猕猴伸展抓握过程中的spike与LFP锁相相位分布特征分析

神经元动作电位(spike)的发放和局部场电位(local field potential,LFP)之间的锁相关系是重要的神经编码信息,但是目前的研究在连续运动过程中对锁相相位分布特征的分析仍比较缺乏.利用猕猴伸展抓握运动范式下的spike和LFP delta节律的锁相特性,分别在不同运动阶段,不同事件前后100 ms内,以及连续时间窗3种时间尺度下对M1、S1、PPC脑区的锁相相位分布变化进行了分析,实验发现在猕猴的连续运动中的不同阶段,spike和LFP的锁相相位分布具有不同的相位分布特点和相位分布峰值位置;对关键的事件TargetOn、CenterRelease、TargetHit发生前后各100 ms内的锁相相位分布进行分析,结果发现事件发生前后100 ms内的锁相相位分布具有显著差异性,锁相相位的峰值位置跟随时间增大;使用连续时间窗对运动中的锁相相位分布进行分析,结果表明锁相的相位分布在跟随时间变化,这种变化在CenterRelease事件发生前后更加剧烈,对相邻时间窗的均值差异分析表明伸手阶段内的锁相相位分布变化最为剧烈.对连续运动中不同的时间阶段锁相相位分布变化的分析所发现的规律,可以为解析大脑对运动过程中神经信息编码提供新的思路.     

Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys

Preclinical studies of human immunodeficiency virus type 1 (HIV-1) vaccine candidates have typically shown post-infection virological control, but protection against acquisition of infection has previously only been reported against neutralization-sensitive virus challenges. Here we demonstrate vaccine protection against acquisition of fully heterologous, neutralization-resistant simian immunodeficiency virus (SIV) challenges in rhesus monkeys. Adenovirus/poxvirus and adenovirus/adenovirus-vector-based vaccines expressing SIV(SME543) Gag, Pol and Env antigens resulted in an 80% or greater reduction in the per-exposure probability of infection against repetitive, intrarectal SIV(MAC251) challenges in rhesus monkeys. Protection against acquisition of infection showed distinct immunological correlates compared with post-infection virological control and required the inclusion of Env in the vaccine regimen. These data demonstrate the proof-of-concept that optimized HIV-1 vaccine candidates can block acquisition of stringent, heterologous, neutralization-resistant virus challenges in rhesus monkeys.     

Effect of recombinant soluble CD4 in rhesus monkeys infected with simian immunodeficiency virus of macaques

The CD4 molecule is a high-affinity cell-surface receptor for the human immunodeficiency virus (HIV-1) and a soluble truncated form of CD4 produced by recombinant DNA technology is a potent inhibitor of HIV-1 replication and HIV-1-induced cell fusion in vitro. Rhesus monkeys infected with the simian immunodeficiency virus of macaques (SIVMAC), a virus closely related to HIV-1, develop an AIDS-like syndrome, and so provide an important model for the evaluation of potential AIDS therapies. We have assessed the therapeutic effect of recombinant soluble CD4 in SIVMAC-infected rhesus monkeys. Virus was readily isolated from peripheral blood lymphocytes and bone marrow cells of these animals before starting treatment with soluble CD4, but became difficult to isolate soon after treatment had begun. Moreover the diminished growth of both granulocyte-macrophage and erythrocyte progenitor colonies from the bone marrow of these monkeys rose to normal levels during treatment. These findings indicate that soluble CD4 could prove valuable in the treatment of AIDS.     

Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys

A recombinant adenovirus serotype 5 (rAd5) vector-based vaccine for HIV-1 has recently failed in a phase 2b efficacy study in humans. Consistent with these results, preclinical studies have demonstrated that rAd5 vectors expressing simian immunodeficiency virus (SIV) Gag failed to reduce peak or setpoint viral loads after SIV challenge of rhesus monkeys (Macaca mulatta) that lacked the protective MHC class I allele Mamu-A*01 (ref. 3). Here we show that an improved T-cell-based vaccine regimen using two serologically distinct adenovirus vectors afforded substantially improved protective efficacy in this challenge model. In particular, a heterologous rAd26 prime/rAd5 boost vaccine regimen expressing SIV Gag elicited cellular immune responses with augmented magnitude, breadth and polyfunctionality as compared with the homologous rAd5 regimen. After SIV(MAC251) challenge, monkeys vaccinated with the rAd26/rAd5 regimen showed a 1.4 log reduction of peak and a 2.4 log reduction of setpoint viral loads as well as decreased AIDS-related mortality as compared with control animals. These data demonstrate that durable partial immune control of a pathogenic SIV challenge for more than 500 days can be achieved by a T-cell-based vaccine in Mamu-A*01-negative rhesus monkeys in the absence of a homologous Env antigen. These findings have important implications for the development of next-generation T-cell-based vaccine candidates for HIV-1.     

Induction of corneal epithelial progenitors from bone-marrow mesenchymal stem cells of rhesus monkeys in vitro

Bioengineered corneas are substitutes for human donor tissue that are designed to treat severe dis-ease affecting ocular surfaces. However,a shortage of candidate seed cells for bioengineering corneas is still a problem. Bone-marrow mesenchymal stem cells (MSCs) are capable of multilineage differen-tiation. Therefore,we determined whether MSCs differentiate into corneal epithelial cells (ECs). We applied three exoteric-microenvironmental systems to induce MSCs to become ECs. Induced MSC were identified by means of morphologic examination,immunocytochemical analysis,and flow cytometry. MSCs grown in one microenvironment had characteristics similar to those of corneal epithelial pro-genitors. Induced MSCs expressed markers for EC,including integrin β1,Cx43,Pax6,and P63. MSCs were successfully induced to become corneal epithelial progenitors. Therefore,the use of MSCs may hold substantial promise for reconstructing the ocular surface after corneal injury.