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1.
α1‐adrenoceptors (α1‐ARs) stimulation has been found to enhance excitatory processes in many brain regions. A recent study in our laboratory showed that α1‐ARs stimulation enhances glutamatergic transmission via both pre‐ and post‐synaptic mechanisms in layer V/VI pyramidal cells of the rat medial prefrontal cortex (mPFC). However, a number of pre‐synaptic mechanisms may contribute to α1‐ARs‐induced enhancement of glutamate release. In this study, we blocked the possible post‐synaptic action mediated by α1‐ARs to investigate how α1‐ARs activation regulates pre‐synaptic glutamate release in layer V/VI pyramidal neurons of mPFC. We found that the α1‐ARs agonist phenylephrine (Phe) induced a significant enhancement of glutamatergic transmission. The Phe‐induced potentiation was mediated by enhancing pre‐synaptic glutamate release probability and increasing the number of release vesicles via a protein kinase C‐dependent pathway. The mechanisms of Phe‐induced potentiation included interaction with both glutamate release machinery and N‐type Ca2+ channels, probably via a pre‐synaptic Gq/phospholipase C/protein kinase C pathway. Our results may provide a cellular and molecular mechanism that helps explain α1‐ARs‐mediated influence on PFC cognitive functions.

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2.
MUC2 is the major gel-forming mucin of the colon forming a protective gel barrier organized into an inner stratified and an outer loose layer. The MUC2 N-terminus (D1-D2-D′D3 domains) has a dual function in building a net-like structure by disulfide-bonded trimerization and packing the MUC2 polymer into an N-terminal concatenated polygonal platform with the C-termini extending perpendicularly by pH- and calcium-dependent interactions. We studied the N-terminal D′D3 domain by producing three recombinant variants, with or without Myc tag and GFP (green fluorescent protein), and analyzed these by gel filtration, electron microscopy and single particle image processing. The three variants were all trimers when analyzed upon denaturing conditions but eluted as hexamers upon gel filtration under native conditions. Studies by electron microscopy and three-dimensional maps revealed cage-like structures with 2- and 3-fold symmetries. The structure of the MUC2 D3 domain confirms that the MUC2 mucin forms branched net-like structures. This suggests that the MUC2 mucin is stored with two N-terminal concatenated ring platforms turned by 180° against each other, implicating that every second unfolded MUC2 net in mature mucus is turned upside down.  相似文献   
3.
The sex hormone testosterone and the neurotransmitter serotonin exert opposite effects on several aspects of behavior including territorial aggression. It is however not settled if testosterone exerts its pro-aggressive effects by reducing serotonin transmission and/or if the anti-aggressive effect of serotonin requires the presence of the androgen. Using the resident intruder test, we now show that administration of the serotonin synthesis inhibitor para-chlorophenylalanine (300 mg/kg x 3 days) increases the total time of attack as well as the percentage amount of social behavior spent on attack but not that spent on threat – i.e. that it induces a pattern of unrestricted, maladaptive aggression – in gonadectomized C57Bl/6 male mice receiving testosterone replacement; in contrast, it failed to reinstate aggression in those not given testosterone. Whereas these results suggest the pro-aggressive effect of testosterone to be independent of serotonin, and not caused by an inhibition of serotonergic activity, the pCPA-induced induction of maladaptive aggression appears to require the presence of the hormone. In line with these findings, pCPA enhanced the total time of attack as well the relative time spent on attacks but not threats also in wild-type gonadally intact male C57Bl/6 mice, but failed to reinstate aggression in mice rendered hypo-aggressive by early knock-out of androgen receptors in the brain (ARNesDel mice). We conclude that androgenic deficiency does not dampen aggression by unleashing an anti-aggressive serotonergic influence; instead serotonin seems to modulate aggressive behavior by exerting a parallel-coupled inhibitory role on androgen-driven aggression, which is irrelevant in the absence of the hormone, and the arresting of which leads to enhanced maladaptive aggression.  相似文献   
4.
We have investigated methionine adenosyltransferase activity (MAT) in extracts of a variety of normal and malignant human tissues and cultured cell lines. MAT activity assayed from 17 different cultured cell lines varied to a great extent. Ramos (human, Burkitt's lymphoma) and EL4 (mouse, T cell lymphoma) cell showed MAT activity near 300 pmol/mg per min. Daudi (human, Burkitt's lymphoma) and almost all monolayer cells had MAT activity below 100 pmol/mg per min. Human peripheral blood lymphocytes had MAT activity of 36 pmol/mg permin. The MAT activity of the cell lines can be related to doubling time: cell lines with short doubling times have much higher MAT activity than other cell lines. A large variation in MAT activity in different human tissues was observed. In autopsy samples MAT activity was highest in the brain and in the colon. Malignant tissue samples gave much higher MAT activity than normal tissues. Lung cancer (carcinoma squamocellulare pulmonis) had MAT activity of 30.7 pmol/mg per min, while in normal lung it was 2.4 pmol/mg per min.  相似文献   
5.
Summary Resting cells of a mutant ofArthrobacter sp. (DSM 3747) were used for the bioconversion of D,L-5-benzylhydantoin and related compounds to the corresponding L-amino acids. After optimization of the reaction conditions in shake flask experiments, bioconversions were performed in a preparative scale in a 2-l-bioreactor under nitrogen atmosphere. Specific productivities of 0.4 (p-NO2-L-phenylalanine) up to 3.9 mM amino acid x g cell dry mass–1 x h–1 (p-Cl-L-phenylalanine) were obtained. D,L-5-p-COOH-Benzylhydantoin, D,L-5-phenylhydantoin and D,L-5-p-OH-phenylhydantoin were not accepted as substrates.  相似文献   
6.
Summary In the superposition eyes of the sphingid moth Deilephila and the neuropteran Ascalaphus, adjustment to different intensities is subserved by longitudinal migrations of screening pigment in specialized pigment cells. Using ophthalmoscopic techniques we have localized the light-sensitive trigger that controls pigment position.In both species, local illumination of a small spot anywhere within the eye glow of a dark-adapted eye evokes local light adaptation in the ommatidia whose facets receive the light. Details of the response pattern demonstrate that a distal light-sensitive trigger is located axially in the ommatidium, just beneath the crystalline cone, and extends with less sensitivity deep into the clear zone. The distal trigger in Deilephila was shown to be predominantly UV sensitive, and a UV-absorbing structure, presumably the distal trigger, was observed near the proximal tip of the crystalline cone.In Ascalaphus we also found another trigger located more proximally, which causes local pigment reaction in the ommatidia whose rhabdoms are illuminated (the centre of the eye glow). The light-sensitive trigger for this response appears to be the rhabdom itself.  相似文献   
7.
The angiotensin I-converting enzyme (peptidyl-dipeptide hydrolase, EC 3.4.15.1) inhibitor, ramiprilat (2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-Ala]-(1S,3S,5S)-2- azabicyclo[3.3.0]octane-3-carboxylic acid), is shown to exist in tow conformational isomers, cis and trans, which interconvert around the amide bond. The two conformers were separated by reversed-phase high-performance liquid chromatography. The conformers were identified by nuclear Overhauser effect measurements. From line shape analysis the isomerization rate constants were determined to be kcis----trans = 15 s-1 and ktrans----cis = 5 s-1 at 368 K in [2H]phosphate buffer (p2H 7.5). By enzyme kinetic studies using 3-(2-furylacryloyl)-L-Phe-Gly-Gly as substrate, the trans conformer was found to be the most potent enzyme inhibitor, whereas the cis conformer had a very low inhibitory effect. A new inhibition mechanism is presented for this type of slow, tight-binding inhibitors that contain an amide bond. This mechanism involves an equilibrium between the two conformers and the enzyme-bound inhibitor complex.  相似文献   
8.
The restriction deficient mutant 8195 of Acholeplasma laidlawii strain JA1 was transformed by the promiscuous streptococcal plasmid vector pNZ18 at a frequency of 4 x 10(-4)/cfu. The plasmid was maintained without structural rearrangements but was lost in the absence of a selection pressure, i.e. kanamycin or neomycin. Transformed primary colonies were easily recognized due to a different colony morphology. Replica filter plating, previously not obtained with mycoplasmas, was achieved using pNZ18 as a marker by incubating the replica filters with the cell side down on the new agar plates. These findings should greatly facilitate the genetic and functional analysis of A. laidlawii.  相似文献   
9.
Protected areas (PAs) are recognized as the flagship tool to offset biodiversity loss on Earth. Spatial conservation planning seeks optimal designs of PAs that meet multiple targets such as biodiversity representation and population persistence. Since connectivity between PAs is a fundamental requirement for population persistence, several methods have been developed to include connectivity into PA design algorithms. Among these, the eigenvalue decomposition of the connectivity matrix allows for identifying clusters of strongly connected sites and selecting the sites contributing the most to population persistence. So far, this method was only suited to optimize an entire network of PAs without considering existing PAs in the new design. However, a more cost‐effective and realistic approach is to optimize the design of an extended network to improve its connectivity and thus population persistence. Here, we develop a flexible algorithm based on eigenvalue decomposition of connectivity matrices to extend existing networks of PAs while optimizing connectivity and population growth rate. We also include a splitting algorithm to improve cluster identification. The new algorithm accounts for the change in connectivity due to the increased biological productivity often observed in existing PAs. We illustrate the potential of our algorithm by proposing an extension of the network of ~100 Mediterranean marine PAs to reach the targeted 10% surface area protection from the current 1.8%. We identify differences between the clean slate scenario, where all sites are available for protection, irrespective of their current protection status, and the scenario where existing PAs are forced to be included into the optimized solution. By integrating this algorithm to existing multi‐objective and multi‐specific algorithms of PA selection, the demographic effects of connectivity can be explicitly included into conservation planning.  相似文献   
10.
Summary The experiment was performed in two phases. During the first phase (phase 1) the dominance hierarchy was determined in 4 groups of Arctic charr (Salvelinus alpinus L.), each group consisting of 4 fish. Phase 2 was started by rearranging phase 1 fish into 4 new groups. Group 1 consisted of previously dominant fish and groups 2, 3 and 4 of fish that previously held rank 2, 3 and 4, respectively. After phase 2 telencephalon and brain stem were analyzed with regard to their contents of serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), the principle metabolite of 5-HT. No correlation was found between the social rank (measured as dominance index) during phase 1 and the brain serotonergic activity (measured as the ratio 5-HIAA/5-HT) determined after phase 2. However, most important, the 5-HIAA/5-HT ratio was significantly correlated with the last experienced social rank, i.e. that acquired during phase 2. These results shows that the difference in brain serotonergic activity between dominant and subordinate fish develops through social interactions. Further, we found that previous subordinate experience inhibited aggressive behavior, an effect which, in the light of available information on stress and 5-HT, could be related to the increase in brain serotonergic activity. We hypothesize that stress induces an increased serotonergic activity which in turn inhibits the neuronal circuitry which mediates aggressive behavior.Abbreviations 5-HT serotonin (5-hydroxytryptamine) - 5-HIAA 5-hydroxyindoleacetic acid  相似文献   
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