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991.
992.
Biosimilar drugs must closely resemble the pharmacological attributes of innovator products to ensure safety and efficacy to obtain regulatory approval. Glycosylation is one critical quality attribute that must be matched, but it is inherently difficult to control due to the complexity of its biogenesis. This usually implies that costly and time‐consuming experimentation is required for clone identification and optimization of biosimilar glycosylation. Here, a computational method that utilizes a Markov model of glycosylation to predict optimal glycoengineering strategies to obtain a specific glycosylation profile with desired properties is described. The approach uses a genetic algorithm to find the required quantities to perturb glycosylation reaction rates that lead to the best possible match with a given glycosylation profile. Furthermore, the approach can be used to identify cell lines and clones that will require minimal intervention while achieving a glycoprofile that is most similar to the desired profile. Thus, this approach can facilitate biosimilar design by providing computational glycoengineering guidelines that can be generated with a minimal time and cost.  相似文献   
993.
A number of filamentous fungi are known to produce high levels of saline-soluble and low-molecular-mass lectins. The function of these proteins are not clear but it has been proposed that they are involved in storage of nutrients, development, recognition of other organisms, and defense reactions. A gene encoding such a lectin (AOL) was deleted in the nematode-trapping fungus Arthrobotrys oligospora by homologous recombination. The deletion mutants did not express any hemagglutinating activity or protein cross-reacting with AOL antibodies. There were no significant differences between the DeltaAOL and wild-type strains in spore (conidia) germination, saprophytic growth, and pathogenicity. Furthermore, there was no significant difference in the growth and reproduction of collembolan feeding on the various strains of A. oligospora. Thus either the previous proposed functions of AOL are not correct, or the fungus can compensate for the absence of the lectin by expressing other proteins with similar function(s) as AOL.  相似文献   
994.

Purpose

Odour is an important aspect of systems for human and agricultural waste management and many technologies are developed with the sole purpose of reducing odour. Compared with greenhouse gas assessment and the assessment of toxicity, odour assessment has received little attention in the life cycle assessment (LCA) community. This article aims to redress this.

Methods

Firstly, a framework for the assessment of odour impacts in LCA was developed considering the classical LCA framework of emissions, midpoint and endpoint indicators. This suggested that an odour footprint midpoint indicator was worth striving for. An approach to calculating an areal indicator we call “odour footprint”, which considers the odour detection threshold, the diffusion rate and the kinetics of degradation of odourants, was implemented in MATLAB. We demonstrated the use of the characterisation factors we calculated in a case study based on odour removal technology applied to a pig barn.

Results and discussion

We produced a list of 33 linear characterisation factors based on hydrogen sulphide equivalents, analogous to the linear carbon dioxide equivalency factors in use in carbon footprinting, or the dichlorobenzene equivalency factors developed for assessment of toxic impacts in LCA. Like the latter, this odour footprint method does not take local populations and exposure pathway analysis into account—its intent is not to assess regulatory compliance or detailed design. The case study showed that despite the need for materials and energy, large factor reductions in odour footprint and eutrophication potential were achieved at the cost of a smaller factor increase in greenhouse emissions.

Conclusions

The odour footprint method is proposed as an improvement on the established midpoint method for odour assessment in LCA. Unlike it, the method presented here considers the persistence of odourants. Over time, we hope to increase the number of characterised odourants, enabling analysts to perform simple site-generic LCA on systems with odourant emissions.  相似文献   
995.
996.
Feather mites are arthropods that live on or in the feathers of birds, and are among the commonest avian ectosymbionts. However, the nature of the ecological interaction between feather mites and birds remains unclear, some studies reporting negative effects of feather mites on their hosts and others reporting positive or no effects. Here we use a large dataset comprising 20 189 measurements taken from 83 species of birds collected during 22 yr in 151 localities from seven countries in Europe and North Africa to explore the correlation between feather mite abundance and body condition of their hosts. We predicted that, if wing‐dwelling feather mites are parasites, a negative correlation with host body condition should be found, while a mutualistic interaction should yield positive correlation. Although negative relationships between feather mite abundance and host body condition were found in a few species of birds, the sign of the correlation was positive in most bird species (69%). The overall effect size was only slightly positive (r =0.066). The effect of feather mite abundance explained <10% of variance in body condition in most species (87%). Results suggest that feather mites are not parasites of birds, but rather that they hold a commensalistic relationship where feather mites may benefit from feeding on uropygial gland secretions of their hosts and birds do not seem to obtain a great benefit from the presence of feather mites.  相似文献   
997.
Kv7.1 (KCNQ1) channels are regulators of several physiological processes including vasodilatation, repolarization of cardiomyocytes, and control of secretory processes. A number of Kv7.1 pore mutants are sensitive to extracellular potassium. We hypothesized that extracellular potassium also modulates wild-type Kv7.1 channels. The Kv7.1 currents were measured in Xenopus laevis oocytes at different concentrations of extracellular potassium (1–50 mM). As extracellular potassium was elevated, Kv7.1 currents were reduced significantly more than expected from theoretical calculations based on the Goldman-Hodgkin-Katz flux equation. Potassium inhibited the steady-state current with an IC50 of 6.0 ± 0.2 mM. Analysis of tail-currents showed that potassium increased the fraction of channels in the inactivated state. Similarly, the recovery from inactivation was slowed by potassium, suggesting that extracellular potassium stabilizes an inactivated state in Kv7.1 channels. The effect of extracellular potassium was absent in noninactivating Kv7.1/KCNE1 and Kv7.1/KCNE3 channels, further supporting a stabilized inactivated state as the underlying mechanism. Interestingly, coexpression of Kv7.1 with KCNE2 did not attenuate the inhibition by potassium. In a number of other Kv channels, including Kv1.5, Kv4.3, and Kv7.2–5 channels, currents were only minimally reduced by an increase in extracellular potassium as expected. These results show that extracellular potassium modulates Kv7.1 channels and suggests that physiological changes in potassium concentrations may directly control the function of Kv7.1 channels. This may represent a novel regulatory mechanism of excitability and of potassium transport in tissues expressing Kv7.1 channels.  相似文献   
998.
Gao F  Luo Y  Li S  Li J  Lin L  Nielsen AL  Sørensen CB  Vajta G  Wang J  Zhang X  Du Y  Yang H  Bolund L 《PloS one》2011,6(10):e25901
Animal breeding via Somatic Cell Nuclear Transfer (SCNT) has enormous potential in agriculture and biomedicine. However, concerns about whether SCNT animals are as healthy or epigenetically normal as conventionally bred ones are raised as the efficiency of cloning by SCNT is much lower than natural breeding or In-vitro fertilization (IVF). Thus, we have conducted a genome-wide gene expression and DNA methylation profiling between phenotypically normal cloned pigs and control pigs in two tissues (muscle and liver), using Affymetrix Porcine expression array as well as modified methylation-specific digital karyotyping (MMSDK) and Solexa sequencing technology. Typical tissue-specific differences with respect to both gene expression and DNA methylation were observed in muscle and liver from cloned as well as control pigs. Gene expression profiles were highly similar between cloned pigs and controls, though a small set of genes showed altered expression. Cloned pigs presented a more different pattern of DNA methylation in unique sequences in both tissues. Especially a small set of genomic sites had different DNA methylation status with a trend towards slightly increased methylation levels in cloned pigs. Molecular network analysis of the genes that contained such differential methylation loci revealed a significant network related to tissue development. In conclusion, our study showed that phenotypically normal cloned pigs were highly similar with normal breeding pigs in their gene expression, but moderate alteration in DNA methylation aspects still exists, especially in certain unique genomic regions.  相似文献   
999.
1000.
From a previously published theory (Israelsson and Johnsson 1967) for circumnutations in Helianthus annuus it is possible to predict the geotropical curvatures of the hypocotyls. This extension of the theory is given in the present paper and some geotropical experiments are performed and discussed. The agreement between the theory and the experiments has been verified in the case of gravitational stimulation during relatively short stimulation periods, in the case of continuous gravitational stimulation, etc. Restrictions in the proposed model are discussed.  相似文献   
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