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1.
Circumcision is often claimed to be simpler, safer and more cost-effective when performed in the neonatal period as opposed to later in life, with a greater benefit-to-risk ratio. In the first part of this paper, we critically examine the evidence base for these claims, and find that it is not as robust as is commonly assumed. In the second part, we demonstrate that, even if one simply grants these claims for the sake of argument, it still does not follow that neonatal circumcision is ethically permissible absent urgent medical necessity. Based on a careful consideration of the relevant evidence, arguments and counterarguments, we conclude that medically unnecessary penile circumcision—like other medically unnecessary genital procedures, such as ‘cosmetic’ labiaplasty—should not be performed on individuals who are too young (or otherwise unable) to provide meaningful consent to the procedure.  相似文献   

2.
In observations by confocal or conventional fluorescence microscopy, important factors should be considered in order to obtain accurate images. One of them, such as the fluorescence bleaching from highest intensity to lowest signal of fluorescence is a common problem with several DNA fluorochromes and especially for DAPI stain. The fluorescence of DAPI fades rapidly when it is exposed to UV light, under optimal conditions of observation. Although the fading process can be retarded using a mounting medium with antifading reagents, the photochemical process underlying the fluorescence decay has not yet been fully explained. In addition, no relationship between fluorescence fading and nuclear DNA content has been tested. In order to test this relationship, we measured by means of image analysis the DAPI-fluorescence intensity in several cellular types (spermatozoa, erythrocytes and haemocytes) during their fluorescence bleaching. An algorithm specifically built in MATLAB software was used for this approach. The correlation coefficient between nuclear DNA content and DAPI-fluorescence fading was found equal to 99%. This study demonstrates the feasibility to measure nuclear DNA content by fluorescence fading quantification, as an alternative method concurrently with image analysis procedures.  相似文献   

3.
Summary A new statistical test has been developed to detect selection on silent sites. This test compares the codon usage within a gene and thus does not require knowledge of which genes are under the greatest selection, that there exist common trends in codon usage across genes, or that genes have the same mutation pattern. It also controls for mutational biases that might be introduced by the adjacent bases. The test was applied to 62 mammalian sequences, the significant codon usage biases were detected in all three species examined (humans, rats, and mice). However, these biases appear not to be the consequence of selection, but of the first base pair in the codon influencing the mutation pattern at the third position.  相似文献   

4.
The activity of soluble cyclodextrin glycosyltransferase was increased by 40% without formation of inclusion bodies by induction at low temperature with the addition of 10 mM CaCl2 into the medium, when the corresponding gene was expressed in two recombinant E. coli. Furthermore, the protein expressed at 25°C had approximately 30% higher specific activity than that expressed at 30°C. The two different hosts, promoters, and media showed the same result, indicating that this simple method can be used in expressing other proteins.  相似文献   

5.
We explore the use of classical Linear Response Theory (LRT) as an alternative strategy to the use of Molecular Mechanics/Poisson-Boltzmann strategies to compute the solvation free energy of macromolecules from molecular dynamics simulations using an explicit representation of solvent. The method reproduces well the free energy of solvation of standard amino acid side chains, small peptides, and proteins. The use of a fully discrete representation of solvent avoids the possible problems of continuum models to represent the solvation of systems containing tightly bound water molecules.  相似文献   

6.
Stanley P 《Cell》2007,129(1):27-29
Cell-surface glycoprotein receptors have varying numbers of N-glycan sites. In this issue of Cell, Lau et al. (2007) report that increasing intracellular UDP-GlcNAc leads to increased branching of N-glycans, increased receptor association with cell-surface galectin-3, and enhanced signaling. They also show that the kinetics of this response differ between growth-promoting receptors, which have 8-16 N-glycans, and those that induce growth arrest, which have very few N-glycans, suggesting that hexosamine flux may regulate the transition from growth to arrest.  相似文献   

7.
《MABS-AUSTIN》2013,5(8):1391-1401
ABSTRACT

In the biopharmaceutical environment, controlling the Critical Quality Attributes (CQA) of a product is essential to prevent changes that affect its safety or efficacy. Physico-chemical techniques and bioassays are used to screen and monitor these CQAs. The higher order structure (HOS) is a CQA that is typically studied using techniques that are not commonly considered amenable to quality control laboratories. Here, we propose a peptide mapping-based method, named native peptide mapping, which could be considered as straightforward for HOS analysis and applicable for IgG4 and IgG1 antibodies. The method was demonstrated to be fit-for-purpose as a stability-indicating assay by showing differences at the peptide level between stressed and unstressed material. The unfolding pathway induced by a heat stress was also studied via native peptide mapping assay. Furthermore, we demonstrated the structure–activity relationship between HOS and biological activity by analyzing different types of stressed samples with a cell-based assay and the native peptide mapping. The correlation between both sets of results was highlighted by monitoring peptides located in the complementary-determining regions and the relative potency of the biotherapeutic product. This relationship represents a useful approach to interrogate the criticality of HOS as a CQA of a drug.  相似文献   

8.
A simple linear relationship between the J coupling constant and the linewidth (1/2) of in-phase NMR peaks has been identified. This relationship permits the rapid and accurate determination of polypeptide J coupling constants from a simple inspection of amide cross peaks in homonuclear 1H TOCSY or 1H NOESY spectra. By using the appropriate set of processing parameters we show that J = 0.5(1/2) – MW/5000 + 1.8 for TOCSY spectra and J = 0.6(1/2) – MW/5000 – 0.9 for NOESY spectra, where 1/2 is the half-height linewidth in Hz and MW is the molecular weight of the protein in Da. The simplicity of this relationship, combined with the ease with which 1/2 measurements can be made, means that J coupling constants can now be rapidly determined (up to 100 measurements in less than 30 min) without the need for any complex curve-fitting algorithms. Tests on 11 different polypeptides involving more than 650 separate J measurements have shown that this method yields coupling constants with an rmsd error (relative to X-ray data) of less than 0.9 Hz. Furthermore, the correlation coefficient between the predicted NMR coupling constants and those derived from high-resolution X-ray crystal structures is typically better than 0.89. These simple linear relationships have been found to be valid for peptides as small as 1 kDa to proteins as large as 20 kDa. Despite the method's simplicity, these results are comparable to the accuracy and precision of the best techniques published to date.  相似文献   

9.
A method is described whereby a Bělehrádek function is fitted to experimentally derived data for embryonic development duration at a range of temperatures. The method is applied to data for the freshwater copepods Cyclops abyssorum and Eudiaptomus gracilis from Lough Neagh, Northern Ireland. Differences in duration of embryonic development of Lough Neagh populations and that of previously published data for these species are discussed.  相似文献   

10.
The mosquito is a very important vector involved in the worldwide transmission of disease-causing viruses and parasites. Controlling the mosquito population remains one of the best means for preventing the serious infectious diseases of malaria, yellow fever, dengue, filariasis and so on and there has been an increasing interest in developing biopesticides as a useful substitute to chemical insecticides. As a result, Bacillus thuringiensis subsp. israelensis (Bti) has been extensively used due to its specificity and high toxicity to a variety of mosquito larvae. However it is prudent to seek alternatives to Bti with alternative spectra of mosquitocidal activity or that are able to overcome any resistance that might develop against Bti. The Bt S2160-1 strain was isolated from soil samples collected from Southern China and found to have a comparable mosquitocidal activity to Bti. However there were significant differences in terms of their plasmid profiles, crystal proteins produced and cry gene complement. A PCR-restriction fragment length polymorphism identification system was developed and used in order to identify novel cry-type genes and four such genes (cry30Ea, cry30Ga, cry50Ba and cry54Ba) were identified in Bt S2160-1. In conclusion, Bt S2160-1 has been identified as a potential alternative to Bti, which could be used for the control of mosquito populations in order to reduce the incidence of mosquito-borne diseases.  相似文献   

11.
Immobilized protein receptors and enzymes are tools for isolating or enriching ligands and substrates based on affinity. For example, glutathione S-transferase (GST) is fused to proteins as a tag for binding to its substrate glutathione (GSH) linked to solid supports. One issue with this approach is that high-affinity interactions between receptors and ligands require harsh elution conditions such as low pH, which can result in leached receptor. Another issue is the inherent nonspecific chemical conjugation of reactive groups such as N-hydroxysuccinimide (NHS) that couple lysines to solid supports; the nonspecificity of NHS may result in residue modifications near the binding site(s) of the receptor that can affect ligand specificity. In this study, a simple conjugation procedure is presented that overcomes these limitations and results in immobilized GST fusion proteins that are functional and specific. Here, the affinity of GST for GSH was used to generate an enzyme–substrate site-specific cross-linking reaction; GSH–Sepharose was preactivated with 1-ethyl-3-(dimethylaminopropyl)carbodiimide (EDC) and then incubated Fc gamma receptor IIIa (FcγRIIIa)–GST. The immobilized FcγRIIIa–GST more specifically bound glycosylated immunoglobulin G1s (IgG1s) and was used to enrich nonfucosylated IgG1s from weaker binding species. This technique can be used when modifications of amino acids lead to changes in activity.  相似文献   

12.
Mating systems are well known to influence the dispersing sex,but the magnitude of the sex-biased dispersal has not actuallybeen measured, whereas many theoretical predictions have beenmade. In this study, we tested a new prediction about the coevolutionbetween natal dispersal and sociality from a recent evolutionarilystable strategy (ESS) approach. From a comparative approach,we showed that, in agreement with the model, the male-biaseddispersal increases with increasing level of sociality in polygynousground-dwelling sciurids. In addition, the increase in male-biaseddispersal with increasing sociality results from an increasein male dispersal rates, whereas female dispersal rates remainconstant, contrary to what is expected from the ESS model. Althoughthe mating system through the level of polygyny could act asa confounding factor, our results strengthen previous work thatstates that inbreeding avoidance plays a major role in the evolutionof dispersal for the most social mammalian species.  相似文献   

13.
A new and simple HPLC–MS method was developed for monitoring iodinated casein in feed premixes. In this method, feed premixes were hydrolyzed, and the iodotyrosines thus released were analyzed. Sample pretreatment included precipitation of transition metals ions with Na2S, hydrolysis with sodium hydroxide, and cleaning up with an Oasis SAX cartridge. Gradient elution was carried out on a C18 column with water (containing 0.1% formic acid) and acetonitrile. Ion detection was performed using ESI positive SIM at m/z 262, 308, 388, and 434. Iodinated casein levels were monitored by qualitative analysis of the iodotyrosines released upon sample hydrolysis and by quantifying the 3,5-diiodotyrosine released. The validation data demonstrated that the method was selective and sensitive (≤0.2 mg g?1) for iodinated casein and had acceptable accuracy (recoveries: 81.3–106.7%) and precision (RSD: 1.7–16.0%).  相似文献   

14.
This article comments on: Combined use of herbivore‐induced plant volatiles and sex pheromones for mate location in braconid parasitoids  相似文献   

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18.
Daphne pseudomezereum A. Gray (Dpm) appears to be the only woody species in the north temperate forest that sheds its leaves in the summer while remaining green over winter (i.e. wintergreen leaf habit). Yet, the reason for this odd leaf habit has not been explored. To this end, we examined the microclimatic settings and ecophysiological traits of Dpm and its three native congeners in a field study of eight natural populations. In addition, we conducted a common garden experiment using Dpm plants where potential carbon gain across the seasons was estimated, using actual field microclimate data. Together, these data tested the hypothesis that Dpm retained traits of an open-grown upland ancestor, unable to adapt to the deep summer shade, it survived by becoming summer dormant and wintergreen. Our hypothesis was supported by patterns of leaf ecophysiological traits and carbon gain simulations in Dpm, consistent with the energetic feasibility of a summer dormancy followed by an autumn leaf sprout. We also conclude that carbon deficit driven by low light and high respiration cost is the trigger for the leaf habit of Dpm and assert that its phenological strategy represents a rare but viable alternative strategy for persistence in the temperate understory.  相似文献   

19.
We tested for an association between divorce rate and site fidelity in 42 avian species belonging to the order Ciconiiforms, using comparative methods that account for the influences of phylogenetic relationships on the data. Our methods enabled us to detect evidence of correlated evolution and provided information on the temporal ordering of evolutionary changes in these two variables. We found a significant correlation between divorce rate and site fidelity, indicating that species with little or no site fidelity are more likely to divorce. Our data suggest that the coupled evolution of divorce and site fidelity can be summarized by three major events. The first event corresponds to a transition from species showing high divorce rate and low or no site fidelity to species that tended to reuse the same nests over consecutive breeding seasons. This was followed by a transition towards higher mate fidelity, with the preservation of pair bonds over consecutive breeding attempts. In a third stage, divorce rate and the rate of site fidelity varied, independently of each other. We discuss our results within the context of the ancestor species and the past environments in which the traits originated, and address the importance of the potential for individual recognition in shaping the observed patterns of covariation between mate fidelity and site fidelity in Ciconiiforms. Copyright 2000 The Association for the Study of Animal Behaviour.  相似文献   

20.
This study presents a multivariate behavioural genetic analysis of the relationship between education, intelligence and age of first birth. Analyses investigated the mediational role of education in explaining the relationship between intelligence and age of first birth at both the phenotypic and behavioural genetic level. The data come from the National Longitudinal Survey of Youth (NLSY), a nationally representative survey that included genetically informative full- and half-sibling pairs (n = 1423 pairs). Respondents were aged 14 to 22 when contacted in 1979. Heritability estimates were 0.32, 0.50 and 0.06 for IQ, education and age of first birth, respectively. Shared environment estimates were 0.35, 0.23 and 0.20 respectively. Common genetic and shared environmental factors were substantial in explaining the relationship between intelligence and education, and also education and age of first birth. Education partially mediated the relationship between intelligence and age of first birth only in the phenotypic analyses. After considering the genetic and shared environmental factors that influence all three variables, evidence for mediation was less convincing. This pattern of results suggests that the apparent mediational role of education at the phenotypic level is in fact the result of underlying genetic and shared environmental influences that affect education, IQ and age of first birth in common.  相似文献   

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