GABA and its agonists improved visual cortical function in senescent monkeys

Human cerebral cortical function degrades during old age. Much of this change may result from a degradation of intracortical inhibition during senescence. We used multibarreled microelectrodes to study the effects of electrophoretic application of gamma-aminobutyric acid (GABA), the GABA type a (GABAa) receptor agonist muscimol, and the GABAa receptor antagonist bicuculline, respectively, on the properties of individual V1 cells in old monkeys. Bicuculline exerted a much weaker effect on neuronal responses in old than in young animals, confirming a degradation of GABA-mediated inhibition. On the other hand, the administration of GABA and muscimol resulted in improved visual function. Many treated cells in area V1 of old animals displayed responses typical of young cells. The present results have important implications for the treatment of the sensory, motor, and cognitive declines that accompany old age.

CRANIODENTAL VARIATION OF MACAQUES ( Macaca ): SIZE,FUNCTION AND PHYLOGENY

为了研究猕猴属的颅骨差异性, 从而探 讨种间在形态、功能和系统分化方面的相互联系, 测定了11 个猕猴种类的77 个颅骨变量, 用于主成 分分析和判别分析。应用巢式分析方法, 分析过程 包括3 个步骤。所有变量根据功能和部位的不同首 先分为7 个单位: 下颌、下颌齿、上颌齿、上面 颅、下面颅、面颅后部和颅腔。第2 步根据它们所 揭示的相似性(具有相同的种间及种内差异性类 型) 合并为3 个解剖区域: 咀嚼器官(下颌、下颌 齿、上颌齿) , 面颅(上面颅和下面颅) 和整个面 颅后(面颅后和颅腔) 。第3 步从3 个解剖区域筛 选出27 个变量代表整个颅骨的形态结构。除了寻 找不同的功能单位, 解剖区域及总的颅骨具有不同 的种间和种内差异类型外, 此过程对筛出研究意义 不大的变量起很重要的作用。上述分析过程分别用 于对雌、雄性和两性的研究。所研究的11 个猕猴 种类间形成了3 聚类。第1 类包括食蟹猴(Macaca f ascicularis) 、戴帽猴( M1 sinica) 和头巾猴( M1 radiata) ; 第2 类包括猕猴( M1 mulatta ) 、熊猴 (M1 assensis ) 、平顶猴( M1 nemestrina ) 和黑猿 (M1 nigra) ; 第3 类包括蛮猴( M1 sylvanus ) 、日 本猴( M1 f uscata) 、短尾猴( M1 arctoides ) 和藏 酋猴(M1 thibetana) 。分别从两性差异、食物、生态、分类和系统分化方面进行了差异性讨论, 结果 认为猕猴种间颅骨的差异性主要是由于系统分化不 同而引起个体差异所致, 即种间和种内存在的个体 差异。在主成分分析中, 这些差异在不同的区域表 现在不同的成分上。在咀嚼器官上种间的差异在第 1 主成分上, 种内的差异则在第2 主成分上。面颅 的情况则刚好相反。这两种差异在面颅后及颅腔上 则被第1 和第2 主成分所平分。这样, 种间的差异 在咀嚼器官上大于种内的差异。种内的差异在面颅 上则大于种间的差异。这两种差异在面颅后和颅腔 上则几乎大小相等。这一研究结果表明, 与传统的 概念不同, 第2 主成分不仅仅表现形态、形状的差 异, 而如同第1 主成分一样, 也表现形态的大小成 分。此研究所揭示的猕猴种间关系部分与Foden (1976 , 1980) 和Delson (1980) 相同。如平顶猴 与黑猿、短尾猴、藏酋猴和熊猴的关系。食蟹猴、 头巾猴和戴帽猴的关系则不同, 并已得到有关分子 生物学的支持, 此3 种可能来自同一祖先并经历相 同的扩散过程。此研究所设计的巢式分析过程提供 了一种很好的差异性研究手段。最终结果暗示在形 态学研究中仅仅考虑某一区域的形态结构是很不够 的, 因为不同的部分具有不同的种间及种内差异类 型。这在化石研究中尤其要注意。

Molecular modeling on some human interleukins sharing gamma c of interleukin-2 receptor, and structure-function relationships

Five models for human interleukin-7 (HIL-7), HIL-9, HIL-13, HIL-15 and HIL-17 have been generated by SYBYL software package. The primary models were optimized using molecular dynamics and molecular mechanics methods. The final models were optimized using a steepest descent algorithm and a subsequent conjugate gradient method. The complexes with these interleukins and the common gamma chain of interleukin-2 receptor (IL-2R) were constructed and subjected to energy minimization. We found residues, such as Gln127 and Tyr103, of the common gamma chain of IL-2R are very important. Other residues, e.g. Lys70, Asn128 and Glu162, are also significant. Four hydrophobic grooves and two hydrophilic sites converge at the active site triad of the gamma chain. The binding sites of these interleukins interaction with the common gamma chain exist in the first helical and/or the fourth helical domains. Therefore, we conclude that these interleukins binds to the common gamma chain of IL-2R by the first and the fourth helix domain. Especially at the binding sites of some residues (lysine, arginine, asparagine, glutamic acid and aspartic acid), with a discontinuous region of the common gamma chain of IL-2R, termed the interleukins binding sites (103-210). The study of these sites can be important for the development of new drugs. (C) 2000 Elsevier Science B.V. All rights reserved.

Structure-function relationship of three neurotoxins from the venom of Naja kaouthia: a comparison between the NMR-derived structure of NT2 with its homologues, NT1 and NT3

Three homologous short-chain neurotoxins, named NT1, NT2 and NT3, were purified from the venom of Naja kaouthia. NT1 has an identical amino acid sequence to cobrotoxin from Naja naja atra [Biochemistry 32 (1993) 2131]. NT3 shares the same sequence with cobrotoxin b [J. Biochem. (Tokyo) 122 (1997) 1252], whereas NT2 is a novel 6 1 -residue neurotoxin. Tests of their physiological functions indicate that NT1 shows a greater inhibition of muscle contraction induced by electrical stimulation of the nerve than do NT2 and NT3. Homonuclear proton two-dimensional NMR methods were utilized to study the solution tertiary structure of NT2. A homology model-building method was employed to predict the structure of NT3. Comparison of the structures of these three toxins shows that the surface conformation of NT1 facilitates the substituted base residues, Arg28, Arg30, and Arg36, to occupy the favorable spatial location in the central region of loop 11, and the cation groups of all three arginines face out of the molecular surface of NT1 This may contribute greatly to the higher binding of NT1 with AchR compared to NT2 and NT3. (C) 2002 Elsevier Science B,V. All rights reserved.

Fish-Specific Duplicated dmrt2b Contributes to a Divergent Function through Hedgehog Pathway and Maintains Left-Right Asymmetry Establishment Function

Gene duplication is thought to provide raw material for functional divergence and innovation. Fish-specific dmrt2b has been identified as a duplicated gene of the dmrt2a/terra in fish genomes, but its function has remained unclear. Here we reveal that Dmrt2b knockdown zebrafish embryos display a downward tail curvature and have U-shaped somites. Then, we demonstrate that Dmrt2b contributes to a divergent function in somitogenesis through Hedgehog pathway, because Dmrt2b knockdown reduces target gene expression of Hedgehog signaling, and also impairs slow muscle development and neural tube patterning through Hedgehog signaling. Moreover, the Dmrt2b morphants display defects in heart and visceral organ asymmetry, and, some lateral-plate mesoderm (LPM) markers expressed in left side are randomized. Together, these data indicate that fish-specific duplicated dmrt2b contributes to a divergent function in somitogenesis through Hedgehog pathway and maintains the common function for left-right asymmetry establishment.

Transcriptome of embryonic and neonatal mouse cortex by high-throughput RNA sequencing

Brain structure and function experience dramatic changes from embryonic to postnatal development. Microarray analyses have detected differential gene expression at different stages and in disease models, but gene expression information during early brain development is limited. We have generated >27 million reads to identify mRNAs from the mouse cortex for>16,000 genes at either embryonic day 18 (E18) or postnatal day 7 (P7), a period of significant synapto-genesis for neural circuit formation. In addition, we devised strategies to detect alternative splice forms and uncovered more splice variants. We observed differential expression of 3,758 genes between the 2 stages, many with known functions or predicted to be important for neural development. Neurogenesis-related genes, such as those encoding Sox4, Sox11, and zinc-finger proteins, were more highly expressed at E18 than at P7. In contrast, the genes encoding synaptic proteins such as synaptotagmin, complexin 2, and syntaxin were up-regulated from E18 to P7. We also found that several neurological disorder-related genes were highly expressed at E18. Our transcriptome analysis may serve as a blueprint for gene expression pattern and provide functional clues of previously unknown genes and disease-related genes during early brain development.