Mechanisms of Metabonomic for a Gateway Drug: Nicotine Priming Enhances Behavioral Response to Cocaine with Modification in Energy Metabolism and Neurotransmitter Level

Nicotine, one of the most commonly used drugs, has become a major concern because tobacco serves as a gateway drug and is linked to illicit drug abuse, such as cocaine and marijuana. However, previous studies mainly focused on certain genes or neurotransmitters which have already been known to participate in drug addiction, lacking endogenous metabolic profiling in a global view. To further explore the mechanism by which nicotine modifies the response to cocaine, we developed two conditioned place preference (CPP) models in mice. In threshold dose model, mice were pretreated with nicotine, followed by cocaine treatment at the dose of 2 mg/kg, a threshold dose of cocaine to induce CPP in mice. In high-dose model, mice were only treated with 20 mg/kg cocaine, which induced a significant CPP. ¹H nuclear magnetic resonance based on metabonomics was used to investigate metabolic profiles of the nucleus accumbens (NAc) and striatum. We found that nicotine pretreatment dramatically increased CPP induced by 2 mg/kg cocaine, which was similar to 20 mg/kg cocaine-induced CPP. Interestingly, metabolic profiles showed considerable overlap between these two models. These overlapped metabolites mainly included neurotransmitters as well as the molecules participating in energy homeostasis and cellular metabolism. Our results show that the reinforcing effect of nicotine on behavioral response to cocaine may attribute to the modification of some specific metabolites in NAc and striatum, thus creating a favorable metabolic environment for enhancing conditioned rewarding effect of cocaine. Our findings provide an insight into the effect of cigarette smoking on cocaine dependence and the underlying mechanism.     

Genome-Wide Association Study Identifies Variants in PMS1 Associated with Serum Ferritin in a Chinese Population

Only a small proportion of genetic variation in serum ferritin has been explained by variant genetic studies, and genome-wide association study (GWAS) for serum ferritin has not been investigated widely in Chinese population. We aimed at exploring the novel genetic susceptibility to serum ferritin, and performed this two stage GWAS in a healthy Chinese population of 3,495 men aged 20–69 y, including 1,999 unrelated subjects in the first stage and 1,496 independent individuals in the second stage. Serum ferritin was measured with electrochemiluminescence immunoassay, and DNA samples were collected for genotyping. A total of 1,940,243 SNPs were tested by using multivariate linear regression analysis. After adjusting for population stratification, age and BMI, the rs5742933 located in the 5′UTR region of PMS1 gene on chromosome 2 was the most significantly associated with ferritin concentrations (P-combined = 2.329×10⁻¹⁰) (β = −0.11, 95% CI: −0.14, −0.07). Moreover, this marker was about 200kb away from the candidate gene SLC40A1 which is responsible for iron export. PMS1 gene was the novel genetic susceptibility to serum ferritin in Chinese males and its relation to SLC40A1 needs further study.     

Viral MicroRNAs Targeting Virus Genes Promote Virus Infection in Shrimp In Vivo

Viral microRNAs (miRNAs), most of which are characterized in cell lines, have been found to play important roles in the virus life cycle to avoid attack by the host immune system or to keep virus in the latency state. Viral miRNAs targeting virus genes can inhibit virus infection. In this study, in vivo findings in Marsupenaeus japonicus shrimp revealed that the viral miRNAs could target virus genes and further promote the virus infection. The results showed that white spot syndrome virus (WSSV)-encoded miRNAs WSSV-miR-66 and WSSV-miR-68 were transcribed at the early stage of WSSV infection. When the expression of WSSV-miR-66 and WSSV-miR-68 was silenced with sequence-specific anti-miRNA oligonucleotides (AMOs), the number of copies of WSSV and the WSSV-infected shrimp mortality were significantly decreased, indicating that the two viral miRNAs had a great effect on virus infection. It was revealed that the WSSV wsv094 and wsv177 genes were the targets of WSSV-miR-66 and that the wsv248 and wsv309 genes were the targets of WSSV-miR-68. The data demonstrate that the four target genes play negative roles in the WSSV infection. The targeting of the four virus genes by WSSV-miR-66 and WSSV-miR-68 led to the promotion of virus infection. Therefore, our in vivo findings show a novel aspect of viral miRNAs in virus-host interactions.     

Differential proteomic studies of the genic male-sterile line and fertile line anthers of upland cotton (Gossypium hirsutum L.)

Pollen development is disturbed in the microspore development stage of the double-recessive nuclear male-sterile line ms5ms6 (Gossypium hirsutum L.). This study aimed to identify differentially expressed anther proteins and their potential roles in pollen development and male sterility. We compared the proteomes of sterile and fertile anthers of the double recessive nuclear male-sterile line ms5ms6. Approximately 1,390 protein spots were detected by two-dimensional differential gel electrophoresis. Proteins with altered accumulation levels in sterile anthers compared with fertile anthers were identified by mass spectrometry and the NCBInr and Viridiplantae EST databases. Down-regulated proteins in the sterile anthers included cytosolic ascorbate peroxidase 1 and glutaminyl-tRNA synthetase (glutamine-tRNA ligase). Several carbohydrate metabolism- and photosynthesis-related enzymes were also present at lower levels in the mutant anthers. By contrast, ATP-dependent RNA helicase eIF4A-13, NADH dehydrogenase subunit 1, enolase, gibberellin 20-oxidase, gibberellin 3-hydroxylase 1, alcohol dehydrogenase 2d, 3-ketoacyl-CoA synthase, and trehalose 6-phosphate synthase were expressed at higher levels in sterile anthers than in fertile anthers. The regulation of upland cotton pollen development involves a complex network of differentially expressed genes. This study provides the foundation for future investigations of gene function in upland cotton pollen development and male sterility.     

Chemical chaperone 4-phenylbutyrate prevents endoplasmic reticulum stress induced by T17M rhodopsin

Background

Rhodopsin mutations are associated with the autosomal dominant form of retinitis pigmentosa. T17M mutation in rhodopsin predisposes cells to endoplasmic reticulum (ER) stress and induces cell death. This study aimed to examine whether chemical chaperone 4-phenylbutyrate prevents ER stress induced by rhodopsin T17M.

Results

ARPE-19 cells were transfected with myc-tagged wild-type (WT) and T17M rhodopsin constructs. Turnover of WT and T17M rhodopsin was measured by cycloheximide chase analysis. The activity of ubiquitin-proteasome system was evaluated by GFPU reporter. We found that T17M rhodopsin was misfolded, ubiqutinated and eliminated by ER-associated degradation pathway (ERAD) in ARPE-19 cells. Accumulated T17M rhodopsin induced unfolded protein response, but had no effect on the activity of ubiquitin proteasome system. Moreover, chemical chaperone 4-phenylbutyrate facilitated the turnover of T17M rhodopsin and prevented apoptosis and ER stress induced by T17M rhodopsin.

Conclusions

Chemical chaperone could attenuate UPR signaling and ER stress induced by T17M rhodopsin and has potential therapeutic significance for retinitis pigmentosa.

     

尖峰岭自然保护区扩大区域植物多样性研究

尖峰岭自然保护区2002年由省级上升为国家级自然保护区, 面积由原来的7,762 hm²增加至20,170 hm²。为建立一个比较完善的国家级自然保护区管理体系, 海南大学于2003年10月通过路线调查与标准样方相结合的方法对保护区扩大区域展开了植被资源调查工作。本次调查共记录到43种尖峰岭地区新记录种, 其中黄毛马兜铃(Aristolochia fulvicoma)、海南地不容(Stephania hainanensis)、卵叶石笔木(Tutcheria ovalifolia)、蜜茱萸(Melicope patulinervia)和南烛(Lyonia ovalifolia)等5种为海南特有种。在本次调查的9,600 m²天然林标准样方中共记录到高1.5 m以上的立木3,466株398种, 隶属于69科161属。在扩大区域内共有国家级珍稀濒危和保护植物41种, 其中国家I级保护植物4种, 新记录到的尖峰岭地区国家级濒危植物2种, 即毛茶(Antirhea chinensis)和琼棕(Chuniophoenix hainanensis), 并基本确定了这些植物的垂直分布状况。扩大区域热带低地雨林、热带山地雨林、热带山顶矮林3种群落类型的物种多样性指数均较高, 且Simpson指数(D)及Shannon-Wiener指数(H＇)均是热带山地雨林>热带低地雨林>热带山顶矮林; 均匀度则是热带山地雨林>热带山顶矮林>热带低地雨林。表明经过多年封山育林及实施天然林保护工程, 扩大区域内曾经受过强烈干扰的热带低地雨林和山地雨林已经得到了很好的恢复。     

濒危植物秦岭冷杉种群数量动态

为了对濒危植物秦岭冷杉种群数量动态评价和预测,通过样地调查和数据统计,研究了秦岭冷杉种群的年龄结构、静态生命表及其与环境因子关系,运用时间序列模型预测了种群数量动态.结果表明,多数秦岭冷杉种群幼龄级个体数较少,中老龄个体数量较大,呈衰退趋势.仅处于低海拔地区的秦岭冷杉-木蓝-苔草群丛中的种群(D种群)由于立地条件较好,幼龄级个体数量相对丰富,种群稳定.不同秦岭冷杉种群生命表和存活曲线的分析表明,尽管生境条件差异,但存活曲线基本接近DeeveyⅢ型;不同种群偏离典型存活曲线的程度与幼苗缺乏程度有关,一般Ⅲ～Ⅴ龄级死亡率较高.时间序列分析表明,在未来20、40和80年中,不同秦岭冷杉种群均会呈现老龄级株数先增后减的趋势,种群稳定性长期维持困难.对影响秦岭冷杉种群增长的10个环境因子通过主成分分析(PCA)发现,乔木层盖度、土壤有机质含量和空气湿度对种群发挥有利影响,而人为干扰和光照强度对秦岭冷杉种群增长发挥不利影响.应充分利用秦岭冷杉性喜荫、耐寒、种子活力较强的特点,加强现有林分就地保护,重点是具有结实能力的中老龄个体;在阴坡地带,对林下灌木比较密集的群丛,通过砍灌、清理林下活地被物等抚育措施,为幼苗发育创造良好的环境条件;就地采种育苗,扩大人工种群.     

热带滨海沙滩上森林植被的组成成分与土壤性质的研究

1　前　言在 1 96 3年张宏达提到分布在海南万宁海岸沙滩上的青梅林 (Ｖａｔｉｃａｍａｎ ｇａｃｈａｐｏｉｆｏｒｅｓｔ)时 ,就认为该森林缺乏雨林的结构[1 ],但仍把它归入平地及低山的原生植被里[2 ]。 1 981年 ,胡玉佳对海南龙脑香林进行比较研究后指出 ,这是一块分布在特殊环境里的热带雨林类型 ,由于土壤条件恶劣和常年受海风的影响 ,形成了这一特殊森林[3 ]。 1 987年王伯荪在讨论季雨林的概念时 ,进一步指出这块森林属于土壤顶极森林群落[4 ]。尽管前人未曾对这一块热带滨海沙滩上的森林植被性质与土壤性质的相互关系开展过详细的比…     

Nor1, a novel cytokine-responsive regulator of pancreatic β-cell mass and function mediated by disruption of mitochondrial networks

Type 2 diabetes(T2D)is a chronic metabolic disease characterized by insulin resistance and hyperglycemia,which is ultimately linked to the loss of pancreaticβ-cells and their function[1].Understanding the pathological mechanisms ofβ-cell dysfunction in T2D may lead to development of new therapeutic approaches.Recently,compelling evidence suggests that members of the nuclear receptor 4A(NR4A)subgroup play a pivotal role inβ-cell loss[2].Nor1,also known as NR4A3,belongs to the NR4A subfamily,which also includes Nur77(NR4A1)and Nurr1(NR4A2),and is defined as a true orphan nuclear receptor with an unknown endogenous ligand or ligand independent[3].As a regulator of gene expression located in the nucleus,Nor1 exhibits tissue-specific expression,which selectively controls diverse biological processes,including cell proliferation,apoptosis,differentiation,immune homeostasis,and fuel utilization[4].Thus far,it was reported that Nor1 is involved in numerous pathologies such as cancer,inflammatory diseases,and Parkinson’s disease[4].     

2000-2015年中国陆地生态系统蒸散时空变化及其影响因素

准确量化区域蒸散时空格局及其影响因素对理解陆地生态系统碳水循环具有十分重要的意义。近年来中国经历了严重的空气污染及气候波动,亟须探讨蒸散的时空变化及其影响因素。基于PT-JPL（Priestly-Taylor Jet Propulsion Laboratory）模型,集成遥感数据和气象数据模拟了中国陆地生态系统2000-2015年蒸散,并分析其时空变化及影响因素。结果表明：1）参数优化后PT-JPL模型可解释蒸散年际变化的68%,优于原始模型及MODIS蒸散产品;2）中国地区多年平均蒸散为440.16 mm/a,呈东南沿海到西北内陆逐渐递减的空间格局;3）2000-2015年蒸散整体呈轻微下降趋势（slope=6.48 Gt/a,P=0.17）,但具有年代际差异,2000-2010年中国地区蒸散呈显著下降趋势（slope=21.05,P < 0.01）,占全国蒸散总量45.05%的内蒙古地区、甘新地区、黄土高原地区及青藏地区解释了61.88%的年际变化;2010-2015年呈轻微上升趋势（slope=10.48,P=0.71）,各地区均无显著变化趋势;4）辐射主导了蒸散的年代际差异,分别解释了2010年前后蒸散下降及上升趋势的51.45%、85.26%。蒸散呈显著变化趋势的内蒙古地区、黄土高原地区及青藏地区主要受辐射控制,甘新地区主要受降水和温度的影响。