Distinct pathogenic sequela in rhesus macaques infected with CCR5 or CXCR4 utilizing SHIVs

Infection of macaques with chimeric simian-human immunodeficiency virus (SHIV) provides an excellent in vivo model for examining the influence of envelope on HIV-1 pathogenesis. Infection with a pathogenic CCR5 (R5)-specific enveloped virus, SHIVSF162P, was compared with infection with the CXCR4 (X4)-specific SHIVSF33A.2. Despite comparable levels of viral replication, animals infected with the R5 and X4 SHIV had distinct pathogenic outcomes. SHIVSF162P caused a dramatic loss of CD4+ intestinal T cells followed by a gradual depletion in peripheral CD4+ T cells, whereas infection with SHIVSF33A.2 caused a profound loss in peripheral T cells that was not paralleled in the intestine. These results suggest a critical role of co-receptor utilization in viral pathogenesis and provide a reliable in vivo model for preclinical examination of HIV-1 vaccines and therapeutic agents in the context of the HIV-1 envelope protein.     

Cognitive imitation in rhesus macaques

Experiments on imitation typically evaluate a student's ability to copy some feature of an expert's motor behavior. Here, we describe a type of observational learning in which a student copies a cognitive rule rather than a specific motor action. Two rhesus macaques were trained to respond, in a prescribed order, to different sets of photographs that were displayed on a touch-sensitive monitor. Because the position of the photographs varied randomly from trial to trial, sequences could not be learned by motor imitation. Both monkeys learned new sequences more rapidly after observing an expert execute those sequences than when they had to learn new sequences entirely by trial and error.     

Dendritic cell stimulation by mycobacterial Hsp70 is mediated through CCR5

An effective host immune response to mycobacterial infection must control pathogen dissemination without inducing immunopathology. Constitutive overexpression of mycobacterial heat shock protein (myHsp70) is associated with impaired bacterial persistence, but the immune-mediated mechanisms are unknown. We found that myHsp70, in addition to enhancing antigen delivery to human dendritic cells, signaled through the CCR5 chemokine receptor, promoting dendritic cell aggregation, immune synapse formation between dendritic cells and T cells, and the generation of effector immune responses. Thus, CCR5 acts as a pattern-recognition receptor for myHsp70, which may have implications for both the pathophysiology of tuberculosis and the use of myHsps in tumor-directed immunotherapy.     

Integrase inhibitors and cellular immunity suppress retroviral replication in rhesus macaques

We describe the efficacy of L-870812, an inhibitor of HIV-1 and SIV integrase, in rhesus macaques infected with the simian-human immunodeficiency virus (SHIV) 89.6P. When initiated before CD4 cell depletion, L-870812 therapy mediated a sustained suppression of viremia, preserving CD4 levels and permitting the induction of virus-specific cellular immunity. L-870812 was also active in chronic infection; however, the magnitude and durability of the effect varied in conjunction with the pretreatment immune response and viral load. These studies demonstrate integrase inhibitor activity in vivo and suggest that cellular immunity facilitates chemotherapeutic efficacy in retroviral infections.     

Demographic histories and patterns of linkage disequilibrium in Chinese and Indian rhesus macaques

To understand the demographic history of rhesus macaques (Macaca mulatta) and document the extent of linkage disequilibrium (LD) in the genome, we partially resequenced five Encyclopedia of DNA Elements regions in 9 Chinese and 38 captive-born Indian rhesus macaques. Population genetic analyses of the 1467 single-nucleotide polymorphisms discovered suggest that the two populations separated about 162,000 years ago, with the Chinese population tripling in size since then and the Indian population eventually shrinking by a factor of four. Using coalescent simulations, we confirmed that these inferred demographic events explain a much faster decay of LD in Chinese (r(2) approximately 0.15 at 10 kilobases) versus Indian (r(2) approximately 0.52 at 10 kilobases) macaque populations.     

Dendrodendritic inhibition through reversal of dopamine transport

Synapses in the central nervous system are usually defined by presynaptic exocytotic release sites and postsynaptic differentiations. We report here a demonstration of dendrodendritic inhibition that does not engage a conventional synapse. Using amperometric and patch-clamp recordings in rat brain slices of the substantia nigra, we found that blockade of the dopamine transporter abolished the dendritic release of dopamine and the resulting self-inhibition. These findings demonstrate that dendrodendritic autoinhibition entails the carrier-mediated release of dopamine rather than conventional exocytosis. This suggests that some widely used antidepressants that inhibit the dopamine transporter may benefit patients in the early stages of Parkinson's disease.     

Recent expansion of Toxoplasma through enhanced oral transmission

The global predominance of three clonal Toxoplasma gondii lineages suggests that they are endowed with an exceptional trait responsible for their current parasitism of nearly all warm-blooded vertebrates. Genetic polymorphism analyses indicate that these clonal lineages emerged within the last 10,000 years after a single genetic cross. Comparison with ancient strains (approximately 1 million years) suggests that the success of the clonal lineages resulted from the concurrent acquisition of direct oral infectivity. This key adaptation circumvented sexual recombination, simultaneously promoting transmission through successive hosts, hence leading to clonal expansion. Thus, changes in complex life cycles can occur rapidly and can profoundly influence pathogenicity.     

Spin selectivity in electron transmission through self-assembled monolayers of double-stranded DNA

In electron-transfer processes, spin effects normally are seen either in magnetic materials or in systems containing heavy atoms that facilitate spin-orbit coupling. We report spin-selective transmission of electrons through self-assembled monolayers of double-stranded DNA on gold. By directly measuring the spin of the transmitted electrons with a Mott polarimeter, we found spin polarizations exceeding 60% at room temperature. The spin-polarized photoelectrons were observed even when the photoelectrons were generated with unpolarized light. The observed spin selectivity at room temperature was extremely high as compared with other known spin filters. The spin filtration efficiency depended on the length of the DNA in the monolayer and its organization.     

Mobile DNA in Old World monkeys: a glimpse through the rhesus macaque genome

The completion of the draft sequence of the rhesus macaque genome allowed us to study the genomic composition and evolution of transposable elements in this representative of the Old World monkey lineage, a group of diverse primates closely related to humans. The L1 family of long interspersed elements appears to have evolved as a single lineage, and Alu elements have evolved into four currently active lineages. We also found evidence of elevated horizontal transmissions of retroviruses and the absence of DNA transposon activity in the Old World monkey lineage. In addition, approximately 100 precursors of composite SVA (short interspersed element, variable number of tandem repeat, and Alu) elements were identified, with the majority being shared by the common ancestor of humans and rhesus macaques. Mobile elements compose roughly 50% of primate genomes, and our findings illustrate their diversity and strong influence on genome evolution between closely related species.     

Prevention of fungal infection of plants by specific inhibition of cutinase

Specific antibodies prepared against cutinase from Fusarium solani pisi and diisopropylfluorophosphate, a potent inhibitor of this enzyme, prevented infection of the host (pea epicotyl) by this organism, without affecting the viability of the spores. This finding shows that enzymatic penetration of cuticle is involved in pathogenesis.     

Transgenic inhibition of synaptic transmission reveals role of CA3 output in hippocampal learning

The hippocampus is an area of the brain involved in learning and memory. It contains parallel excitatory pathways referred to as the trisynaptic pathway (which carries information as follows: entorhinal cortex --> dentate gyrus --> CA3 --> CA1 --> entorhinal cortex) and the monosynaptic pathway (entorhinal cortex --> CA1 --> entorhinal cortex). We developed a generally applicable tetanus toxin-based method for transgenic mice that permits inducible and reversible inhibition of synaptic transmission and applied it to the trisynaptic pathway while preserving transmission in the monosynaptic pathway. We found that synaptic output from CA3 in the trisynaptic pathway is dispensable and the short monosynaptic pathway is sufficient for incremental spatial learning. In contrast, the full trisynaptic pathway containing CA3 is required for rapid one-trial contextual learning, for pattern completion-based memory recall, and for spatial tuning of CA1 cells.     

Toxoplasma gondii: transmission through feces in absence of Toxocara cati eggs

When incubated at room temperature (23 degrees C) for 3 to 14 days, feces from cats infected 4 to 8 days with Toxoplasma gondii, and free of Toxocara cati eggs, produced toxoplasmosis in mice. Results indicate that the nematode egg is not necessary for transmission of the parasite.     

Insecticide inhibition of 5alpha-dihydrotestosterone binding in the rat ventral prostate

The chlorinated hydrocarbon insecticides dieldrin and o,p'-DDT inhibit binding of 5alpha-dihydrotestosterone to specific receptor proteins in rat prostate cytosol. Dieldrin is less inhibitory than o,p'-DDT.     

植物羟基肉桂酰辅酶A还原酶的生物信息学分析

分析GenBank公布的68条蕨类、裸子、单子叶和双子叶植物的CCR蛋白,发现单子叶植物CCR基因的GC含量最高,CCR一级结构的理化性质基本一致,但主要氨基酸种类和含量不同;CCR是一类无导肽、信号肽及跨膜结构域的亲水性蛋白质,N-端存在3β-羟基类固醇脱氢酶/差向异构酶/NAD结合蛋白的结构域,存在9个功能保守区;进化树表明,该基因可用于植物高等级单元的分类;同源建模表明其三级结构稳定,建模结果可靠;CCR蛋白亚细胞定位于细胞质、叶绿体和内质网,除黑麦草和番茄外,同一物种CCR不同成员的亚细胞定位基本相同.     

输变电工程对土壤环境的影响及其防控

输变电工程建设及其营运对变电站场和线路工程区及周边局部区域的水土资源产生一定影响,本文就输变电工程对土壤理化性质、土壤生物、水土保持的影响,工程活动可能带来的外来物种入侵生态风险等进行综述分析,并通过地处亚热带地区的广东沿海某500 kV输变电工程项目的实际案例,总结了防控输变电工程土壤侵蚀等环境影响的具体措施。     

CCL25/CCR9和CCL28/CCR10在仔猪胃肠道组织中的表达

【研究目的】旨在探讨CCL25/CCR9、CCL28/CCR10在仔猪胃肠道中的表达规律。【方法】通过常规RT-PCR检测CCL25/CCR9、CCL28/CCR10分别在15日龄和30日龄仔猪胃肠道不同部位的表达。【结果】CCL25mRNA主要在小肠表达,而CCR9mRNA在小肠、大肠及胃中均表达,且表达量较高;CCL28mRNA和CCR10mRNA在小肠、大肠及胃中均表达,并以后段肠道的表达量较高。CCL25/CCR9、CCL28/CCR10在30日龄仔猪胃肠道中的表达高于15日龄仔猪。【结论】初步得出CCL25/CCR9、CCL28/CCR10在仔猪胃肠道中的表达规律,并为进一步揭示在其它组织中的表达及它们的生物学作用奠定了基础。     

Adenosine 3'5'-monophosphate: inhibition of complement-mediated cell lysis

An increase in adenosine 3',5'-monophosphate (cyclic AMP) in rat mast cells, achieved by stimulating the cells with prostaglandin E(1), by preventing cyclic AMP breakdown with aminophylline, or by adding exogenous dibutyryl cyclic AMP, prevented complement-mediated cytolysis as assessed by both histamine release and vital dye exclusion. Dibutyryl cyclic AMP also suppressed water-induced osmotic lysis.