BOLD responses reflecting dopaminergic signals in the human ventral tegmental area

Current theories hypothesize that dopamine neuronal firing encodes reward prediction errors. Although studies in nonhuman species provide direct support for this theory, functional magnetic resonance imaging (fMRI) studies in humans have focused on brain areas targeted by dopamine neurons [ventral striatum (VStr)] rather than on brainstem dopaminergic nuclei [ventral tegmental area (VTA) and substantia nigra]. We used fMRI tailored to directly image the brainstem. When primary rewards were used in an experiment, the VTA blood oxygen level-dependent (BOLD) response reflected a positive reward prediction error, whereas the VStr encoded positive and negative reward prediction errors. When monetary gains and losses were used, VTA BOLD responses reflected positive reward prediction errors modulated by the probability of winning. We detected no significant VTA BOLD response to nonrewarding events.     

Uniform inhibition of dopamine neurons in the ventral tegmental area by aversive stimuli

Dopamine neurons play a key role in reward-related behaviors. Reward coding theories predict that dopamine neurons will be inhibited by or will not respond to aversive stimuli. Paradoxically, between 3 and 49% of presumed dopamine neurons are excited by aversive stimuli. We found that, in the ventral tegmental area of anesthetized rats, the population of presumed dopamine neurons that are excited by aversive stimuli is actually not dopaminergic. The identified dopamine neurons were inhibited by the aversive stimulus. These findings suggest that dopamine neurons are specifically excited by reward and that a population of nondopamine neurons is excited by aversive stimuli.     

Requirement of AMPA receptor GluR2 phosphorylation for cerebellar long-term depression

Cerebellar long-term depression (LTD) is a model of synaptic memory that requires protein kinase C (PKC) activation and is expressed as a reduction in the number of postsynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors. LTD was absent in cultured cerebellar Purkinje cells from mutant mice lacking the AMPA receptor GluR2 subunit and could be rescued by transient transfection with the wild-type GluR2 subunit. Transfection with a point mutant that eliminated PKC phosphorylation of Ser880 in the carboxy-terminal PDZ ligand of GluR2 failed to restore LTD. In contrast, transfection with a point mutant that mimicked phosphorylation at Ser880 occluded subsequent LTD. Thus, PKC phosphorylation of GluR2 Ser880 is a critical event in the induction of cerebellar LTD.     

Cell size and rate of protein synthesis in ventral horn neurones

Autoradiographic studies show that small ventral horn neurones synthesize protein at a greater rate per unit area of cytoplasm than do large ones. It is suggested that this is related to the faster rate of firing of the smaller neurones.     

Slow synaptic excitation in sympathetic ganglion cells: evidence for synaptic inactivation of potassium conductance

The slow excitatory postsynaptic potential (EPSP) was investigated in frog sympathetic ganglion cells. In contrast to the increased conductance associated with other known EPSP's, during the slow EPSP resting membrane conductance was decreased. Electrical depolarization of the membrane potentiated the slow EPSP, whereas progressive hyperpolarization decreased its size and then reversed it to a hyperpolarizing potential (the opposite of the effect of membrane polarization on other EPSP's). The reversal potential of the slow EPSP was close to the potassium equilibrium potential. We propose that the slow EPSP, in contrast to classical EPSP's, is generated by an inactivation of resting potassium conductance.     

2 + 2] photocycloadditions in the synthesis of chiral molecules

A strategy for the synthesis of chiral molecules that receives growing popularity among organic chemists employs the photochemically mediated [2 + 2] cycloaddition reaction. These reactions can be performed on a multigram scale and often proceed with high yield and with stereocontrol. These features, in combination with the useful properties of the four-membered ring photoproducts in subsequent chemical transformations, make them attractive options in the early stage of a synthesis design. Various combinations of unsaturated functional groups can participate in this reaction process. Accordingly, these chemical reactions can be economical solutions to problems relating to the synthesis of a variety of target molecules.     

汞离子胶体金免疫层析试纸条的研制

基于特异性识别汞离子的单克隆抗体,以胶体金标记抗体作为检测探针,样品中的汞离子和检测线上的包被抗原竞争与免疫探针结合,建立了一种快速测定水样中汞离子的胶体金免疫层析试纸条方法.在最优实验条件下,试纸条对汞离子的检出限为100μg/L,与其他金属离子没有交叉反应,样品的加标回收实验结果与酶联免疫吸附分析方法(ELISA)有很好的相关性.整个分析过程在10min内可以完成,表明该方法可以快速直接检测汞离子,不需要复杂的样品预处理过程.     

The ground state of the ventral appendage in Drosophila

In Drosophila melanogaster, the antennae, legs, genitalia, and analia make up a serially homologous set of ventral appendages that depend on different selector genes for their unique identities. The diversity among these structures implies that there is a common ground state that selector genes modify to generate these different appendage morphologies. Here we show that the ventral appendage that forms in the absence of selector gene activity is leglike but consists of only two segments along its proximo-distal axis: a proximal segment and a distal tarsus. These results raise the possibility that, during evolution, leglike appendages could have developed without selector gene activity.     

A biochemical correlate of the critical period for synaptic modification in the visual cortex

Stimulation of phosphoinositide hydrolysis by excitatory amino acids was studied in synaptoneurosomes of kitten striate cortex at several postnatal ages. Ibotenate and glutamate stimulated phosphoinositide turnover during the second and third postnatal months; N-methyl-D-aspartate and DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) were without effect. The developmental profile of ibotenate-stimulated phosphoinositide turnover parallels the postnatal changes in cortical susceptibility to visual deprivation. The transient increase in ibotenate-stimulated phosphoinositide turnover does not occur in visual cortex of kittens reared in complete darkness.     

Alpha 2-antiplasmin Enschede: alanine insertion and abolition of plasmin inhibitory activity

An abnormal alpha 2-antiplasmin that is associated with a serious bleeding tendency has been found in a Dutch family and is referred to as alpha 2-antiplasmin Enschede. This abnormal alpha 2-antiplasmin is converted from an inhibitor of plasmin to a substrate. The molecular defect of alpha 2-antiplasmin Enschede, as revealed by sequencing of cloned genomic DNA fragments, consists of an alanine insertion near the active site region of the molecule. Substitution of this fragment into complementary DNA for a wild-type alpha 2-antiplasmin yields a translation product with physical and functional properties typical of the abnormal alpha 2-antiplasmin Enschede. The naturally occurring mutant may serve as a model for investigating the structures that determine the properties of an inhibitor versus those of a substrate in serine protease inhibitors.     

Regulation of area identity in the mammalian neocortex by Emx2 and Pax6

The contribution of extrinsic and genetic mechanisms in determining areas of the mammalian neocortex has been a contested issue. This study analyzes the roles of the regulatory genes Emx2 and Pax6, which are expressed in opposing gradients in the neocortical ventricular zone, in specifying areas. Changes in the patterning of molecular markers and area-specific connections between the cortex and thalamus suggest that arealization of the neocortex is disproportionately altered in Emx2 and Pax6 mutant mice in opposing manners predicted from their countergradients of expression: rostral areas expand and caudal areas contract in Emx2 mutants, whereas the opposite effect is seen in Pax6 mutants. These findings suggest that Emx2 and Pax6 cooperate to regulate arealization of the neocortex and to confer area identity to cortical cells.     

An insertion in the human thyrotropin receptor critical for high affinity hormone binding

Thyrotropin (TSH), luteinizing hormone (LH), and chorionic gonadotropin (CG) are structurally related glycoprotein hormones, which bind to receptors that share a high degree of sequence similarity. However, comparison of the primary amino acid sequences of the TSH and LH-CG receptors reveals two unique insertions of 8 and 50 amino acids in the extracellular domain of the TSH receptor. The functional significance of these insertions were determined by site-directed mutagenesis. Deletion of the 50-amino acid tract (residues 317 to 366) had no effect on TSH binding or on TSH and thyroid-stimulating immunoglobulin (TSI) biological activities. In contrast, either deletion or substitution of the eight-amino acid region (residues 38 to 45) abolished these activities. This eight-amino acid tract near the amino terminus of the TSH receptor appears to be an important site of interaction for both TSH and TSI.     

重金属快速检测方法的研究进展

由于重金属污染问题日趋严重,在食品、医药、环境等诸多方面都引起了人们广泛的重视,对重金属快速检测方法的研究也随之在近年来增多。重金属快速检测法主要包括酶分析法、免疫分析法、生物化学传感器法、试纸法等,对方法原理、研究现状、适用检测离子、方法检出限和它们在环境中的应用进行了综合评述,并阐述了重金属快速检测方法的发展方向和存在的问题。     

一种快速提取烟草病毒的方法

为寻找高效快速提取植物总RNA的检测方法,以白肋烟叶片为材料,用Trizol试剂盒提取总RNA。依据黄瓜花叶病毒和马铃薯X病毒的外壳蛋白保守序列设计特异性引物,进行RT-PCR检测,从感病叶片中分别扩增出326bp、392bp的目的片断,而对照叶片中无此扩增带。将PCR产物连接pGEM-T载体上,转化大肠杆菌DH5α,得到了含有目的片断的重组子。序列分析表明,与Gene Bank中报道的这两种病毒核苷酸序列进行比较,同源性均达到96%以上。从而证明Trizol试剂盒可以在1 h内提取到纯度高、含量高、完整性好的总RNA,快速、简便、可靠。     

Dissociable roles of ventral and dorsal striatum in instrumental conditioning

Instrumental conditioning studies how animals and humans choose actions appropriate to the affective structure of an environment. According to recent reinforcement learning models, two distinct components are involved: a "critic," which learns to predict future reward, and an "actor," which maintains information about the rewarding outcomes of actions to enable better ones to be chosen more frequently. We scanned human participants with functional magnetic resonance imaging while they engaged in instrumental conditioning. Our results suggest partly dissociable contributions of the ventral and dorsal striatum, with the former corresponding to the critic and the latter corresponding to the actor.     

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.     

Gallamine (Flaxedil) and synaptic transmission in the spinal cord

A paralyzing dose of gallamine (Flaxedil) (1 to 2 milligrams per kilogram of body weight) has no effect on synaptic transmission in the cat's spinal cord. In spinal cats ventilated with oxygen, we stimulated a dorsal spinal root and recorded the compound ventral root potential. The reflex potential was not affected by 6.25 milligrams of gallamine per kilogram. Giving 12.5 milligrams of gallamine per kilogram had no significant effect on the monosynaptic spike height, but the polysynaptic response rose briefly to 12 percent above control. Increased magnitude of the polysynaptic response appeared related to a concomitant rise in blood pressure.     

Functional insertion of an Alu type 2 (B2 SINE) repetitive sequence in murine class I genes

The regulation of expression of the family of MHC (major histocompatibility complex) class I genes is complex. Sequence analysis has revealed that class I genes from the H-2D subregion of the MHC (which includes the D and L genes) differ from the class I gene from the H-2K subregion (the K gene) by the insertion of a type 2 Alu-like repetitive element (the murine B2 sequence) within the 3' noncoding region of the D and L genes. The consequence of this insertion in the D and L genes is the introduction of a novel polyadenylation signal, which is preferentially used over the more distal signal, the analog of that found in the K gene. The insertion of the type 2 Alu-like sequence results in a change in the preferred site for endonucleolytic cleavage which is necessary for generating a correct 3' terminus for polyadenylation. The data demonstrate that the type 2 Alu-like sequence has a function; the data also suggest a possible regulatory role of this sequence in the expression of class I genes.