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81.
Maggio CD Jennings SR Robichaux JL Stapor PC Hyman JM 《Bulletin of mathematical biology》2012,74(1):143-158
We extend and analyze the Wang and Politi modified Hai–Murphy model of smooth muscle cell contractions to capture uterine
muscle cell response to variations in intracellular calcium concentrations. This model is used to estimate values of unknown
parameters in uterine smooth muscle cell cross-bridging. Uterine motility is responsible for carrying out important processes
throughout all phases of the nonpregnant female reproductive cycle, including sperm transport, menstruation, and embryo implantation.
The modified Hai–Murphy partial differential equation model accounts for the displacement of myosin cross-bridge heads relative
to their binding sites. This model was originally developed for the study of airway contractions; we now extended it for use
in modeling nonisometric uterine contractions. Our extended model incorporates cross-bridge position and contractile velocity
into the original model, resulting in more accurate modeling of the initial stages of contraction and modeling nonisometric
contractions. Numerical simulations show that the contraction rate in our extended model is faster than the original Hai–Murphy
model. These simulations provide quantitative estimates for the increased level of responsiveness of our extended model to
intracellular calcium concentrations. The extended model and new parameter estimates for the cross-bridging can be coupled
with uterine flow models to advance our understanding of embryonic motility and intrauterine flow. 相似文献
82.
Jennings BL Bell JD Hyodo S Toop T Donald JA 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2007,177(5):557-567
This study investigated vasodilator mechanisms in the dorsal aorta of the elephant fish, Callorhinchus milii, using anatomical and physiological approaches. Nitric oxide synthase could only be located in the perivascular nerve fibres
and not the endothelium of the dorsal aorta, using NADPH histochemistry and immunohistochemistry. In vitro organ bath experiments
demonstrated that a NO/soluble guanylyl cyclase (GC) system appeared to be absent in the vascular smooth muscle, since the
NO donors SNP (10−4 mol l−1) and SIN-1 (10−5 mol l−1) were without effect. Nicotine (3 × 10−4 mol l−1) mediated a vasodilation that was not affected by ODQ (10−5 mol l−1), l-NNA (10−4 mol l−1), indomethacin (10−5 mol l−1), or removal of the endothelium. In contrast, the voltage-gated sodium channel inhibitor, tetrodotoxin (10−5 mol l−1), significantly decreased the dilation induced by nicotine, suggesting that it contained a neural component. Pre-incubation
of the dorsal aorta with the calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP8–37 (10−6 mol l−1) also caused a significant decrease in the nicotine-induced dilation. We propose that nicotine is mediating a neurally-derived
vasodilation in the dorsal aorta that is independent of NO, prostaglandins and the endothelium, and partly mediated by CGRP. 相似文献
83.
As with the budding yeast Saccharomyces cerevisiae, the completion of the Schizosaccharomyces pombe genome sequence has opened new opportunities to investigate the functional organization of a eukaryotic cell. These include analysis of gene expression patterns, comprehensive gene knockout and synthetic lethal screens, global protein localization analysis, and direct protein interaction mapping. We describe here the tandem affinity purification or TAP approach combined with DALPC mass spectrometry to identify components of protein complexes as we have applied it to S. pombe. This approach can theoretically be applied to the entire proteome as has been done in S. cerevisiae to gain insight into functional protein assemblies and to elucidate functions of uncharacterized proteins. 相似文献
84.
There is marked heterogeneity of nucleotide composition in mitochondrial
DNA across divergent animals. Differences in nucleotide composition
presumably reflect differences in directional nucleotide substitution for
A+T or G+C nucleotides. In mitochondrial DNA, there is A+T directional
nucleotide substitution in most (if not all) animals surveyed, and the
magnitude of directional A+T nucleotide substitution differs greatly within
and among groups. Differences in directional nucleotide substitution among
lineages of mammals can be explained by changes in metabolic physiology.
This relationship is thought to be mediated by the effect of oxygen
radicals because these toxic compounds are by-products of aerobic
metabolism and are known mutagens. Association between metabolism and
nucleotide composition provides additional evidence in favor of the
hypothesis that rates and patterns of nucleotide substitution in
mitochondrial DNA can be influenced by factors that impinge on rates of
endogenous DNA damage.
相似文献
85.
Michael D. Jennings Jonathan Hoekstra Jonathan Higgins Timothy Boucher 《Biodiversity and Conservation》2008,17(4):833-840
In conservation planning, species richness and species endemism are the most often used metrics for describing the biodiversity
importance of areas. However, when it comes to prioritizing regions for conservation actions these measures alone are insufficient
because they do not reveal how similar or different the actual composition of species may be from one area to another. For
comparative analysis an additional useful metric would be one that indicates the degree to which the species assemblage in
one area is also represented in—or is distinct from—species assemblages of other areas. Here we describe a method for quantifying
the compositional representativeness of species assemblages among geographic regions. The method generates asymmetric pairwise
similarity coefficients that are then used to calculate separate measures for the representativeness and the distinctiveness
of species assemblages in the regions being compared. We demonstrate the method by comparing fish communities among freshwater
ecoregions of the Mississippi Basin, and then among smaller hydrological units within two individual freshwater ecoregions.
At both scales of analysis, our measures of representativeness and distinctiveness reveal patterns of fish species composition
that differ from patterns of species richness. This information can enhance conservation planning processes by ensuring that
priority-setting explicitly consider the most representative and distinctive species assemblages. 相似文献
86.
Daniel Padfield Chris Lowe Angus Buckling Richard Ffrench‐Constant Student Research Team Simon Jennings Felicity Shelley Jón S. Ólafsson Gabriel Yvon‐Durocher 《Ecology letters》2017,20(10):1250-1260
Gross primary production (GPP) is the largest flux in the carbon cycle, yet its response to global warming is highly uncertain. The temperature dependence of GPP is directly linked to photosynthetic physiology, but the response of GPP to warming over longer timescales could also be shaped by ecological and evolutionary processes that drive variation in community structure and functional trait distributions. Here, we show that selection on photosynthetic traits within and across taxa dampens the effects of temperature on GPP across a catchment of geothermally heated streams. Autotrophs from cold streams had higher photosynthetic rates and after accounting for differences in biomass among sites, biomass‐specific GPP was independent of temperature in spite of a 20 °C thermal gradient. Our results suggest that temperature compensation of photosynthetic rates constrains the long‐term temperature dependence of GPP, and highlights the importance of considering physiological, ecological and evolutionary mechanisms when predicting how ecosystem‐level processes respond to warming. 相似文献
87.
Interleukin-1 beta (IL-1 beta) is a cytokine and a member of the beta-trefoil superfamily of protein structures. An interesting feature in the folding of IL-1 beta, shared with some other members of the same topological family, is the existence of a slow step in folding to the native conformation from a discrete intermediate. Wanting to probe the nature of this slow step in the folding of WT IL-1 beta (tau(1)=45 seconds), we made ten sequence variants of IL-1 beta (L10A, T9Q, T9G, C8S, C8A, N7G, N7D, L6A, R4P, and R4Q), where all mutations are located along strand 1. This strand is not protected from hydrogen exchange until late in folding. Most of the mutations showed little effect on the kinetics of folding for IL-1 beta. However, C8 is clearly involved in both the late and the early steps in folding, while sequence variants at L10 and L6 affect only late events in folding. The value of the slowest relaxation time, tau(1), which is associated with the rate of native protein formation, increased for the refolding of C8S, while C8A, L6A, and L10A showed smaller but systematic increases in the value of tau(1.)For both C8S and C8A, the value of the step associated with formation of the intermediate, tau(2), was independent of denaturant concentration. In addition, mutations in the hydrophobic core (L10A, C8A, C8S, and L6A) and, surprisingly, along the surface (T9G, T9Q, and N7G) alter the stability. The most destabilizing mutations show changes in equilibrium unfolding cooperativity, which is atypical for destabilizing mutations in IL-1 beta. Crystallographic studies indicate that mutations along strand 1 may alter the number of ordered water molecules within the core. Thus, side-chain replacement in this region can disrupt essential main-chain interactions mediated by ordered water contacts in a highly cooperative network of hydrogen bonding. 相似文献
88.
A fibrinogenase (Ba100) with an apparent molecular mass of 100 kDa under non-reducing conditions and a pI of 5.4 was purified from the venom of the African puff adder (Bitis arietans) by fibrinogen affinity chromatography. Under reducing conditions the protease dissociates into subunits of 21 kDa and 16 kDa. N-Terminal amino acid sequencing showed these two chains to have 66.7% homology and homology to C-type lectins. The fibrinogenase activity of Ba100 cleaves the Aalpha and Bbeta chain of fibrinogen rendering the molecule unable to polymerise into fibrin clots. Ba100 inhibited platelet aggregation in platelet rich plasma, and clot formation in whole blood, in a concentration dependent manner. 相似文献
89.
Newlon MG Roy M Morikis D Hausken ZE Coghlan V Scott JD Jennings PA 《Nature structural biology》1999,6(3):222-227
Compartmentalization of signal transduction enzymes into signaling complexes is an important mechanism to ensure the specificity of intracellular events. Formation of these complexes is mediated by specialized protein motifs that participate in protein-protein interactions. The adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA) is localized through interaction of the regulatory (R) subunit dimer with A-kinase-anchoring proteins (AKAPs). We now report the solution structure of the type II PKA R-subunit fragment RIIalpha(1-44), which encompasses both the AKAP-binding and dimerization interfaces. This structure incorporates an X-type four-helix bundle dimerization motif with an extended hydrophobic face that is necessary for high-affinity AKAP binding. NMR data on the complex between RIIalpha(1-44) and an AKAP fragment reveals extensive contacts between the two proteins. Interestingly, this same dimerization motif is present in other signaling molecules, the S100 family. Therefore, the X-type four-helix bundle may represent a conserved fold for protein-protein interactions in signal transduction. 相似文献
90.
Zhang C Yang J Jennings LK 《American journal of physiology. Heart and circulatory physiology》2004,287(2):H659-H666
Increased oxidative stress is a major characteristic of restenosis after angioplasty. The oxidative stress is mainly created by oxidants such as reactive oxygen species (ROS), which are assumed to play an important role in neointima formation after angioplasty. DNA is a sensitive target for oxidants; however, oxidative DNA damage remains a poorly examined field in the pathogenesis of restenosis. In the present study, we demonstrated that the expression of the oxidative DNA damage marker 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) was quickly increased in rat carotid arteries after balloon injury. It reached its peak at 14 days after injury and still kept high expression at 28 days after injury. The immunostaining of 8-oxo-dG was present predominantly in the neointima. In response to oxidative DNA damage, the DNA repair enzyme poly(ADP-ribose) polymerase-1 (PARP-1) was significantly increased after balloon injury. The time course change and location of PARP-1 is similar to that of 8-oxo-dG. Daily injections of the PARP-1 inhibitor PJ34 (5 mg.kg(-1).day(-1) ip) attenuated neointima formation by approximately 40% at 7, 14, and 28 days after balloon injury. Treatment with PJ34 inhibited leukocyte infiltration and improved both anatomic (reendothelialization) and functional (endothelial function) recovery of endothelial cells after balloon injury. In conclusion, levels of oxidative DNA damage and the DNA repair enzyme PARP-1 are increased in vessels after balloon injury. Inhibition of PARP-1 attenuates neointima formation through inhibition of leukocyte infiltration and improvement of endothelial cell recovery after balloon injury. Targeting of the DNA repair enzyme might be a therapeutic strategy for restenosis. 相似文献