frasnian–Famennian boundary elsewhere on the shelf, supports earlier interpretations of a major phase of basin‐margin uplift related to extension along basin‐bounding faults.
Effects of cocaine‐induced behavioural sensitization on GABA transmission within rat medial prefrontal cortex
Authors: Jayaram Prathiba , Steketee Jeffery D.
Published: May 2005

Studies support the involvement of mPFC dopaminergic and glutamatergic systems in the development of cocaine sensitization. GABA is known to modulate dopamine and glutamatergic systems in the mPFC. In addition, recent reports have suggested that cocaine sensitization might be associated with a decrease in GABAB receptor responsiveness in the mPFC. Hence, in vivo microdialysis of the mPFC was performed to examine the effects on extracellular GABA levels within the mPFC of a cocaine challenge subsequent to repeated cocaine administration. Male Sprague‐Dawley rats were given four daily injections of saline (1.0 mL/kg, i.p.) or cocaine (15 mg/kg, i.p.) and challenged with the same dose of saline or cocaine 1, 7 or 28 days later. Acute cocaine produced a motor‐stimulant response that was significantly augmented in repeated cocaine animals at all withdrawal time points. Moreover, sensitized animals exhibited a significant increase in extracellular GABA levels after 1 and 7 days but not 28 days following repeated cocaine exposure. These data suggest that cocaine‐induced sensitization is associated with a transient increase in mPFC GABA transmission.
A semaphorin code defines subpopulations of spinal motor neurons during mouse development
Authors: Cohen Samia , Funkelstein Lydiane , Livet Jean , Rougon Geneviève , Henderson Christopher E. , Castellani Valerie , Mann Fanny
Published: May 2005

In the spinal cord, motor neurons (MNs) with similar muscle targets and sensory inputs are grouped together into motor pools. To date, relatively little is known about the molecular mechanisms that control the establishment of pool‐specific circuitry. Semaphorins, a large family of secreted and cell surface proteins, are important mediators of developmental processes such as axon guidance and cell migration. Here, we used mRNA in situ hybridization to study the expression patterns of semaphorins and their receptors, neuropilins and plexins, in the embryonic mouse spinal cord. Our data show that semaphorins and their receptors are differentially expressed in MNs that lie in distinct locations within the spinal cord. Furthermore, we report a combinatorial expression of class 3 (secreted) semaphorins and their receptors that characterizes distinct motor pools within the brachial and lumbar spinal cord. Finally, we found that a secreted semaphorin, Sema3A, elicits differential collapse responses in topologically distinct subpopulations of spinal MNs. These findings lead us to propose that semaphorins and their receptors might play important roles in the sorting of motor pools and the patterning of their afferent and efferent projections.
Striatal expression of GDNF and differential vulnerability of midbrain dopaminergic cells
Authors: Barroso‐Chinea Pedro , Cruz‐Muros Ignacio , Aymerich María S. , Rodríguez‐Díaz Manuel , Afonso‐Oramas Domingo , Lanciego José L. , González‐Hernández Tomás
Published: May 2005

Glial cell line‐derived neurotrophic factor (GDNF) is a member of the transforming growth factor‐β superfamily that when exogenously administrated exerts a potent trophic action on dopaminergic (DA) cells. Although we know a lot about its signalling mechanisms and pharmacological effects, physiological actions of GDNF on the adult brain remain unclear. Here, we have used morphological and molecular techniques, and an experimental model of Parkinson's disease in rats, to investigate whether GDNF constitutively expressed in the adult mesostriatal system plays a neuroprotective role on midbrain DA cells. We found that although all midbrain DA cells express both receptor components of GDNF (GFRα1 and Ret), those in the ventral tegmental area (VTA) and rostromedial substantia nigra (SNrm) also contain GDNF but not GDNFmRNA. The levels of GDNFmRNA are significantly higher in the ventral striatum (vSt), the target region of VTA and SNrm cells, than in the dorsal striatum (dSt), the target region of DA cells in the caudoventral substantia nigra (SNcv). After fluoro‐gold injection in striatum, VTA and SNrm DA cells show triple labelling for tyrosine hydroxylase, GDNF and fluoro‐gold, and after colchicine injection in the lateral ventricle, they become GDNF‐immunonegative, suggesting that GDNF in DA somata comes from their striatal target. As DA cells in VTA and SNrm are more resistant than those in SNcv to intracerebroventricular injection of 6‐OHDA, as occurs in Parkinson's disease, we can suggest that the fact that they project to vSt, where GDNF expression is significantly higher than in the dSt, is a neuroprotective factor involved in the differential vulnerability of midbrain DA neurons.
Blockade of melanocortin transmission inhibits cocaine reward
Authors: Hsu Richard , Taylor Jane R. , Newton Samuel S. , Alvaro John D. , Haile Colin , Han G. , Hruby Victor J. , Nestler Eric J. , Duman Ronald S.
Published: May 2005

Melanocortins and the melanocortin‐4 receptor (MC4‐R) are enriched in the nucleus accumbens, a brain region that has been implicated in the rewarding action of cocaine and other drugs of abuse. In the present study we use a number of rat behavioral models to show that infusion of a melanocortin peptide antagonist into the nucleus accumbens blocks the reinforcing, incentive motivational, and locomotor sensitizing effects of cocaine. We also show that locomotor responses to repeated cocaine exposure are completely blocked in MC4‐R null mutant mice and reduced in Agouti mice that overexpress an endogenous inhibitor of melanocortins in the brain. The results also demonstrate that cocaine administration increases the expression of MC4‐R in the nucleus accumbens and striatum, and that MC4‐R is co‐localized with prodynorphin in medium spiny neurons in the nucleus accumbens. Together, these findings indicate that the behavioral actions of cocaine are dependent on activation of MC4‐R, and suggest that upregulation of this receptor by drug exposure may contribute to sensitization of these behavioral responses. Modulation of cocaine reward is a novel action of the melanocortin–MC4‐R system and could be targeted for the development of new medications for cocaine addiction.
Crown architecture in sun and shade environments: assessing function and trade‐offs with a three‐dimensional simulation model
Authors: Pearcy Robert W. , Muraoka Hiroyuki , Valladares Fernando
Published: May 2005

Sun and shade environments place markedly different constraints on the photosynthetic performance of plants. Leaf‐level photosynthetic responses to sun and shade have been extensively investigated, whereas there has been much less research on the functional role of crown architecture in these environments. This paper focuses on the role of architecture in maximizing light capture and photosynthesis in shaded understories and in minimizing exposure to excess radiation in open high light environments. Understanding these contrasting roles of architecture is facilitated by application of a three‐dimensional structural–functional model, Y‐plant. Surveys of understory plants reveal a diversity of architectures but a strong convergence at only modest light‐capture efficiencies because of significant self‐shading. Simulations with Psychotria species revealed that increasing internode lengths would increase light‐capture efficiencies and whole plant carbon gain. However, the costs of the additional required biomechanical support was high, which, in terms of relative growth rates, would override the advantage provided by higher light‐capture efficiencies. In high light environments, leaf angles and self‐shading provide structural photoprotection, minimizing potential damage from photoinhbition. Simulations reveal that without these structural protections photoinhibition of photosynthesis is likely to be much greater with daily carbon gain significantly reduced.
A Latent Growth Curve Analysis of the Structure of Aggression, Drug Use, and Delinquent Behaviors and Their Interrelations Over Time in Urban and Rural Adolescents
Authors: Farrell Albert D. , Sullivan Terri N. , Esposito Layla E. , Meyer Aleta L. , Valois Robert F.
Published: May 2005

Latent growth curve analysis was used to examine the structure and interrelations among aggression, drug use, and delinquent behavior during early adolescence. Five waves of data were collected from 667 students at three urban middle schools serving a predominantly African American population, and from a more ethnically diverse sample of 950 students at four rural middle schools. One set of models focused on changes in individual behaviors; the other on changes in a global problem behavior factor. Models with separate growth trajectories for aggression, drug use, and delinquent behavior provided the best fit for both samples and revealed relations between initial levels of aggression and subsequent changes in the other behaviors. Boys and girls differed in their initial levels of these behaviors, but not their patterns of change. Differences in growth curve trajectories were found across samples. These findings have important implications for assessment and prevention of problem behaviors in adolescents.
Judging Fund Managers by the Company They Keep
Authors: COHEN RANDOLPH B. , COVAL JOSHUA D. , PÁSTOR ĽUBOŠ
Published: May 2005

We develop a performance evaluation approach in which a fund manager's skill is judged by the extent to which the manager's investment decisions resemble the decisions of managers with distinguished performance records. The proposed performance measures use historical returns and holdings of many funds to evaluate the performance of a single fund. Simulations demonstrate that our measures are particularly useful in ranking managers. In an application that relies on such ranking, our measures reveal strong predictability in the returns of U.S. equity funds. Our measures provide information about future fund returns that is not contained in the standard measures.
The Theory of Bank Risk Taking and Competition Revisited
Authors: BOYD JOHN H. , DE NICOLÓ GIANNI
Published: May 2005

There is a large body of literature that concludes that—when confronted with increased competition—banks rationally choose more risky portfolios. We argue that this literature has had a significant influence on regulators and central bankers. We review the empirical literature and conclude that the evidence is best described as “mixed.” We then show that existing theoretical analyses of this topic are fragile, since there exist fundamental risk‐incentive mechanisms that operate in exactly the opposite direction, causing banks to become more risky as their markets become more concentrated. These mechanisms should be essential ingredients of models of bank competition.
To Steal or Not to Steal: Firm Attributes, Legal Environment, and Valuation
Authors: DURNEV ART , KIM E. HAN
Published: May 2005

Data on corporate governance and disclosure practices reveal wide within‐country variation that decreases with the strength of investors' legal protection. A simple model identifies three firm attributes related to that variation: investment opportunities, external financing, and ownership structure. Using firm‐level governance and transparency data from 27 countries, we find that all three firm attributes are related to the quality of governance and disclosure practices, and firms with higher governance and transparency rankings are valued higher in stock markets. All relations are stronger in less investor‐friendly countries, demonstrating that firms adapt to poor legal environments to establish efficient governance practices.