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21.
Akar FG Wu RC Deschenes I Armoundas AA Piacentino V Houser SR Tomaselli GF 《American journal of physiology. Heart and circulatory physiology》2004,286(2):H602-H609
The Ca(2+)-independent transient outward K(+) current (I(to)) plays an important electrophysiological role in normal and diseased hearts. However, its contribution to ventricular repolarization remains controversial because of differences in its phenotypic expression and function across species. The dog, a frequently used model of human cardiac disease, exhibits altered functional expression of I(to). To better understand the relevance of electrical remodeling in dogs to humans, we studied the phenotypic differences in ventricular I(to) of both species with electrophysiological, pharmacological, and protein-chemical techniques. Several notable distinctions were elucidated, including slower current decay, more rapid recovery from inactivation, and a depolarizing shift of steady-state inactivation in human vs. canine I(to). Whereas recovery from inactivation of human I(to) followed a monoexponential time course, canine I(to) recovered with biexponential kinetics. Pharmacological sensitivity to flecainide was markedly greater in human than canine I(to), and exposure to oxidative stress did not alter the inactivation kinetics of I(to) in either species. Western blot analysis revealed immunoreactive bands specific for Kv4.3, Kv1.4, and Kv channel-interacting protein (KChIP)2 in dog and human, but with notable differences in band sizes across species. We report for the first time major variations in phenotypic properties of human and canine ventricular I(to) despite the presence of the same subunit proteins in both species. These data suggest that differences in electrophysiological and pharmacological properties of I(to) between humans and dogs are not caused by differential expression of the K channel subunit genes thought to encode I(to), but rather may arise from differences in molecular structure and/or posttranslational modification of these subunits. 相似文献
22.
Pea (Pisum sativum) stem mitochondria, energized by NADH, succinate or malate plus glutamate, underwent a spontaneous low-amplitude permeability transition (PT), which could be monitored by dissipation of the electrical potential (deltapsi) or swelling. The occurrence of the latter effects was dependent on O2 availability, because O2 shortage anticipated the manifestation of both deltapsi dissipation and swelling. Spontaneous deltapsi collapse was also monitored in sucrose-resuspended mitochondria and again O2 deprivation caused an anticipation of the phenomenon. However, in this case deltapsi dissipation was not accompanied by a parallel mitochondrial swelling. The latter effect was, indeed, evident only if mitochondria were resuspended in KCl (as osmoticum), or other cations with a molecular mass up to 100 Da (choline+). PT was also induced by protonophores (carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) or free fatty acids) or valinomycin (only in KCl). The FCCP-induced dissipation of deltapsi and swelling were inhibited by ATP and stimulated (anticipated) by cyclosporin A or O2 shortage. The FCCP-induced PT was accompanied by the release of pyridine nucleotides from the matrix and of cytochrome c from the intermembrane space of KCl-resuspended mitochondria. The spontaneous and FCCP-induced low-amplitude PT of plant mitochondria are interpreted as due to the activity of a recently identified K(ATP)+ channel whose open/closed state is dependent on polarization of the inner membrane and on the oxidoreductive state of some sulfhydryl groups. 相似文献
23.
24.
Bergquist P Te'o V Gibbs M Cziferszky A de Faria FP Azevedo M Nevalainen H 《Extremophiles : life under extreme conditions》2002,6(3):177-184
Bulk production of xylanases from thermophilic microorganisms is a prerequisite for their use in industrial processes. As effective secretors of gene products, fungal expression systems provide a promising, industrially relevant alternative to bacteria for heterologous enzyme production. We are currently developing the yeast Kluyveromyces lactis and the filamentous fungus Trichoderma reesei for the extracellular production of thermophilic enzymes for the pulp and paper industry. The K. lactis system has been tested with two thermophilic xylanases and secretes gram amounts of largely pure xylanase A from Dictyoglomus thermophilum in chemostat culture. The T. reesei expression system involves the use of the cellobiohydrolase I (CBHI) promoter and gene fusions for the secretion of heterologous thermostable xylanases of both bacterial and fungal origin. We have reconstructed the AT-rich xynB gene of Dictyoglomus thermophilum according to Trichoderma codon preferences and demonstrated a dramatic increase in expression. A heterologous fungal gene, Humicola grisea xyn2, could be expressed without codon modification. Initial amounts of the XYN2 protein were of a gram per liter range in shake-flask cultivations, and the gene product was correctly processed by the heterologous host. Comparison of the expression of three thermophilic heterologous microbial xylanases in T. reesei demonstrates the need for addressing each case individually. 相似文献
25.
Peripheral benzodiazepine receptor ligand-melphalan conjugates for potential selective drug delivery to brain tumors 总被引:3,自引:0,他引:3
Trapani G Laquintana V Latrofa A Ma J Reed K Serra M Biggio G Liso G Gallo JM 《Bioconjugate chemistry》2003,14(4):830-839
To gain insight into the strategy to target PBR ligand-drug conjugates to brain tumors, novel N-imidazopyridinacetyl-melphalan conjugates and the corresponding ethyl esters have been prepared and evaluated for their cytotoxicity in melphalan-sensitive human (SF126, SF188) and rat (RG-2) glioma cell lines. These conjugates exhibited PBR binding affinity with IC(50) values ranging from 57 and 2614 nM. By a computational approach it can be predicted that these conjugates possess significant brain penetration. The stability of the conjugates in 0.05 M phosphate buffer at pH 7.4 and, in some cases, in dilute human serum solution was determined. All the ethyl ester derivatives were stable in 0.05 M phosphate buffer at pH 7.4 and their half-lives exceeded 28 h. Conversely, under the same conditions, the corresponding acids were found to undergo a fast cleavage within a few minutes. HPLC-MS analysis of the mixture from degradation in buffer and physiological medium of the representative cases allowed the identification of their main degradation products. A plausible degradation pathway accounting for the available experimental data is presented. 相似文献
26.
Interest in the use of low-copy nuclear genes for phylogenetic analyses of
plants has grown rapidly, because highly repetitive genes such as those
commonly used are limited in number. Furthermore, because low- copy genes
are subject to different evolutionary processes than are plastid genes or
highly repetitive nuclear markers, they provide a valuable source of
independent phylogenetic evidence. The gene for granule-bound starch
synthase (GBSSI or waxy) exists in a single copy in nearly all plants
examined so far. Our study of GBSSI had three parts: (1) Amino acid
sequences were compared across a broad taxonomic range, including grasses,
four dicotyledons, and the microbial homologs of GBSSI. Inferred structural
information was used to aid in the alignment of these very divergent
sequences. The informed alignments highlight amino acids that are conserved
across all sequences, and demonstrate that structural motifs can be highly
conserved in spite of marked divergence in amino acid sequence. (2)
Maximum-likelihood (ML) analyses were used to examine exon sequence
evolution throughout grasses. Differences in probabilities among
substitution types and marked among-site rate variation contributed to the
observed pattern of variation. Of the parameters examined in our set of
likelihood models, the inclusion of among-site rate variation following a
gamma distribution caused the greatest improvement in likelihood score. (3)
We performed cladistic parsimony analyses of GBSSI sequences throughout
grasses, within tribes, and within genera to examine the phylogenetic
utility of the gene. Introns provide useful information among very closely
related species, but quickly become difficult to align among more divergent
taxa. Exons are variable enough to provide extensive resolution within the
family, but with low bootstrap support. The combined results of amino acid
sequence comparisons, maximum-likelihood analyses, and phylogenetic studies
underscore factors that might affect phylogenetic reconstruction. In this
case, accommodation of the variable rate of evolution among sites might be
the first step in maximizing the phylogenetic utility of GBSSI.
相似文献
27.
Hao-Han Chang Bernard Choong Anthony RJ Phillips Kerry M Loomes 《Experimental biology and medicine (Maywood, N.J.)》2015,240(1):8-14
Diabetic nephropathy is a serious complication of diabetes mellitus with a pressing need for effective metabolic markers to detect renal impairment. Of potential significance are the inositol compounds, myo-inositol (MI), and the less abundant stereoisomer, D-chiro-inositol (DCI), which are excreted at increased levels in the urine in diabetes mellitus, a phenomenon known as inosituria. There is also a selective urinary excretion of DCI compared to MI. As the biological origins of altered inositol metabolism in diabetes mellitus are unknown, the aim of this study was to determine whether the diabetic kidney was directly responsible. Kidneys isolated from four-week streptozotocin-induced diabetic rats were characterized by a 3-fold reduction in glomerular filtration rate (GFR) compared to matched non-diabetic kidneys. When perfused with fixed quantities of MI (50 µM) and DCI (5 µM) under normoglycemic conditions (5 mM glucose), GFR-normalized urinary excretion of MI was increased by 1.7-fold in diabetic vs. non-diabetic kidneys. By comparison, GFR-normalized urinary excretion of DCI was increased by 4-fold. Perfusion conditions replicating hyperglycemia (20 mM glucose) potentiated DCI but not MI urinary excretion in both non-diabetic and diabetic kidneys. Overall, there was a 2.4-fold increase in DCI urinary excretion compared to MI in diabetic kidneys that was independent of glucose ambience. This increased urinary excretion of DCI and MI in diabetic kidneys occurred despite increased renal expression of the inositol transporters, sodium myo-inositol transporter subtype 1 and 2 (SMIT1 and SMIT2). These findings show that the diabetic kidney primarily mediates inosituria and altered urinary partitioning of MI and DCI. Urinary inositol levels might therefore serve as an indicator of impaired renal function in diabetes mellitus with wider implications for monitoring chronic kidney disease. 相似文献
28.
Barbara Bottazzi Laura Santini Silvana Savino Marzia M. Giuliani Ana I. Due?as Díez Giuseppe Mancuso Concetta Beninati Marina Sironi Sonia Valentino Livija Deban Cecilia Garlanda Giuseppe Teti Mariagrazia Pizza Rino Rappuoli Alberto Mantovani 《PloS one》2015,10(3)
Long pentraxin 3 (PTX3) is a non-redundant component of the humoral arm of innate immunity. The present study was designed to investigate the interaction of PTX3 with Neisseria meningitidis. PTX3 bound acapsular meningococcus, Neisseria-derived outer membrane vesicles (OMV) and 3 selected meningococcal antigens (GNA0667, GNA1030 and GNA2091). PTX3-recognized microbial moieties are conserved structures which fulfil essential microbial functions. Ptx3-deficient mice had a lower antibody response in vaccination protocols with OMV and co-administration of PTX3 increased the antibody response, particularly in Ptx3-deficient mice. Administration of PTX3 reduced the bacterial load in infant rats challenged with Neisseria meningitidis. These results suggest that PTX3 recognizes a set of conserved structures from Neisseria meningitidis and acts as an amplifier/endogenous adjuvant of responses to this bacterium. 相似文献
29.
A Fazzolari B Valentino G Zummo S Damiani 《Bollettino della Società italiana di biologia sperimentale》1981,57(19):1957-1962
The Authors studied the Human normal full term placenta and in the feto-maternal Rh and ABO incompatibilities. In the Human normal full term placenta the sincitium trophoblastum coat shows the usual microvillosity and the normal cytoplasmatic organules; in the placenta of ABO isoimmunized subjects the sincitium trophoblastum coat is intensely vacuolyzated; in the placenta of Rh isoimmunized subjects the lamina sincitiale vacuolyzation is more evident in the basal side. Discussion on the morphology related to the placenta barrier function. 相似文献
30.
Wounding induces resistance to pathogens with different lifestyles in tomato: role of ethylene in cross-protection 总被引:1,自引:0,他引:1
Francia D Demaria D Calderini O Ferraris L Valentino D Arcioni S Tamietti G Cardinale F 《Plant, cell & environment》2007,30(11):1357-1365
Many reports point to the existence of a network of regulatory signalling occurring in plants during the interaction with micro-organisms (biotic stress) and abiotic stresses such as wounding. However, the focus is on shared intermediates/components and/or common molecular outputs in differently triggered signalling pathways, and not on the degree and modes of effective influence between abiotic and biotic stresses nor the range of true plant-pathogen interactions open to such influence. We report on local and systemic wound-induced protection in tomato (Solanum lycopersicum L.) to four pathogens with a range of lifestyles (Botrytis cinerea, Fusarium oxysporum f.sp. lycopersici, Phytophthora capsici and Pseudomonas syringae pv. tomato). The role of ethylene (ET) in the phenomenon and in the induction by wounding of several markers of defense was investigated by using the never-ripe tomato mutant plants impaired in ET perception. We showed that PINIIb, PR1b, PR5, PR7 and peroxidase (POD) are influenced locally and/or systemically by wounding and, with the exception of POD activity, by ET perception. We also demonstrated that ET, although not essential, is positively (B. cinerea, P. capsici) or negatively (F. oxysporum, P. syringae pv. tomato) involved not only in basal but also in wound-induced resistance to each pathogen. 相似文献