bluuebunny/crossref_metadata_2025 huggingface dataset:
Re-plumbing in a Mediterranean sponge
Authors: Mendola D , van den Boogaart J.G.M , van Leeuwen J.L , Wijffels R.H
Published: September 2007

Observations are reported for
Dysidea avara
sponges where once functioning oscula (outlets) are converted through internal re-plumbing into functioning oversized ostia (OSO; inlets). Flow tank studies employed high-speed photography and particle tracking of laser-illuminated 0.5–6.0 μm diameter glass beads to trace particles streaming into OSO. A fluorescein dye/glass bead uptake experiment showed that an oversized ostium was connected through internal structures to the lone osculum. Beginning 30 s after uptake and continuing over a 20 min period, dye streamed from the osculum, but no beads emerged. Scanning electron microscopy revealed that beads were deposited only on the inhalant side of particle filtering choanocyte chambers and not on the exhalant side, suggesting that internal re-plumbing had occurred. Functioning OSO were also found on freshly collected specimens in the field, making it highly unlikely that formation of OSO was only an artefact of sponges being held in a laboratory tank.
Elevated substitution rates estimated from ancient DNA sequences
Authors: Ho Simon Y.W , Kolokotronis Sergios-Orestis , Allaby Robin G
Published: September 2007

Ancient DNA sequences are able to offer valuable insights into molecular evolutionary processes, which are not directly accessible via modern DNA. They are particularly suitable for the estimation of substitution rates because their ages provide calibrating information in phylogenetic analyses, circumventing the difficult task of choosing independent calibration points. The substitution rates obtained from such datasets have typically been high, falling between the rates estimated from pedigrees and species phylogenies. Many of these estimates have been made using a Bayesian phylogenetic method that explicitly accommodates heterochronous data. Stimulated by recent criticism of this method, we present a comprehensive simulation study that validates its performance. For datasets of moderate size, it produces accurate estimates of rates, while appearing robust to assumptions about demographic history. We then analyse a large collection of 749 ancient and 727 modern DNA sequences from 19 species of animals, plants and bacteria. Our new estimates confirm that the substitution rates estimated from ancient DNA sequences are elevated above long-term phylogenetic levels.
Extrinsic effects, estimating opponents' RHP, and the structure of dominance hierarchies
Authors: Dugatkin Lee Alan , Dugatkin Aaron David
Published: September 2007

We examined the impact of winner and loser effects on dominance hierarchy formation when individuals are capable of estimating their opponent's resource holding power (RHP). The accuracy of such estimates was a variable in our simulations, and we considered cases in which all individuals err within the same bounds, as well as cases in which some individuals consistently overestimate, while others consistently underestimate their opponent's fighting RHP. In all cases, we found a clearly defined linear hierarchy. In most simulations, the vast majority of interactions were ‘attack–retreats’, and the remainder of interactions were almost all ‘fights’. Error rates had no effect on the linearity of the hierarchy or the basic attack–retreat nature of interactions, and consistent over and underestimation did not affect the ultimate position of an individual in a hierarchy.
Focused tsunami waves
Authors: Berry M.V
Published: September 2007

Shallower regions in the oceans can act as lenses, focusing the energy of tsunamis, typically onto cusp points where two caustic lines meet. Diffraction theory enables calculation of the profile of a tsunami wave propagating through a cusp. The wave elevation depends on position, time and two main parametersMandB: the large parameterMis the distance of the cusp from the lens, divided by the local wavelength of the tsunami without focusing, andBquantifies the spatial extent of the initial disturbance. Focusing amplifies the wave by a factorAproportional toM1/4and can potentially multiply the tsunami energy (proportional toA2) 10-fold over a transverse range of tens of kilometres.
Boundary layers and stress concentration in the circular shearing of annular thin films
Authors: Coman Ciprian D , Bassom Andrew P
Published: September 2007

This work addresses a generalization of Dean's classical problem, which sought to explain how an annular thin elastic plate buckles under uniform shearing forces applied around its edges. We adapt the original setting by assuming that the outer edge is radially stretched while the inner rim undergoes in-plane rotation through some small angle. Boundary-layer methods are used to investigate analytically the deformation pattern which is set up and localized around the inner hole when this angle reaches a well-defined critical wrinkling value. Linear stability theory enables us to identify both the critical load and the preferred number of wrinkles appearing in the deformed configuration. Our asymptotic results are compared with a number of direct numerical simulations.
Socially induced brain differentiation in a cooperatively breeding songbird
Authors: Voigt Cornelia , Leitner Stefan , Gahr Manfred
Published: September 2007

Birds living in social groups establish dominance hierarchies, and taking up the dominant position influences behaviour and physiological parameters. In cooperatively breeding white-browed sparrow weavers (Plocepasser mahali), the transition from subordinate helper to dominant breeder male induces the production of a new type of song. This song contains a large number of new syllables and differs in temporal pattern from duet songs produced by all other group members. Here we show that this change in social status of adult males affects the morphology of a behavioural control circuit, the song control system of songbirds that is composed of large neuron populations. The volume of the song control areas HVC and RA and their gene-expression levels depend on males' social status. Dominant males have several times larger testes than subordinates, which is not reflected in circulating androgen and oestrogen levels. Our findings suggest a remarkable differentiation of adult vertebrate brains in relation to changing social cues.
Spatial considerations for the allocation of pre-pandemic influenza vaccination in the United States
Authors: Wu Joseph T , Riley Steven , Leung Gabriel M
Published: September 2007

The impact of the next influenza pandemic may be mitigated by inducing immunity in individuals prior to the start of national epidemics using a pre-pandemic vaccine targeted against current avian influenza strains. The US Department of Health and Human Services (HHS) intends that pre-pandemic vaccines will be allocated to states in proportion to the size of their population in predefined priority groups, i.e. approximately pro-rata. We show that such an equitable policy is likely to be the least efficient in terms of the number of infections averted. We demonstrate that the potential benefits could be substantial if a fully discretionary policy is allowed, i.e. if some regions are allocated sufficient vaccines to achieve herd immunity while other regions are allocated no vaccine. Since such an inequitable policy may be impractical, we consider the sensitivity of an intermediate policy (in which 50% of the stockpile is allocated on a pro-rata basis) to key transmission uncertainties. The benefits of the 50% discretionary policy are sensitive to parameter values which cannot be known in advance. Therefore, despite substantial potential benefits of non-pro-rata policies, our results suggest that the current HHS policy of pro-rata allocation by state is a good compromise in terms of simplicity, robustness, equity and efficiency.
Computer simulation of feeding behaviour in the thylacine and dingo as a novel test for convergence and niche overlap
Authors: Wroe Stephen , Clausen Philip , McHenry Colin , Moreno Karen , Cunningham Eleanor
Published: September 2007

The extinct marsupial thylacine (
Thylacinus cynocephalus
) and placental grey wolf (
Canis lupus
) are commonly presented as an iconic example of convergence. However, various analyses suggest distinctly different behaviours and specialization towards either relatively small or large prey in the thylacine, bringing the degree of apparent convergence into question. Here we apply a powerful engineering tool, three-dimensional finite element analysis incorporating multiple material properties for bone, to examine mechanical similarity and niche overlap in the thylacine and the wolf subspecies implicated in its extinction from mainland Australia,
Canis lupus dingo
. Comparisons of stress distributions not only reveal considerable similarity, but also informative differences. The thylacine's mandible performs relatively poorly where only the actions of the jaw muscles are considered, although this must be considered in the light of relatively high bite forces. Stresses are high in the posterior of the thylacine's cranium under loads that simulate struggling prey. We conclude that relative prey size may have been comparable where both species acted as solitary predators, but that the dingo is better adapted to withstand the high extrinsic loads likely to accompany social hunting of relatively large prey. It is probable that there was considerable ecological overlap. As a large mammalian hypercarnivore adapted to taking small-medium sized prey, the thylacine may have been particularly vulnerable to disturbance.
The role of gap phase processes in the biomass dynamics of tropical forests
Authors: Feeley Kenneth J , Davies Stuart J , Ashton Peter S , Bunyavejchewin Sarayudh , Nur Supardi M.N , Kassim Abd Rahman , Tan Sylvester , Chave Jérôme
Published: September 2007

The responses of tropical forests to global anthropogenic disturbances remain poorly understood. Above-ground woody biomass in some tropical forest plots has increased over the past several decades, potentially reflecting a widespread response to increased resource availability, for example, due to elevated atmospheric CO2and/or nutrient deposition. However, previous studies of biomass dynamics have not accounted for natural patterns of disturbance and gap phase regeneration, making it difficult to quantify the importance of environmental changes. Using spatially explicit census data from large (50 ha) inventory plots, we investigated the influence of gap phase processes on the biomass dynamics of four ‘old-growth’ tropical forests (Barro Colorado Island (BCI), Panama; Pasoh and Lambir, Malaysia; and Huai Kha Khaeng (HKK), Thailand). We show that biomass increases were gradual and concentrated in earlier-phase forest patches, while biomass losses were generally of greater magnitude but concentrated in rarer later-phase patches. We then estimate the rate of biomass change at each site independent of gap phase dynamics using reduced major axis regressions and ANCOVA tests. Above-ground woody biomass increased significantly at Pasoh (+0.72% yr−1) and decreased at HKK (−0.56% yr−1) independent of changes in gap phase but remained stable at both BCI and Lambir. We conclude that gap phase processes play an important role in the biomass dynamics of tropical forests, and that quantifying the role of gap phase processes will help improve our understanding of the factors driving changes in forest biomass as well as their place in the global carbon budget.
Soil health in agricultural systems
Authors: Kibblewhite M.G , Ritz K , Swift M.J
Published: September 2007

Soil health is presented as an integrative property that reflects the capacity of soil to respond to agricultural intervention, so that it continues to support both the agricultural production and the provision of other ecosystem services. The major challenge within sustainable soil management is to conserve ecosystem service delivery while optimizing agricultural yields. It is proposed that soil health is dependent on the maintenance of four major functions: carbon transformations; nutrient cycles; soil structure maintenance; and the regulation of pests and diseases. Each of these functions is manifested as an aggregate of a variety of biological processes provided by a diversity of interacting soil organisms under the influence of the abiotic soil environment. Analysis of current models of the soil community under the impact of agricultural interventions (particularly those entailing substitution of biological processes with fossil fuel-derived energy or inputs) confirms the highly integrative pattern of interactions within each of these functions and leads to the conclusion that measurement of individual groups of organisms, processes or soil properties does not suffice to indicate the state of the soil health. A further conclusion is that quantifying the flow of energy and carbon between functions is an essential but non-trivial task for the assessment and management of soil health.
Assessing the impacts of agricultural intensification on biodiversity: a British perspective
Authors: Firbank Les G , Petit Sandrine , Smart Simon , Blain Alasdair , Fuller Robert J
Published: September 2007

Agricultural intensification is best considered as the level of human appropriation of terrestrial net primary production. The global value is set to increase from 30%, increasing pressures on biodiversity. The pressures can be classified in terms of spatial scale, i.e. land cover, landscape management and crop management. Different lowland agricultural landscapes in Great Britain show differences among these pressures when habitat diversity and nutrient surplus are used as indicators. Eutrophication of plants was correlated to N surplus, and species richness of plants correlated with broad habitat diversity. Bird species diversity only correlated with habitat diversity when the diversity of different agricultural habitats was taken into account. The pressures of agricultural change may be reduced by minimizing loss of large habitats, minimizing permanent loss of agricultural land, maintaining habitat diversity in agricultural landscapes in order to provide ecosystem services, and minimizing pollution from nutrients and pesticides from the crops themselves. While these pressures could potentially be quantified using an internationally consistent set of indicators, their impacts would need to be assessed using a much larger number of locally applicable biodiversity indicators.
A systems biology approach for pathway level analysis
Authors: Draghici Sorin , Khatri Purvesh , Tarca Adi Laurentiu , Amin Kashyap , Done Arina , Voichita Calin , Georgescu Constantin , Romero Roberto
Published: September 2007

A common challenge in the analysis of genomics data is trying to understand the underlying phenomenon in the context of all complex interactions taking place on various signaling pathways. A statistical approach using various models is universally used to identify the most relevant pathways in a given experiment. Here, we show that the existing pathway analysis methods fail to take into consideration important biological aspects and may provide incorrect results in certain situations. By using a systems biology approach, we developed an impact analysis that includes the classical statistics but also considers other crucial factors such as the magnitude of each gene’s expression change, their type and position in the given pathways, their interactions, etc. The impact analysis is an attempt to a deeper level of statistical analysis, informed by more pathway-specific biology than the existing techniques. On several illustrative data sets, the classical analysis produces both false positives and false negatives, while the impact analysis provides biologically meaningful results. This analysis method has been implemented as a Web-based tool, Pathway-Express, freely available as part of the Onto-Tools (http://vortex.cs.wayne.edu).
Computational identification and functional validation of regulatory motifs in cartilage-expressed genes
Authors: Davies Sherri R. , Chang Li-Wei , Patra Debabrata , Xing Xiaoyun , Posey Karen , Hecht Jacqueline , Stormo Gary D. , Sandell Linda J.
Published: September 2007

Chondrocyte gene regulation is important for the generation and maintenance of cartilage tissues. Several regulatory factors have been identified that play a role in chondrogenesis, including the positive transacting factors of the SOX family such as SOX9, SOX5, and SOX6, as well as negative transacting factors such as C/EBP and delta EF1. However, a complete understanding of the intricate regulatory network that governs the tissue-specific expression of cartilage genes is not yet available. We have taken a computational approach to identify cis-regulatory, transcription factor (TF) binding motifs in a set of cartilage characteristic genes to better define the transcriptional regulatory networks that regulate chondrogenesis. Our computational methods have identified several TFs, whose binding profiles are available in the TRANSFAC database, as important to chondrogenesis. In addition, a cartilage-specific SOX-binding profile was constructed and used to identify both known, and novel, functional paired SOX-binding motifs in chondrocyte genes. Using DNA pattern-recognition algorithms, we have also identified cis-regulatory elements for unknown TFs. We have validated our computational predictions through mutational analyses in cell transfection experiments. One novel regulatory motif, N1, found at high frequency in the COL2A1 promoter, was found to bind to chondrocyte nuclear proteins. Mutational analyses suggest that this motif binds a repressive factor that regulates basal levels of the COL2A1 promoter.
The evolution of genome compression and genomic novelty in RNA viruses
Authors: Belshaw Robert , Pybus Oliver G. , Rambaut Andrew
Published: September 2007

The genomes of RNA viruses are characterized by their extremely small size and extremely high mutation rates (typically 10 kb and 10−4/base/replication cycle, respectively), traits that are thought to be causally linked. One aspect of their small size is the genome compression caused by the use of overlapping genes (where some nucleotides code for two genes). Using a comparative analysis of all known RNA viral species, we show that viruses with larger genomes tend to have less gene overlap. We provide a numerical model to show how a high mutation rate could lead to gene overlap, and we discuss the factors that might explain the observed relationship between gene overlap and genome size. We also propose a model for the evolution of gene overlap based on the co-opting of previously unused ORFs, which gives rise to two types of overlap: (1) the creation of novel genes inside older genes, predominantly via +1 frameshifts, and (2) the incremental increase in overlap between originally contiguous genes, with no frameshift preference. Both types of overlap are viewed as the creation of genomic novelty under pressure for genome compression. Simulations based on our model generate the empirical size distributions of overlaps and explain the observed frameshift preferences. We suggest that RNA viruses are a good model system for the investigation of general evolutionary relationship between genome attributes such as mutational robustness, mutation rate, and size.
Biased clustered substitutions in the human genome: The footprints of male-driven biased gene conversion
Authors: Dreszer Timothy R. , Wall Gregory D. , Haussler David , Pollard Katherine S.
Published: September 2007

We examined fixed substitutions in the human lineage since divergence from the common ancestor with the chimpanzee, and determined what fraction are AT to GC (weak-to-strong). Substitutions that are densely clustered on the chromosomes show a remarkable excess of weak-to-strong “biased” substitutions. These unexpected biased clustered substitutions (UBCS) are common near the telomeres of all autosomes but not the sex chromosomes. Regions of extreme bias are enriched for genes. Human and chimp orthologous regions show a striking similarity in the shape and magnitude of their respective UBCS maps, suggesting a relatively stable force leads to clustered bias. The strong and stable signal near telomeres may have participated in the evolution of isochores. One exception to the UBCS pattern found in all autosomes is chromosome 2, which shows a UBCS peak midchromosome, mapping to the fusion site of two ancestral chromosomes. This provides evidence that the fusion occurred as recently as 740,000 years ago and no more than ∼3 million years ago. No biased clustering was found in SNPs, suggesting that clusters of biased substitutions are selected from mutations. UBCS is strongly correlated with male (and not female) recombination rates, which explains the lack of UBCS signal on chromosome X. These observations support the hypothesis that biased gene conversion (BGC), specifically in the male germline, played a significant role in the evolution of the human genome.
Causes for the intriguing presence of tRNAs in phages
Authors: Bailly-Bechet Marc , Vergassola Massimo , Rocha Eduardo
Published: September 2007

Phages have highly compact genomes with sizes reflecting their capacity to exploit the host resources. Here, we investigate the reasons for tRNAs being the only translation-associated genes frequently found in phages. We were able to unravel the selective processes shaping the tRNA distribution in phages by analyzing their genomes and those of their hosts. We found ample evidence against tRNAs being selected to facilitate phage integration in the prokaryotic chromosomes. Conversely, there is a significant association between tRNA distribution and codon usage. We support this observation by introducing a master equation model, where tRNAs are randomly gained from their hosts and then lost either neutrally or according to a set of different selection mechanisms. Those tRNAs present in phages tend to correspond to codons that are simultaneously highly used by the phage genes, while rare in the host genome. Accordingly, we propose that a selective recruitment of tRNAs compensates for the compositional differences between the phage and the host genomes. To further understand the importance of these results in phage biology, we analyzed the differences between temperate and virulent phages. Virulent phages contain more tRNAs than temperate ones, higher codon usage biases, and more important compositional differences with respect to the host genome. These differences are thus in perfect agreement with the results of our master equation model and further suggest that tRNA acquisition may contribute to higher virulence. Thus, even though phages use most of the cell’s translation machinery, they can complement it with their own genetic information to attain higher fitness. These results suggest that similar selection pressures may act upon other cellular essential genes that are being found in the recently uncovered large viruses.
Prediction of individual genetic risk to disease from genome-wide association studies
Authors: Wray Naomi R. , Goddard Michael E. , Visscher Peter M.
Published: September 2007

Empirical studies suggest that the effect sizes of individual causal risk alleles underlying complex genetic diseases are small, with most genotype relative risks in the range of 1.1–2.0. Although the increased risk of disease for a carrier is small for any single locus, knowledge of multiple-risk alleles throughout the genome could allow the identification of individuals that are at high risk. In this study, we investigate the number and effect size of risk loci that underlie complex disease constrained by the disease parameters of prevalence and heritability. Then we quantify the value of prediction of genetic risk to disease using a range of realistic combinations of the number, size, and distribution of risk effects that underlie complex diseases. We propose an approach to assess the genetic risk of a disease in healthy individuals, based on dense genome-wide SNP panels. We test this approach using simulation. When the number of loci contributing to the disease is >50, a large case-control study is needed to identify a set of risk loci for use in predicting the disease risk of healthy people not included in the case-control study. For diseases controlled by 1000 loci of mean relative risk of only 1.04, a case-control study with 10,000 cases and controls can lead to selection of ∼75 loci that explain >50% of the genetic variance. The 5% of people with the highest predicted risk are three to seven times more likely to suffer the disease than the population average, depending on heritability and disease prevalence. Whether an individual with known genetic risk develops the disease depends on known and unknown environmental factors.
The anatomy of microbial cell state transitions in response to oxygen
Authors: Schmid Amy K. , Reiss David J. , Kaur Amardeep , Pan Min , King Nichole , Van Phu T. , Hohmann Laura , Martin Daniel B. , Baliga Nitin S.
Published: September 2007

Adjustment of physiology in response to changes in oxygen availability is critical for the survival of all organisms. However, the chronology of events and the regulatory processes that determine how and when changes in environmental oxygen tension result in an appropriate cellular response is not well understood at a systems level. Therefore, transcriptome, proteome, ATP, and growth changes were analyzed in a halophilic archaeon to generate a temporal model that describes the cellular events that drive the transition between the organism’s two opposing cell states of anoxic quiescence and aerobic growth. According to this model, upon oxygen influx, an initial burst of protein synthesis precedes ATP and transcription induction, rapidly driving the cell out of anoxic quiescence, culminating in the resumption of growth. This model also suggests that quiescent cells appear to remain actively poised for energy production from a variety of different sources. Dynamic temporal analysis of relationships between transcription and translation of key genes suggests several important mechanisms for cellular sustenance under anoxia as well as specific instances of post-transcriptional regulation.
The CYP2D6 polymorphism in relation to the metabolism of amitriptyline and nortriptyline in the Faroese population
Authors: Halling Jónrit , Weihe Pál , Brosen Kim
Published: September 2007

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The metabolisms of amitriptyline (AT) to (E)‐10‐hydroxyamitriptyline and of nortripyline (NT) to (E)‐10‐hydroxynortriptyline are catalysed by CYP2D6.

• A correlation between the sparteine metabolic ratio and the NT/(E)‐10‐hydroxynortriptyline and the AT/(E)‐10‐hydroxyamitriptyline ratios, respectively, has been observed in patients in treatment with the same dose of AT or NT.

• The frequency of CYP2D6 poor metabolizers (PMs) is 15% (twofold compared with other Whites) among healthy Faroese.

• This frequency has not been investigated in Faroese patients in AT treatment and the consequences of the CYP2D6 PM phenotype for dose and plasma concentrations of AT and metabolites are not known in these patients.

WHAT THIS STUDY ADDS

• In patients treated with different daily dosages (5–100 mg) of AT a correlation between the sparteine metabolic ratio and the NT/(E)‐10‐hydroxynortriptyline and AT/(E)‐10‐hydroxyamitriptyline ratios was observed.

• A high proportion (22%) of CYP2D6 PMs in a Faroese patient group medicated with AT was observed.

• However, similar doses of AT and concentrations of AT and NT were noted in extensive metabolizers and in PMs.

AIM

To determine the frequency of CYP2D6 poor metabolizers (PMs) in a Faroese patient group medicated with amitriptyline (AT) and to investigate plasma concentrations of AT and metabolites in relation to CYP2D6.

METHODS

CYP2D6 phenotype and genotype were determined in 23 Faroese patients treated with AT. Plasma concentrations of AT and metabolites were determined by high‐performance liquid chromatography and investigated in relation to CYP2D6 activity.

RESULTS

Of the 23 patients phenotyped and genotyped, five (22%) (95% confidence interval 7.5, 43.7) were CYP2D6 PMs. No difference was found in AT daily dosage between PMs (median 25 mg day−1; range 5–80) and extensive metabolizers (EMs) (median 27.5 mg day−1; range 10–100). The (E)‐10‐OH‐nortriptyline (NT)/dose concentrations were higher in EMs than in PMs and the NT/(E)‐10‐OH‐NT and AT/(E)‐10‐OH‐AT ratios were higher in PMs compared with EMs. The log sparteine metabolic ratio correlated positively with the NT/(E)‐10‐OH‐NT ratio (rs = 0.821; P < 0.0005) and the AT/(E)‐10‐OH‐AT ratio (rs = 0.605; P < 0.006).

CONCLUSION

A high proportion of CYP2D6 PMs was found in a Faroese patient group medicated with AT. However, similar doses of AT and concentrations of AT and NT were noted in EMs and PMs, probably due to varying doses and indications for AT treatment.
Muscular exercise can cause highly pathological liver function tests in healthy men
Authors: Pettersson Jonas , Hindorf Ulf , Persson Paula , Bengtsson Thomas , Malmqvist Ulf , Werkström Viktoria , Ekelund Mats
Published: September 2007

What is already known about this subject

• The occurrence of idiosyncratic drug hepatotoxicity is a major problem in all phases of clinical drug development and the leading cause of postmarketing warnings and withdrawals.

• Physical exercise can result in transient elevations of liver function tests.

• There is no consensus in the literature on which forms of exercise may cause changes in liver function tests and to what extent.

What this study adds

• Weightlifting results in profound increases in liver function tests in healthy men used to moderate physical activity, not including weightlifting.

• Liver function tests are significantly increased for at least 7 days after weightlifting.

• It is important to impose relevant restrictions on heavy muscular exercise prior to and during clinical studies.

Aim

To investigate the effect of intensive muscular exercise (weightlifting) on clinical chemistry parameters reflecting liver function in healthy men.

Methods

Fifteen healthy men, used to moderate physical activity not including weightlifting, performed an 1 h long weightlifting programme. Blood was sampled for clinical chemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LD), gamma‐glutamyl transferase (γGT), alkaline phosphatase (ALP), bilirubin, creatine kinase (CK) and myoglobin] at repeated intervals during 7 days postexercise and at a follow‐up examination 10–12 days postexercise.

Results

Five out of eight studied clinical chemistry parameters (AST, ALT, LD, CK and myoglobin) increased significantly after exercise (P < 0.01) and remained increased for at least 7 days postexercise. Bilirubin, γGT and ALP remained within the normal range.

Conclusion

The liver function parameters, AST and ALT, were significantly increased for at least 7 days after the exercise. In addition, LD and, in particular, CK and myoglobin showed highly elevated levels. These findings highlight the importance of imposing restrictions on weightlifting prior to and during clinical studies. Intensive muscular exercise, e.g. weightlifting, should also be considered as a cause of asymptomatic elevations of liver function tests in daily clinical practice.
Thioridazine: resurrection as an antimicrobial agent?
Authors: Thanacoody H. K. R.
Published: September 2007

The emergence of multiresistant bacterial strains and the continuing burden of infectious disease globally point to the urgent need for novel affordable antimicrobial drugs. Thioridazine is a phenothiazine antipsychotic drug with well‐recognized antimicrobial activity, but this property has not been harnessed for clinical use as a result of its central nervous system and cardiac side‐effects. The cardiotoxicity of thioridazine has recently been shown to be structurally specific at a molecular level, whereas its antimicrobial properties are shared by a number of phenothiazine analogues. This raises the possibility that its enantiomers or its inactive metabolite, the ring sulphoxide, may act as a lead compound in the future development of antimicrobial drugs to face the new challenges in infectious disease.
The impact of joint bleeding and synovitis on physical ability and joint function in a murine model of haemophilic synovitis
Authors: MEJIA‐CARVAJAL C. , HAKOBYAN N. , ENOCKSON C. , VALENTINO L. A.
Published: September 2007

Summary.  Haemophilia is a congenital disorder that commonly results in musculoskeletal bleeding and orthopaedic complications. After an acute joint haemorrhage, an increase in intra‐articular pressure and inflammation cause pain, swelling and limited motion. Blood in the joint space provokes a proliferative disorder known as haemophilic synovitis. Overgrowth of the synovial membrane causes mechanical dysfunction. Eventually, there is destruction of the articular surface and underlying bone. The aim of this project was to test the hypothesis that a minimum number of haemarthroses negatively impacts on joint function and that this would be reflected by decreased physical performance of experimental animals. Mice deficient in factor VIII coagulant activity were trained to ambulate on a rotating rod then injured three times at weekly intervals. Their ability to walk was then compared to a group of uninjured mice. Cohorts of mice were killed after 1, 2 or 3 months and the knee joints examined by gross and histological methods. The results supported the following conclusions: (i) haemophilic mice can be trained to ambulate on a rotating rod; (ii) acute hemarthrosis temporarily impairs their ability to ambulate and (iii) following recovery from acute injury, mice developing synovitis demonstrated inferior physical ability compared to mice not developing synovitis. This is the first description of a quantitative assay to monitor joint function in experimental animals and should be useful to evaluate the efficacy of new therapies developed to prevent and treat bleeding and to test strategies to counter the devastating effects of synovitis.
Circulating CD4+ CD25+ regulatory T cells correlate with chronic hepatitis B infection
Authors: Peng Guoping , Li Shuping , Wu Wei , Sun Zhen , Chen Yiqiong , Chen Zhi
Published: September 2007

Circulating CD4+ CD25+ regulatory T cells (Tregs) have been demonstrated to maintain immunotolerance and suppress the antigen‐specific or antigen‐non‐specific T‐cell responses, but their role in chronic hepatitis B (CHB) infection in humans has not been well characterized. In this study, we analysed the frequency and phenotypic characteristics of CD4+ CD25+ Tregs in patients of different hepatitis B virus (HBV) infection status, and investigated the effect of Tregs on antiviral immune responses in CHB patients, and the mechanism of this effect. A total of 137 subjects, including 79 CHB patients, 26 asymptomatic HBV carriers (ASCs), 12 acute hepatitis B (AHB) patients and 20 healthy controls, were enrolled in the study. We found that the frequency of CD4+ CD25high Tregs in AHB patients was comparable to that in healthy controls, while it was significantly increased in CHB patients. CD4+ CD25+ Tregs produced interleukin (IL)‐10 but little or no interferon (IFN)‐γ under anti‐CD3 stimulation. In CHB patients, the frequency of CD4+ CD25high Tregs positively correlated with serum viral load, and the Tregs were capable of suppressing the proliferation and IFN‐γ production of autologous peripheral blood mononuclear cells (PBMC) mediated by HBV antigen stimulation in vitro. However, combined administration of anti‐programmed death‐1 (PD‐1) and anti‐cytotoxic lymphocyte antigen‐4 (CTLA‐4) monoclonal antibody slightly enhanced the cellular proliferation and significantly increased the IFN‐γ production of PBMC cocultured with Tregs at a ratio of 2 : 1. Thus, the frequency of circulating CD4+ CD25+ Tregs is increased in patients with CHB, and this may play an important role in viral persistence by modulating virus‐specific immune responses.
Generalized idiopathic root resorption: a case report
Authors: BHATT NEHA , HOLROYD ISABELLE
Published: September 2007

Background.  Cases of generalized idiopathic root resorption have been reported in the literature. However the majority of previously reported cases have affected adults, and it has been rare that a possible link to a medical condition has been found.

Case Report.  The subject of this case report was 11 years old when generalized root resorption was first diagnosed. This case report is unusual in that the resorption may be connected to a bone dysplasia. The possible medical diagnoses and links to tooth resorption have been discussed for this very rare case.

Conclusion.  The investigation into the exact diagnosis of the patient and the treatment of tooth resorption is still ongoing and has required input from many disciplines of Medicine and Dentistry.
Mothers as facilitators of oral hygiene in early childhood
Authors: MOHEBBI SIMIN Z. , VIRTANEN JORMA I. , MURTOMAA HEIKKI , VAHID‐GOLPAYEGANI MOJTABA , VEHKALAHTI MIIRA M.
Published: September 2007

Background.  Toothbrushing twice daily is a recommended component of oral self‐care soon after the eruption of primary dentition.

Aim.  This study aims to investigate oral hygiene and frequency of oral cleaning in children up to 3 years, in relation to mother‐related factors.

Design.  A cross‐sectional study of 504 children aged 12–36 months in Tehran, Iran was implemented. Mothers answered questions about their own oral self‐care and their activity in their children's oral hygiene. The child's oral hygiene was assessed on the basis of visible dental plaque on the labial surfaces of the upper central incisors. Data analysis included chi‐square test, analysis of variance (anova) and logistic regression.

Results.  Twice daily oral cleaning was reported for 5% of all children and once daily cleaning for 19% of the 12‐ to 15‐month‐old children, 18% of the 16‐ to 23‐month‐old children, and 48% of the 24‐ to 36‐month‐old children. Of the mothers, 59% stated that they lacked the skill to clean their children's teeth. Dental plaque was observed in 65–76% of the children. Clean teeth were more likely (OR = 1·7, 95% CI 1.3–2.3) in children of mothers who themselves have a higher toothbrushing frequency.

Conclusions.  To improve oral hygiene in early childhood, more emphasis should be placed on mothers’ own toothbrushing and their skills in their children's oral cleaning.
A survey of 460 supernumerary teeth in Brazilian children and adolescents
Authors: DE OLIVEIRA GOMES CARLOS , DRUMMOND SERGIO NEVES , JHAM BRUNO CORREIA , ABDO EVANDRO NEVES , MESQUITA RICARDO ALVES
Published: September 2007

Objective.  This study aimed to survey the demographic profile of supernumerary teeth (ST) in Brazilian children and adolescents.

Methods.  A retrospective analysis was carried out of all nonsyndromic patients with ST attended at the Pediatric Oral Surgery Service of the Universidade Federal de Minas Gerais between 1995 and 2004. Diagnosis of ST was based on clinical and radiographic examination. Chi‐squared test was used for statistical analysis.

Results.  This study included 460 ST found in 305 patients. Radiographic assessment (32.1%) was the main care‐seeking reason and also the means through which most (97.6%) permanent ST were identified. Most cases were single (63.0%), conical (44.6%), and unerupted (76.8%) ST. Most teeth were fully developed (41.3%), normally orientated (78.9%), placed in a palatal/lingual‐sagittal position (84.1%), adjacent to the crown of permanent teeth (50.2%) (P < 0.001). The most frequent clinical complication was permanent teeth displacement (36.0%). Treatment was surgical removal followed by orthodontics (61.6%).

Conclusions.  The demographic profile of ST herein presented will be useful to provide additional epidemiological information. A wide range of factors should be considered when evaluating ST. In addition, it is essential to detect ST as early as possible to avoid complications and to assure successful management. Even after treatment, patients must be followed up.
A cyclic‐di‐GMP receptor required for bacterial exopolysaccharide production
Authors: Lee Vincent T. , Matewish Jody M. , Kessler Jennifer L. , Hyodo Mamoru , Hayakawa Yoshihiro , Lory Stephen
Published: September 2007

Bis‐(3′,5′)‐cyclic‐dimeric‐guanosine monophosphate (c‐di‐GMP) has been shown to be a global regulatory molecule that modulates the reciprocal responses of bacteria to activate either virulence pathways or biofilm formation. The mechanism of c‐di‐GMP signal transduction, including recognition of c‐di‐GMP and subsequent phenotypic regulation, remain largely uncharacterized. The key components of these regulatory pathways are the various adaptor proteins (c‐di‐GMP receptors). There is compelling evidence suggesting that, in addition to PilZ domains, there are other unidentified c‐di‐GMP receptors. Here we show that the PelD protein of Pseudomonas aeruginosa is a novel c‐di‐GMP receptor that mediates c‐di‐GMP regulation of PEL polysaccharide biosynthesis. Analysis of PelD orthologues identified a number of conserved residues that are required for c‐di‐GMP binding as well as synthesis of the PEL polysaccharide. Secondary structure similarities of PelD to the inhibitory site of diguanylate cyclase suggest that a common fold can act as a platform to bind c‐di‐GMP. The combination of a c‐di‐GMP binding site with a variety of output signalling motifs within one protein domain provides an explanation for the specificity for different cellular responses to this regulatory dinucleotide.
Aer on the inside looking out: paradigm for a PAS–HAMP role in sensing oxygen, redox and energy
Authors: Taylor Barry L.
Published: September 2007

Aer, the Escherichia coli aerotaxis (oxygen‐sensing) receptor, is representative of a small class of receptors that face the cytoplasm in bacteria. Instead of sensing oxygen directly, Aer detects redox changes in the electron transport system or cytoplasm when the bacteria enter or leave a hypoxic microniche. As a result, Aer sensing also enables bacteria to avoid environments where carbon deficiency, unfavourable reduction potential or other insults would limit energy production. An FAD‐binding PAS domain is the sensor for Aer and a HAMP domain interacts with the PAS domain to form an input–output module for signal transduction. By analogy to the first solution structure of an isolated HAMP domain from Archaeoglobus, Aer HAMP is proposed to fold into a four‐helix bundle that rotates between a signal‐on and signal‐off conformation. Aer is the first protein in which a PAS–HAMP input–output module has been investigated. The structure and signal transduction mechanism of Aer is providing important insights into signalling by PAS and HAMP domains.
A sample of mJy radio sources at 1.4 GHz in the Lynx and Hercules fields – I. Radio imaging, multicolour photometry and spectroscopy
Authors: Rigby E. E. , Snellen I. A. G. , Best P. N.
Published: September 2007

With the goal of identifying high-redshift radio galaxies with Fanaroff–Riley class I (FR I) classification, here are presented high-resolution, wide-field radio observations, near-infrared and optical imaging and multi-object spectroscopy of two fields of the Leiden–Berkeley Deep Survey. These fields, Hercules.1 and Lynx.2, contain a complete sample of 81 radio sources with S1.4 GHz > 0.5 mJy within 0.6 deg2. This sample will form the basis for a study of the population and cosmic evolution of high-redshift, low-power, FR I radio sources which will be presented in Paper II. Currently, the host galaxy identification fraction is 86 per cent with 11 sources remaining unidentified at a level of r′≥ 25.2 mag (Hercules; four sources) or r′≥ 24.4 mag (Lynx; seven sources) or K≳ 20 mag. Spectroscopic redshifts have been determined for 49 per cent of the sample and photometric redshift estimates are presented for the remainder of the sample.
Reassessment of tissue Na+ concentration as a criterion for salinity tolerance in bread wheat
Authors: GENC YUSUF , MCDONALD GLENN K. , TESTER MARK
Published: September 2007

Wheat is the most important crop grown on many of world's saline and sodic soils, and breeding for improved salinity tolerance (ST) is the only feasible way of improving yield and yield stability under these conditions. There are a number of possible mechanisms by which cereals can tolerate high levels of salinity, but these can be considered in terms of Na+ exclusion and tissue tolerance. Na+ exclusion has been the focus of much of the recent work in wheat, but with relatively little progress to date in developing high‐yielding, salt‐tolerant genotypes. Using a diverse collection of bread wheat germplasm, the present study was conducted to assess the value of tissue Na+ concentration as a criterion for ST, and to determine whether ST differs with growth stage. Two experiments were conducted, the first with 38 genotypes and the second with 21 genotypes.

A wide range of Na+ concentrations within the roots and shoots as well as in ST were observed in both experiments. However, maintenance of growth and yield when grown with 100 mm NaCl was not correlated with the ability of a genotype to exclude Na+ either from an individual leaf blade or from the whole shoot. The K+ : Na+ ratio also showed a wide range among the genotypes, but it did not explain the variation in ST among the genotypes. The results suggested that Na+ exclusion and tissue tolerance varied independently, and there was no significant relationship between Na+ exclusion and ST in bread wheat. Consequently, similar levels of ST may be achieved through different combinations of exclusion and tissue tolerance. Breeding for improved ST in bread wheat needs to select for traits related to both exclusion and tissue tolerance.
Issues and challenges of involving users in medical device development
Authors: Bridgelal Ram Mala , Grocott Patricia R. , Weir Heather C. M.
Published: September 2007

Background  User engagement has become a central tenet of health‐care policy. This paper reports on a case study in progress that highlights user engagement in the research process in relation to medical device development.

Objectives  To work with a specific group of medical device users to uncover unmet needs, translating these into design concepts, novel technologies and products. To validate a knowledge transfer model that may be replicated for a range of medical device applications and user groups.

Methods  In depth qualitative case study to elicit and analyse user needs. The focus is on identifying design concepts for medical device applications from unmet needs, and validating these in an iterative feedback loop to the users.

Results  The case study has highlighted three interrelated challenges: ensuring unmet needs drive new design concepts and technology development; managing user expectations and managing the research process.

Conclusion  Despite the challenges, active participation of users is crucial to developing usable and clinically effective devices.