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71.
Meijers R Adolph HW Dauter Z Wilson KS Lamzin VS Cedergren-Zeppezauer ES 《Biochemistry》2007,46(18):5446-5454
The use of substrate analogues as inhibitors provides a way to understand and manipulate enzyme function. Here we report two 1 A resolution crystal structures of liver alcohol dehydrogenase in complex with NADH and two inhibitors: dimethyl sulfoxide and isobutyramide. Both structures present a dynamic state of inhibition. In the dimethyl sulfoxide complex structure, the inhibitor is caught in transition on its way to the active site using a flash-freezing protocol and a cadmium-substituted enzyme. One inhibitor molecule is partly located in the first and partly in the second coordination sphere of the active site metal. A hydroxide ion bound to the active site metal lies close to the pyridine ring of NADH, which is puckered in a twisted boat conformation. The cadmium ion is coordinated by both the hydroxide ion and the inhibitor molecule, providing structural evidence of a coordination switch at the active site metal ion. The structure of the isobutyramide complex reveals the partial formation of an adduct between the isobutyramide inhibitor and NADH. It provides evidence of the contribution of a shift from the keto to the enol tautomer during aldehyde reduction. The different positions of the inhibitors further refine the knowledge of the dynamics of the enzyme mechanism and explain how the crowded active site can facilitate the presence of a substrate and a metal-bound hydroxide ion. 相似文献
72.
Hernández Pérez A E Cerna Chávez JC Delgado Ortiz M Beltrán Beache LM Tapia Vargas YM Ochoa Fuentes 《Phyton》2019,88(1):11-13
Mexico is the main producer, consumer and exporter
of avocado in the world, being Michoacan the main producer state
contributing more than 80% of the national production. There
are phytopathogens that decimate the production causing the
death of the tree. Root samples were collected in avocado trees
that showed the characteristic symptomatology of the disease
known as avocado sadness, the sampling was carried out in four
of the main avocado producing towns, in the state of Michoacan,
Mexico. The isolation consisted in sowing root tissue in Petri
dishes with V8®-PARPH culture medium, subsequently they were
identified morphologically and for species level it was determined
by molecular biology, with the PCR-ITS technique. Pathogenicity
tests were performed in triplicate with avocado seedlings with more
than six leaves. After 24 hours, the inoculated plants expressed
decay in the apical part, after 120 hours the leaves showed yellowing
and after 15 days there was a generalized wilt on the stem and
leaves, re-isolating the phytopathogen Phytopythium vexans.
This study confirms the first report of the oomycete P. vexans
affecting avocado trees in the most important producing region of
the Mexican Republic. 相似文献
73.
Christof J Majoor Marianne A van de Pol Pieter Willem Kamphuisen Joost CM Meijers Richard Molenkamp Katja C Wolthers Tom van der Poll Rienk Nieuwland Sebastian L Johnston Peter J Sterk Elisabeth HD Bel Rene Lutter Koenraad F van der Sluijs 《Respiratory research》2014,15(1):14
Background
Asthma exacerbations are frequently triggered by rhinovirus infections. Both asthma and respiratory tract infection can activate haemostasis. Therefore we hypothesized that experimental rhinovirus-16 infection and asthmatic airway inflammation act in synergy on the haemostatic balance.Methods
28 patients (14 patients with mild allergic asthma and 14 healthy non-allergic controls) were infected with low-dose rhinovirus type 16. Venous plasma and bronchoalveolar lavage fluid (BAL fluid) were obtained before and 6 days after infection to evaluate markers of coagulation activation, thrombin-antithrombin complexes, von Willebrand factor, plasmin-antiplasmin complexes, plasminogen activator inhibitor type-1, endogenous thrombin potential and tissue factor-exposing microparticles by fibrin generation test, in plasma and/or BAL fluid. Data were analysed by nonparametric tests (Wilcoxon, Mann Whitney and Spearman correlation).Results
13 patients with mild asthma (6 females, 19-29 y) and 11 healthy controls (10 females, 19-31 y) had a documented Rhinovirus-16 infection. Rhinovirus-16 challenge resulted in a shortening of the fibrin generation test in BAL fluid of asthma patients (t = -1: 706 s vs. t = 6: 498 s; p = 0.02), but not of controls (t = -1: 693 s vs. t = 6: 636 s; p = 0.65). The fold change in tissue factor-exposing microparticles in BAL fluid inversely correlated with the fold changes in eosinophil cationic protein and myeloperoxidase in BAL fluid after virus infection (r = -0.517 and -0.528 resp., both p = 0.01).Rhinovirus-16 challenge led to increased plasminogen activator inhibitor type-1 levels in plasma in patients with asthma (26.0 ng/mL vs. 11.5 ng/mL in healthy controls, p = 0.04). Rhinovirus-16 load in BAL showed a linear correlation with the fold change in endogenous thrombin potential, plasmin-antiplasmin complexes and plasminogen activator inhibitor type-1.Conclusions
Experimental rhinovirus infection induces procoagulant changes in the airways of patients with asthma through increased activity of tissue factor-exposing microparticles. These microparticle-associated procoagulant changes are associated with both neutrophilic and eosinophilic inflammation. Systemic activation of haemostasis increases with Rhinoviral load.Trial registration
This trial was registered at the Dutch trial registry (http://www.trialregister.nl): NTR1677. 相似文献74.
Regulation of cellular adhesion molecule expression in murine oocytes, peri-implant ation and post-implantation embryos 总被引:2,自引:0,他引:2
DAVID P LU LINA TIAN CHRIS O'''' NEILL NICHOLAS JC KING Department of Pathology University of Sydney NSW AustraliaHuman Reproduction Unit Department of Physiology University of Sydney Royal North Shore Hospital NSW Australia 《Cell research》2002,(Z2)
Expression of the adhesion molecules, ICAM-1, VCAM-1, NCAM, CD44, CD49d (VLA-4, a chain), and CDlla (LFA-1, a chain) on mouse oocytes, and pre- and peri-implantation stage embryos was examined by quantitative indirect immunofluorescence microscopy. ICAM-1 was most strongly expressed at the oocyte stage, gradually declining almost to undetectable levels by the expanded blastocyst stage. NCAM, also expressed maximally on the oocyte, declined to undetectable levels beyond the morula stage. On the other hand, CD44 declined from highest expression at the oocyte stage to show a second maximum at the compacted 8-cell/morula. This molecule exhibited high expression around contact areas between trophecto-derm and zona pellucida during blastocyst hatching. CD49d was highly expressed in the oocyte, remained significantly expressed throughout and after blastocyst hatching was expressed on the polar trophecto-derm. Like CD44, CD49d declined to undetectable levels at the blastocyst outgrowth stage. Expression of both 相似文献
75.
76.
Paul REL Lafond T Müller-Graf CDM Nithiuthai S Brey PT Koella JC 《BMC evolutionary biology》2004,4(1):1-13
Background
Theoretical studies suggest that direct and indirect selection have the potential to cause substantial evolutionary change in female mate choice. Similarly, sexual selection is considered a strong force in the evolution of male attractiveness and the exaggeration of secondary sexual traits. Few studies have, however, directly tested how female mate choice and male attractiveness respond to selection. Here we report the results of a selection experiment in which we selected directly on female mating preference for attractive males and, independently, on male attractiveness in the guppy, Poecilia reticulata. We measured the direct and correlated responses of female mate choice and male attractiveness to selection and the correlated responses of male ornamental traits, female fecundity and adult male and female survival.Results
Surprisingly, neither female mate choice nor male attractiveness responded significantly to direct or to indirect selection. Fecundity did differ significantly among lines in a way that suggests a possible sexually-antagonistic cost to male attractiveness.Conclusions
The opportunity for evolutionary change in female mate choice and male attractiveness may be much smaller than predicted by current theory, and may thus have important consequences for how we understand the evolution of female mate choice and male attractiveness. We discuss a number of factors that may have constrained the response of female choice and male attractiveness to selection, including low heritabilities, low levels of genetic (co)variation in the multivariate direction of selection, sexually-antagonistic constraint on sexual selection and the "environmental covariance hypothesis".77.
Marx PF Havik SR Marquart JA Bouma BN Meijers JC 《The Journal of biological chemistry》2004,279(8):6620-6628
Activated thrombin-activable fibrinolysis inhibitor (TAFIa) is a carboxypeptidase B that can down-regulate fibrinolysis. TAFIa is a labile enzyme that can be inactivated by conformational instability or proteolysis. TAFI is approximately 40% identical to pancreatic carboxypeptidase B (CPB). In contrast to TAFIa, pancreatic CPB is a stable protease. We hypothesized that regions or residues that are not conserved in TAFIa compared with pancreatic CPB play a role in the conformational instability of TAFIa and that replacement of these non-conserved residues with residues of pancreatic CPB would lead to a TAFIa molecule with an increased stability. Therefore, we have expressed, purified, and characterized two TAFI-CPB chimeras: TAFI-CPB-(293-333) and TAFI-CPB-(293-401). TAFI-CPB-(293-333) could be activated by thrombin-thrombomodulin, but not as efficiently as wild-type TAFI. After activation, this mutant was unstable and was hardly able to prolong clot lysis of TAFI-deficient plasma. Binding of TAFI-CPB-(293-333) to both plasminogen and fibrinogen was normal compared with wild-type TAFI. TAFI-CPB-(293-401) could be activated by thrombin-thrombomodulin, although at a lower rate compared with wild-type TAFI. The activated mutant displayed a markedly prolonged half-life of 1.5 h. Plasmin could both activate and inactivate this chimera. Interestingly, this chimera did not bind to plasminogen or fibrinogen. TAFI-CPB-(293-401) could prolong the clot lysis time in TAFI-deficient plasma, although not as efficiently as wild-type TAFI. In conclusion, by replacing a region in TAFI with the corresponding region in pancreatic CPB, we were able to generate a TAFIa form with a highly stable activity. 相似文献
78.
79.
Y Deng J Zhao D Sakurai KM Kaufman JC Edberg RP Kimberly DL Kamen GS Gilkeson CO Jacob RH Scofield CD Langefeld JA Kelly ME Alarcón-Riquelme BIOLUPUS GENLES Networks JB Harley TJ Vyse BI Freedman PM Gaffney KM Sivils JA James TB Niewold RM Cantor W Chen BH Hahn EE Brown PROFILE BP Tsao 《Arthritis research & therapy》2012,14(Z3):A5
80.
In spite of the increasing application of DNA fingerprinting to natural
populations and to the genetic identification of humans, explicit methods
for estimation of basic population genetic parameters from DNA
fingerprinting data have not been developed. Contributing to this omission
is the inability to determine, for multilocus fingerprinting probes,
relatively important genetic information, such as the number of loci, the
number of alleles, and the distribution of these alleles into specific
loci. One of the most useful genetic parameters that could be derived from
such data would be the average heterozygosity, which has traditionally been
employed to measure the level of genetic variation within populations and
to compare genetic variation among different loci. We derive here explicit
formulas for both the estimation of average heterozygosity at multiple
hypervariable loci and a maximum value for this estimate. These estimates
are based upon the DNA restriction-pattern matrices that are typical for
fingerprinting studies of humans and natural populations. For several
empirical data sets from our laboratory, estimates of average and maximal
heterozygosity are shown to be relatively close to each other. Furthermore,
variances of these statistics based on simulation studies are relatively
small. These observations, as well as consideration of the effect of
missing alleles and alternate numbers of loci, suggest that the average
heterozygosity can be accurately estimated using phenotypic DNA fingerprint
patterns, because this parameter is relatively insensitive to the lack of
certain genetic information.
相似文献