Cyclic GMP can increase rod outer-segment light-sensitive current 10-fold without delay of excitation

To test the hypothesis that cyclic GMP is the internal messenger coupling rhodopsin activation to membrane excitation in vertebrate rod photoreceptors, we used a novel technique combining measurement of membrane currents of isolated salamander rods with a suction electrode and the introduction of cyclic GMP through a whole-cell recording patch pipette. Rupture of an attached patch was followed by a rapid (approximately 10 s), approximately 10-fold increase in outer-segment membrane current, all of which was light-sensitive. There was little change in the rising phase of the response to a saturating flash, but the duration of the saturated phase of the response increased approximately 10-fold. The effects reversed completely within 3-4 min after withdrawal of the cyclic GMP-containing patch pipette. A formal kinetic analysis shows that the first two observations are inconsistent with the postulate that cyclic GMP opens the light-sensitive conductance by simple binding to channels, unless free cyclic GMP in the outer segment is assumed to be much lower than published estimates, and most of the outer-segment cyclic GMP is bound and inexchangeable on the timescale of 200 ms. Furthermore, our results suggest that rod cyclic GMP is not involved solely in keeping the light-sensitive conductance open, but may also affect the activity of the phosphodiesterase that mediates cyclic GMP hydrolysis.     

Cyclic GMP increases photocurrent and light sensitivity of retinal cones

Like retinal rods, cone photoreceptors contain cyclic GMP and light-activated phosphodiesterase. The cGMP phosphodiesterase cascade is thought to mediate phototransduction in rods. Biochemical assays of nucleotide content in cone-dominant retinas, however, have failed to demonstrate light-induced changes in cGMP. Changes in cyclic AMP following light exposure have been reported, leading to the suggestion that in cone phototransduction cAMP assumes a role analogous to that played by cGMP in rods. Cyclic GMP introduced from tight-seal pipettes into isolated cones of the larval tiger salamander, Ambystoma tigrinum, rapidly increases light-modulated membrane current more than 10-fold. In cones, as in rods, cGMP also causes an approximately 10-fold increase in photocurrent duration and a 5- to 10-fold increase in light-sensitivity. Cyclic AMP has no effect on cone photocurrents under the same conditions. Because cGMP has similar effects on photocurrent magnitude and kinetics in both rods and cones, we conclude that cGMP plays corresponding roles in transduction in both vertebrate photoreceptor classes.     

myo-Inositol polyphosphate may be a messenger for visual excitation in Limulus photoreceptors

Photoreceptor excitation begins with the absorption of a photon by rhodopsin and proceeds through an unknown sequence of steps that leads to changes in specific ionic conductances. These conductance changes produce the receptor potential. It has been proposed that hydrolysis of phosphoinositides is involved in the control of a variety of physiological processes. Recent studies have implicated inositol 1,4,5-trisphosphate as an intracellular messenger in the cascade mediating hormone-stimulated secretion. We propose that one of the steps in the excitatory cascade in Limulus ventral photoreceptors may be an increase in intracellular concentration of myo-inositol polyphosphates, derived from hydrolysis of the membrane component phosphatidylinositol bisphosphate by a phospholipase. Here we present biochemical and electrophysiological evidence that an inositol polyphosphate may be an intracellular messenger in the cascade mediating excitation, based on the following criteria: the cells possess the synthetic and degradative metabolism for the messenger; the natural stimulus leads to a change in the concentration of the messenger within the cells; and intracellular injection of exogenous messenger mimics naturally occurring electrophysiological events.     

Rhodopsin inactivation is a modulated process in Limulus photoreceptors.

Many G-protein-coupled receptors are only transiently active because an inactivation process stops the receptor from activating G protein molecules. Although this inactivation has been investigated in vitro, the real kinetics of the process can only be obtained from intact cells. Here we describe a method for measuring the inactivation of rhodopsin in intact photoreceptors and the application of this method to the ultraviolet rhodopsin of Limulus median eye. The results show that the inactivation process is very rapid (less than 150 ms) and occurs well before the peak of the receptor potential. We have also investigated whether the inactivation process can itself be modulated. Our results show that light-adaptation accelerates inactivation by about 10-fold, providing evidence that G-protein-mediated transduction can be modulated at this first stage.     

Neurogenesis in the adult is involved in the formation of trace memories

The vertebrate brain continues to produce new neurons throughout life. In the rat hippocampus, several thousand are produced each day, many of which die within weeks. Associative learning can enhance their survival; however, until now it was unknown whether new neurons are involved in memory formation. Here we show that a substantial reduction in the number of newly generated neurons in the adult rat impairs hippocampal-dependent trace conditioning, a task in which an animal must associate stimuli that are separated in time. A similar reduction did not affect learning when the same stimuli are not separated in time, a task that is hippocampal-independent. The reduction in neurogenesis did not induce death of mature hippocampal neurons or permanently alter neurophysiological properties of the CA1 region, such as long-term potentiation. Moreover, recovery of cell production was associated with the ability to acquire trace memories. These results indicate that newly generated neurons in the adult are not only affected by the formation of a hippocampal-dependent memory, but also participate in it.     

药品GMP发展史及实施GMP的工作程序

阐述了药品GMP(Good Mandacturing Practice)的发展状况及我国制药企业实施GMP的必要性，提出了制药企业做好GMP实施和认征工作的措施。     

Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor

Endothelium-derived vascular relaxing factor (EDRF) is a humoral agent that is released by vascular endothelium and mediates vasodilator responses induced by various substances including acetylcholine and bradykinin. EDRF is very unstable, with a half-life of between 6 and 50 s, and is clearly distinguishable from prostacyclin. The chemical structure of EDRF is unknown but it has been suggested that it is either a hydroperoxy- or free radical-derivative of arachidonic acid or an unstable aldehyde, ketone or lactone. We have examined the role of superoxide anion (O-2) in the inactivation of EDRF released from vascular endothelial cells cultured on microcarrier beads and bioassayed using a cascade of superfused aortic smooth muscle strips. With this system, we have now demonstrated that EDRF is protected from breakdown by superoxide dismutase (SOD) and Cu2+, but not by catalase, and is inactivated by Fe2+. These findings indicate that O-2 contributes significantly to the instability of EDRF.     

Functional connectivity in the retina at the resolution of photoreceptors

To understand a neural circuit requires knowledge of its connectivity. Here we report measurements of functional connectivity between the input and ouput layers of the macaque retina at single-cell resolution and the implications of these for colour vision. Multi-electrode technology was used to record simultaneously from complete populations of the retinal ganglion cell types (midget, parasol and small bistratified) that transmit high-resolution visual signals to the brain. Fine-grained visual stimulation was used to identify the location, type and strength of the functional input of each cone photoreceptor to each ganglion cell. The populations of ON and OFF midget and parasol cells each sampled the complete population of long- and middle-wavelength-sensitive cones. However, only OFF midget cells frequently received strong input from short-wavelength-sensitive cones. ON and OFF midget cells showed a small non-random tendency to selectively sample from either long- or middle-wavelength-sensitive cones to a degree not explained by clumping in the cone mosaic. These measurements reveal computations in a neural circuit at the elementary resolution of individual neurons.     

MSG is involved in sperm gelatinolytic activity in the prawn, Macrobrachium rosenbergii

Proteases in male reproductive tract are considered to play key roles in fertilization processes.In contrast to mammals,there are limited data concerning crustacean sperm proteases.We previously identified a novel sperm gelatinase(MSG) from Macrobrachium rosenbergii that was inhibited by a male reproduction-related Kazal-type protease inhibitor(MRPINK) specifically.In the present study,MSG was found to be distributed on the vas deferens and terminal ampullae by Western blot.Immunohistochemical analyses revealed that MSG was expressed in secretory epithelial cells and sperm distributed mainly at the base zone.RNA interference(RNAi) mediated knock-down of MSG resulted in a marked loss of sperm gelatinolytic activity.Taken together,the results show that MSG is closely linked to and probably involved in the fertilization process.     

Muscarinic acetylcholine receptor is involved in acetylcholine regulating stomatal movement

In animal cells, action of acetylcholine depends on its binding with its two specific receptors on the plasma membrane: the nicotinic and muscarinic respectively. The present investigation has shown that agonists of muscarinic receptor (muscarine) could induce stomatal opening, while the antagonists (atropine) could block stomatal opening induced by acetylcholine. Their effects can only be realized in medium containing Ca²⁺, but not in medium containing K⁺. The results tend to reveal that the muscarinic receptor is involved in acetylcholine-induced stomatal movement.     

The mahogany protein is a receptor involved in suppression of obesity

Genetic studies have shown that mutations within the mahogany locus suppress the pleiotropic phenotypes, including obesity, of the agouti-lethal-yellow mutant. Here we identify the mahogany gene and its product; this study, to our knowledge, represents the first positional cloning of a suppressor gene in the mouse. Expression of the mahogany gene is broad; however, in situ hybridization analysis emphasizes the importance of its expression in the ventromedial hypothalamic nucleus, a region that is intimately involved in the regulation of body weight and feeding. We present new genetic studies that indicate that the mahogany locus does not suppress the obese phenotype of the melanocortin-4-receptor null allele or those of the monogenic obese models (Lep(db), tub and Cpe(fat)). However, mahogany can suppress diet-induced obesity, the mechanism of which is likely to have implications for therapeutic intervention in common human obesity. The amino-acid sequence of the mahogany protein suggests that it is a large, single-transmembrane-domain receptor-like molecule, with a short cytoplasmic tail containing a site that is conserved between Caenorhabditis elegans and mammals. We propose two potential, alternative modes of action for mahogany: one draws parallels with the mechanism of action of low-affinity proteoglycan receptors such as fibroblast growth factor and transforming growth factor-beta, and the other suggests that mahogany itself is a signalling receptor.     

Deg1 is involved in the degradation of the PsbO oxygen-evolving protein of photosystem II in Arabidopsis

Deg1, a thylakoid lumen-localized protease, retains both chaperone and protease activities. The in vivo function of Deg1 has been shown to be involved not only in PSII assembly but also in the degradation of PSII reaction center protein D1. Here we used the transgenic plants with reduced Deg1 to examine whether the lumen-localized proteins are also the substrates of Deg1 in vivo. Our results showed that the transgenic plants accumulated degradation products of the PsbO protein while the levels of full-length PsbO were not affected. The PsbO degradation products could be efficiently degraded by the recombinant Deg1. These results suggest that Deg1 is involved in the degradation of the PsbO degradation fragments, but not in the initial cleavage event itself.     

Doubling the estimate of invertebrate biomass in a rainforest canopy

Forest canopies represent the functional interface between 90% of the Earth's terrestrial biomass and the atmosphere and include some of the most threatened of all terrestrial ecosystems. However, we lack even a basic understanding of how the biomass of plants and animals is distributed throughout forest canopies, even though this information is vital for estimating energy flow, carbon cycling, resource use and the transfer of materials within this ecosystem. Here we measure the biomass of invertebrates living in a common rainforest epiphyte, describe a striking relationship between fern size and the biomass of animals within the ferns, and reveal that one large epiphyte may contain an invertebrate biomass similar to that found in the whole of the rest of the tree crown on which it is growing. Using these data, we show that including the fauna of these epiphytes--a neglected component in rainforest ecosystems--can more than double our estimate of the total invertebrate biomass in an entire rainforest canopy.     

有限循环群的刻划以及子群的性质研究

该文从满足方程x^m=e的元素的个数的角度刻划了有限循环群的构造而且就子群的数目及唯一性等方面论述了有限循环群的子群的重要性质．