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1.
Silvio Antoniak Erica M. Sparkenbaugh Michael Tencati Mauricio Rojas Nigel Mackman Rafal Pawlinski 《PloS one》2013,8(11)
Heart failure is a major clinical problem worldwide. Previous studies have demonstrated an important role for G protein-coupled receptors, including protease-activated receptors (PARs), in the pathology of heart hypertrophy and failure. Activation of PAR-2 on cardiomyocytes has been shown to induce hypertrophic growth in vitro. PAR-2 also contributes to myocardial infarction and heart remodeling after ischemia/reperfusion injury. In this study, we found that PAR-2 induced hypertrophic growth of cultured rat neonatal cardiomyocytes in a MEK1/2 and p38 dependent manner. In addition, PAR-2 activation on mouse cardiomyocytes increased expression of the pro-fibrotic chemokine MCP-1. Furthermore, cardiomyocyte-specific overexpression of PAR-2 in mice induced heart hypertrophy, cardiac fibrosis, inflammation and heart failure. Finally, in a mouse model of myocardial infarction induced by permanent ligation of the left anterior descending coronary artery, PAR-2 deficiency attenuated heart remodeling and improved heart function independently of its contribution to the size of the initial infarct. Taken together, our data indicate that PAR-2 signaling contributes to the pathogenesis of hypertrophy and heart failure. 相似文献
2.
Johnathan L Meaders Erica F Geers Belen Fernandez‐Garcia Marvin E Tanenbaum 《The EMBO journal》2012,31(21):4179-4190
The microtubule motor protein kinesin‐5 (Eg5) provides an outward force on centrosomes, which drives bipolar spindle assembly. Acute inhibition of Eg5 blocks centrosome separation and causes mitotic arrest in human cells, making Eg5 an attractive target for anti‐cancer therapy. Using in vitro directed evolution, we show that human cells treated with Eg5 inhibitors can rapidly acquire the ability to divide in the complete absence of Eg5 activity. We have used these Eg5‐independent cells to study alternative mechanisms of centrosome separation. We uncovered a pathway involving nuclear envelope (NE)‐associated dynein that drives centrosome separation in prophase. This NE‐dynein pathway is essential for bipolar spindle assembly in the absence of Eg5, but also functions in the presence of full Eg5 activity, where it pulls individual centrosomes along the NE and acts in concert with Eg5‐dependent outward pushing forces to coordinate prophase centrosome separation. Together, these results reveal how the forces are produced to drive prophase centrosome separation and identify a novel mechanism of resistance to kinesin‐5 inhibitors. 相似文献
3.
George B. Stefano Erica Braham Patrick Finn Edward Aiello Michael K. Leung 《Cellular and molecular neurobiology》1987,7(2):209-219
1. This report further demonstrates that etorphine influences presynaptic dopamine release, which in turn centrally modulates peripheral cilioinhibition. 2. In older animals cilioinhibition has become enhanced due to a lack of responsiveness to endogenous opioids which results in greater dopamine release, causing a higher level of cilioinhibition as demonstrated by challenging the visceral ganglia with etorphine or destroying the dopaminergic component with 6-hydroxydopamine. 3. Only the central cilioinhibitory, not the peripheral inhibitory response, mechanism appears to be altered in older animals. Thus, the alteration appears in the central integrative mechanisms involved with regulating ciliary activity. 4. The KCl-stimulated release of dopamine is unaltered in both young and old organisms, whereas the opiate inhibition of the KCl-stimulated release of dopamine is reduced in older organisms. Thus, the aging-associated alteration is associated with a specific process. 5. The reduction of opioid influence and the resulting enhanced cilioinhibitory activity may make the organisms more susceptible to environmental stress. 相似文献
4.
Steady state kinetics were used to examine the influence of Cd2+ both on K+ stimulation of a membrane-bound ATPase from sugar beet roots (Beta vulgaris L. cv. Monohill) and on K+(86Rb+) uptake in intact or excised beet roots. The in vitro effect of Cd2+ was studied both on a 12000–25000 g root fraction of the (Na++K++Mg2+)ATPase and on the ATPase when further purified by an aqueous polymer two-phase system. The observed data can be summarized as follows: 1) Cd2+ at high concentrations (>100 μM) inhibits the MgATPase activity in a competitive way, probably by forming a complex with ATP. 2) Cd2+ at concentrations <100 μM inhibits the specific K+ activation at both high and low affinity sites for K+. The inhibition pattern appears to be the same in the two ATPase preparations of different purity. In the presence of the substrate MgATP, and at K+ <5 mM, the inhibition by Cd2+ with respect to K+ is uncompetitive. In the presence of MgATP and K+ >10 μM, the inhibition by Cd2+ is competitive. 3) At the low concentrations of K+, Cd2+ also inhibits the 2,4-dinitrophenol(DNP)-sensitive (metabolic) K+(86Rb+) uptake uncompetitively both in excised roots and in roots of intact plants. 4) The DNP-insensitive (non metabolic) K+(86Rb+) uptake is little influenced by Cd2+. As Cd2+ inhibits the metabolic uptake of K+(86Rb+) and the K+ activation of the ATPase in the same way at low concentrations of K+, the same binding site is probably involved. Therefore, under field conditions, when the concentration of K+ is low, the presence of Cd2+ could be disadvantageous. 相似文献
5.
Göran Wingstrand 《Physiologia plantarum》1985,64(2):223-229
Membrane-bound MgATPase activity from roots of young sugar beet ( Beta vulgaris L. cv. Monohill) was investigated in a membrane fraction purified by partition in an aqueous polymer two-phase system. After two steps of "washing" with fresh bottom phase (rich in dextran), the polyethylene glycol rich top phase (U3 ) was practically free of mitochondrial membranes (cytochrome oxidase), and the remaining MgATPase activity showed high substrate specificity for ATP. An optimum for the MgATPase activity was found at pH 7. The activation by Na+ or K+ was strongest on the acid side without any observable shift in pH optimum. Oligomycin had no effect, but vanadate strongly inhibited the U3 MgATPase and the K+ activation was lost. The complex activation pattern achieved by varying the Na+ /K+ ratio at constant total concentration was interpreted as a synergistic (Na+ + K+ )-activation. The U3 fraction MgATP-ase activity showed a 4-fold increase in the presence of 0.01% Triton X-100 implying that the MgATPase activity is located in vesicles of which 75% or more are sealed with the ATP binding site on the inside. Comparison with the properties of plasma membrane. ATPases from other plants indicated that the U3 fraction MgATPase was mainly of plasma membrane origin. 相似文献
6.
Responses of nitrate assimilation and N translocation in tomato (Lycopersicon esculentum Mill) to reduced ambient air humidity 总被引:1,自引:0,他引:1
Erica Brewitz; Larsson Carl-Magnus; Larsson Marie 《Journal of experimental botany》1996,47(7):855-861
The impact of low humidity in ambient air on water relations,nitrate uptake, and translocation of recently absorbed nitrogen,was investigated in 5-week-old tomato (Lycopersicon esculentumMill cv. Ailsa Craig) plants grown hydroponically in a completenutrient solution. Plants were subjected to dry air (relativehumidity 24% for 6 h. The transpiration rate increasedseveral-fold and the shoot water content decreased by almost20%, whereas root water content was unaffected. No effect onin vitro nitrate reductase (NR) activity was detected when usingan EDTA-contraining assay buffer. Replacement of EDTA with Mg2+revealed a significant decline in shoot NR activity, which suggestsphosphorylation of the enzyme during the stress treatment. Plantswere grown in a split-root system, in which one root half wasfed 15N-nitrate during the treatment, in order to determinenitrate uptake and translocation of recently absorbed nitrogenin the plants. Uptake of nitrate was substantially inhibited,but the proportion of absorbed 15N that was translocated tothe shoots was only slightly affected. In untreated plants,71% of the 15N recovered in roots had been retranslocated fromthe shoots, whereas in plants subjected to stress the deliveryof 15N from shoots to roots appeared to be completely inhibited.The data show that lowered humidity in air has significant effectson both uptake of nitrate as well as translocation of nitrogenwithin the plants. Some of these effects appear to be commonwith those observed in plants subjected to reduced water potentialsin the root environment and point to the possibility of theshoot water relations being highly influential on nitrogen uptakeand translocation. Key words: Air humidity, nitrate assimilation, nitrate reductase activity, nitrogen translocation, tomato, water stress 相似文献
7.
Steve S. Sommer Victoria L. Tillotson Erica L. Vielhaber Rhett P. Ketterling Charyl M. Dutton 《Human genetics》1994,93(3):357-358
Long tandem dinucleotide repeats composed of alternating purines and pyrimidines [RY(i)] are abundant and highly polymorphic. Simple RY(i) are predominately composed of one tandem repeat of a dinucleotide sequence. In contrast, cryptic RY(i [cRY(i)] are composed of multiple short dinucleotide repeats. Herein, we describe the racial distribution of alleles for a polymorphic cRY(i) in the factor IX gene. Allele I is absent in Asians, whereas allele III is rare or absent in Caucasians or blacks. A polymorphic cRY(i) analyzed previously shows even more dramatic variation among racial groups, hinting that a battery of cRY(i) might have utility in assessing the racial origin of a DNA sample. 相似文献
8.
Ximena J. Nelson Alex H. Taylor Erica A. Cartmill Heidi Lyn Lauren M. Robinson Vincent Janik Colin Allen 《Biological reviews of the Cambridge Philosophical Society》2023,98(5):1548-1563
The nature and evolution of positive emotion is a major question remaining unanswered in science and philosophy. The study of feelings and emotions in humans and animals is dominated by discussion of affective states that have negative valence. Given the clinical and social significance of negative affect, such as depression, it is unsurprising that these emotions have received more attention from scientists. Compared to negative emotions, such as fear that leads to fleeing or avoidance, positive emotions are less likely to result in specific, identifiable, behaviours being expressed by an animal. This makes it particularly challenging to quantify and study positive affect. However, bursts of intense positive emotion (joy) are more likely to be accompanied by externally visible markers, like vocalisations or movement patterns, which make it more amenable to scientific study and more resilient to concerns about anthropomorphism. We define joy as intense, brief, and event-driven (i.e. a response to something), which permits investigation into how animals react to a variety of situations that would provoke joy in humans. This means that behavioural correlates of joy are measurable, either through newly discovered ‘laughter’ vocalisations, increases in play behaviour, or reactions to cognitive bias tests that can be used across species. There are a range of potential situations that cause joy in humans that have not been studied in other animals, such as whether animals feel joy on sunny days, when they accomplish a difficult feat, or when they are reunited with a familiar companion after a prolonged absence. Observations of species-specific calls and play behaviour can be combined with biometric markers and reactions to ambiguous stimuli in order to enable comparisons of affect between phylogenetically distant taxonomic groups. Identifying positive affect is also important for animal welfare because knowledge of positive emotional states would allow us to monitor animal well-being better. Additionally, measuring if phylogenetically and ecologically distant animals play more, laugh more, or act more optimistically after certain kinds of experiences will also provide insight into the mechanisms underlying the evolution of joy and other positive emotions, and potentially even into the evolution of consciousness. 相似文献
9.
An agent-based perspective in the study of complex systems is well established in diverse disciplines, yet is only beginning to be applied to evolutionary developmental biology. In this essay, we begin by defining agency and associated terminology formally. We then explore the assumptions and predictions of an agency perspective, apply these to select processes and key concept areas relevant to practitioners of evolutionary developmental biology, and consider the potential epistemic roles that an agency perspective might play in evo devo. Throughout, we discuss evidence supportive of agential dynamics in biological systems relevant to evo devo and explore where agency thinking may enrich the explanatory reach of research efforts in evolutionary developmental biology. 相似文献
10.
Amino Acids - Protein arginine N-methyltransferases (PRMTs) have emerged as important actors in the eukaryotic stress response with implications in human disease, aging, and cell signaling.... 相似文献