bluuebunny/crossref_metadata_2025 huggingface dataset:
Specificity and completion time distributions of biochemical processes
Authors: Munsky Brian , Nemenman Ilya , Bel Golan
Published: December 2009

In order to produce specific complex structures from a large set of similar biochemical building blocks, many biochemical systems require high sensitivity to small molecular differences. The first and most common model used to explain this high specificity is kinetic proofreading, which has been extended to a variety of systems from detection of DNA mismatch to cell signaling processes. While the specification properties of kinetic proofreading models are well known and were studied in various contexts, very little is known about their temporal behavior. In this work, we study the dynamical properties of discrete stochastic two-branch kinetic proofreading schemes. Using the Laplace transform of the corresponding chemical master equation, we obtain an analytical solution for the completion time distribution. In particular we provide expressions for the specificity as well as the mean and variance of the process completion times. We also show that, for a wide range of parameters, a process distinguishing between two different products can be reduced to a much simpler three-point process. Our results allow for the systematic study of the interplay between specificity and completion times, as well as testing the validity of the kinetic proofreading model in biological systems.
Water permeability of poly(ethylene terephthalate): A grand canonical ensemble molecular dynamics simulation study
Authors: Eslami Hossein , Müller-Plathe Florian
Published: December 2009

In this work, our previous simulation method on the calculation of solubility of nonpolar solutes in nonpolar polymers [H. Eslami and F. Müller-Plathe, Macromolecules 40, 6413 (2007)] has been extended to the case of solubility calculation for water, as a polar penetrant, in poly(ethylene terephthalate), as a polar polymer. The chemical potentials of water in the polymer phase and in the gas phase have been calculated by employing our grand canonical ensemble molecular dynamics simulation method [H. Eslami and F. Müller-Plathe, J. Comput. Chem. 28, 1763 (2007)]. In this paper it is shown that performing just two independent simulations, one in the polymer phase and one in the vapor phase, in the grand canonical ensemble, is sufficient to calculate the phase coexistence point. The calculated solubilities, diffusion coefficients, and permeability coefficients are in good agreement with experimental data. Also the calculated glass transition temperature of the wet polymer is shown to be in a very good agreement with experiment.
Polarization switching characteristics of BiFeO3 thin films epitaxially grown on Pt/MgO at a low temperature
Authors: Ryu Sangwoo , Son Jong Yeog , Shin Young-Han , Jang Hyun M. , Scott James F.
Published: December 2009

An [001]-oriented BiFeO3 (BFO) thin film having a pseudotetragonal symmetry was epitaxially grown on a Pt/MgO (001) substrate. The Pt-buffered MgO substrate enabled us to fabricate an epitaxial heterostructure at a temperature as low as 500 °C. We examined three major criteria for high-density ferroelectric memories using this BFO/Pt film capacitor. The polarization switching experiment has demonstrated that the film is electrically fatigue-free and possesses stable charge-retention characteristics with a reasonably large sensing margin of 22 μC/cm2. These suggest potential applicability of the present BFO/Pt heteroepitaxial film capacitor to nonvolatile memories.
Photoluminescence induced by thermal annealing in SrTiO3 thin film
Authors: Rho JaeHoon , Jang SeungHun , Ko Young Dong , Kang SeungJin , Kim Dong-Wook , Chung J.-S. , Kim Miyoung , Han Moonsup , Choi Eunjip
Published: December 2009

We have grown SrTiO3 thin films by rf-sputtering and studied its photoluminescence (PL) property after postannealing treatments. While the as-grown film does not show any PL signal, visible frequency PL emissions are induced by high temperature (T>550 °C) annealing. When subsequent low-T (50 °C) and long term (>8 months) annealing was made, the PL-spectra evolved into another pattern in which four distinct luminescence peaks appear simultaneously at λ=1.8, 2.2, 2.7, and 3.1 eV. We propose that these remarkable room temperature PL effects are due to both metastable and energetically stabilized defect states formed inside the band gap.
Selenite enhances arsenate toxicity in Thunbergia alata
Authors: Bluemlein Katharina , Klimm Elizabeth , Raab Andrea , Feldmann Jörg
Published: December 2009

Environmental context. Arsenic and selenium are two elements ubiquitously distributed in our environment. While selenium is not known to be essential to plants, it is certainly toxic as is arsenic. On the other hand selenium is known to be essential for mammals and an increase in selenium concentration in plants when used as feed or food may be beneficial for mammals in regions of low selenium concentration. The wide distribution of these two elements in the soil might result in elevated co-exposure of plants. So far no interactions of those elements in plants have ever been studied, although this might be mandatory when nutritionists would like to increase the selenium concentrations in crops, which are already challenged by elevated levels of arsenic.
Abstract. The suspected antagonism between selenite and arsenite in various mammalian species gave reason to investigate the effect of selenite on arsenate toxicity in higher plants using Thunbergia alata as a model plant. Here, we present a study involving (1) toxicity tests, (2) uptake and translocation experiments as well as (3) selenium–sulfur–arsenic speciation analysis by HPLC-ESMS-ICP-MS (oxygen) of selected plant tissues. The EC50 (effective concentration that inhibits growth by 50%) values, as a result of the toxicity studies, showed that selenite co-exposure enhances arsenate toxicity. The detection of two selenium species, SeII-PC2 complex and Se-cysteinylserine glutathione, suggested that the increased toxicity symptoms might have been a result of the competition of SeII with AsIII for sulfhydryl groups (crucial for arsenite detoxification in plant cells) as binding partners.
Seasonal variations of volatile organic compounds in the coastal Baltic Sea
Authors: Orlikowska Anna , Schulz-Bull Detlef E.
Published: December 2009

Environmental context. Volatile organic compounds (VOCs) play a significant role in the global climate and are engaged in several atmospheric reactions. Relatively large amounts of VOCs are emitted from coastal waters, which is why these zones are expected to have significant impact on the atmospheric chemistry. The abundance of a single compound depends on its source and removal processes as well as on environmental parameters. Thus, seasonal changes can greatly affect the occurrence and behaviour of these trace gases.
Abstract. In order to investigate temporal changes in combination with the influence of different environmental parameters on the concentration and the composition of volatile organic compounds (VOCs), seawater samples from the coastal Baltic Sea were weekly measured from January to November 2008. In most cases, concentrations of VOCs varied seasonally and were influenced by changes in temperature and light conditions or biological species composition. A nearly two-fold increase in the mean concentration was noticed for isoprene, iodomethane and bromoform in the season with higher water temperature. The strongest flux of dimethylsulfide to the atmosphere appeared in May and July. Its high production was related to the presence of Prymnesiophyceae. The highest concentrations of diiodomethane and chloroiodomethane were observed with the spring and autumn phytoplankton bloom; their distribution was strongly controlled by light intensity. Flux calculations showed that coastal regions can affect local atmosphere, especially during biologically active periods. The strongest emission of bromoform and iodomethane was in July and August. The data presented here highlights the need to include seasonal cycles when calculating the global budgets and modelling sea–air fluxes of trace gases.
Riverine macroinvertebrate assemblages up to 8 years after riparian restoration in a semi-rural catchment in Victoria, Australia
Authors: Becker Alistair , Robson Belinda J.
Published: December 2009

Willow removal followed by riparian revegetation is a widespread river restoration practice in Australia, but the ecological response to this has rarely been evaluated. We sampled river macroinvertebrates from six sites each of three riparian vegetation types: revegetated (treatment), willow-dominated (control) and native forest (reference) in the Gellibrand River catchment during austral spring 2007 and autumn 2008, and measured temperature and light intensity. Revegetated sites varied in age from 1 to 8 years since restoration. Abundances of invertebrates were similar across vegetation types, but were higher during autumn. Macroinvertebrate assemblages at revegetated sites (regardless of age) and at willow-dominated sites showed little among-site variation compared with native forest sites, which showed high site-to-site variability. Water temperatures and light intensity were higher at revegetated sites where works had recently been completed and cooler in native forest sites and long-established revegetated sites. The reduced variability in macroinvertebrate communities among revegetated sites may result from their history as willow-dominated sites or from the disturbance created by willow removal. Either way, these results suggest that longer than 8 years is required before macroinvertebrate assemblages in restored stretches of stream show the variation that appears characteristic of natural sites.
Estimation of survival and detection probabilities for multiple tagged salmon stocks with nested migration routes, using a large-scale telemetry array
Authors: Melnychuk Michael C.
Published: December 2009

Mark–recapture models for estimating survival and detection probabilities of tagged animals that migrate past successive receiver stations can incorporate multiple, linked stocks to improve detection probability estimates. When multiple release groups are analysed in a common framework, detection information can be shared to compensate for small sample sizes and provide generality beyond single-stock approaches. Methods for structuring complex detection history data and applying standard mark–recapture models are presented, allowing for information sharing among multiple stocks under nested migration route structures, where some portions of routes are shared with other stocks and other portions are unique. Possible biases from split-route migration patterns within a release group are described, along with a simple method of correcting these biases using stock-specific parameters that incorporate movement probabilities. Environmental covariates can be paired with stock-specific run timing data to model stock-specific detection probabilities that change seasonally. Finally, a method for assessing the redundancy of receivers on a multiple-receiver detection line is described, based on considerations of receiver line geometry. Examples are drawn from detection data of juvenile salmon on the Pacific Ocean Shelf Tracking Project (POST) array, but the methods presented here are transferable to other systems.
Modified hierarchical Bayesian biomass dynamics models for assessment of short-lived invertebrates: a comparison for tropical tiger prawns
Authors: Zhou Shijie , Punt André E. , Deng Roy , Dichmont Catherine M. , Ye Yimin , Bishop Janet
Published: December 2009

Conventional biomass dynamics models express next year’s biomass as this year’s biomass plus surplus production less catch. These models are typically applied to species with several age-classes but it is unclear how well they perform for short-lived species with low survival and high recruitment variation. Two alternative versions of the standard biomass dynamics model (Standard) were constructed for short-lived species by ignoring the ‘old biomass’ term (Annual), and assuming that the biomass at the start of the next year depends on density-dependent processes that are a function of that biomass (Stock-recruit). These models were fitted to catch and effort data for the grooved tiger prawn Penaeus semisulcatus using a hierarchical Bayesian technique. The results from the biomass dynamics models were compared with those from more complicated weekly delay-difference models. The analyses show that: the Standard model is flexible for short-lived species; the Stock-recruit model provides the most parsimonious fit; simple biomass dynamics models can provide virtually identical results to data-demanding models; and spatial variability in key population dynamics parameters exists for P. semisulacatus. The method outlined in this paper provides a means to conduct quantitative population assessments for data-limited short-lived species.
Effect of intrinsic organic carbon on the optical properties of fresh diesel soot
Authors: Adler Gabriella , Riziq Ali Abo , Erlick Carynelisa , Rudich Yinon
Published: December 2009

This study focuses on the retrieval of the normalized mass absorption cross section (MAC) of soot using theoretical calculations that incorporate new measurements of the optical properties of organic carbon (OC) intrinsic to fresh diesel soot. Intrinsic OC was extracted by water and an organic solvent, and the complex refractive index of the extracted OC was derived at 532 and 355-nm wavelengths using cavity ring-down aerosol spectrometry. The extracted OC was found to absorb weakly in the visible wavelengths and moderately at blue wavelengths. The mass ratio of OC and elemental carbon (EC) in the collected particles was evaluated using a thermo-optical method. The measured EC/OC ratio in the soot exhibited substantial variability from measurement to measurement, ranging between 2 and 5. To test the sensitivity of the MAC to this variability, three different EC/OC ratios (2∶1, 1∶1, and 1∶2) were chosen as representative. Particle size and spherule morphology were estimated using scanning electron microscopy, and the soot was found to be primarily in the form of aggregates with a dominant aggregate diameter mode in the range 200–250 nm. The measured refractive index of the extracted OC was used with a variety of theoretical models to calculate the MAC of internally mixed diesel soot at 532 and 355 nm. We conclude that Rayleigh–Debye–Gans theory on clusters of coated spherules and T-matrix of a solid EC spheroid coated by intrinsic OC are both consistent with previous measurements; however, Rayleigh–Debye–Gans theory provides a more realistic physical model for the calculation
Probing ribosome-nascent chain complexes produced in vivo by NMR spectroscopy
Authors: Cabrita Lisa D. , Hsu Shang-Te Danny , Launay Helene , Dobson Christopher M. , Christodoulou John
Published: December 2009

The means by which a polypeptide chain acquires its unique 3-D structure is a fundamental question in biology. During its synthesis on the ribosome, a nascent chain (NC) emerges vectorially and will begin to fold in a cotranslational fashion. The complex environment of the cell, coupled with the gradual emergence of the ribosome-tethered NC during its synthesis, imposes conformational restraints on its folding landscape that differ from those placed on an isolated protein when stimulated to fold following denaturation in solution. To begin to examine cotranslational folding as it would occur within a cell, we produce highly selective, isotopically labeled NCs bound to isotopically silent ribosomes in vivo. We then apply NMR spectroscopy to study, at a residue specific level, the conformation of NCs consisting of different fractional lengths of the polypeptide chain corresponding to a given protein. This combined approach provides a powerful means of generating a series of snapshots of the folding of the NC as it emerges from the ribosome. Application of this strategy to the NMR analysis of the progressive synthesis of an Ig-like domain reveals the existence of a partially folded ribosome-bound species that is likely to represent an intermediate species populated during the cotranslational folding process.
Quantitative biological imaging by ptychographic x-ray diffraction microscopy
Authors: Giewekemeyer Klaus , Thibault Pierre , Kalbfleisch Sebastian , Beerlink André , Kewish Cameron M. , Dierolf Martin , Pfeiffer Franz , Salditt Tim
Published: December 2009

Recent advances in coherent x-ray diffractive imaging have paved the way to reliable and quantitative imaging of noncompact specimens at the nanometer scale. Introduced a year ago, an advanced implementation of ptychographic coherent diffractive imaging has removed much of the previous limitations regarding sample preparation and illumination conditions. Here, we apply this recent approach toward structure determination at the nanoscale to biological microscopy. We show that the projected electron density of unstained and unsliced freeze-dried cells of the bacterium
Deinococcus radiodurans
can be derived from the reconstructed phase in a straightforward and reproducible way, with quantified and small errors. Thus, the approach may contribute in the future to the understanding of the highly disputed nucleoid structure of bacterial cells. In the present study, the estimated resolution for the cells was 85 nm (half-period length), whereas 50-nm resolution was demonstrated for lithographic test structures. With respect to the diameter of the pinhole used to illuminate the samples, a superresolution of about 15 was achieved for the cells and 30 for the test structures, respectively. These values should be assessed in view of the low dose applied on the order of ≃1.3·10
5
 Gy, and were shown to scale with photon fluence.
First Dutch national guidelines ‐ pharmacological care for detained opioid addicts
Authors: Arends M. T. , De Haan H. A. , Van ’T Hoff G.I.C.M.
Published: December 2009

Heterogenic care of addicted detainees in the various prisons in the Netherlands triggered the National Agency of Correctional Institutions of the Ministry of Justice, to order the Dutch Institute for Health Care Improvement (CBO) to formulate the first national guideline titled ‘Pharmacological care for detained addicts’. This article presents the content of this guideline, which mainly focuses on opioid‐dependent addicts. In the Netherlands, approximately 50% of the detainees are problematic substance abusers, while again half of this group suffers from psychiatric co‐morbidity. In addition, somatic co‐morbidity, especially infectious diseases, is also common. Due to the
moderate outcome seen with voluntary drug counselling regimes in prison, there is a policy shift to extent utilization of legally enforced approaches. Continuity of care is of great importance. In case of opioid addicts this, in general, means continuation of methadone maintenance treatment. Aftercare immediately after detention and optimalization of medical information transfer is crucial. This guideline aims to realize optimal and uniform management of addiction disorders in the Dutch prison system.
Enhanced chlamydia surveillance in New South Wales (Australia) prisons, 2005‐2007
Authors: Forrest Garry , Boonwaat Leng , Douglas Jenny , Awofeso Niyi
Published: December 2009

Chlamydia is currently the most frequently notified infectious disease in New South Wales (NSW). Published articles relating to chlamydia prevalence in Australian prison settings are sparse, but studies from the United Kingdom and the United States indicate relatively high chlamydia prevalence among young incarcerated individuals. This article reports on findings from an enhanced chlamydia surveillance programme in NSW prisons between 2005 and 2007. The authors report a relatively low chlamydia prevalence among the general population of NSW prisoners (compared with figures from the United Kingdom and United States), which by the end of 2007 was 4%. The average crude chlamydia notification rate for the NSW prison population during the review period was about four times that of the general NSW community ‐ 716/100,000 during the review period compared with 175/100,000 in the NSW general community. The average crude chlamydia notification rate for Aboriginal prisoners during the review period was 1262/100,000, compared with 1470/100,000 in the general Australian Aboriginal population. The authors grapple with the dilemma of expanding chlamydia screening and treatment services for the sexual health benefits of prison populations with static prison health budgets on one hand, and limited evidence of cost‐effectiveness of such an expensive intervention on the other.
Monitoring harm reduction in European prisons via the Dublin Declaration
Authors: Lines Rick , Stöver Heino , Donochoe Martin C. , Lazarus Jeffrey V.
Published: December 2009

The Dublin Declaration on Partnership to fight HIV/AIDS in Europe and Central Asia is the key policy document on HIV/AIDS in the European Region as a whole Among the Declaration’s 33 actions for governments are many that apply to prison populations. Based upon an analysis of these commitments, and a review of the current status of states in meeting those targets, it is clear that the scale‐up of HIV/AIDS prevention and treatment programmes and services in prisons lags far behind what is needed, what is available outside of prisons, and what is mandated within the Declaration itself.
Heart failure registry: a valuable tool for improving the management of patients with heart failure
Authors: Jonsson Åsa , Edner Magnus , Alehagen Urban , Dahlström Ulf
Published: December 2009

Aims

Guidelines on how to diagnose and treat patients with heart failure (HF) are published regularly. However, many patients do not fulfil the diagnostic criteria and are not treated with recommended drugs. The Swedish Heart Failure Registry (S‐HFR) is an instrument which may help to optimize the handling of HF patients.

Methods and results

The S‐HFR is an Internet‐based registry in which participating centres (units) can record details of their HF patients directly online and transfer data from standardized forms or from computerized patient documentation. Up to December 2007, 16 117 patients from 78 units had been included in the S‐HFR. Of these, 10 229 patients had been followed for at least 1 year, and 2133 deaths were recorded. Online reports from the registry showed that electrocardiograms were available for 97% of the patients. Sinus rhythm was found in 51% of patients and atrial fibrillation in 38%. Echocardiography was performed in 83% of the patients. Overall, 77% of patients were treated with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, 80% were on beta‐blockers, 34% on aldosterone antagonists, and 83% on diuretics.

Conclusion

The S‐HFR is a valuable tool for improving the management of patients with HF, since it enables participating centres to focus on their own potential for improving diagnoses and medical treatment, through the online reports provided.
Using indicators for evaluating, comparing, and communicating the ecological status of exploited marine ecosystems. 1. The IndiSeas project
Authors: Shin Yunne-Jai , Shannon Lynne J.
Published: December 2009

Shin, Y-J., and Shannon, L. J. 2010. Using indicators for evaluating, comparing and communicating the ecological status of exploited marine ecosystems. 1. The IndiSeas project. – ICES Journal of Marine Science, 67: 686–691. One of the challenges faced by the scientific community grappling with the ecosystem approach to fisheries is to propose a generic set of synthetic ecological indicators, which would accurately reflect the effects of fisheries on marine ecosystems, and could support sound communication and management practices. The IndiSeas Working Group was established in 2005 under the auspices of the Eur-Oceans Network of Excellence to develop methods to provide indicators-based assessments of the status of exploited marine ecosystems in a comparative framework. Here, we present the two main outputs of the first phase of the project: a suite of papers documenting a combination of indicator-based methods and results comparing the ecological status of the world's exploited marine ecosystems, and a website aiming to communicate these results beyond scientific audiences.
Relapse of enterococcal prosthetic valve endocarditis with aortic rootabscess following treatment with daptomycin in a patient not fit for surgery
Authors: Enoch D. A. , Phillimore N. , Karas J. A. , Horswill L. , Mlangeni D. A.
Published: December 2009

Daptomycin is a novel lipopeptide with activity against Gram-positive organismsincluding enterococci. It is licensed for the treatment of Staphylococcusaureus bacteraemia and right-sided endocarditis, but not endocarditisdue to Enterococcus spp. We report a case of enterococcal prostheticvalve endocarditis with an aortic root abscess in an elderly patient who wasnot fit for surgery. The patient's endocarditis relapsed 9 weeks aftera 6 week course of daptomycin.
Cytocidal amino acid starvation of Saccharomyces cerevisiae and Candida albicans acetolactate synthase (ilv2Δ) mutants is influenced by the carbon source and rapamycin
Authors: Kingsbury Joanne M. , McCusker John H.
Published: December 2009

The isoleucine and valine biosynthetic enzyme acetolactate synthase (Ilv2p) is an attractive antifungal drug target, since the isoleucine and valine biosynthetic pathway is not present in mammals,Saccharomyces cerevisiae ilv2Δ mutants do not survivein vivo,Cryptococcus neoformans ilv2mutants are avirulent, and bothS. cerevisiaeandCr. neoformans ilv2mutants die upon isoleucine and valine starvation. To further explore the potential of Ilv2p as an antifungal drug target, we disruptedCandida albicans ILV2, and demonstrated thatCa. albicans ilv2Δ mutants were significantly attenuated in virulence, and were also profoundly starvation-cidal, with a greater than 100-fold reduction in viability after only 4 h of isoleucine and valine starvation. As fungicidal starvation would be advantageous for drug design, we explored the basis of the starvation-cidal phenotype in bothS. cerevisiaeandCa. albicans ilv2Δ mutants. Since the mutation ofILV1, required for the first step of isoleucine biosynthesis, did not suppress theilv2Δ starvation-cidal defects in either species, the cidal phenotype was not due toα-ketobutyrate accumulation. We found that starvation for isoleucine alone was more deleterious inCa. albicansthan inS. cerevisiae, and starvation for valine was more deleterious than for isoleucine in both species. Interestingly, while the target of rapamycin (TOR) pathway inhibitor rapamycin further reducedS. cerevisiae ilv2Δ starvation viability, it increasedCa. albicans ilv1Δ andilv2Δ viability. Furthermore, the recovery from starvation was dependent on the carbon source present during recovery forS. cerevisiae ilv2Δ mutants, reminiscent of isoleucine and valine starvation inducing a viable but non-culturable-like state in this species, whileCa. albicans ilv1Δ andilv2Δ viability was influenced by the carbon source present during starvation, supporting a role for glucose wasting in theCa. albicanscidal phenotype.
Metals, minerals and microbes: geomicrobiology and bioremediation
Authors: Gadd Geoffrey Michael
Published: December 2009

Microbes play key geoactive roles in the biosphere, particularly in the areas of element biotransformations and biogeochemical cycling, metal and mineral transformations, decomposition, bioweathering, and soil and sediment formation. All kinds of microbes, including prokaryotes and eukaryotes and their symbiotic associations with each other and ‘higher organisms’, can contribute actively to geological phenomena, and central to many such geomicrobial processes are transformations of metals and minerals. Microbes have a variety of properties that can effect changes in metal speciation, toxicity and mobility, as well as mineral formation or mineral dissolution or deterioration. Such mechanisms are important components of natural biogeochemical cycles for metals as well as associated elements in biomass, soil, rocks and minerals, e.g. sulfur and phosphorus, and metalloids, actinides and metal radionuclides. Apart from being important in natural biosphere processes, metal and mineral transformations can have beneficial or detrimental consequences in a human context. Bioremediation is the application of biological systems to the clean-up of organic and inorganic pollution, with bacteria and fungi being the most important organisms for reclamation, immobilization or detoxification of metallic and radionuclide pollutants. Some biominerals or metallic elements deposited by microbes have catalytic and other properties in nanoparticle, crystalline or colloidal forms, and these are relevant to the development of novel biomaterials for technological and antimicrobial purposes. On the negative side, metal and mineral transformations by microbes may result in spoilage and destruction of natural and synthetic materials, rock and mineral-based building materials (e.g. concrete), acid mine drainage and associated metal pollution, biocorrosion of metals, alloys and related substances, and adverse effects on radionuclide speciation, mobility and containment, all with immense social and economic consequences. The ubiquity and importance of microbes in biosphere processes make geomicrobiology one of the most important concepts within microbiology, and one requiring an interdisciplinary approach to define environmental and applied significance and underpin exploitation in biotechnology.
QTL for body weight, morphometric traits and stress response in European sea bass Dicentrarchus labrax
Authors: Massault C. , Hellemans B. , Louro B. , Batargias C. , Van Houdt J. K. J. , Canario A. , Volckaert F. A. M. , Bovenhuis H. , Haley C. , De Koning D. J.
Published: December 2009

Natural mating and mass spawning in the European sea bass (Dicentrarchus labrax L., Moronidae, Teleostei) complicate genetic studies and the implementation of selective breeding schemes. We utilized a two‐step experimental design for detecting QTL in mass‐spawning species: 2122 offspring from natural mating between 57 parents (22 males, 34 females and one missing) phenotyped for body weight, eight morphometric traits and cortisol levels, had been previously assigned to parents based on genotypes of 31 DNA microsatellite markers. Five large full‐sib families (five sires and two dams) were selected from the offspring (570 animals), which were genotyped with 67 additional markers. A new genetic map was compiled, specific to our population, but based on the previously published map. QTL mapping was performed with two methods: half‐sib regression analysis (paternal and maternal) and variance component analysis accounting for all family relationships. Two significant QTL were found for body weight on linkage group 4 and 6, six significant QTL for morphometric traits on linkage groups 1B, 4, 6, 7, 15 and 23 and three suggestive QTL for stress response on linkage groups 3, 14 and 23. The QTL explained between 8% and 38% of phenotypic variance. The results are the first step towards identifying genes involved in economically important traits like body weight and stress response in European sea bass.
Blood coagulation, fibrinolysis and lipid profile in patients with prolactinoma
Authors: Erem Cihangir , Kocak Mustafa , Nuhoglu İrfan , Yılmaz Mustafa , Ucuncu Ozge
Published: December 2009

Objective  Although the strong association between hyperprolactinaemia and platelet aggregation is well recognized, there are no studies on changes in coagulation and fibrinolytic status in patients with prolactinoma. To our knowledge, tissue plasminogen activator inhibitor‐1 (PAI‐1), plasma tissue factor pathway inhibitor (TFPI) and thrombin‐activatable fibrinolysis inhibitor (TAFI) levels in these patients have not been investigated. Therefore, the main purpose of this study was to evaluate the markers of endogenous coagulation/fibrinolysis, including TFPI and TAFI, and to investigate the relationships between prolactin (PRL) and these haemostatic parameters and serum lipid profile in patients with prolactinoma.

Research methods and procedures  Twenty‐two patients with untreated, newly diagnosed prolactinoma and 20 age‐matched healthy controls were included in the study. Platelet count, mean platelet volume, prothrombin time, activated partial thromboplastin time, fibrinogen, factors V, VII, VIII, IX and X activities, von Willebrand factor, antithrombin III (AT‐III), protein C, protein S, tissue plasminogen activator (t‐PA), PAI‐1, TFPI and TAFI, as well as common lipid variables, were measured. The relationships between serum PRL and these haemostatic parameters were evaluated.

Results  Compared with the control subjects, total cholesterol, low density lipoprotein cholesterol, apolipoprotein B, platelet count, fibrinogen, AT‐III, PAI‐1 and PAI‐1/t‐PA ratio were significantly increased in patients with prolactinoma (P < 0·0001, P < 0·001, P < 0·05, P < 0·05, P < 0·0001, P < 0·05, P < 0·0001 and P < 0·0001, respectively), whereas TFPI levels were significantly decreased (P < 0·01). Plasma TAFI Ag levels were not significantly different in patients with prolactinoma compared with the controls. In patients with prolactinoma, serum PRL was positively correlated with plasma FVII levels and apo B (r: 0·679, P < 0·05; r: 0·548, P < 0·05, respectively).

Conclusion  We found some important differences in the haemostatic parameters between the patients with prolactinoma and healthy controls. Increased platelet count, fibrinogen, PAI‐1 and decreased TFPI in patients with prolactinoma may represent a potential hypercoagulable and hypofibrinolytic state, which might augment the risk for atherosclerotic and atherothrombotic complications. Thus, disturbances of the haemostatic system and dyslipidaemia may lead to the excess mortality in patients with prolactinoma.
Partial growth hormone deficiency is associated with an adverse cardiovascular risk profile and increased carotid intima‐medial thickness
Authors: Murray Robert D. , Wieringa Gilbert , Lawrance Jeremy A. , Adams Judith E. , Shalet Stephen M.
Published: December 2009

Objective  To quantify the relative prevalence of surrogate markers of vascular risk in adults with partial GH deficiency (GH insufficiency, GHI).

Context  Hypopituitary adults with untreated GH deficiency (GHD) have an excess vascular mortality and demonstrate clustering of adverse vascular risk factors. The vascular risk profile of GHI adults has yet to be comprehensively studied.

Design  A cross‐sectional case controlled study.

Patients  Thirty GHD adults, 24 GHI, and 30 age‐ and sex‐matched controls. GHI adults were defined biochemically using two GH stimulation tests (peak GH 3–7 μg/l).

Measurements  Serum lipids and apolipoproteins, plasminogen activator inhibitor type‐I (PAI‐I), C‐reactive protein (CRP), lipoprotein (a) [Lp(a)], fibrinogen, blood pressure and carotid intima‐medial thickness (IMT).

Results  IGF‐I levels of GHI adults were lower than controls (373 ± 123 vs 295 ± 104 μg/l; P < 0·001). Total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C) and triglycerides (TG) values were consistently between those of, but not significantly different from, GHD and control subjects. GHI adults showed significantly elevated PAI‐I levels [80 (13–98) vs 50·5 (3–98) ng/ml; P = 0·01], although no there were differences in CRP, Lp(a), and fibrinogen levels compared with control subjects. No differences in systolic or diastolic blood pressure were shown between study groups. In parallel with the increased vascular risk profile of GH‐insufficient adults, carotid IMT was significantly increased (0·503 ± 0·08 vs 0·578 ± 0·130 mm; P = 0·02). TC, LDL‐C, Waist‐Hip Ratio (WHR), truncal fat mass, and IMT correlated with IGF‐I levels and GH status. TG, KITT, and PAI‐I additionally correlated with GH status, but not with IGF‐I levels.

Conclusion  GHI adults are at elevated vascular risk, reflected by adverse surrogate markers and increased carotid IMT. The surrogate risk marker profile parallels GHD adults, but is less divergent from that observed in healthy individuals. No data are yet available as to whether these anomalies will be reflected in an increased vascular mortality in GHI adults.
Outcome of fractionated stereotactic radiotherapy in patients with pituitary adenomas resistant to conventional treatments: a 5·25‐year follow‐up study
Authors: Schalin‐Jäntti Camilla , Valanne Leena , Tenhunen Mikko , Setälä Kirsi , Paetau Anders , Sane Timo , Kouri Mauri
Published: December 2009

Objective  To investigate the long‐term outcome of fractionated stereotactic radiotherapy (FSRT) [45 Gy (range 45–54) in 25 fractions] in patients with pituitary adenomas characterized by tumour progression or hormonally active disease despite surgery and/or medical therapy.

Design  This was an observational follow‐up study of 5·25 years (median; range 1·7–10·4).

Patients and measurements  Pituitary tumour volume, visual acuity/fields, hypersecretion, hypopituitarism, cerebrovascular disease, second brain tumours and mortality were examined at regular intervals after FSRT in 30 patients with pituitary adenomas (20 nonfunctioning macroadenomas, 10 functioning). Prior to FSRT, 83% had been operated 1–3 times, 47% had visual field deficits/impaired vision and 50% pituitary dysfunction. Progressive disease, stable disease, partial and complete tumour response were defined by MRI.

Results  Tumour growth control was 100%. At the end of follow‐up, 30% had stable disease, 60% partial and 10% complete tumour response. Visual function was preserved and 36% of patients with prior field deficits improved. GH decreased from 4·2 (range, 2·3–6·5) to 1·1 (range, 0·5–1·5) μg/l (P < 0·001) in patients with acromegaly, and medical therapy could be reduced. In large prolactinomas, partial response or complete tumour response was achieved. FSRT was well tolerated. Pituitary function remained normal in 27%, 33% of patients had stable dysfunction, 17% deteriorated further and 23% developed new dysfunction. There were no cerebrovascular events, second brain tumours or FSRT‐related deaths.

Conclusion  According to this long‐term follow‐up study, FSRT is an efficient and safe adjuvant therapy for pituitary adenomas refractory to conventional treatments.
Influence of physiological dietary selenium supplementation on the natural course of autoimmune thyroiditis
Authors: Nacamulli Davide , Mian Caterina , Petricca Daniela , Lazzarotto Francesca , Barollo Susi , Pozza Dina , Masiero Stefano , Faggian Diego , Plebani Mario , Girelli Maria E. , Mantero Franco , Betterle Corrado
Published: December 2009

Objective  Our study aimed to investigate whether physiological doses of selenium (Se) influence the natural course of autoimmune thyroiditis (AIT).

Design and Patients  A total of 76 consecutive patients (65F, 11M, median 43, range 15‐75 years) with AIT, normal or slightly elevated TSH and fT4 within the normal range were divided into two groups: Group 0 (30 cases) was given no treatment while Group 1 (46 cases) was treated with sodium selenite 80 μg/day as a single oral dose for 12 months. Thyroperoxidase and thyroglobulin autoantibodies (TPO‐Ab; Tg‐Ab), TSH, fT4 and urine iodine concentrations (UIC) were measured at baseline and after 6 and 12 months of follow‐up. Thyroid ultrasonography (US) was performed at each follow‐up point. Echogenicity was measured by histographic analysis of gray‐scale pixels (gsp) ranging from 0 = black to 255 = white.

Results  Thyroid echogenicity decreased significantly in both groups after 6 months, but after 12 months, it had changed no more in Group 1, whereas it had dropped further in Group 0. No significant variation in TPO‐Ab or Tg‐Ab levels was observed between the two groups after 6 months, but both values decreased significantly after 12 months in Group 1, and five patients in this group became negative for TPO‐Ab. TSH and FT4 showed no significant variations in either group.

Conclusions  Dietary supplementation with physiological doses of Se seems to be effective in preventing a reduction in thyroid echogenicity after 6 months of treatment and in reducing TPO‐Ab and Tg‐Ab after 12 months, but does not modify TSH or FT4.
The Metabolic syndrome is associated with subclinical atherosclerosis independent of insulin resistance: the Guangzhou Biobank Cohort Study‐CVD
Authors: Xu Lin , Jiang Chao Qiang , Lam Tai Hing , Lin Jie Ming , Yue Xiao Jun , Cheng Kar Keung , Liu Bin , Jin Ya Li , Zhang Wei Sen , Thomas G Neil
Published: December 2009

Objective  We examined whether the association of the metabolic syndrome (MetS) and subclinical atherosclerosis is independent of insulin resistance in a Chinese community sample with no history of type 2 diabetes.

Methods  Five hundred and ninety‐six men and 526 women from a substudy of the Guangzhou Biobank Cohort Study (GBCS‐CVD) had carotid intimal‐medial thickness (IMT) measured by B‐mode ultrasonography, and brachial‐ankle pulse wave velocity (PWV) and ankle‐brachial systolic blood pressure index (ABI) measured simultaneously by a noninvasive automatic waveform analyser.

Results  Fourteen percentage had MetS as defined by the International Diabetes Federation. Obesity indices, systolic and diastolic blood pressure and pulse pressure, lipids, fasting and postload glucose and insulin, homeostatic model assessment of insulin resistance, glycosylated haemoglobin A1c, leptin, high‐sensitivity C‐reactive protein, IMT and PWV increased and high‐density lipoprotein‐cholesterol, adiponectin and ABI decreased significantly with increasing number of MetS components after adjusting for age and sex (P for trend from 0·004 to <0·001). After adjusting for traditional cardiovascular risk factors and insulin resistance, the odds ratios [OR (95% CI)] of thicker IMT (≥1·0 mm), higher PWV (≥14·0 m/s) and low ABI (≤1·0) for MetS were significantly increased [2.28 (1.19−4.38), 2.17 (1.36−3.46) and 1.72 (1.14−2.59), respectively, all P < 0.01] but were lower than the adjusted OR for those with three or more MetS components.

Conclusion  MetS was associated with subclinical atherosclerosis independent of insulin resistance. The presence of increasing number of MetS risk factors appeared to be more important than the diagnosis of MetS in predicting subclinical atherosclerosis. Early screening for MetS risk factors might identify those at greater cardiovascular risk.
Influence of various confounding variables and storage conditions on metanephrine and normetanephrine levels in plasma
Authors: Deutschbein Timo , Unger Nicole , Jaeger Andrea , Broecker‐Preuss Martina , Mann Klaus , Petersenn Stephan
Published: December 2009

Objective  Measurements of plasma free metanephrines have been advocated as first‐line tests for phaeochromocytoma. The aim of the study was to assess the impact of potential confounding variables.

Design  Comparative study between 2008 and 2009.

Subjects  Hundred and eighty healthy subjects.

Measurements  The effects of age, BMI, gender, menstrual cycle (sampling every 2 days), time of day (sampling every 2 h), venepunture (0, 15, 30, 60, 90 and 120 min), physical exercise (0, 15 and 30 min), coffee (0 and 60 min), breakfast (0 and 60 min) and various body positions (standing and supine rest, each 0 and 120 min) were evaluated. In addition, whole blood and plasma samples were stored at 4 °C or at 22 °C for 0, 1, 3, 24 and 72 h. Plasma free metanephrines were measured using radioimmunoassay (LDN).

Results  While metanephrine was significantly influenced by sex and age, BMI and sex were significant predictors of normetanephrine. Coffee (+20%) and food (+8%) elevated normetanephrine significantly (P < 0·05), while metanephrine remained stable. Physical exercise increased metanephrine (+82%) as well as normetanephrine (+84%) significantly (P < 0·005). Supine rest significantly decreased both metanephrine (−34%) and normetanephrine (−19%) when compared to standing rest (P < 0·01). Metanephrine and normetanephrine were not significantly influenced by time of day, menstrual cycle or venepuncture. When plasma samples were stored at 4 °C, metanephrine and normetanephrine were stable for 72 h.

Conclusions  Physical exercise may lead to relevant changes in metanephrine and normetanephrine and should therefore be avoided prior to sampling. Although effects of age, sex and BMI were small, these variables should be considered when interpreting biochemical results. Blood should be taken in the supine position, and samples should be immediately centrifuged and stored at 4 °C to improve stability.
The effect of DPP‐4 inhibition with sitagliptin on incretin secretion and on fasting and postprandial glucose turnover in subjects with impaired fasting glucose
Authors: Bock Gerlies , Man Chiara Dalla , Micheletto Francesco , Basu Rita , Giesler Paula D. , Laugen Jeanette , Deacon Carolyn F. , Holst Jens J. , Toffolo Gianna , Cobelli Claudio , Rizza Robert A. , Vella Adrian
Published: December 2009

Objective  Low glucagon‐like peptide‐1 (GLP‐1) concentrations have been observed in impaired fasting glucose (IFG). It is uncertain whether these abnormalities contribute directly to the pathogenesis of IFG and impaired glucose tolerance. Dipeptidyl peptidase‐4 (DPP‐4) inhibitors raise incretin hormone concentrations enabling an examination of their effects on glucose turnover in IFG.

Research design and methods  We studied 22 subjects with IFG using a double‐blinded, placebo‐controlled, parallel‐group design. At the time of enrolment, subjects ate a standardized meal labelled with [1‐13C]‐glucose. Infused [6‐3H] glucose enabled measurement of systemic meal appearance (MRa). Infused [6,6‐2H2] glucose enabled measurement of endogenous glucose production (EGP) and glucose disappearance (Rd). Subsequently, subjects were randomized to 100 mg of sitagliptin daily or placebo. After an 8‐week treatment period, the mixed meal was repeated.

Results  As expected, subjects with IFG who received placebo did not experience any change in glucose concentrations. Despite raising intact GLP‐1 concentrations, treatment with sitagliptin did not alter either fasting or postprandial glucose, insulin or C‐peptide concentrations. Postprandial EGP (18·1 ± 0·7 vs 17·6 ± 0·8 μmol/kg per min, P = 0·53), Rd (55·6 ± 4·3 vs 58·9 ± 3·3 μmol/kg per min, P = 0·47) and MRa (6639 ± 377 vs 6581 ± 316 μmol/kg per 6 h, P = 0·85) were unchanged. Sitagliptin was associated with decreased total GLP‐1 implying decreased incretin secretion.

Conclusions  DPP‐4 inhibition did not alter fasting or postprandial glucose turnover in people with IFG. Low incretin concentrations are unlikely to be involved in the pathogenesis of IFG.