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Appetite enhancement and weight gain by peripheral administration of TrkB agonists in non-human primates 总被引:1,自引:0,他引:1
Lin JC Tsao D Barras P Bastarrachea RA Boyd B Chou J Rosete R Long H Forgie A Abdiche Y Dilley J Stratton J Garcia C Sloane DL Comuzzie AG Rosenthal A 《PloS one》2008,3(4):e1900
Loss of function mutations in the receptor tyrosine kinase TrkB pathway resulted in hyperphagia and morbid obesity in human and rodents. Conversely, peripheral or central stimulation of TrkB by its natural ligands BDNF or NT4 reduced body weight and food intake in mice, supporting the idea that TrkB is a key anorexigenic signal downstream of the melanocortin-4 receptor (Mc4r) system. Here we show that in non-human primates TrkB agonists were anorexigenic when applied centrally, but surprisingly orexigenic, leading to gain in appetite, body weight, fat deposits and serum leptin levels, when given peripherally. The orexigenic and pro-obesity effects of peripherally administered TrkB agonists appear to be dose dependent, not associated with fluid retention nor with evidence of receptor down regulation. Our findings revealed that TrkB signaling exerts dual control on energy homeostasis in the primates that could be targeted for the treatment of either wasting disorders or obesity. 相似文献
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van den Bogaart G Guzmán JV Mika JT Poolman B 《The Journal of biological chemistry》2008,283(49):33854-33857
The mechanism of pore formation of lytic peptides, such as melittin from bee venom, is thought to involve binding to the membrane surface, followed by insertion at threshold levels of bound peptide. We show that in membranes composed of zwitterionic lipids, i.e. phosphatidylcholine, melittin not only forms pores but also inhibits pore formation. We propose that these two modes of action are the result of two competing reactions: direct insertion into the membrane and binding parallel to the membrane surface. The direct insertion of melittin leads to pore formation, whereas the parallel conformation is inactive and prevents other melittin molecules from inserting, hence preventing pore formation. 相似文献
96.
Sex identification in young sea turtles is challenging. Sea turtle neonates lack external dimorphic characteristics and heteromorphic sex chromosomes. We compared the morphology of the gonads and reproductive ducts of dead formalin-preserved hatchling and post-hatchling Caretta caretta, Dermochelys coriacea, and Chelonia mydas and identified sex-specific differences in these structures that are useful in assigning sex. We tested 11 gross gonadal and reproductive duct characteristics in 57 neonate sea turtles and verified the sex by histological examination. A suite of four characters was found to reliably indicate sex in the three species considered: paramesonephric duct size, mobility of the duct, presence of a complete lumen and gonad mobility. Additionally, gonad shape and edge form were dependable sex-specific characters in cheloniids but not in D. coriacea. Together, these morphological characteristics provide new and reliable methods to quickly distinguish sex in preserved neonate sea turtles without using more extensive histological methods. 相似文献
97.
The monoecious understory herb Begonia urophylla blooms in the dry season at Las Cruces, Costa Rica, and bloom is partially synchronized. A laboratory experiment investigated reduced photoperiod as an unambiguous cue for flowering. The inductive period was 3 weeks for flowers but less for bud formation. Variation in bloom time may be an adaptation to enhance fitness gain of plants, such as B. urophylla, with sequential male and female phases. 相似文献
98.
Teresa E. Koper Amal F. El-Sheikh Jeanette M. Norton Martin G. Klotz 《Applied microbiology》2004,70(4):2342-2348
Many but not all ammonia-oxidizing bacteria (AOB) produce urease (urea amidohydrolase, EC 3.5.1.5) and are capable of using urea for chemolithotrophic growth. We sequenced the urease operons from two AOB, the β-proteobacterium Nitrosospira sp. strain NpAV and the γ-proteobacterium Nitrosococcus oceani. In both organisms, all seven urease genes were contiguous: the three structural urease genes ureABC were preceded and succeeded by the accessory genes ureD and ureEFG, respectively. Green fluorescent protein reporter gene fusions revealed that the ure genes were under control of a single operon promoter upstream of the ureD gene in Nitrosococcus oceani. Southern analyses revealed two copies of ureC in the Nitrosospira sp. strain NpAV genome, while a single copy of the ure operon was detected in the genome of Nitrosococcus oceani. The ureC gene encodes the alpha subunit protein containing the active site and conserved nickel binding ligands; these conserved regions were suitable primer targets for obtaining further ureC sequences from additional AOB. In order to develop molecular tools for detecting the ureolytic ecotype of AOB, ureC genes were sequenced from several β-proteobacterial AOB. Pairwise identity values ranged from 80 to 90% for the UreC peptides of AOB within a subdivision. UreC sequences deduced from AOB urease genes and available UreC sequences in the public databases were used to construct alignments and make phylogenetic inferences. The UreC proteins from β-proteobacterial AOB formed a distinct monophyletic group. Unexpectedly, the peptides from AOB did not group most closely with the UreC proteins from other β-proteobacteria. Instead, it appears that urease in β-proteobacterial autotrophic ammonia oxidizers is the product of divergent evolution in the common ancestor of γ- and β-proteobacteria that was initiated before their divergence during speciation. Sequence motifs conserved for the proteobacteria and variable regions possibly discriminatory for ureC from β-proteobacterial AOB were identified for future use in environmental analysis of ureolytic AOB. These gene sequences are the first publicly available for ure genes from autotrophic AOB. 相似文献
99.
Inactivation of Feline Calicivirus and Adenovirus Type 40 by UV Radiation 总被引:10,自引:9,他引:1 下载免费PDF全文
Jeanette A. Thurston-Enriquez Charles N. Haas Joseph Jacangelo Kelley Riley Charles P. Gerba 《Applied microbiology》2003,69(1):577-582
Little information regarding the effectiveness of UV radiation on the inactivation of caliciviruses and enteric adenoviruses is available. Analysis of human calicivirus resistance to disinfectants is hampered by the lack of animal or cell culture methods that can determine the viruses' infectivity. The inactivation kinetics of enteric adenovirus type 40 (AD40), coliphage MS-2, and feline calicivirus (FCV), closely related to the human caliciviruses based on nucleic acid organization and capsid architecture, were determined after exposure to low-pressure UV radiation in buffered demand-free (BDF) water at room temperature. In addition, UV disinfection experiments were also carried out in treated groundwater with FCV and AD40. AD40 was more resistant than either FCV or coliphage MS-2 in both BDF water and groundwater. The doses of UV required to achieve 99% inactivation of AD40, coliphage MS-2, and FCV in BDF water were 109, 55, and 16 mJ/cm2, respectively. The doses of UV required to achieve 99% inactivation of AD40, coliphage MS-2, and FCV in groundwater were slightly lower than those in BDF water. FCV was inactivated by 99% by 13 mJ/cm2 in treated groundwater. A dose of 103 mJ/cm2 was required for 99% inactivation of AD40 in treated groundwater. The results of this study indicate that if FCV is an adequate surrogate for human caliciviruses, then their inactivation by UV radiation is similar to those of other single-stranded RNA enteric viruses, such as poliovirus. In addition, AD40 appears to be more resistant to UV disinfection than previously reported. 相似文献
100.
Detection of genotyping errors and integration of such errors in statistical analysis are relatively neglected topics, given their importance in gene mapping. A few inopportunely placed errors, if ignored, can tremendously affect evidence for linkage. The present study takes a fresh look at the calculation of pedigree likelihoods in the presence of genotyping error. To accommodate genotyping error, we present extensions to the Lander-Green-Kruglyak deterministic algorithm for small pedigrees and to the Markov-chain Monte Carlo stochastic algorithm for large pedigrees. These extensions can accommodate a variety of error models and refrain from simplifying assumptions, such as allowing, at most, one error per pedigree. In principle, almost any statistical genetic analysis can be performed taking errors into account, without actually correcting or deleting suspect genotypes. Three examples illustrate the possibilities. These examples make use of the full pedigree data, multiple linked markers, and a prior error model. The first example is the estimation of genotyping error rates from pedigree data. The second-and currently most useful-example is the computation of posterior mistyping probabilities. These probabilities cover both Mendelian-consistent and Mendelian-inconsistent errors. The third example is the selection of the true pedigree structure connecting a group of people from among several competing pedigree structures. Paternity testing and twin zygosity testing are typical applications. 相似文献