Hyperleptinemia in obese adolescents deregulates neuropeptides during weight loss

Leptin has emerged over the past decade as a key hormone not only in energy balance regulation but also in neuroendocrine and inflammatory processes. The aim of the present study was to evaluate whether hyperleptinemia deregulates neuropeptides during weight loss. A total of 86 post-pubertal obese adolescents (with or without hyperleptinemia) participated in one year of interdisciplinary weight loss therapy (clinical, nutritional, psychological and exercise-related). Adipokine and neuropeptide concentrations were measured by ELISA, visceral fat was measured by ultrasound and body composition was measured by pletismography. The hyperleptinemic patients presented a lower alpha-MSH concentration and higher NPY/AgRP ratio while the adiponectin/leptin (A/L) ratio was lower compared with the non-hyperleptinemic group. After therapy, significant improvements in BM, BMI, body fat mass, visceral and subcutaneous fat, HOMA-IR, QUICKI, total cholesterol and triglycerides were observed in both groups. Indeed, we observed significant increases in adiponectin and A/L as well as reductions in leptin and NPY/AgRP ratio in the hyperleptinemic group. In the stepwise multiple linear regression analysis with leptin concentration as the dependent variable, α-MSH and body fat mass (%) were the independent predictors to explain leptin concentration. For the entire group, we found positive correlations between leptinemia and BMI and body fat mass (%) as well as a negative correlation with free fat mass (%) and alpha-MSH. Finally, we verified negative correlations between adiponectin/leptin ratio with total cholesterol and LDL-c, only in hyperleptinemic patients. In conclusion, the hyperleptinemia in obese adolescents deregulates neuropeptides during weight loss.     

中国沼石蛾科五新种记述(昆虫纲,毛翅目)

记述沼石蛾科5新种:挪氏长须沼石蛾Nothopsyche nozakii Yang et Leng,sp.nov.、史氏弧缘沼石蛾Anabolia schmidi Leng et Yang,sp.nov.、云南弧缘沼石蛾Anabolia yunnanensis Leng et Yang,sp.nov.、中华多斑沼石蛾Lenarchus sinensis Yang et Leng,sp.nov.和浙江沼石蛾Limnephilus zhejiangensis Leng et Yang,sp.nov..新种模式标本保存于南京农业大学昆虫标本室.     

Antibody-Mediated Protection against Mucosal Simian-Human Immunodeficiency Virus Challenge of Macaques Immunized with Alphavirus Replicon Particles and Boosted with Trimeric Envelope Glycoprotein in MF59 Adjuvant

We have previously shown that rhesus macaques were partially protected against high-dose intravenous challenge with simian-human immunodeficiency virus SHIV_SF162P4 following sequential immunization with alphavirus replicon particles (VRP) of a chimeric recombinant VEE/SIN alphavirus (derived from Venezuelan equine encephalitis virus [VEE] and the Sindbis virus [SIN]) encoding human immunodeficiency virus type 1 HIV-1_SF162 gp140ΔV2 envelope (Env) and trimeric Env protein in MF59 adjuvant (R. Xu, I. K. Srivastava, C. E. Greer, I. Zarkikh, Z. Kraft, L. Kuller, J. M. Polo, S. W. Barnett, and L. Stamatatos, AIDS Res. Hum. Retroviruses 22:1022-1030, 2006). The protection did not require T-cell immune responses directed toward simian immunodeficiency virus (SIV) Gag. We extend those findings here to demonstrate antibody-mediated protection against mucosal challenge in macaques using prime-boost regimens incorporating both intramuscular and mucosal routes of delivery. The macaques in the vaccination groups were primed with VRP and then boosted with Env protein in MF59 adjuvant, or they were given VRP intramuscular immunizations alone and then challenged with SHIV_SF162P4 (intrarectal challenge). The results demonstrated that these vaccines were able to effectively protect the macaques to different degrees against subsequent mucosal SHIV challenge, but most noteworthy, all macaques that received the intramuscular VRP prime plus Env protein boost were completely protected. A statistically significant association was observed between the titer of virus neutralizing and binding antibodies as well as the avidity of anti-Env antibodies measured prechallenge and protection from infection. These results highlight the merit of the alphavirus replicon vector prime plus Env protein boost vaccine approach for the induction of protective antibody responses and are of particular relevance to advancing our understanding of the potential correlates of immune protection against HIV infection at a relevant mucosal portal of entry.After more than 25 years of human immunodeficiency virus (HIV) research, a prophylactic vaccine able to control or prevent the worldwide spread of HIV/AIDS remains an elusive goal. Recent results in Thailand with the recombinant canary pox (ALVAC-HIV, vCP1521; Sanofi-Pasteur) prime-gp120 (AIDSVAX B/E) protein boost vaccine approach give us hope that such a vaccine is achievable (45). Nevertheless, the results from this trial as well as the disappointing outcome of the Step Study trial (7, 29, 46) vividly highlight the need to better understand the immune correlates of protection and the immune responses engendered by the diverse new vaccine technologies currently under evaluation (13, 18, 20, 49). In the case of viral vectors, this is particularly critical, as the spectrum of immune responses elicited in animal models does not necessarily predict those eventually observed in human clinical trials and will require more thorough evaluations in order to identify the most predictive models. At the moment, nonhuman primate models, such as simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) infection of macaques appear to be the most informative for guiding vaccine development (3, 24, 47, 55), and more rigorous application of these models has begun to yield new and encouraging insights into protective immunity (5, 19, 27, 56). Moreover, as most HIV transmissions occur through mucosal membranes, understanding the correlates of protection, following successful vaccinations, against mucosal challenge is of strong interest.Alphaviruses are positive-sense single-stranded 11.5-kb RNA viruses in the Togaviridae family. They are relatively simple enveloped viruses of approximately 60-nm diameter that have a cytoplasmic RNA-based life cycle and mature at the plasma membranes of infected cells. Recombinant alphavirus replicon particles used for vaccine applications are composed of a replicon vector that encodes the viral replicases (nonstructural proteins [NSPs]) and the vaccine antigen of interest and two packaging vectors that encode the major viral structural proteins (capsid and glycoproteins E1 and E2) required for particle formation. The chimeric (VEE/SIN) alphavirus vector system used in this study was derived from Venezuelan equine encephalitis virus (VEE) and the Sindbis virus (SIN). The recombinant VEE, SIN, and Semliki viruses expressing SIV or HIV antigens as well as antigens from a diverse and growing list of pathogens have been evaluated extensively in animals by several groups (6, 15, 16, 17, 22, 32, 34, 35, 36, 38, 42, 44, 57, 58). The chimeric alphavirus replicon particles (VRP) used here were designed to combine the immune potency of the VEE replicon with the safety profile of the SIN structural proteins (38).In previous studies, we showed that rhesus macaques could be protected against high-dose intravenous challenges with SHIV_SF162P4 following sequential immunization with chimeric recombinant VRP encoding human immunodeficiency virus type 1 (HIV-1) SF162 gp140ΔV2 envelope (Env) and trimeric SF162 gp140ΔV2 Env in the MF59 adjuvant (57). We also showed the Env protein delivered with potent adjuvants (the LTK63 mucosal adjuvant and the MF59 adjuvant) using intramuscular (i.m.) or combined mucosal (intranasal [i.n.]) plus i.m. vaccine regimens provided complete protection against intravaginal (IVAG) challenge with SHIV_SF162P4 (2)_. The current work extends these studies by investigating the immunogenicity and protective efficacy of recombinant VRP delivered either mucosally, by the i.n. or intrarectal (i.r.) route, or parenterally by the i.m. route as a vector system for priming humoral immune responses prior to mucosal i.r. SHIV_SF162P4 challenge in the rhesus macaque model.In these studies, the alphavirus vector priming immunizations are followed by sequential booster immunizations with a highly purified and well-characterized trimeric V2-deleted envelope glycoprotein delivered in MF59, an oil-in-water emulsion, as an adjuvant. The HIV-1 Env antigen used in both the recombinant alphavirus prime and protein boost was derived from the macrophage-tropic chemokine (C-C motif) receptor 5 (CCR5)-utilizing HIV-1_SF162 strain, which closely matches the envelope of the SHIV_SF162P4 used for the i.r. challenge. This vaccine challenge study design thus serves as a useful starting point to better understand the mechanisms of immune protection against a relevant challenge virus and also the route of challenge in an active immunization model. Despite accelerated efforts in our laboratory and many others to identify the next generation of Env immunogens, evaluations of the breadth of protection are reserved for ongoing and future studies.     

应用PCR-SSCP技术快速检测我国水稻条纹病毒的分子变异

应用PCR SSCP技术快速检测我国水稻条纹病毒病害特异性蛋白 (SP)基因和外壳蛋白 (CP)基因的分子变异。结果发现我国水稻条纹病毒 7个分离物之间存在广泛的变异 ,其中 ,PJ分离物的SP基因和JD分离物的CP基因不能扩增出来 ,能扩增出的 6个分离物的CP基因变性电泳后带型各不相同 ,但SP基固表现出 5种带型 ,其中云南省的YL和BS分离物带型一样。