Co-release of glutamate and aspartate from cholinergic and GABAergic synaptosomes

Glutamate and aspartate are known to be released in a calcium-dependent fashion by depolarizing stimulation of mammalian brain synaptosomes (isolated nerve endings), an observation which strengthens their claims to be neurotransmitter candidates. The source of these compounds has been interpreted as the exclusively glutamatergic or aspartatergic synaptosome sub-populations assumed to be present in the standard heterogeneous preparations from mammalian brain. Several neurotransmitter-specific synaptosomal surface markers have recently been identified by immunolysis studies and these have allowed separation of subpopulations of synaptosomes by an affinity purification method. These markers appear to be closely related to the biosynthetic enzyme for the principal neurotransmitter released by each sub-category of synaptosome. We have isolated highly purified, metabolically active, GABAergic and cholinergic synaptosomes from cerebral cortex using antisera recognizing either glutamate decarboxylase (GAD) or choline acetyltransferase (ChAT), in conjunction with magnetic microspheres covalently coupled to Protein A (ref. 8), and now report that these synaptosomes release both glutamate and aspartate, in addition to their principal neurotransmitter, when treated with chemical depolarizing agents.     

Renal and pressor actions of angiotensin in salt loaded and depleted rabbits

Résumé Chez les lapins auxquels on a administré du sel, l'angiotensine en doses de 0.005-0.00005µg/kg/min a réduit l'excrétion urinaire de sodium à une quantité correspondant au logarithme de la dose, tandis que des doses inférieures à 0.005µg/kg/min n'ont eu aucun effet sur la tension artérielle. Chez les mêmes lapins lors d'une déplétion de sel, de telles doses n'ont eu aucun effet sur l'excrétion de sodium. Des doses fortes (> 0.05µg/kg/min) qui élevaient toujours la pression sanguine, provoquèrent souvent une augmentation lente de l'excrétion de sodium, beaucoup plus marquée quand l'animal était exempt de sel que lors qu'il en était pourvu. On suggère que l'angiotensine agit normalement comme une hormone qui retient le sodium, action produite par de petites quantités sans effet sur la tension artérielle.     

部分剪切连接的组合梁强度和延性性能

对部分剪切连接的钢－混凝土组合梁的截面特性进行了全过程分析,同时将计算机分析结果与简单的刚塑性手算方法进行比较,并对部分剪切连接的组合梁的强度和延性进行了探讨。     

Frequent somatic mutations in MAP3K5 and MAP3K9 in metastatic melanoma identified by exome sequencing

We sequenced eight melanoma exomes to identify new somatic mutations in metastatic melanoma. Focusing on the mitogen-activated protein (MAP) kinase kinase kinase (MAP3K) family, we found that 24% of melanoma cell lines have mutations in the protein-coding regions of either MAP3K5 or MAP3K9. Structural modeling predicted that mutations in the kinase domain may affect the activity and regulation of these protein kinases. The position of the mutations and the loss of heterozygosity of MAP3K5 and MAP3K9 in 85% and 67% of melanoma samples, respectively, together suggest that the mutations are likely to be inactivating. In in vitro kinase assays, MAP3K5 I780F and MAP3K9 W333* variants had reduced kinase activity. Overexpression of MAP3K5 or MAP3K9 mutants in HEK293T cells reduced the phosphorylation of downstream MAP kinases. Attenuation of MAP3K9 function in melanoma cells using siRNA led to increased cell viability after temozolomide treatment, suggesting that decreased MAP3K pathway activity can lead to chemoresistance in melanoma.     

Recurrent network activity drives striatal synaptogenesis

Neural activity during development critically shapes postnatal wiring of the mammalian brain. This is best illustrated by the sensory systems, in which the patterned feed-forward excitation provided by sensory organs and experience drives the formation of mature topographic circuits capable of extracting specific features of sensory stimuli. In contrast, little is known about the role of early activity in the development of the basal ganglia, a phylogenetically ancient group of nuclei fundamentally important for complex motor action and reward-based learning. These nuclei lack direct sensory input and are only loosely topographically organized, forming interlocking feed-forward and feed-back inhibitory circuits without laminar structure. Here we use transgenic mice and viral gene transfer methods to modulate neurotransmitter release and neuronal activity in vivo in the developing striatum. We find that the balance of activity between the two inhibitory and antagonist pathways in the striatum regulates excitatory innervation of the basal ganglia during development. These effects indicate that the propagation of activity through a multi-stage network regulates the wiring of the basal ganglia, revealing an important role of positive feedback in driving network maturation.     

Distributional changes and population status of amphibians in the eastern Mojave Desert

Several amphibian species historically inhabited sparsely distributed wetlands in the Mojave Desert of western North America, habitats that have been dramatically altered or eliminated as a result of human activities. The population status and distributional changes of amphibians were investigated over a 20,000-km 2 area in the eastern Mojave Desert in 2 ways. For upland sites (i.e., sites outside of major valleys and river floodplains), where wetland habitat is almost exclusively springs, encounter surveys were conducted at 128 sites in 1997-1999, and results were compared to historical (pre-1970) locality records. For lowland sites (i.e., sites within major valleys and river floodplains), locality records and field surveys in 1995-2004 were reviewed to detect changes in distribution over time. Amphibians were found at 79% of upland sites. By far the most common species was the red-spotted toad ( Bufo punctatus , 73% of sites), followed by the Pacific chorus frog ( Pseudacris regilla ), Woodhouse's toad ( B. woodhousii ), relict leopard frog ( Rana onca ), and the introduced American bullfrog ( R. catesbeiana ). Taxa observed or collected in the lowlands since 1990 were Woodhouse's toad, Pacific chorus frog, American bullfrog, and the introduced tiger salamander ( Ambystoma tigrinum ). Four taxa (Vegas Valley leopard frog [ Rana sp.], Arizona toad [ B. microscaphus ], Great Plains toad [ B. cognatus ], and Great Basin spadefoot [ Spea intermontana ]) had historical records but no evidence of occurrence in the study area within the past 5 decades. The amphibian fauna of the study area has changed dramatically in the past century, primarily at lowland sites where habitat loss and modification have been extreme. Striking changes are the nearly complete replacement of native leopard frogs (i.e., Vegas Valley and relict leopard frogs) with the introduced bullfrog, and the complete replacement of the Arizona toad in Las Vegas Valley with Woodhouse's toad or hybrids with predominantly Woodhouse's traits. In contrast, the distributions of 2 species characteristic of upland springs, red-spotted toad and Pacific chorus frog, appear to have changed little from their historical distributions, despite habitat modification at many sites.