Pharmacokinetics of recombinant human erythropoietin applied subcutaneously to children with chronic renal failure

The single-dose pharmacokinetics of recombinant human erythropoietin (rHuEPO) given SC was investigated in 20 patients aged 7-20 years at different stages of chronic renal failure. In a pilot study we confirmed the lower bioavailability of the drug in 2 children when given SC compared with the IV route (24% and 43%, respectively). Following administration of 4,000 units/m2, rHuEPO SC effective serum erythropoietin concentrations increased from a mean baseline level (+/- SD) of 23 +/- 13 units/l to a mean peak concentration of 265 +/- 123 units/l, which was reached after 14.3 +/- 9.4 h, followed by a slow decline until baseline values were attained at 72 h. Mean residence time was 30 +/- 9 h and mean elimination half-time 14.3 +/- 7 h. The single-dose kinetics of SC rHuEPO in children with different degrees of renal failure are comparable to those in adult patients. Possibly, the higher efficacy of SC rHuEPO in patients with renal anaemia compared with IV rHuEPO is related to its prolonged action

Combined stellar structure and atmosphere models for massive stars; 1, interior evolution and wind properties on the main sequence

We present the first "combined stellar structure and atmosphere models" (CoStar) for massive stars, which consistently treat the entire mass loosing star from the center out to the asymptotic wind velocity. The models use up-to-date input physics and state-of-the-art techniques to model both the stellar interior and the spherically expanding non--LTE atmosphere including line blanketing. Our models thus yield consistent predictions regarding not only the basic stellar parameters, including abundances, but also theoretical spectra along evolutionary tracks. On the same ground they allow us to study the influence of stellar winds on evolutionary models. In this first paper, we present our method and investigate the wind properties and the interior evolution on the main sequence (MS) at solar metallicity. The wind momentum and energy deposition associated with the MS evolution is given and the adopted wind properties are discussed. From our atmosphere calculations, we also derive theoretical estimates of mass loss driven by radiation pressure. These values are compared with the predictions from recent wind models of the Munich group. We find an overall agreement with most of their results. In addition, our models are better in reproducing the strong wind momentum rates observed in supergiants than those of Puls et al. (1995). A comparison between boundary conditions given by the conventional plane parallel and the new spherically expanding atmosphere approach is made. For the MS evolution the evolutionary tracks and the interior evolution are found to be basically unchanged by the new treatment of the outer layers. Given the small spherical extension of the continuum forming layers in the considere

Combined stellar structure and atmosphere models for massive stars; 2, spectral evolution on the main sequence

In Schaerer et al. (1995, Paper I) we have presented the first "combined stellar structure and atmosphere models" (CoStar) for massive stars, which consistently treat the entire mass loosing star from the center out to the outer region of the stellar wind. The models use up-to-date input physics and state-of-the-art techniques to model both the stellar interior and the spherically expanding non--LTE atmosphere including line blanketing. Paper II covers the spectral evolution corresponding to the MS interior evolution discussed in Paper I. The CoStar results presented comprise: a) flux distributions, from the EUV to the far IR, and the ionizing fluxes in the H and He continua, b) absolute UBVRIJHKL MN photometric data and UV colors, c) detailed line blanketed UV spectra, and d) non-LTE H and He line spectra in the optical and IR, including theoretical K band spectra. These results may, e.g., be used for population synthesis models intended to study the massive star content in young starforming regions. We compare our results with other predictions from LTE and non-LTE plane parallel models and point out the improvements and the importance of using adequate atmosphere models including stellar winds for massive stars. We compare the UV spectral evolution with observations, including continuum indices and several metal line signatures of P-Cygni lines and broad absorption features. Good agreement is found for most UV features. We are able to reproduce the strong observed FeIII 1920 A feature in late O and early B giants and supergiants. This feature is found to depend sensitively on temperature and may be used to derive effective temperatures for these stars. We also derive a simple formula to determine mass loss rates from the equivalent width of hydrogen recombination lines for OB stars showing ne

Sperm competition and the evolution of spermatogenesis

Spermatogenesis is a long and complex process that, despite the shared overall goal of producing the male gamete, displays striking amounts of interspecific diversity. In this review, we argue that sperm competition has been an important selection pressure acting on multiple aspects of spermatogenesis, causing variation in the number and morphology of sperm produced, and in the molecular and cellular processes by which this happens. We begin by reviewing the basic biology of spermatogenesis in some of the main animal model systems to illustrate this diversity, and then ask to what extent this variation arises from the evolutionary forces acting on spermatogenesis, most notably sperm competition. We explore five specific aspects of spermatogenesis from an evolutionary perspective, namely: (i) interspecific diversity in the number and morphology of sperm produced; (ii) the testicular organizations and stem cell systems used to produce them; (iii) the large number and high evolutionary rate of genes underpinning spermatogenesis; (iv) the repression of transcription during spermiogenesis and its link to the potential for haploid selection; and (v) the phenomenon of selection acting at the level of the germline. Overall we conclude that adopting an evolutionary perspective can shed light on many otherwise opaque features of spermatogenesis, and help to explain the diversity of ways in which males of different species perform this fundamentally important proces

Protein interface classification by evolutionary analysis

Background Distinguishing biologically relevant interfaces from lattice contacts in protein crystals is a fundamental problem in structural biology. Despite efforts towards the computational prediction of interface character, many issues are still unresolved. Results We present here a protein-protein interface classifier that relies on evolutionary data to detect the biological character of interfaces. The classifier uses a simple geometric measure, number of core residues, and two evolutionary indicators based on the sequence entropy of homolog sequences. Both aim at detecting differential selection pressure between interface core and rim or rest of surface. The core residues, defined as fully buried residues (>95% burial), appear to be fundamental determinants of biological interfaces: their number is in itself a powerful discriminator of interface character and together with the evolutionary measures it is able to clearly distinguish evolved biological contacts from crystal ones. We demonstrate that this definition of core residues leads to distinctively better results than earlier definitions from the literature. The stringent selection and quality filtering of structural and sequence data was key to the success of the method. Most importantly we demonstrate that a more conservative selection of homolog sequences - with relatively high sequence identities to the query - is able to produce a clearer signal than previous attempts. Conclusions An evolutionary approach like the one presented here is key to the advancement of the field, which so far was missing an effective method exploiting the evolutionary character of protein interfaces. Its coverage and performance will only improve over time thanks to the incessant growth of sequence databases. Currently our method reaches an accuracy of 89% in classifying interfaces of the Ponstingl 2003 datasets and it lends itself to a variety of useful applications in structural biology and bioinformatics. We made the corresponding software implementation available to the community as an easy-to-use graphical web interface at http://www.eppic-web.org.ISSN:1471-210

Detection of the fire blight biocontrol agent Bacillus subtilis BD170 (Biopro®) in a Swiss apple orchard

Fire blight, caused by Erwinia amylovora, is a major disease threat to apple, pear and other pome fruit worldwide. The disease is widespread in Europe and has recently become established in Switzerland. Antibiotics are the most effective controls used in North America but these are not permitted for agricultural use in most European countries. A newly registered biological control product Biopro®, based on the antagonist Bacillus subtilis strain BD170, is being used as an alternative strategy for fire blight management. A specific molecular marker was developed for monitoring the spread of this agent on blossoms after Biopro® spray application in a Swiss apple orchard throughout the bloom period for 2years. Direct spraying resulted in efficient primary colonisation of pistils in flowers that were open at the time of treatment. Subsequent bacterial dissemination (secondary colonisation) of flowers that were closed or at bud stage at the time of treatment was observed but was found to be dependent on the timing of treatments relative to bloom stage in the orchard. Foraging honeybees were shown to be disseminators of Biopro®. We also report detection of the biocontrol agent in honey collected from hives where bees were exposed by placing Biopro® at the entrance or in the hatching nest and from hives that were simply placed in sprayed orchard

Climatic suitability ranking of biological control candidates: a biogeographic approach for ragweed management in Europe

Biological control using natural antagonists has been a most successful management tool against alien invasive plants that threaten biodiversity. The selection of candidate agents remains a critical step in a biocontrol program before more elaborate and time-consuming experiments are conducted. Here, we propose a biogeographic approach to identify candidates and combinations of candidates to potentially cover a large range of the invader. We studied Ambrosia artemisiifolia (common ragweed), native to North America (NA) and invasive worldwide, and six NA biocontrol candidates for the introduced Europe (EU) range of ragweed, both under current and future bioclimatic conditions. For the first time, we constructed species distribution models based on worldwide occurrences and important bioclimatic variables simultaneously for a plant invader and its biocontrol candidates in view of selecting candidates that potentially cover a large range of the target invader. Ordination techniques were used to explore climatic constraints of each species and to perform niche overlap tests with ragweed. We show a large overlap in climatic space between candidates and ragweed, but a considerable discrepancy in geographic range overlap between EU (31.4%) and NA (83.3%). This might be due to niche unfilling and expansion of ragweed in EU and the fact that habitats with high ragweed occurrences in EU are rare in NA and predicted to be unsuitable for the candidates. Total geographic range of all candidates combined is expected to decrease under climate change in both ranges, but they will respond differently. The relative geographic coverage of a plant invader by biocontrol candidates at home is largely transferable to the introduced range, even when the invader shifts its niche. Our analyses also identified which combination of candidates is expected to cover the most area and for which abiotic conditions to select in order to develop climatically adapted strains for particular regions, where ragweed is currently unlikely to be controlled

Sperm competition-induced plasticity in the speed of spermatogenesis

Background: Sperm competition between rival ejaculates over the fertilization of ova typically selects for the production of large numbers of sperm. An obvious way to increase sperm production is to increase testis size, and most empirical work has focussed on this parameter. Adaptive plasticity in sperm production rate could also arise due to variation in the speed with which each spermatozoon is produced, but whether animals can respond to relevant environmental conditions by modulating the kinetics of spermatogenesis in this way has not been experimentally investigated. Results: Here we demonstrate that the simultaneously hermaphroditic flatworm Macrostomum lignano exhibits substantial plasticity in the speed of spermatogenesis, depending on the social context: worms raised under higher levels of sperm competition produce sperm faster. Conclusions: Our findings overturn the prevailing view that the speed of spermatogenesis is a static property of a genotype, and demonstrate the profound impact that social environmental conditions can exert upon a key developmental process. We thus identify, to our knowledge, a novel mechanism through which sperm production rate is maximised under sperm competition