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1.
We have cloned and sequenced a genomic region centromeric of the HLA-B locus from different MHC ancestral haplotypes. These haplotypes are associated with several diseases. The sequences were analyzed for coding potential and their relevance to disease associations were assessed with respect to the level of polymorphism. Analysis of sequences located approximately 25kb centromeric of HLA-B reveals the existence of fibroblast growth factor receptor related sequences. These sequences designated PERB1 (FGFR6 ) reveal 80% homology, at both nucleic acid and amino acid level, to the immunoglobulin domain 1 (Ig-1) of the human fibroblast growth factor receptor 3 ( FGFR3 ) gene. Amino acid comparison of the Ig-1 domain of PERB1 to those of other FGFR molecules indicates that PERB1 is more closely related to FGFR3 and FGFR5 than to FGFR1 , FGFR2 or FGFR4 . Genomic sequence analysis, however, reveals no consensus splice sites and indicates the existence of inframe premature stop codons in the putative coding sequences. The results suggest that these sequences may represent FGFR gene fragments existing within the central MHC. Sequence analysis of the Mhc in 6 chimpanzee and one orangutan indicates that the existence of PERB 1 predates the spe-ciation of the three species. The fact that the MHC contains a mixture of functional and nonfunctional (pseudo) genes suggests that a functional copy of PERB1 (FGFR6 ) may exist within or in close proximity to the MHC.  相似文献   
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Virtually every eukaryotic cell has an endogenous circadian clock and a biological sex. These cell-based clocks have been conceptualized as oscillators whose phase can be reset by internal signals such as hormones, and external cues such as light. The present review highlights the inter-relationship between circadian clocks and sex differences. In mammals, the suprachiasmatic nucleus (SCN) serves as a master clock synchronizing the phase of clocks throughout the body. Gonadal steroid receptors are expressed in almost every site that receives direct SCN input. Here we review sex differences in the circadian timing system in the hypothalamic–pituitary–gonadal axis (HPG), the hypothalamic–adrenal–pituitary (HPA) axis, and sleep–arousal systems. We also point to ways in which disruption of circadian rhythms within these systems differs in the sexes and is associated with dysfunction and disease. Understanding sex differentiated circadian timing systems can lead to improved treatment strategies for these conditions.  相似文献   
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Purpose

The purpose was to evaluate the efficacy of treatment and the occurrence of aggression-related adverse events among children receiving perampanel (PER) with concomitant levetiracetam (LEV).

Methods

Patients were selected according to the following criteria: 1) between 12 and 18 years old; 2) seizures refractory to at least 2 first-line drugs; 3) at least 4 seizures a month before PER administration; and 4) at least 12 months of follow-up. Patients were subdivided into groups with and without LEV as concomitant treatment. PER was administered at a dose of 2 mg/day, increasing by 2 mg/day every 2 weeks up to 12 mg/day if seizures appeared. In comparison with the baseline seizure frequency, response to PER treatment was classified as follows: complete cessation (100% seizure control); response (≥50% reduction in seizures); and exacerbation (≥50% increase in seizures). Responders were identified as patients showing complete cessation or response.

Results

The study group comprised 39 outpatients with a mean age of 13.7 years at enrollment. Responder status was seen in 13 of the 19 patients with LEV and 4 of the 20 patients without LEV. PER appeared significantly more effective in patients with LEV than in those without LEV (p = 0.0076). Seizure-free status was significantly more frequent among patients with LEV (47.4%) than among those without LEV (15.0% (p = 0.0407)). Aggression was present in 2 patients without LEV, but none with LEV.

Conclusion

The present study suggests the utility of PER with concomitant LEV for children with drug-resistant epilepsy.  相似文献   
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PER2, a key molecular component of the mammalian circadian clock, is expressed rhythmically in many brain areas and peripheral tissues in mammals. Here we review findings from our work on the nature and regulation of rhythms of expression of PER2 in two anatomically and neurochemically defined subregions of the central extended amygdala, the oval nucleus of the bed nucleus of the stria terminalis (BNSTov) and the central nucleus of the amygdala (CEA). Daily rhythms in the expression of PER2 in these regions are coupled to those of the master circadian pacemaker, the suprachiasmatic nucleus (SCN) but, importantly, they are sensitive to homeostatic perturbations and to hormonal states that directly influence motivated behavior.  相似文献   
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Chronic nutritional stress can have a negative impact on an individual's learning ability and memory. However, in social animals that share food among group members, such as the honey bee (Apis mellifera L.), it is unknown whether group-level nutritional stress is manifested in the learning performance of individuals. Accordingly, we examined learning and memory in honey bee workers reared by colonies exposed to varying degrees of long-term pollen stress. Pollen provides honey bee workers with almost all of the proteins, lipids, vitamins, and minerals that they require as larvae and adults. Colonies were created that were either chronically pollen poor or pollen rich, or were intermediate in pollen supply; treatments altered colonies' pollen stores and brood-rearing capacity. Workers from these colonies were put through a series of olfactory-conditioning assays using proboscis-extension response (PER). PER thresholds were determined, then workers learned in olfactory-conditioning trials to associate two floral odors (one novel and the other presented previously without reward) with stimulation with sucrose and a sucrose reward. The strength of the memory that was formed for the odor/sucrose association was tested after olfactory-conditioning assays ended. Colony-level nutritional status had no effect on worker learning or memory (response threshold of workers to sucrose, acquisition of the odor/sucrose association, occurrence of latent inhibition, or memory retention over 72 h). We conclude that potential effects of chronic, colony-wide nutrient deprivation on learning and memory are not found in workers, probably because colonies use brood-rearing capacity to buffer nutrient stress at the level of the individual.  相似文献   
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Abnormal expression of period 1 (PER1) in endometrial carcinoma   总被引:2,自引:0,他引:2  
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Heavy use of alcohol can lead to addictive behaviors and to eventual alcohol‐related tissue damage. While increased consumption of alcohol has been attributed to various factors including level of alcohol exposure and environmental factors such as stress, data from behavioral scientists and physiological researchers are revealing roles for the circadian rhythm in mediating the development of behaviors associated with alcohol use disorder as well as the tissue damage that drives physiological disease. In this work, we compile recent work on the complex mutually influential relationship that exists between the core circadian rhythm and the pharmacodynamics of alcohol. As we do so, we highlight implications of the relationship between alcohol and common circadian mechanisms of effected organs on alcohol consumption, metabolism, toxicity, and pathology.  相似文献   
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