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41.
Lennart Hilbert Genevieve Bates Horia N. Roman Jenna L. Blumenthal Nedjma B. Zitouni Apolinary Sobieszek Michael C. Mackey Anne-Marie Lauzon 《PLoS computational biology》2013,9(10)
The proteins involved in smooth muscle''s molecular contractile mechanism – the anti-parallel motion of actin and myosin filaments driven by myosin heads interacting with actin – are found as different isoforms. While their expression levels are altered in disease states, their relevance to the mechanical interaction of myosin with actin is not sufficiently understood. Here, we analyzed in vitro actin filament propulsion by smooth muscle myosin for -actin (A), -actin-tropomyosin- (A-Tm), -actin-tropomyosin- (A-Tm), -actin (A), -actin-tropomyosin- (A-Tm), and -actin-tropomoysin- (A-Tm). Actin sliding analysis with our specifically developed video analysis software followed by statistical assessment (Bootstrapped Principal Component Analysis) indicated that the in vitro motility of A, A, and A-Tm is not distinguishable. Compared to these three ‘baseline conditions’, statistically significant differences () were: A-Tm – actin sliding velocity increased 1.12-fold, A-Tm – motile fraction decreased to 0.96-fold, stop time elevated 1.6-fold, A-Tm – run time elevated 1.7-fold. We constructed a mathematical model, simulated actin sliding data, and adjusted the kinetic parameters so as to mimic the experimentally observed differences: A-Tm – myosin binding to actin, the main, and the secondary myosin power stroke are accelerated, A-Tm – mechanical coupling between myosins is stronger, A-Tm – the secondary power stroke is decelerated and mechanical coupling between myosins is weaker. In summary, our results explain the different regulatory effects that specific combinations of actin and smooth muscle tropomyosin have on smooth muscle actin-myosin interaction kinetics. 相似文献
42.
Haploinsufficiency of SF3B4, a component of the pre-mRNA spliceosomal complex, causes Nager syndrome
Bernier FP Caluseriu O Ng S Schwartzentruber J Buckingham KJ Innes AM Jabs EW Innis JW Schuette JL Gorski JL Byers PH Andelfinger G Siu V Lauzon J Fernandez BA McMillin M Scott RH Racher H;FORGE Canada Consortium Majewski J Nickerson DA Shendure J Bamshad MJ Parboosingh JS 《American journal of human genetics》2012,90(5):925-933
Nager syndrome, first described more than 60 years ago, is the archetype of a class of disorders called the acrofacial dysostoses, which are characterized by craniofacial and limb malformations. Despite intensive efforts, no gene for Nager syndrome has yet been identified. In an international collaboration, FORGE Canada and the National Institutes of Health Centers for Mendelian Genomics used exome sequencing as a discovery tool and found that mutations in SF3B4, a component of the U2 pre-mRNA spliceosomal complex, cause Nager syndrome. After Sanger sequencing of SF3B4 in a validation cohort, 20 of 35 (57%) families affected by Nager syndrome had 1 of 18 different mutations, nearly all of which were frameshifts. These results suggest that most cases of Nager syndrome are caused by haploinsufficiency of SF3B4. Our findings add Nager syndrome to a growing list of disorders caused by mutations in genes that encode major components of the spliceosome and also highlight the synergistic potential of international collaboration when exome sequencing is applied in the search for genes responsible for rare Mendelian phenotypes. 相似文献
43.
Mossman KL Mian MF Lauzon NM Gyles CL Lichty B Mackenzie R Gill N Ashkar AA 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(10):6702-6706
Several TLR ligands of bacterial origin induce innate immune responses. Although FimH, the adhesin portion of type 1 fimbria, plays an important role in the pathogenicity of some gram-negative bacteria, its ability to stimulate the innate immune system via TLR signaling remains unclear. In this study we report that FimH induces potent innate responses in a MyD88-dependent fashion. The FimH-induced innate activity was restricted to cells expressing TLR4. In addition, FimH was able to bind directly to TLR4. More importantly, cells unresponsive to LPS were responsive to FimH and the presence or absence of MD-2 and CD14 had no effect on FimH activity. Our data suggest that TLR4 is a functional receptor for the adhesin portion of bacterial type 1 fimbria. 相似文献
44.
棉铃虫单核衣壳核多角体病毒组织蛋白酶基因的序列分析和进化研究 总被引:3,自引:0,他引:3
对棉铃虫单核衣壳核多角体病毒(HaSNPV)的组织蛋白酶(v-cath)基因进行了序列分析,此基因编码区长1098bp,预防编码一个366个氨基酸的蛋白产物,序列分析表明,HaSNPV的V-CATH蛋白与共它杆状病毒的同源蛋白具有相似的保守结构并保留有相同的酶活性位点,根据已知的杆状病毒组织蛋白酶序列构建了v-cath基因的进化树,发现HaSNPV的v-cath位于NPV组中一个单独的分枝,结合v-cath基因在棉铃虫病毒基因组中的位置与其它NPV有较大不同,推测HaSNPV的v-cath基因可能拥有特殊的进化历程。 相似文献
45.
The purpose of our study was to compare on a seasonal basis the emergence, the drift and the benthos on a short and uniform section (18.5 m)of a stream in the Laurentian Hills of Québec. Nineteen species occurred on this stretch, but only six were abundant: Leptophlebia cupida (Say), Habrophlebia vibrans Needham, Baetis pygmaeus (Hagen), Eurylophella verisimilis (McDunnough), Stenonema modestum (Banks), and Stenonema vicarium (Walker). Emergence was monitored for 5 years; densities differed from one trap to the next, as did species dominance, but total densities were similar. These data conform to Illies' rules of constancy and harmony. Nymphal densities were high (mean of 16000 m−2 ). The dominant species were univoltine, except H. vibrans (semivoltine), and B. pygmaeus (polyvoltine). Larger species contributed relatively more to the production of the reach despite their low densities than did the more abundant smaller species, especially those with long life cycles. Drift was low during most of the year, except during spring and species composition varied considerably. A comparison of the three data sets (emergence, drift and benthos) shows a general agreement for the less abundant species, but for three of the dominants, H. vibrans, L. cupida and E. verisimilis , movements of individuals to and from the reach at various times in the life cycle (adult flight, nymphal drift and migration) must be taken into account in order to correlate the data. None of the methods alone gives a satisfactory picture of the community structure, each is to some extent misleading and needs to be used in conjunction with the others; the conflicting results obtained from the data sets often reveal interesting life history traits which otherwise would not have been detected. 相似文献
46.
Expression of a Conserved Family of Cytoplasmic Low Molecular Weight Heat Shock Proteins during Heat Stress and Recovery 总被引:2,自引:1,他引:2
Plants synthesize several families of low molecular weight (LMW) heat shock proteins (HSPs) in response to elevated temperatures. We have characterized two cDNAs, HSP18.1 and HSP17.9, that encode members of the class I family of LMW HSPs from pea (Pisum sativum). In addition, we investigated the expression of these HSPs at the mRNA and protein levels during heat stress and recovery. HSP18.1 and HSP17.9 are 82.1% identical at the amino acid level and are 80.8 to 92.9% identical to class I LMW HSPs of other angiosperms. Heat stress experiments were performed using intact seedlings subjected to a gradual temperature increase and held at a maximum temperature of 30 to 42 degrees Celsius for 4 hours. HSP18.1 and HSP17.9 mRNA levels peaked at the beginning of the maximum temperature period and declined rapidly after the stress period. Antiserum against a HSP18.1 fusion protein recognized both HSP18.1 and HSP17.9 but not members of other families of LMW HSPs. The accumulation of HSP18.1-immunodetected protein was proportional to the severity of the heat stress, and the protein had a half-life of 37.7 ± 8 hours. The long half-life of these proteins supports the hypothesis that they are involved in establishing thermotolerance. 相似文献
47.
Coiled-coil unwinding at the smooth muscle myosin head-rod junction is required for optimal mechanical performance 下载免费PDF全文
Myosin II has two heads that are joined together by an alpha-helical coiled-coil rod, which can separate in the region adjacent to the head-rod junction (Trybus, K. M. 1994. J. Biol. Chem. 269:20819-20822). To test whether this flexibility at the head-rod junction is important for the mechanical performance of myosin, we used the optical trap to measure the unitary displacements of heavy meromyosin constructs in which a stable coiled-coil sequence derived from the leucine zipper was introduced into the myosin rod. The zipper was positioned either immediately after the heads (0-hep zip) or following 15 heptads of native sequence (15-hep zip). The unitary displacement (d) decreased from d = 9.7 +/- 0.6 nm for wild-type heavy meromyosin (WT HMM) to d = 0.1 +/- 0.3 nm for the 0-hep zip construct (mean +/- SE). Native values were restored in the 15-hep zip construct (d = 7.5 +/- 0.7 nm). We conclude that flexibility at the myosin head-rod junction, which is provided by an unstable coiled-coil region, is essential for optimal mechanical performance. 相似文献
48.
Horia Nicolae Roman Nedjma B. Zitouni Linda Kachmar Andrea Benedetti Apolinary Sobieszek Anne-Marie Lauzon 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
Studies conducted at the whole muscle level have shown that smooth muscle can maintain tension with low Adenosine triphosphate (ATP) consumption. Whereas it is generally accepted that this property (latch-state) is a consequence of the dephosphorylation of myosin during its attachment to actin, free dephosphorylated myosin can also bind to actin and contribute to force maintenance. We investigated the role of caldesmon (CaD) in regulating the binding force of unphosphorylated tonic smooth muscle myosin to actin.Methods
To measure the effect of CaD on the binding of unphosphorylated myosin to actin (in the presence of ATP), we used a single beam laser trap assay to quantify the average unbinding force (Funb) in the absence or presence of caldesmon, extracellular signal-regulated kinase (ERK)-phosphorylated CaD, or CaD plus tropomyosin.Results
Funb from unregulated actin (0.10 ± 0.01 pN) was significantly increased in the presence of CaD (0.17 ± 0.02 pN), tropomyosin (0.17 ± 0.02 pN) or both regulatory proteins (0.18 ± 0.02 pN). ERK phosphorylation of CaD significantly reduced the Funb (0.06 ± 0.01 pN). Inspection of the traces of the Funb as a function of time suggests that ERK phosphorylation of CaD decreases the binding force of myosin to actin or accelerates its detachment.Conclusions
CaD enhances the binding force of unphosphorylated myosin to actin potentially contributing to the latch-state. ERK phosphorylation of CaD decreases this binding force to very low levels.General significance
This study suggests a mechanism that likely contributes to the latch-state and that explains the muscle relaxation from the latch-state. 相似文献49.
H.L. Lauzon S. Gudmundsdottir A. Steinarsson M. Oddgeirsson S.K. Petursdottir E. Reynisson R. Bjornsdottir B.K. Gudmundsdottir 《Journal of applied microbiology》2010,108(2):624-632
Aims: To assess the effects of bacterial treatment at the earliest stages of cod rearing on the microbial load, larval development and performance, testing three bacterial strains (Carnobacterium divergens V41, Arthrobacter sp. and Enterococcus sp.) in vivo that were previously shown to have inhibitory potential towards fish pathogens in vitro. Methods and Results: A bacterial mixture was added eight times to the rearing water from the prehatch to the mid‐larval stage (a 38‐day period). Microbiological analysis of ova, larvae and rearing water was performed regularly. Larval performance and development were evaluated by survival rate, hypersalinity tolerance and physiological measurements. Different larval survival rates were observed within and between treatments, and possibly explained by variations in larval microflora and established probionts. Larvae from one silo, which had been bathed in the bacterial suspension, showed the highest survival rate (42·1%), lowest Vibrio levels, and were significantly heavier (19·3%) and more stress tolerant than control larvae (P < 0·01). This coincided with the intestinal establishment of two of the tested bacteria. Conclusions: Arthrobacter and Enterococcus strains added regularly to the rearing water from the postfertilized egg stage can become established in larval gastrointestinal tract. The Enterococcus strain was associated with increased larval growth, performance and microflora control, indicating its probiotic nature. Significance and Impact of the Study: Regular application of autochthonous probionts may promote larval welfare, development and stress tolerance at early stages, hence increasing production yield in intensive cod larviculture. 相似文献
50.
S Mondragón-Rodríguez E Trillaud-Doppia A Dudilot C Bourgeois M Lauzon N Leclerc J Boehm 《The Journal of biological chemistry》2012,287(38):32040-32053
Amyloid-β and tau protein are the two most prominent factors in the pathology of Alzheimer disease. Recent studies indicate that phosphorylated tau might affect synaptic function. We now show that endogenous tau is found at postsynaptic sites where it interacts with the PSD95-NMDA receptor complex. NMDA receptor activation leads to a selective phosphorylation of specific sites in tau, regulating the interaction of tau with Fyn and the PSD95-NMDA receptor complex. Based on our results, we propose that the physiologically occurring phosphorylation of tau could serve as a regulatory mechanism to prevent NMDA receptor overexcitation. 相似文献