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1.
Maria J. Erkkil? Robert Leah Hannu Ahokas Verena Cameron-Mills 《Plant physiology》1998,117(2):679-685
The wild ancestor of cultivated barley, Hordeum vulgare subsp. spontaneum (K. Koch) A. & Gr. (H. spontaneum), is a source of wide genetic diversity, including traits that are important for malting quality. A high β-amylase trait was previously identified in H. spontaneum strains from Israel, and transferred into the backcross progeny of a cross with the domesticated barley cv Adorra. We have used Southern-blot analysis and β-amy1 gene characterization to demonstrate that the high β-amylase trait in the backcross line is co-inherited with the β-amy1 gene from the H. spontaneum parent. We have analyzed the β-amy1 gene organization in various domesticated and wild-type barley strains and identified three distinct β-amy1 alleles. Two of these β-amy1 alleles were present in modern barley, one of which was specifically found in good malting barley cultivars. The third allele, linked with high grain β-amylase activity, was found only in a H. spontaneum strain from the Judean foothills in Israel. The sequences of three isolated β-amy1 alleles are compared. The involvement of specific intron III sequences, in particular a 126-bp palindromic insertion, in the allele-dependent expression of β-amylase activity in barley grain is proposed. 相似文献
2.
The production of β-lactamases is the most important mechanism of Gram-negative rod resistance to β-lactams. Resistance to ceftazidime and cefepime in clinical isolates of Enterobacteriaceae (especially ESβL-positive E. coli and K. pneumoniae) and P. aeruginosa is life-threatening. However, all strains of the above mentioned species possess chromosomally encoded RND efflux pump systems in addition to β-lactamase production. The main goal of this study was to assess the role of efflux pump systems in cefepime and/or ceftazidime resistant phenotypes of ESβL-positive clinical strains of Enterobacteriaceae and P. aeruginosa. The influence of the efflux pump inhibitor PAβN on the minimum inhibitory concentration (MIC) values of tested cephalosporins was species-dependent. Generally, a significant reduction (at least four-fold) of β-lactam MICs was observed in the presence of PAβN only in the case of P. aeruginosa clinical isolates as well as the ESβL-producing transformant PAO1161 ΔampC. The usage of this agent resulted in the restoration of susceptibility to cefepime and/or ceftazidime in the majority of the P. aeruginosa ESβL-positive strains with low and moderate resistance to the above cephalosporins. Moreover, an outer membrane permeabilizing effect in the presence of PAβN was identified. Strain-dependent β-lactamase leakage upon PAβN or β-lactam treatment was demonstrated. The most important observation was the restoration of susceptibility of P. aeruginosa WUM226 to cefepime (MIC decrease from 32 to 4 mg/L) and ceftazidime (MIC decrease from 128 to 4 mg/L) in the presence of PAβN, which occurred despite an almost complete lack of β-lactamase leakage from bacterial cells. In conclusion, these data indicate that RND efflux pumps can modify the susceptibility to β-lactams in Gram-negative rods producing ESβLs. However, this phenomenon occurs only in P. aeruginosa strains and was not observed among E. coli and K. pneumoniae strains, representing the Enterobacteriaceae family. 相似文献
3.
The level of susceptibility to tuberculosis (TB) infection depends upon allelic variations in numerous interacting genes. In our mouse model system, the whole-genome quantitative trait loci (QTLs) scan revealed three QTLs involved in TB control on chromosomes 3, 9, and in the vicinity of the H2 complex on chromosome 17. For the present study, we have established a panel of new congenic, MHC-recombinant mouse strains bearing differential small segments of chromosome 17 transferred from the TB-susceptible I/St (H2
j) strain onto the genetic background of TB-resistant C57BL/6 (B6) mice (H2
b). This allowed narrowing the QTL interval to 17Ch: 33, 77–34, 34 Mb, containing 36 protein-encoding genes. Cloning and sequencing of the H2
j allelic variants of these genes demonstrated profound polymorphic variations compare to the H2
b haplotype. In two recombinant strains, B6.I-249.1.15.100 and B6.I-249.1.15.139, recombination breakpoints occurred in different sites of the H2-Aβ 1 gene (beta-chain of the Class II heterodimer H2-A), providing polymorphic variations in the domain β1 of the Aβ-chain. These variations were sufficient to produce different TB-relevant phenotypes: the more susceptible B6.I-249.1.15.100 strain demonstrated shorter survival time, more rapid body weight loss, higher mycobacterial loads in the lungs and more severe lung histopathology compared to the more resistant B6.I-249.1.15.139 strain. CD4+ T cells recognized mycobacterial antigens exclusively in the context of the H2-A Class II molecule, and the level of IFN-γ-producing CD4+ T cells in the lungs was significantly higher in the resistant strain. Thus, we directly demonstrated for the first time that the classical H2- Ab1 Class II gene is involved in TB control. Molecular modeling of the H2-Aj product predicts that amino acid (AA) substitutions in the Aβ-chain modify the motif of the peptide–MHC binding groove. Moreover, unique AA substitutions in both α- and β-chains of the H2-Aj molecule might affect its interactions with the T-cell receptor (TCR). 相似文献
4.
Kazuki Matsubara Eiji Yamamoto Nobuya Kobayashi Takuro Ishii Junichi Tanaka Hiroshi Tsunematsu Satoshi Yoshinaga Osamu Matsumura Jun-ichi Yonemaru Ritsuko Mizobuchi Toshio Yamamoto Hiroshi Kato Masahiro Yano 《PloS one》2016,11(3)
Biomass yield of rice (Oryza sativa L.) is an important breeding target, yet it is not easy to improve because the trait is complex and phenotyping is laborious. Using progeny derived from a cross between two high-yielding Japanese cultivars, we evaluated whether quantitative trait locus (QTL)-based selection can improve biomass yield. As a measure of biomass yield, we used plant weight (aboveground parts only), which included grain weight and stem and leaf weight. We measured these and related traits in recombinant inbred lines. Phenotypic values for these traits showed a continuous distribution with transgressive segregation, suggesting that selection can affect plant weight in the progeny. Four significant QTLs were mapped for plant weight, three for grain weight, and five for stem and leaf weight (at α = 0.05); some of them overlapped. Multiple regression analysis showed that about 43% of the phenotypic variance of plant weight was significantly explained (P < 0.0001) by six of the QTLs. From F2 plants derived from the same parental cross as the recombinant inbred lines, we divergently selected lines that carried alleles with positive or negative additive effects at these QTLs, and performed successive selfing. In the resulting F6 lines and parents, plant weight significantly differed among the genotypes (at α = 0.05). These results demonstrate that QTL-based selection is effective in improving rice biomass yield. 相似文献
5.
Marcus R. Streit Celine S. Weiss S?ren Meyer Marco M. Ochs Marco Hagenmueller Johannes H. Riffel Sebastian J. Buss Thomas Heger Hugo A. Katus Stefan E. Hardt 《PloS one》2016,11(1)
Aims
Inhibition of β-adrenergic signalling plays a key role in treatment of heart failure. Gsα is essential for β-adrenergic signal transduction. In order to reduce side-effects of beta-adrenergic inhibition diminishing β-adrenergic signalling in the heart at the level of Gsα is a promising option.Methods and Results
We analyzed the influence of Gsα on regulation of myocardial function and development of cardiac hypertrophy, using a transgenic mouse model (C57BL6/J mice) overexpressing a dominant negative Gsα-mutant under control of the α-MHC-promotor. Cardiac phenotype was characterized in vivo and in vitro and under acute and chronic β-adrenergic stimulation. At rest, Gsα-DN-mice showed bradycardia (602 ± 13 vs. 660 ± 17 bpm, p<0.05) and decreased dp/dtmax (5037 ± 546- vs. 6835 ± 505 mmHg/s, p = 0.02). No significant differences were found regarding ejection fraction, heart weight and cardiomyocyte size. β-blockade by propranolol revealed no baseline differences of hemodynamic parameters between wildtype and Gsα-DN-mice. Acute adrenergic stimulation resulted in decreased β-adrenergic responsiveness in Gsα-DN-mice. Under chronic adrenergic stimulation, wildtype mice developed myocardial hypertrophy associated with increase of LV/BW-ratio by 23% (4.4 ± 0.2 vs. 3.5 ± 0.1 mg/g, p<0.01) and cardiac myocyte size by 24% (14927 ± 442 px vs. 12013 ± 583 px, p<0.001). In contrast, both parameters were unchanged in Gsα-DN-mice after chronic isoproterenol stimulation.Conclusion
Overexpression of a dominant negative mutant of Gsα leads to decreased β-adrenergic responsiveness and is protective against isoproterenol-induced hypertrophy. Thus, Gsα-DN-mice provide novel insights into β-adrenergic signal transduction and its modulation in myocardial overload and failure. 相似文献6.
Heike Vogel Dirk Montag Timo Kanzleiter Wenke Jonas Daniela Matzke Stephan Scherneck Alexandra Chadt Jonas T?le Reinhart Kluge Hans-Georg Joost Annette Schürmann 《PloS one》2013,8(1)
A region on mouse distal chromosome 1 (Chr. 1) that is highly enriched in quantitative trait loci (QTLs) controlling neural and behavioral phenotypes overlaps with the peak region of a major obesity QTL (Nob3.38), which we identified in an intercross of New Zealand Obese (NZO) mice with C57BL/6J (B6). By positional cloning we recently identified a microdeletion within this locus causing the disruption of Ifi202b that protects from adiposity by suppressing expression of 11β-Hsd1. Here we show that the Nob3.38 segment also corresponds with the QTL rich region (Qrr1) on Chr. 1 and associates with increased voluntary running wheel activity, Rota-rod performance, decreased grip strength, and anxiety-related traits. The characterization of a subcongenic line carrying 14.2 Mbp of Nob3.38 with a polymorphic region of 4.4 Mbp indicates that the microdeletion and/or other polymorphisms in its proximity alter body weight, voluntary activity, and exploration. Since 27 out of 32 QTL were identified in crosses with B6, we hypothesized that the microdeletion and or adjacent SNPs are unique for B6 mice and responsible for some of the complex Qrr1-mediated effects. Indeed, a phylogenic study of 28 mouse strains revealed a NZO-like genotype for 22 and a B6-like genotype for NZW/LacJ and 4 other C57BL strains. Thus, we suggest that a Nob3.38 interval (173.0–177.4 Mbp) does not only modify adiposity but also neurobehavioral traits by a haplotype segregating with C57BL strains. 相似文献
7.
Rebecca A. Capel Emma L. Bolton Wee K. Lin Daniel Aston Yanwen Wang Wei Liu Xin Wang Rebecca-Ann B. Burton Duncan Bloor-Young Kai-Ting Shade Margarida Ruas John Parrington Grant C. Churchill Ming Lei Antony Galione Derek A. Terrar 《The Journal of biological chemistry》2015,290(50):30087-30098
Ca2+-permeable type 2 two-pore channels (TPC2) are lysosomal proteins required for nicotinic acid adenine dinucleotide phosphate (NAADP)-evoked Ca2+ release in many diverse cell types. Here, we investigate the importance of TPC2 proteins for the physiology and pathophysiology of the heart. NAADP-AM failed to enhance Ca2+ responses in cardiac myocytes from Tpcn2−/− mice, unlike myocytes from wild-type (WT) mice. Ca2+/calmodulin-dependent protein kinase II inhibitors suppressed actions of NAADP in myocytes. Ca2+ transients and contractions accompanying action potentials were increased by isoproterenol in myocytes from WT mice, but these effects of β-adrenoreceptor stimulation were reduced in myocytes from Tpcn2−/− mice. Increases in amplitude of L-type Ca2+ currents evoked by isoproterenol remained unchanged in myocytes from Tpcn2−/− mice showing no loss of β-adrenoceptors or coupling mechanisms. Whole hearts from Tpcn2−/− mice also showed reduced inotropic effects of isoproterenol and a reduced tendency for arrhythmias following acute β-adrenoreceptor stimulation. Hearts from Tpcn2−/− mice chronically exposed to isoproterenol showed less cardiac hypertrophy and increased threshold for arrhythmogenesis compared with WT controls. Electron microscopy showed that lysosomes form close contacts with the sarcoplasmic reticulum (separation ∼25 nm). We propose that Ca2+-signaling nanodomains between lysosomes and sarcoplasmic reticulum dependent on NAADP and TPC2 comprise an important element in β-adrenoreceptor signal transduction in cardiac myocytes. In summary, our observations define a role for NAADP and TPC2 at lysosomal/sarcoplasmic reticulum junctions as unexpected but major contributors in the acute actions of β-adrenergic signaling in the heart and also in stress pathways linking chronic stimulation of β-adrenoceptors to hypertrophy and associated arrhythmias. 相似文献
8.
Luyang Sun Shikai Liu Ruijia Wang Yanliang Jiang Yu Zhang Jiaren Zhang Lisui Bao Ludmilla Kaltenboeck Rex Dunham Geoff Waldbieser Zhanjiang Liu 《PloS one》2014,9(10)
Domestication and selection for important performance traits can impact the genome, which is most often reflected by reduced heterozygosity in and surrounding genes related to traits affected by selection. In this study, analysis of the genomic impact caused by domestication and artificial selection was conducted by investigating the signatures of selection using single nucleotide polymorphisms (SNPs) in channel catfish (Ictalurus punctatus). A total of 8.4 million candidate SNPs were identified by using next generation sequencing. On average, the channel catfish genome harbors one SNP per 116 bp. Approximately 6.6 million, 5.3 million, 4.9 million, 7.1 million and 6.7 million SNPs were detected in the Marion, Thompson, USDA103, Hatchery strain, and wild population, respectively. The allele frequencies of 407,861 SNPs differed significantly between the domestic and wild populations. With these SNPs, 23 genomic regions with putative selective sweeps were identified that included 11 genes. Although the function for the majority of the genes remain unknown in catfish, several genes with known function related to aquaculture performance traits were included in the regions with selective sweeps. These included hypoxia-inducible factor 1β· HIFιβ ¨ and the transporter gene ATP-binding cassette sub-family B member 5 (ABCB5). HIF1β· is important for response to hypoxia and tolerance to low oxygen levels is a critical aquaculture trait. The large numbers of SNPs identified from this study are valuable for the development of high-density SNP arrays for genetic and genomic studies of performance traits in catfish. 相似文献
9.
Sabine Lutz-Wahl Peter Fischer Claudia Schmidt-Dannert Wolfgang Wohlleben Bernhard Hauer Rolf D. Schmid 《Applied microbiology》1998,64(10):3878-3881
A total of 215 Streptomyces strains were screened for their capacity to regio- and stereoselectively hydroxylate β- and/or α-ionone to the respective 3-hydroxy derivatives. With β-ionone as the substrate, 15 strains showed little conversion to 4-hydroxy- and none showed conversion to the 3-hydroxy product as desired. Among these 15 Streptomyces strains, S. fradiae Tü 27, S. arenae Tü 495, S. griseus ATCC 13273, S. violaceoniger Tü 38, and S. antibioticus Tü 4 and Tü 46 converted α-ionone to 3-hydroxy-α-ionone with significantly higher hydroxylation activity compared to that of β-ionone. Hydroxylation of racemic α-ionone [(6R)-(−)/(6S)-(+)] resulted in the exclusive formation of only the two enantiomers (3R,6R)- and (3S,6S)-hydroxy-α-ionone. Thus, the enzymatic hydroxylation of α-ionone by the Streptomyces strains tested proceeds with both high regio- and stereoselectivity. 相似文献
10.
Background
β2-adrenoceptor agonists elicit bronchodilator responses by binding to β2-adrenoceptors on airway smooth muscle (ASM). In vivo, the time between drug administration and clinically relevant bronchodilation varies significantly depending on the agonist used. Our aim was to utilise a fluorescent cyclic AMP reporter probe to study the temporal profile of β2-adrenoceptor-mediated signaling induced by isoproterenol and a range of clinically relevant agonists in human primary ASM (hASM) cells by using a modified Epac protein fused to CFP and a variant of YFP.Methods
Cells were imaged in real time using a spinning disk confocal system which allowed rapid and direct quantification of emission ratio imaging following direct addition of β2-adrenoceptor agonists (isoproterenol, salbutamol, salmeterol, indacaterol and formoterol) into the extracellular buffer. For pharmacological comparison a radiolabeling assay for whole cell cyclic AMP formation was used.Results
Temporal analysis revealed that in hASM cells the β2-adrenoceptor agonists studied did not vary significantly in the onset of initiation. However, once a response was initiated, significant differences were observed in the rate of this response with indacaterol and isoproterenol inducing a significantly faster response than salmeterol. Contrary to expectation, reducing the concentration of isoproterenol resulted in a significantly faster initiation of response.Conclusions
We conclude that confocal imaging of the Epac-based probe is a powerful tool to explore β2-adrenoceptor signaling in primary cells. The ability to analyse the kinetics of clinically used β2-adrenoceptor agonists in real time and at a single cell level gives an insight into their possible kinetics once they have reached ASM cells in vivo. 相似文献11.
Tadasuke Komori Minoru Tanaka Emiko Senba Atsushi Miyajima Yoshihiro Morikawa 《The Journal of biological chemistry》2014,289(20):13821-13837
Oncostatin M (OSM) belongs to the IL-6 family of cytokines and has diverse biological effects, including the modulation of inflammatory responses. In the present study we analyzed the roles of OSM signaling in obesity and related metabolic disorders. Under a high-fat diet condition, OSM receptor β subunit-deficient (OSMRβ−/−) mice exhibited increases in body weight and food intake compared with those observed in WT mice. In addition, adipose tissue inflammation, insulin resistance, and hepatic steatosis were more severe in OSMRβ−/− mice than in wild-type (WT) mice. These metabolic phenotypes did not improve when OSMRβ−/− mice were pair-fed with WT mice, suggesting that the effects of OSM signaling on these phenotypes are independent of the increases in the body weight and food intake. In the liver of OSMRβ−/− mice, the insulin-induced phosphorylation of p70 S6 kinase remained intact, whereas insulin-induced FOXO1 phosphorylation was impaired. In addition, OSMRβ−/− mice displayed a higher expression of genes related to de novo lipogenesis in the liver than WT mice. Furthermore, treatment of genetically obese ob/ob mice with OSM improved insulin resistance, adipose tissue inflammation, and hepatic steatosis. Intraportal administration of OSM into ob/ob mice activated STAT3 and increased the expression of long-chain acyl-CoA synthetase (ACSL) 3 and ACSL5 with decreased expression of fatty acid synthase in the liver, suggesting that OSM directly induces lipolysis and suppresses lipogenesis in the liver of obese mice. These findings suggest that defects in OSM signaling promote the deterioration of high-fat diet-induced obesity and related metabolic disorders. 相似文献
12.
In eukaryotes, proteins enter the secretory pathway through the translocon pore of the endoplasmic reticulum. This protein translocation channel is composed of three major subunits, called Sec61α, β and γ in mammals. Unlike the other subunits, the β subunit is dispensable for translocation and cell viability in all organisms studied. Intriguingly, the knockout of the Sec61β encoding genes results in different phenotypes in different species. Nevertheless, the β subunit shows a high level of sequence homology across species, suggesting the conservation of a biological function that remains ill-defined. To address its cellular roles, we characterized the homolog of Sec61β in the fission yeast Schizosaccharomyces pombe (Sbh1p). Here, we show that the knockout of sbh1
+ results in severe cold sensitivity, increased sensitivity to cell-wall stress, and reduced protein secretion at 23°C. Sec61β homologs from Saccharomyces cerevisiae and human complement the knockout of sbh1
+ in S. pombe. As in S. cerevisiae, the transmembrane domain (TMD) of S. pombe Sec61β is sufficient to complement the phenotypes resulting from the knockout of the entire encoding gene. Remarkably, the TMD of Sec61β from S. cerevisiae and human also complement the gene knockouts in both yeasts. Together, these observations indicate that the TMD of Sec61β exerts a cellular function that is conserved across species. 相似文献
13.
Bradford E. Hall Umesh D. Wankhade Joanne E. Konkel Karthik Cherukuri Chandrasekharam N. Nagineni Kathleen C. Flanders Praveen R. Arany Wanjun Chen Sushil G. Rane Ashok B. Kulkarni 《The Journal of biological chemistry》2013,288(44):32074-32092
Three homologues of TGF-β exist in mammals as follows: TGF-β1, TGF-β2, and TGF-β3. All three proteins share high homology in their amino acid sequence, yet each TGF-β isoform has unique heterologous motifs that are highly conserved during evolution. Although these TGF-β proteins share similar properties in vitro, isoform-specific properties have been suggested through in vivo studies and by the unique phenotypes for each TGF-β knock-out mouse. To test our hypothesis that each of these homologues has nonredundant functions, and to identify such isoform-specific roles, we genetically exchanged the coding sequence of the mature TGF-β1 ligand with a sequence from TGF-β3 using targeted recombination to create chimeric TGF-β1/3 knock-in mice (TGF-β1Lβ3/Lβ3). In the TGF-β1Lβ3/Lβ3 mouse, localization and activation still occur through the TGF-β1 latent associated peptide, but cell signaling is triggered through the TGF-β3 ligand that binds to TGF-β receptors. Unlike TGF-β1−/− mice, the TGF-β1Lβ3/Lβ3 mice show neither embryonic lethality nor signs of multifocal inflammation, demonstrating that knock-in of the TGF-β3 ligand can prevent the vasculogenesis defects and autoimmunity associated with TGF-β1 deficiency. However, the TGF-β1Lβ3/Lβ3 mice have a shortened life span and display tooth and bone defects, indicating that the TGF-β homologues are not completely interchangeable. Remarkably, the TGF-β1Lβ3/Lβ3 mice display an improved metabolic phenotype with reduced body weight gain and enhanced glucose tolerance by induction of beneficial changes to the white adipose tissue compartment. These findings reveal both redundant and unique nonoverlapping functional diversity in TGF-β isoform signaling that has relevance to the design of therapeutics aimed at targeting the TGF-β pathway in human disease. 相似文献
14.
Ian Catchpole Volker Germaschewski Jaimie Hoh Kam Peter Lundh von Leithner Susannah Ford Gerald Gough Peter Adamson Philip Overend Jan Hilpert Francisco J. López Yin Shan Eric Ng Pete Coffey Glen Jeffery 《PloS one》2013,8(6)
Age-related macular degeneration (AMD) is a leading cause of legal blindness in the Western world. There are effective treatments for the vascular complications of neo-vascular AMD, but no effective therapies are available for the dry/atrophic form of the disease. A previously described transgenic CFH-gene deficient mouse model, (cfh−/−), shows hallmarks of early AMD. The ocular phenotype has been further analysed to demonstrate amyloid beta (Aβ) rich basement membrane deposits associated with activated complement C3. Cfh−/− mice were treated systemically in both prophylactic and therapeutic regimes with an anti-Aβ monoclonal antibody (mAb), 6F6, to determine the effect on the cfh−/− retinal phenotype. Prophylactic treatment with 6F6 demonstrated a dose dependent reduction in the accumulation of both Aβ and activated C3 deposition. A similar reduction in the retinal endpoints could be seen after therapeutic treatment. Serum Aβ levels after systemic administration of 6F6 show accumulation of Aβ in the periphery suggestive of a peripheral sink mechanism. In summary, anti-Aβ mAb treatment can partially prevent or reverse ocular phenotypes of the cfh−/− mouse. The data support this therapeutic approach in humans potentially modulating two key elements in the pathogenesis of AMD – Aβ and activated, complement C3. 相似文献
15.
Dependence on Mating Type for the Overproduction of Iso-2-Cytochrome c in the Yeast Mutant CYC7–H2 总被引:10,自引:0,他引:10
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The CYC7–H2 mutation causes an approximately 20-fold overproduction of iso–2–cytochromo c in a and α haploid strains of the yeast Saccharomyces cerevisiae due to an alteration in the nontranslated regulatory region that is presumably contiguous with the structural region. In this investigation, we demonstrated that heterozygosity at the mating type locus, a/α or a/a/α/α, prevents expression of the overproduction, while homozygosity, a/a and α/α, and hemizygosity, a/0 and α/0, allow full expression of the CYC7–H2 mutation, equivalent to the expression observed in a and α haploid strains. There is no decrease in the overproduction of iso-2-cytochrome c in a/α diploid strains containing either of the other two similar mutations, CYC7–H1 and CYC7–H3. It appears as if active expression of one or another of the mating-type alleles is required for the overproduction of iso-2-cytochrome c in CYC7–H2 mutants. 相似文献
16.
Il Kwon Sung-Yu Hong Young Dae Kim Hyo Suk Nam Sungsoo Kang Seung-Hee Yang Ji Hoe Heo 《PloS one》2013,8(11)
Saxatilin, a novel disintegrin purified and cloned from the venom of the Korean snake Gloydius saxatilis, strongly inhibits activation and aggregation of platelets. Glycoprotein (GP) IIb/IIIa receptor antagonists can resolve thrombus, so saxatilin might also have thrombolytic effects. We investigated the thrombolytic effects of saxatilin in mice using a ferric chloride-induced carotid arterial thrombosis model. Thrombotic occlusion and thrombus resolution were evaluated quantitatively by measuring blood flow in the carotid artery with an ultrasonic flow meter and calculating the degree of flow restoration on a minute-by-minute basis; results were confirmed by histological examination. Saxatilin dissolved thrombi in a dose-dependent manner. Saxatilin at 5 mg/kg restored blood flow to baseline levels. As saxatilin dose increased, time to recanalization decreased. A bolus injection of 10% of a complete dose with continuous infusion of the remaining dose for 60 minutes resulted in effective recanalization without reocclusion. The thrombolytic effect of saxatilin was also demonstrated in vitro using platelet aggregometry by administering saxatilin in preformed thrombi. Bleeding complications were observed in 2 of 71 mice that received saxatilin. Fibrin/fibrinogen zymography and platelet aggregometry studies indicated that saxatilin does not have fibrinolytic activity, but exerted its action on platelets. Integrin-binding assays showed that saxatilin inhibited multiple integrins, specifically α2bβ3 (GP IIb/IIIa), α5β1, αvβ3, αvβ1, and αvβ5, which act on platelet adhesion/aggregation. Saxatilin inhibited multiple integrins by acting on platelets, and was safe and effective in resolving thrombi in mice. 相似文献
17.
Background and Aims
Plant competition studies are restricted by the difficulty of quantifying root systems of competitors. Analyses are usually limited to above-ground traits. Here, a new approach to address this issue is reported.Methods
Root system weights of competing plants can be estimated from: shoot weights of competitors; combined root weights of competitors; and slopes (scaling exponents, α) and intercepts (allometric coefficients, β) of ln-regressions of root weight on shoot weight of isolated plants. If competition induces no change in root : shoot growth, α and β values of competing and isolated plants will be equal. Measured combined root weight of competitors will equal that estimated allometrically from measured shoot weights of each competing plant. Combined root weights can be partitioned directly among competitors. If, as will be more usual, competition changes relative root and shoot growth, the competitors'' combined root weight will not equal that estimated allometrically and cannot be partitioned directly. However, if the isolated-plant α and β values are adjusted until the estimated combined root weight of competitors matches the measured combined root weight, the latter can be partitioned among competitors using their new α and β values. The approach is illustrated using two herbaceous species, Dactylis glomerata and Plantago lanceolata.Key Results
Allometric modelling revealed a large and continuous increase in the root : shoot ratio by Dactylis, but not Plantago, during competition. This was associated with a superior whole-plant dry weight increase in Dactylis, which was ultimately 2·5-fold greater than that of Plantago. Whole-plant growth dominance of Dactylis over Plantago, as deduced from allometric modelling, occurred 14–24 d earlier than suggested by shoot data alone.Conclusion
Given reasonable assumptions, allometric modelling can analyse competitive interactions in any species mixture, and overcomes a long-standing problem in studies of competition. 相似文献18.
William Pitchers Jason B. Wolf Tom Tregenza John Hunt Ian Dworkin 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2014,369(1649)
A fundamental question in evolutionary biology is the relative importance of selection and genetic architecture in determining evolutionary rates. Adaptive evolution can be described by the multivariate breeders'' equation (), which predicts evolutionary change for a suite of phenotypic traits () as a product of directional selection acting on them (β) and the genetic variance–covariance matrix for those traits (G). Despite being empirically challenging to estimate, there are enough published estimates of G and β to allow for synthesis of general patterns across species. We use published estimates to test the hypotheses that there are systematic differences in the rate of evolution among trait types, and that these differences are, in part, due to genetic architecture. We find some evidence that sexually selected traits exhibit faster rates of evolution compared with life-history or morphological traits. This difference does not appear to be related to stronger selection on sexually selected traits. Using numerous proposed approaches to quantifying the shape, size and structure of G, we examine how these parameters relate to one another, and how they vary among taxonomic and trait groupings. Despite considerable variation, they do not explain the observed differences in evolutionary rates. 相似文献
19.
Genetic and genomic analysis of a fat mass trait with complex inheritance reveals marked sex specificity
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The integration of expression profiling with linkage analysis has increasingly been used to identify genes underlying complex phenotypes. The effects of gender on the regulation of many physiological traits are well documented; however, “genetical genomic” analyses have not yet addressed the degree to which their conclusions are affected by sex. We constructed and densely genotyped a large F2 intercross derived from the inbred mouse strains C57BL/6J and C3H/HeJ on an apolipoprotein E null (ApoE−/−) background. This BXH.ApoE−/− population recapitulates several “metabolic syndrome” phenotypes. The cross consists of 334 animals of both sexes, allowing us to specifically test for the dependence of linkage on sex. We detected several thousand liver gene expression quantitative trait loci, a significant proportion of which are sex-biased. We used these analyses to dissect the genetics of gonadal fat mass, a complex trait with sex-specific regulation. We present evidence for a remarkably high degree of sex-dependence on both the cis and trans regulation of gene expression. We demonstrate how these analyses can be applied to the study of the genetics underlying gonadal fat mass, a complex trait showing significantly female-biased heritability. These data have implications on the potential effects of sex on the genetic regulation of other complex traits. 相似文献
20.
Bile Salt 3α- and 12α-Hydroxysteroid Dehydrogenases from Eubacterium lentum and Related Organisms
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Ian A. Macdonald Joanne F. Jellett David E. Mahony Lillian V. Holdeman 《Applied microbiology》1979,37(5):992-1000
Thirty-two strains of Eubacterium lentum and phenotypically similar anaerobic gram-positive bacilli were screened for intracellular bile salt 3α- and 12α-hydroxysteroid dehydrogenase (HSDHase) activities. These organisms were categorized into four groups: (A) those containing 12α-HSDHase only (10 strains), (B) those containing 3α- and 12α-HSDHase (13 strains), (C) those containing 3α-HSDHase only (2 strains), and (D) those devoid of any measurable HSDHase activity (7 strains). Of the respective four groups, 9/10, 13/13, 0/2, and 0/7 were like the neotype strain of E. lentum (ATCC 25559) in that they produced H2S in a triple sugar iron agar butt, reduced nitrate to nitrite, and weakly decomposed hydrogen peroxide. The other strains were variable for nitrate reduction and activity on hydrogen peroxide, but all the organisms in the first three categories (with one exception) were H2S producers (triple sugar iron agar butt) and all (with one exception) were designated E. lentum, whereas the organisms of category B were non-H2S producers (triple sugar iron agar butt). Five of these seven were not stimulated by arginine and are designated “phenotypically similar organisms.” Thin-layer chromatography of extracted spent bacterial medium of four representative strains from each group grown in the presence of cholate revealed the presence of (A) 12-oxo product, (B) 12-oxo and 3-oxo products, (C) 3-oxo product, and (D) the absence of any of these products. The 12α-HSDHase of category B organisms was unstable unless 10−3 M dithioerythritol was added to the buffer. With the exception of 3 out of 32 strains, there was a positive correlation between the production of measurable amounts of 12α-HSDHase and H2S production. Growth curves and the effect of arginine on growth and the production of 3α- and 12α-HSDHase were examined in representative strains of categories A, B, and C. Both enzymes were shown to bind onto a nicotinamide adenine dinucleotide-Sepharose column and could be eluted by high-ionic-strength buffer, resulting in approximately 25-fold and 18-fold purification, respectively. Molecular weight estimations by Sephadex G-200 gave values of 205,000 and 125,000 for the 3α- and 12α-HSDHase, respectively. Purified 12α-HSDHase was investigated with respect to pH requirement, substrate specificity, and enzyme kinetics. 相似文献