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61.
Connected gene neighborhoods in prokaryotic genomes 总被引:12,自引:1,他引:11
Rogozin IB Makarova KS Murvai J Czabarka E Wolf YI Tatusov RL Szekely LA Koonin EV 《Nucleic acids research》2002,30(10):2212-2223
A computational method was developed for delineating connected gene neighborhoods in bacterial and archaeal genomes. These gene neighborhoods are not typically present, in their entirety, in any single genome, but are held together by overlapping, partially conserved gene arrays. The procedure was applied to comparing the orders of orthologous genes, which were extracted from the database of Clusters of Orthologous Groups of proteins (COGs), in 31 prokaryotic genomes and resulted in the identification of 188 clusters of gene arrays, which included 1001 of 2890 COGs. These clusters were projected onto actual genomes to produce extended neighborhoods including additional genes, which are adjacent to the genes from the clusters and are transcribed in the same direction, which resulted in a total of 2387 COGs being included in the neighborhoods. Most of the neighborhoods consist predominantly of genes united by a coherent functional theme, but also include a minority of genes without an obvious functional connection to the main theme. We hypothesize that although some of the latter genes might have unsuspected roles, others are maintained within gene arrays because of the advantage of expression at a level that is typical of the given neighborhood. We designate this phenomenon ‘genomic hitchhiking’. The largest neighborhood includes 79 genes (COGs) and consists of overlapping, rearranged ribosomal protein superoperons; apparent genome hitchhiking is particularly typical of this neighborhood and other neighborhoods that consist of genes coding for translation machinery components. Several neighborhoods involve previously undetected connections between genes, allowing new functional predictions. Gene neighborhoods appear to evolve via complex rearrangement, with different combinations of genes from a neighborhood fixed in different lineages. 相似文献
62.
Regulation of Wnt signaling during adipogenesis 总被引:17,自引:0,他引:17
Bennett CN Ross SE Longo KA Bajnok L Hemati N Johnson KW Harrison SD MacDougald OA 《The Journal of biological chemistry》2002,277(34):30998-31004
We have identified Wnt10b as a potent inhibitor of adipogenesis that must be suppressed for preadipocytes to differentiate in vitro. Here, we demonstrate that a specific inhibitor of glycogen synthase kinase 3, CHIR 99021, mimics Wnt signaling in preadipocytes. CHIR 99021 stabilizes free cytosolic beta-catenin and inhibits adipogenesis by blocking induction of CCAAT/enhancer-binding protein alpha and peroxisome proliferator-activated receptor gamma. Preadipocyte differentiation is inhibited when 3T3-L1 cells are exposed to CHIR 99021 for any 24 h period during the first 3 days of adipogenesis. Consistent with this time frame of inhibition, expression of Wnt10b mRNA is suppressed upon induction of differentiation, with a 50% decline by 6 h and complete inhibition by 36 h. Of the agents used to induce differentiation, exposure of 3T3-L1 cells to methyl-isobutylxanthine or cAMP is sufficient to suppress expression of Wnt10b mRNA. Inhibition of adipogenesis by Wnt10b is likely mediated by Wnt receptors, Frizzled 1, 2, and/or 5, and co-receptors low density lipoprotein receptor-related proteins 5 and 6. These receptors, like Wnt10b, are highly expressed in preadipocytes and stromal vascular cells. Finally, we demonstrate that disruption of extracellular Wnt signaling by expression of secreted Frizzled related proteins causes spontaneous adipocyte conversion. 相似文献
63.
Baydar T Papp A Aydin A Nagymajtenyi L Schulz H Isimer A Sahin G 《Biological trace element research》2003,92(3):231-244
The present study was undertaken to examine possible aluminum (Al) accumulation in the brain of rats and to investigate whether
subchronic exposure to the metal leads to behavioral and neurophysiological changes in both treated and control groups. Each
of the groups consisted of 10 animals. Aluminum chloride (AlCl3) at a low (50 mg/kg/d) or high (200 mg/kg/d) dose was applied to male Wistar rats by gavage for 8 wk. Al-free water by gavage
was given to the control group throughout the experiment. Behavioral effects were evaluated by open-field (OF) motor activity
and by acoustic startle response (ASR). Electrophysiological examination was done by recording spontaneous activity and sensory-evoked
potentials from the visual, somatosensory, as well as auditory cortex. The Al content of each whole brain was determined by
electrothermal atomic absorption spectrophotometry. Subchronic Al exposure slightly caused some changes in the evoked potentials
and electrocorticograms and in the OF and ASR performance, but these results were not statistically significant. The brain
Al levels of the control and the low and high dose of Al-exposed groups were measured as 0.717±0.208 μg/g (wet weight), 0.963±0.491
μg/g (wet weight) and 1.816±1.157 μg/g (wet weight), respectively. 相似文献
64.
Exposure of isolated nerve terminals to hydrogen peroxide (25-500 microM) for 10 min produced a partially reversible decrease in the total and reduced glutathione level. No release and resynthesis of glutathione by the oxidant was involved in this effect. Loss of reduced glutathione was associated with elimination of H(2)O(2), which was very quick with >70% of the oxidant eliminated within 5 min. Recovery of both total and reduced glutathione was pronounced after 10 min when the majority of H(2)O(2) was eliminated. Previously we have reported that glutamate metabolism under oxidative stress contributes to the operation of the Krebs cycle, thus to the production of NAD(P)H [J. Neurosci. 20 (2000) 8972]. In the present study we addressed whether metabolism of endogenous glutamate plays a role in the maintenance of glutathione level in nerve terminals. Glutamine and beta-hydroxybutyrate (5mM), alternative metabolites in synaptosomes, were able to decrease the loss of total and reduced glutathione induced by hydrogen peroxide. Metabolic consumption of glutamate was reduced at the same time. In addition an increased demand on the glutathione system by the catalase inhibitor aminotriazole augmented the metabolic consumption of glutamate. It is concluded that under oxidative stress glutamate metabolism contributes to the maintenance of glutathione level, thus to the antioxidant capacity of nerve terminals. 相似文献
65.
Reciprocal Innervation between Serotonergic and GABAergic Neurons in Raphe Nuclei of the Rat 总被引:1,自引:0,他引:1
Midbrain slices containing the dorsal and medial raphe nuclei were prepared from rat brain in order to study serotonergic-GABAergic interaction. The slices were loaded with either [3H] serotonin or [3H]GABA, superfused and the electrically induced efflux of radioactivity was determined. The GABAA receptor agonist muscimol (3 to 30 M) and the GABAB receptor agonist baclofen (30 and 100 M) inhibited [3H]serotonin and [3H]GABA release. These effects of muscimol were reversed by the GABAA antagonists bicuculline (100 M). The GABAB antagonist phaclofen (100 M) also antagonized the baclofen-induced inhibition of [3H]serotonin and [3H]GABA release. Phaclofen by itself increased [3H]serotonin release but it did not alter [3H]GABA overflow. Muscimol (10 M) and baclofen (100 M) also inhibited [3H]serotonin release after depletion of GABAergic neurons by isoniazid pretreatment. These findings indicate the presence of postsynaptic GABAA and GABAB receptors located on serotonergic neurons. The 5-HT1A receptor agonist 8-OH-DPAT (0.01 to 1 M) and the 5-HT1B receptor agonist CGS-12066A (0.01 to 1 M) inhibited the electrically stimulated [3H]serotonin and [3H]GABA release. The 5-HT1A antagonist WAY-100135 (1 M) was without effect on [3H]serotonin and [3H]GABA efflux by itself but it reversed the 8-OH-DPAT-induced transmitter release inhibition. During KCl (22 mM)-induced depolarization, tetrodotoxin (1 M) did not alter the inhibitory effect of CGS-12066A (1 M) on [3H]GABA release, it did blocked, however, the ability of 8-OH-DPAT (1 M) to reduce [3H]GABA efflux. After depletion of raphe serotonin neurons by p-chlorophenylalanine pretreatment, CGS-12066A (1 M) still inhibited [3H]GABA release whereas in serotonin-depleted slices, 8-OH-DPAT (1 M) was without effect on the release. We conclude that reciprocal influence exists between serotonergic projection neurons and the GABAergic interneurons or afferents in the raphe nuclei and these interactions may be mediated by 5-HT1A/B and GABAA/B receptors. Both synaptic and non-synaptic neurotransmission may be operative in the 5-HTergic-GABAergic reciprocal interaction which may serve as a local tuning in the neural connection between cerebral cortex and midbrain raphe nuclei. 相似文献
66.
A β-glucosidase that cleaves the biologically inactive hormone conjugates cytokinin-O- and kinetin-N3-glucosides is encoded
by the maize Zm-p60.1 gene. The expression of the Zm-p60.1 gene was analyzed by Northern blot analysis and in-situ hybridization. It was found that the expression levels of the Zm-p60.1-specific mRNA changed after pollination of carpellate inflorescences. The Zm-p60.1 cDNA was expressed in E. coli and antibodies were raised against this protein. An antibody was used to determine the tissue-specific localization of this
protein. By in situ immunolocalization experiments, this protein was found to be located in cell layers below the epidermis
and around the vascular bundles of the coleoptile. In the primary leaf, the Zm-p60.1 protein was detected in cells of the
outermost cell layer and around the vascular tissue. In floral tissue, Zm-p60.1 was present in the glumes, the carpels and
in the outer cell layer of the style. In coleoptiles, as determined by immuno-electronmicroscopy, the Zm-p60.1 protein was
located exclusively in the plastids.
Received: 11 August 1998 / Accepted: 30 December 1998 相似文献
67.
Melanin-concentrating hormone (MCH), found both peripherally and centrally, is involved in food ingestion. Although its expression in brain is increased by fasting, it is not known whether it crosses the blood-brain barrier (BBB). Use of the sensitive method of multiple-time regression analysis has shown that almost all of the peptides and polypeptides tested cross the BBB at a rate faster than the vascular marker albumin. With this same method, however, we found that the 19-amino acid 125I-Phe13,Tyr19-MCH did not cross faster than 99mTc-albumin. Several mechanisms were excluded as possible explanations for the slow rate of influx. These included degradation, association with capillary endothelial cells, and transport from brain to blood. When Phe13,Tyr19-MCH was perfused in blood-free buffer, however, it entered the brain significantly faster than albumin. This suggested protein binding as an explanation for the slow rate of influx when the MCH was administered in blood. Protein binding was confirmed by capillary zone electrophoresis, which showed that almost all of the Phe13,Tyr19-MCH added to blood migrated with a large-molecular-weight substance. Sodium dodecyl sulfate-capillary gel electrophoresis of Phe13,Tyr19-MCH in buffer additionally showed that the MCH aggregated as a trimer, a factor not preventing its influx by blood-free perfusion. Thus, the results show that blood-borne Phe13,Tyr19-MCH does not significantly cross the BBB, probably because of its binding to serum proteins. 相似文献
68.
69.
Aysar Al-Husseini Dayanjan S. Wijesinghe Laszlo Farkas Donatas Kraskauskas Jennifer I. Drake Ben Van Tassel Antonio Abbate Charles E. Chalfant Norbert F. Voelkel 《PloS one》2015,10(3)
Inflammation and altered immunity are recognized components of severe pulmonary arterial hypertension in human patients and in animal models of PAH. While eicosanoid metabolites of cyclooxygenase and lipoxygenase pathways have been identified in the lungs from pulmonary hypertensive animals their role in the pathogenesis of severe angioobliterative PAH has not been examined. Here we investigated whether a cyclooxygenase-2 (COX-2) inhibitor or diethylcarbamazine (DEC), that is known for its 5-lipoxygenase inhibiting and antioxidant actions, modify the development of PAH in the Sugen 5416/hypoxia (SuHx) rat model. The COX-2 inhibitor SC-58125 had little effect on the right ventricular pressure and did not prevent the development of pulmonary angioobliteration. In contrast, DEC blunted the muscularization of pulmonary arterioles and reduced the number of fully obliterated lung vessels. DEC treatment of SuHx rats, after the lung vascular disease had been established, reduced the degree of PAH, the number of obliterated arterioles and the degree of perivascular inflammation. We conclude that the non-specific anti-inflammatory drug DEC affects developing PAH and is partially effective once angioobliterative PAH has been established. 相似文献
70.
Laszlo Revesz Achim Schlapbach Reiner Aichholz Janet Dawson Roland Feifel Stuart Hawtin Amanda Littlewood-Evans Guido Koch Markus Kroemer Henrik Möbitz Clemens Scheufler Juraj Velcicky Christine Huppertz 《Bioorganic & medicinal chemistry letters》2010,20(15):4719-4723
Spirocyclopropane- and spiroazetidine-substituted tetracycles 13D–E and 16A are described as orally active MK2 inhibitors. The spiroazetidine derivatives are potent MK2 inhibitors with IC50 <3 nM and inhibit the release of TNFα (IC50<0.3 μM) from hPBMCs and hsp27 phosphorylation in anisomycin stimulated THP-1 cells. The spirocyclopropane analogues are less potent against MK2 (IC50 = 0.05–0.23 μM), less potent in cells (IC50 <1.1 μM), but show good oral absorption. Compound 13E (100 mg/kg po; bid) showed oral activity in rAIA and mCIA, with significant reduction of swelling and histological score. 相似文献