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241.
Oligodendrocytes (OLs) are responsible for axon myelination and are the principal cells targeted in preterm white matter injury. The cellular and molecular mechanisms involved in white matter development and immature OL injury are incompletely understood. Metabotropic glutamate receptors (mGluRs) modulate neuronal development and survival, and have recently been identified in oligodendrocyte progenitor cells (OPCs). Using the highly homogeneous CG-4 OPC line and O4 marker-immunoselected primary OLs, we established the differentiation stage-specific expression profile of mGluR3 and mGluR5 mRNAs and proteins in the oligodendroglial lineage and type-2-astrocytes (ASTs). Our quantitative analysis indicated no changes in mGluR3, but a significant down-regulation of mGluR5a mRNA and protein expression during differentiation of OPCs into OLs or ASTs. The down-regulation of mGluR5a had functional consequences, with significantly fewer OLs and ASTs than OPCs responding to the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine with intracellular Ca(2+) concentration oscillations. Neither stimulation nor inhibition of mGluR3 or mGluR5 altered OPC migration, suggesting that these receptors do not play prominent roles in the regulation of OPC motility. The activation of mGluR5 completely protected OPCs and substantially reduced staurosporine-induced apoptosis in OLs. This suggests that the down-regulation of mGluR5 in premyelinating OLs is likely to contribute to their increased vulnerability, and that the targeting of mGluR5 may be a potential therapeutic strategy for future development.  相似文献   
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The aim of our study was to measure globotriaosylceramide (Gb(3)) and lyso-Gb(3) levels by tandem mass spectrometry in the urine and kidney in Fabry (gla knockout) mice and wild-type controls. We found that urine Gb(3) of male and female Fabry mice was higher than wild-type mice of the same sex but also significantly higher in male mice compared with females of the same genotype. In kidney tissue, sex and genotype-dependent differences in Gb(3) levels paralleled those in the urine. Isoforms C16, C22:1, and C24OHA were particularly higher in males compared with females in both wild-type and Fabry mice. Similarly, kidney lyso-Gb(3) concentrations were significantly higher in 12-month-old male Fabry mice than in their homozygous female counterparts. However, lyso-Gb(3) was undetectable in wild-type mice of both sexes. α-Galactosidase A activity and mRNA levels in kidney were significantly lower in male wild-type mice compared with female mice. This study shows the sex differences in kidney and urine Gb(3) and kidney lyso-Gb(3) levels in both wild-type and Fabry mice, and it suggests that these male-female differences should be taken into consideration when using murine models for Fabry disease.  相似文献   
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Background  

Reverse engineering in systems biology entails inference of gene regulatory networks from observational data. This data typically include gene expression measurements of wild type and mutant cells in response to a given stimulus. It has been shown that when more than one type of experiment is used in the network inference process the accuracy is higher. Therefore the development of generally applicable and effective methodologies that embed multiple sources of information in a single computational framework is a worthwhile objective.  相似文献   
246.
Incubation temperature is an important maternal effect in birds that can influence numerous offspring traits. For example, ducklings from eggs incubated at lower temperatures have lower growth rates, protein content, and are in poorer body condition than ducklings from eggs incubated at higher temperatures. Based on these observations, we predicted that incubation temperature would indirectly influence performance through its direct effects on body size. Wood duck (Aix sponsa) eggs were incubated at three ecologically relevant temperatures (35, 35.9, 37°C). After hatching, all ducklings were housed under identical conditions and were subjected to aquatic and terrestrial racing trials at 15 and 20 days posthatch (dph). Contrary to our prediction, incubation temperature did not influence most duckling body size parameters at 15 or 20?dph. However, incubation temperature did have a strong influence on locomotor performance independent of body size and body condition. Ducklings hatched from eggs incubated at the lowest temperature had significantly reduced maximum aquatic swim velocity than ducklings from higher temperatures. Maximum terrestrial sprint velocity followed a similar pattern, but did not differ statistically among incubation treatments. To our knowledge, this is the first study to demonstrate that slight changes in incubation temperature can directly affect locomotor performance in avian offspring and thus provide a significant source of phenotypic variation in natural wood duck populations.  相似文献   
247.
The value of age is well recognized in human societies, where older individuals often emerge as leaders in tasks requiring specialized knowledge, but what part do such individuals play in other social species? Despite growing interest in how effective leadership might be achieved in animal social systems, the specific role that older leaders may play in decision-making has rarely been experimentally investigated. Here, we use a novel playback paradigm to demonstrate that in African elephants (Loxodonta africana), age affects the ability of matriarchs to make ecologically relevant decisions in a domain critical to survival—the assessment of predatory threat. While groups consistently adjust their defensive behaviour to the greater threat of three roaring lions versus one, families with younger matriarchs typically under-react to roars from male lions despite the severe danger they represent. Sensitivity to this key threat increases with matriarch age and is greatest for the oldest matriarchs, who are likely to have accumulated the most experience. Our study provides the first empirical evidence that individuals within a social group may derive significant benefits from the influence of an older leader because of their enhanced ability to make crucial decisions about predatory threat, generating important insights into selection for longevity in cognitively advanced social mammals.  相似文献   
248.
Human-carnivore conflict (HCC) is an increasingly important issue in Tanzania, especially where humans live adjacent to protected areas (PAs). We conducted semi-structured interviews (n = 300) to compile information on livestock husbandry practices and evaluate perceptions about the effectiveness of these methods in the Tarangire-Simanjiro ecosystem of northern Tanzania. Fortified bomas were perceived to be very effective (97.7%) in reducing nighttime depredations, while adult herders were perceived to be effective (71%) in reducing daytime depredations. Domestic dogs were perceived to be more effective at night, but an equal number of respondents found them to be effective during herding as those who found them to be not effective. Our results also show that boma type had a significant effect on livestock depredation. We recommend the use of fortified bomas as a long-term solution to prevent nocturnal livestock loss and adult herders for livestock during the day.  相似文献   
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Combining protein evolution and secondary structure   总被引:10,自引:9,他引:10  
An evolutionary model that combines protein secondary structure and amino acid replacement is introduced. It allows likelihood analysis of aligned protein sequences and does not require the underlying secondary (or tertiary) structures of these sequences to be known. One component of the model describes the organization of secondary structure along a protein sequence and another specifies the evolutionary process for each category of secondary structure. A database of proteins with known secondary structures is used to estimate model parameters representing these two components. Phylogeny, the third component of the model, can be estimated from the data set of interest. As an example, we employ our model to analyze a set of sucrose synthase sequences. For the evolution of sucrose synthase, a parametric bootstrap approach indicates that our model is statistically preferable to one that ignores secondary structure.   相似文献   
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