The human polyomavirus, JCV, uses serotonin receptors to infect cells

The human polyomavirus, JCV, causes the fatal demyelinating disease progressive multifocal leukoencephalopathy in immunocompromised patients. We found that the serotonergic receptor 5HT2AR could act as the cellular receptor for JCV on human glial cells. The 5HT2A receptor antagonists inhibited JCV infection, and monoclonal antibodies directed at 5HT2A receptors blocked infection of glial cells by JCV, but not by SV40. Transfection of 5HT2A receptor-negative HeLa cells with a 5HT2A receptor rescued virus infection, and this infection was blocked by antibody to the 5HT2A receptor. A tagged 5HT2A receptor colocalized with labeled JCV in an endosomal compartment following internalization. Serotonin receptor antagonists may thus be useful in the treatment of progressive multifocal leukoencephalopathy.     

Alterations in 5-HT1B receptor function by p11 in depression-like states

The pathophysiology of depression remains enigmatic, although abnormalities in serotonin signaling have been implicated. We have found that the serotonin 1B receptor [5-hydroxytryptamine (5-HT1B) receptor] interacts with p11. p11 increases localization of 5-HT1B receptors at the cell surface. p11 is increased in rodent brains by antidepressants or electroconvulsive therapy, but decreased in an animal model of depression and in brain tissue from depressed patients. Overexpression of p11 increases 5-HT1B receptor function in cells and recapitulates certain behaviors seen after antidepressant treatment in mice. p11 knockout mice exhibit a depression-like phenotype and have reduced responsiveness to 5-HT1B receptor agonists and reduced behavioral reactions to an antidepressant.     

Serotonin transporter genetic variation and the response of the human amygdala

A functional polymorphism in the promoter region of the human serotonin transporter gene (SLC6A4) has been associated with several dimensions of neuroticism and psychopathology, especially anxiety traits, but the predictive value of this genotype against these complex behaviors has been inconsistent. Serotonin [5- hydroxytryptamine, (5-HT)] function influences normal fear as well as pathological anxiety, behaviors critically dependent on the amygdala in animal models and in clinical studies. We now report that individuals with one or two copies of the short allele of the serotonin transporter (5-HTT) promoter polymorphism, which has been associated with reduced 5-HTT expression and function and increased fear and anxiety-related behaviors, exhibit greater amygdala neuronal activity, as assessed by BOLD functional magnetic resonance imaging, in response to fearful stimuli compared with individuals homozygous for the long allele. These results demonstrate genetically driven variation in the response of brain regions underlying human emotional behavior and suggest that differential excitability of the amygdala to emotional stimuli may contribute to the increased fear and anxiety typically associated with the short SLC6A4 allele.     

Structure of an agonist-bound human A2A adenosine receptor

Activation of G protein-coupled receptors upon agonist binding is a critical step in the signaling cascade for this family of cell surface proteins. We report the crystal structure of the A(2A) adenosine receptor (A(2A)AR) bound to an agonist UK-432097 at 2.7 angstrom resolution. Relative to inactive, antagonist-bound A(2A)AR, the agonist-bound structure displays an outward tilt and rotation of the cytoplasmic half of helix VI, a movement of helix V, and an axial shift of helix III, resembling the changes associated with the active-state opsin structure. Additionally, a seesaw movement of helix VII and a shift of extracellular loop 3 are likely specific to A(2A)AR and its ligand. The results define the molecule UK-432097 as a "conformationally selective agonist" capable of receptor stabilization in a specific active-state configuration.     

昆虫5-羟色胺受体的研究进展

对5-羟色胺及其受体进行介绍,并阐述了昆虫5-羟色胺受体结构和功能以及5-HT受体的信号转导机制的国内外研究现状及其发展动态。最后,分析基于5-羟色胺受体分子靶标的新药剂的研发现状。     

5-HT及5-HT1A受体在不同妊娠阶段大鼠子宫中的分布

 【目的】研究5-羟色胺（5-hydroxytryptamine,5-HT）及5-HT1A受体在SD大鼠妊娠期子宫中的分布情况和变化规律。【方法】选取均为正常妊娠的30 只雌性SD大鼠分为妊娠3 d、妊娠5 d、妊娠7 d、妊娠13 d、妊娠19 d及产后第1天6组,处死各组大鼠,取子宫制作石蜡切片,经免疫组织化学SP 法染色后,进行观察分析。【结果】5-HT及5-HT1A受体免疫阳性产物广泛存在于子宫内膜上皮细胞、子宫腺上皮细胞、血管内皮细胞、基质细胞、蜕膜细胞、免疫细胞及肌纤维中;5-HT在妊娠7 d和妊娠13 d着色最深,5-HT1A受体在妊娠13 d着色最深。5-HT及5-HT1A受体免疫阳性产物相对表达量的T检验表明,子宫内膜5-HT在妊娠7 d和妊娠13 d的表达较妊娠3 d、妊娠5 d和产后极显著的增加（P＜0.01）,较妊娠19 d显著增加（P＜0.05）;子宫肌层5-HT在妊娠19 d的表达较妊娠7 d显著减少（P＜0.05）,较妊娠13 d极显著的减少（P＜0.01）。子宫内膜5-HT1A受体在妊娠13 d较妊娠3 d、妊娠5 d、妊娠19 d及产后极显著的增加（P＜0.01）,较妊娠7 d显著增加（P＜0.05）;子宫肌层5-HT1A受体在妊娠13 d较妊娠各个时期极显著增加（P＜0.01）。5-HT和5-HT1A受体在妊娠期子宫中的表达,具有极显著的正相关性。【结论】5-HT和5-HT1A受体在妊娠期子宫中的表达具有一定规律,5-HT通过5-HT1A受体参与妊娠的调节。     

Identification and assay of 5-hydroxytryptamine in molluscan tissues by fluorescence method

The fluorescence assay method has been used in the identification and quantitative estimation of 5-hydroxytryptamine (5-HT) in mollusks. Ganglia of a representative pelecypod contain more 5-HT than those of a gastropod. Most non-nerve tissues have low levels of 5-HT, which, except in "kidneys," may derive from nerve endings.     

家蚕5-羟色胺受体基因的克隆及表达分析

【目的】5-羟色胺（5-HT）在许多生理过程中扮演重要角色,克隆介导5-HT生理效应的家蚕5-HT受体及组织表达分析,为研究家蚕5-TH受体基因功能奠定基础。【方法】利用基因组数据及半定量real-time PCR技术,鉴定克隆4种家蚕5-HT受体基因; 应用生物信息学方法分析5-HT受体在物种间同源性并构建系统进化树; 利用半定量real-time PCR方法分析它们在幼虫和成虫不同组织的表达情况。【结果】根据预测基因序列,设计特异引物,克隆得到4种5-HT受体基因序列,分别命名为5-HT1ABm、5-HT1BBm、5-HT2Bm、5-HT7Bm（GenBank登录号KM236100-KM236103）,其开放阅读框分别为1 395、1 341、1 881和1 497 bp,可编码464、446、626和498氨基酸。4种5-HT受体属于典型的G蛋白偶联受体。选择已报道的昆虫及脊椎动物的5-HT受体氨基酸序列进行比对并系统发生树构建,结果显示家蚕4种5-HT受体间的氨基酸序列相似度仅为30.4%。5-HT1A、5-HT1B、5-HT2、5-HT7 4种受体在昆虫中的相似性分别为45.4%、61.4%、48.4%、54.1%。另外,家蚕5-HT受体与其他昆虫甚至脊椎动物有较高的同源性,跨膜区的保守性比非跨膜区高。不同物种间的同一家族5-HT受体的相似性高于同一物种内不同家族5-HT受体的相似性,家蚕5-HT受体的进化关系与烟草天蛾最近。半定量real-time PCR结果显示,5-HT1ABm、5-HT1BBm在幼虫所有组织中均有表达。5-HT2Bm仅在幼虫的头、腹部神经索、精巢表达。5-HT7Bm在幼虫头部、腹部神经索、中肠、脂肪体、精巢、卵巢表达。5-HT1ABm、5-HT1BBm、5-HT7Bm在成虫中除雌性头部以外的组织中均有表达,而5-HT7Bm在雄蛾的生殖系统中表达量明显高于其他组织。5-HT2Bm在成虫中不表达。【结论】鉴定和克隆的4种家蚕5-HT受体基因,在昆虫和脊椎动物中具有较高的保守性,与烟草天蛾同源关系最近,它们在幼虫和成虫的组织表达模式具有多样性。     

地黄叶片遗传转化再生系统的建立

以地黄85-5无菌苗为材料,对叶片再生系统及其对卡那霉素和羧苄西林钠的天然耐性进行了初步研究。结果表明:MS 6 BA 2.0mg/L NAA 0.05mg/L是叶片再生的最适培养基;在地黄遗传转化中,卡那霉素的筛选压和羧苄西林钠的抑菌浓度分别以20mg/L和400mg/L为宜。     

Ectopic expression of the serotonin 1c receptor and the triggering of malignant transformation

Neurotransmitter receptors are usually restricted to neuronal cells, but the signaling pathways activated by these receptors are widely distributed in both neural and non-neural cells. The functional consequences of activating a brain-specific neurotransmitter receptor, the serotonin 5HT1c receptor, in the unnatural environment of a fibroblast were examined. Introduction of functional 5HT1c receptors into NIH 3T3 cells results, at high frequency, in the generation of transformed foci. Moreover, the generation and maintenance of transformed foci requires continued activation of the serotonin receptor. In addition, the injection of cells derived from transformed foci into nude mice results in the generation of tumors. The serotonin 5HT1c receptor therefore functions as a protooncogene when expressed in NIH 3T3 fibroblasts.     

"人"与制度设计--从两个事例谈起

从制度设计与"人"的关系的角度,探讨了有关制度设计的问题.指出由于人极可能会按自己的自主行为选择来行动,因此,制度要求的行为模式与人的现实行动选择可能会发生冲突.因而,鉴于人的行为与制度运作的高度相关性,为避免因这种冲突而可能会导致的制度失灵,制度设计必须重视对"人"的考察,并将"人"的因素纳入制度设计的框架,以在人的自觉行为的带动下,实现自身的良性运作.     

Reprogramming control of an allosteric signaling switch through modular recombination

Many eukaryotic signaling proteins are composed of simple modular binding domains, yet they can display sophisticated behaviors such as allosteric gating and multi-input signal integration, properties essential for complex cellular circuits. To understand how such behavior can emerge from combinations of simple domains, we engineered variants of the actin regulatory protein N-WASP (neuronal Wiskott-Aldrich syndrome protein) in which the "output" domain of N-WASP was recombined with heterologous autoinhibitory "input" domains. Synthetic switch proteins were created with diverse gating behaviors in response to nonphysiological inputs. Thus, this type of modular framework can facilitate the evolution or engineering of cellular signaling circuits.     

5-HT4(a) receptors avert opioid-induced breathing depression without loss of analgesia

Opiates are widely used analgesics in anesthesiology, but they have serious adverse effects such as depression of breathing. This is caused by direct inhibition of rhythm-generating respiratory neurons in the Pre-Boetzinger complex (PBC) of the brainstem. We report that serotonin 4(a) [5-HT4(a)] receptors are strongly expressed in respiratory PBC neurons and that their selective activation protects spontaneous respiratory activity. Treatment of rats with a 5-HT4 receptor-specific agonist overcame fentanyl-induced respiratory depression and reestablished stable respiratory rhythm without loss of fentanyl's analgesic effect. These findings imply the prospect of a fine-tuned recovery from opioid-induced respiratory depression, through adjustment of intracellular adenosine 3',5'-monophosphate levels through the convergent signaling pathways in neurons.     

Biased signaling pathways in β2-adrenergic receptor characterized by 19F-NMR

Extracellular ligand binding to G protein-coupled receptors (GPCRs) modulates G protein and β-arrestin signaling by changing the conformational states of the cytoplasmic region of the receptor. Using site-specific (19)F-NMR (fluorine-19 nuclear magnetic resonance) labels in the β(2)-adrenergic receptor (β(2)AR) in complexes with various ligands, we observed that the cytoplasmic ends of helices VI and VII adopt two major conformational states. Changes in the NMR signals reveal that agonist binding primarily shifts the equilibrium toward the G protein-specific active state of helix VI. In contrast, β-arrestin-biased ligands predominantly impact the conformational states of helix VII. The selective effects of different ligands on the conformational equilibria involving helices VI and VII provide insights into the long-range structural plasticity of β(2)AR in partial and biased agonist signaling.     

饲粮中添加色氨酸对仔猪混群后行为及相关激素的影响

【目的】研究饲粮中添加色氨酸对仔猪混群后行为、相关激素水平和 5-羟色胺受体2A（5-HT2A）基因表达的影响。【方法】将144头体重相近（8.00±0.25）kg 的28日龄断奶仔猪随机分为3个处理组,即对照组、处理组Ⅰ和Ⅱ;每组设6个重复,每个重复有8头猪。对照组饲喂色氨酸含量为0.21%的基础饲粮,处理组I和Ⅱ分别在基础饲粮的基础上添加0.1%和0.2%的色氨酸,饲喂28 d后混群,观察猪的争斗行为和日常行为,测定唾液皮质醇浓度、下丘脑5-羟色胺含量和5-HT2A基因表达量。【结果】混群后,与对照组相比,添加色氨酸的处理组仔猪争斗时间和争斗次数显著降低（P＜0.05）,趴卧行为显著提高（P＜0.05）,站立行为显著降低（P＜0.05）,采食、犬坐行为无显著差异（P＞0.05）;随饲粮色氨酸水平的提高,仔猪唾液皮质醇含量显著降低（P＜0.05）,下丘脑中5-羟色胺浓度显著升高（P＜0.05）,下丘脑中5-HT2A mRNA相对表达量依次降低,其中添加0.2%的色氨酸组与对照组相比差异显著（P＜0.05）。【结论】在满足仔猪色氨酸营养需要（0.21%）的基础上,额外添加0.1%和0.2%的色氨酸能提高仔猪下丘脑5-羟色胺的含量,调控5-HT2A基因mRNA的表达水平,降低仔猪混群后唾液皮质醇的含量,进而缓解仔猪混群后的应激行为。     

杂交茶香月季演化与遗传背景分析

通过文献收集、整理,融合最新研究成果,以时间为轴,大量分析包括图象资料在内的中外文献材料,明确了杂交茶香月季演化历程,解析其遗传背景,为杂交茶香月季育种提供参考。绘制了更为详细的杂交茶香月季历史演化图,通过对比发现切花月季最主要花型"中高型或高芯型"品种特性可能源自于中国古老月季资源月月粉,总结出杂交茶香月季的遗传背景。杂交茶香月季遗传背景较为复杂,主要来源于中国的Rosa chinensis(月月红、月月粉)、R.ordorata(淡黄香水月季、彩晕香水月季)、巨花蔷薇(R.gigantea)以及欧洲的法国蔷薇、大马士革蔷薇、麝香革蔷薇、异味蔷薇等9个原种及其变种,甚至包括一些人为的外源基因。     

Myocyte adrenoceptor signaling pathways

Adrenoceptors (ARs), members of the G protein-coupled receptor superfamily, form the interface between the sympathetic nervous system and the cardiovascular system, with integral roles in the rapid regulation of myocardial function. However, in heart failure, chronic catecholamine stimulation of adrenoceptors has been linked to pathologic cardiac remodeling, including myocyte apoptosis and hypertrophy. In cardiac myocytes, activation of AR subtypes results in coupling to different G proteins and induction of specific signaling pathways, which is partly regulated by the subtype-specific distribution of receptors in plasma membrane compartments containing distinct complexes of signaling molecules. The Connections Maps of the Adrenergic and Myocyte Adrenergic Signaling Pathways bring into focus the specific signaling pathways of individual AR subtypes and their relevant functions in vivo.     

Genetic Analysis of Cold Tolerance at Seedling Stage and Heat Tolerance atAnthesis in Rice (Oryza sativa L.)

A set of 240 introgression lines derived from the advanced backcross population of a cross between a japonica cultivar,Xiushui 09, and an indica breeding line, IR2061, was developed to dissect QTLs affecting cold tolerance (CT) at seedlingstage and heat tolerance (HT) at anthesis. Survival rate of seedlings (SRS) and spikelet fertility (SF), the index traits of CTand HT, showed significant differences between the two parents under stresses. A total of four QTLs (qSRS1, qSRS7,qSRS11a and qSRS11b) for CT were identified on chromosomes 1, 7, 11, and the Xiushui 09 alleles increased SRS at all lociexcept qSRS7. Four QTLs for SF were identified on chromosomes 4, 5, 6, and 11. These QTLs could be classified into twomajor types based on their behaviors under normal and stress conditions. The first was QTL expressed only under normalcondition; and the second QTL was apparently stress induced and only expressed under stress. Among them, two QTLs(qSF4 and qSF6) which reduced the trait difference between heat stress and normal conditions must have contributed toHT because of their obvious contribution to trait stability, and the IR2061 allele at the qSF6 and the Xiushui 09 allele at the qSF4improved HT, respectively. No similar QTL was found between CT at seedling stage and HT at anthesis. Therefore, it ispossible to breed a new variety with CT and HT by pyramiding the favorable CT- and HT-improved alleles at above locifrom Xiushui 09 and IR2061, respectively, through marker-assisted selection (MAS).     

基于转录组分析油菜素内酯对高温胁迫下酿酒葡萄花色苷合成及果实品质的调控机制

【目的】分析高温胁迫下参与油菜素内酯调控葡萄花色苷及果实品质合成的相关基因,探讨油菜素内酯调控果实花色苷及品质合成的机制。【方法】以酿酒葡萄‘赤霞珠’为试材,转色前一周利用红外辐射器模拟高温环境,并全树喷施0.6 mg·L^-1的2,4-表油菜素内酯(2,4-Epibrassinolide,EBR),测定花色苷、总糖及相关品质指标,选择转色中期(花后70 d)的果实进行转录组测序,从分子水平阐述EBR对高温胁迫下花色苷合成的影响。【结果】从转色开始,各处理花色苷含量逐渐升高;成熟时,高温组(HT)花色苷总量显著低于对照组(CK),高温油菜素内酯组(HTE)花色苷含量高于HT组。总糖、还原糖、蔗糖变化规律与花色苷相似,HT组含量均在成熟期时低于CK组,成熟期各种糖含量为CK组>HTE组>HT组。分析3种处理下‘赤霞珠’果实基因水平的差异,通过GO和KEGG富集发现了14个与蔗糖和淀粉代谢途经相关的差异基因,其中HT和HTE处理显著上调了10个基因,显著下调了4个基因;苯丙氨酸代谢途径有11个差异基因,其中有7个参与花色苷合成的基因在HT处理中上调,有4个参...     

The coevolution of parochial altruism and war

Altruism-benefiting fellow group members at a cost to oneself-and parochialism-hostility toward individuals not of one's own ethnic, racial, or other group-are common human behaviors. The intersection of the two-which we term "parochial altruism"-is puzzling from an evolutionary perspective because altruistic or parochial behavior reduces one's payoffs by comparison to what one would gain by eschewing these behaviors. But parochial altruism could have evolved if parochialism promoted intergroup hostilities and the combination of altruism and parochialism contributed to success in these conflicts. Our game-theoretic analysis and agent-based simulations show that under conditions likely to have been experienced by late Pleistocene and early Holocene humans, neither parochialism nor altruism would have been viable singly, but by promoting group conflict, they could have evolved jointly.