Glucose-induced period-doubling cascade in the electrical activity of pancreatic β-cells

 In the presence of stimulatory concentrations of glucose, the membrane potential of pancreatic β-cells may experience a transition from periods of rapid spike-like oscillations alternating with a pseudo-steady state to spike-only oscillations. Insulin secretion from β-cells closely correlates the periods of spike-like oscillations. The purpose of this paper is to study the mathematical structure which underlines this transitional stage in a pancreatic β-cell model. It is demonstrated that the transition can be chaotic but becomes more and more regular with increase in glucose. In particular, the system undergoes a reversed period-doubling cascade leading to the spike-only oscillations as the glucose concentration crosses a threshold. The transition interval in glucose concentration is estimated to be extremely small in terms of the rate of change for the calcium dynamics in the β-cells. The methods are based on the theory of unimodal maps and the geometric and asymptotic theories of singular perturbations. Received: 25 October 1996/Revised version: 18 August 1997     

Comparison of functional aspects of the coagulation cascade in human and sea turtle plasmas

Functional hemostatic pathways are critical for the survival of all vertebrates and have been evolving for more than 400 million years. The overwhelming majority of studies of hemostasis in vertebrates have focused on mammals with very sparse attention paid to reptiles. There have been virtually no studies of the coagulation pathway in sea turtles whose ancestors date back to the Jurassic period. Sea turtles are often exposed to rapidly altered environmental conditions during diving periods. This may reduce their blood pH during prolonged hypoxic dives. This report demonstrates that five species of turtles possess only one branch of the mammalian coagulation pathway, the extrinsic pathway. Mixing studies of turtle plasmas with human factor-deficient plasmas indicate that the intrinsic pathway factors VIII and IX are present in turtle plasma. These two factors may play a significant role in supporting the extrinsic pathway by feedback loops. The intrinsic factors, XI and XII are not detected which would account for the inability of reagents to induce coagulation via the intrinsic pathway in vitro. The analysis of two turtle factors, factor II (prothrombin) and factor X, demonstrates that they are antigenically/functionally similar to the corresponding human factors. The turtle coagulation pathway responds differentially to both pH and temperature relative to each turtle species and relative to human samples. The coagulation time (prothrombin time) increases as the temperature decreases between 37 and 15 °C. The increased time follows a linear relationship, with similar slopes for loggerhead, Kemps ridley and hawksbill turtles as well as for human samples. Leatherback turtle samples show a dramatic nonlinear increased time below 23 °C, and green turtle sample responses were similar but less dramatic. All samples also showed increased prothrombin times as the pH decreased from 7.8 to 6.4, except for three turtle species. The prothrombin times decreased, to varying extents, in a linear fashion relative to reduced pH with the rate of change greatest in leatherbacks>greenloggerhead turtles. All studies were conducted with reagents developed for human samples which would impact on the quantitative results with the turtle samples, but are not likely to alter the qualitative results. These comparative studies of the coagulation pathway in sea turtles and humans could enhance our knowledge of structure/function relationships and evolution of coagulation factors.     

Characterization of the enzymatic activity of human kallikrein 6: Autoactivation,substrate specificity,and regulation by inhibitors

Human kallikrein 6 (hK6) is a trypsin-like serine protease, member of the human kallikrein gene family. Studies suggested a potential involvement of hK6 in the development and progression of Alzheimer's disease. The serum levels of hK6 might be used as a biomarker for ovarian cancer. To gain insights into the physiological role of this enzyme, we sought to determine its substrate specificity and its interactions with various inhibitors. We produced the proform of hK6 and showed that this enzyme was able to autoactivate, as well as proteolyse itself, leading to inactivation. Kinetic studies indicated that hK6 cleaved with much higher efficiency after Arg than Lys and with a preference for Ser or Pro in the P2 position. The efficient degradation of fibrinogen and collagen types I and IV by hK6 indicated that this kallikrein might play a role in tissue remodeling and/or tumor invasion and metastasis. We also demonstrated proteolysis of amyloid precursor protein by hK6 and determined the cleavage sites at the N-terminal end of the protein. Inhibition of hK6 was achieved via binding to different serpins, among which antithrombin III was the most efficient.     

Fragmentation of riverine systems: the genetic effects of dams on bull trout (Salvelinus confluentus) in the Clark Fork River system

Migratory bull trout (Salvelinus confluentus) historically spawned in tributaries of the Clark Fork River, Montana and inhabited Lake Pend Oreille as subadult and adult fish. However, in 1952 Cabinet Gorge Dam was constructed without fish passage facilities disrupting the connectivity of this system. Since the construction of this dam, bull trout populations in upstream tributaries have been in decline. Each year adult bull trout return to the base of Cabinet Gorge Dam when most migratory bull trout begin their spawning migration. However, the origin of these fish is uncertain. We used eight microsatellite loci to compare bull trout collected at the base of Cabinet Gorge Dam to fish sampled from both above and further downstream from the dam. Our data indicate that Cabinet Gorge bull trout are most likely individuals that hatched in above-dam tributaries, reared in Lake Pend Oreille, and could not return to their natal tributaries to spawn. This suggests that the risk of outbreeding depression associated with passing adults over dams in the Clark Fork system is minimal compared to the potential genetic and demographic benefits to populations located above the dams.     

MAP kinase cascades in elicitor signal transduction

 Protein kinases play important roles in elicitor signal transduction. In this article, I describe the current view of the role of mitogen-activated protein kinase (MAPK) cascades in elicitor signal transduction of plant cells based on our own research and recent developments in this field. In the past several years, it has become apparent that MAPK cascades play important roles in elicitor signal transduction in plants. Our early studies demonstrated the identification of p47 MAPK in tobacco as an elicitor-responsive protein kinase and possible involvement of p47 MAPK in elicitor signal transduction to induce defense responses, including defense gene expression and hypersensitive cell death. However, the molecular identity of p47 MAPK is still unclear. Recent important studies suggest that tobacco MAPK cascades that include SIPK, and/or WIPK, and NtMEK2, an upstream kinase for both SIPK and WIPK, have a crucial function in induction of defense responses and hypersensitive cell death. The orthologs of these protein kinases in Arabidopsis and alfalfa are also suggested to have similar functions. Furthermore, the identification of loss-of-function mutation in Arabidopsis reveals a negative regulatory role for putative MAPK cascades in plant defense mechanisms. Received: February 7, 2002 / Accepted: February 25, 2002     

Tunable, monochromatic X-rays: an enabling technology for molecular/cellular imaging and therapy

Pulsed, tunable, monochromatic X-rays hold great potential as a cellular and molecular probe. These beams can be tuned to the binding energy of orbital electrons in atoms, making them extremely useful in diagnostic k-edge imaging and Auger cascade radiotherapy. Their wide tunability makes them ideal for the performance of various techniques as disparate as protein crystallography and three-dimensional, compressionless, monochromatic mammography. Since only the frequency best suited to the task at hand is used, radiation exposure to patients or animals is exceedingly low when compared to standard X-ray techniques.     

Loss of cannabinoid-stimulated guanosine 5'-O-(3-[(35)S]Thiotriphosphate) binding without receptor down-regulation in brain regions of anandamide-tolerant rats

The endogenous cannabinoid anandamide has been reported to produce well-defined behavioral tolerance, but studies on the possible mechanisms underlying this process are few and often contradictory. The present study was designed to survey the cellular events involved in anandamide tolerance, in terms of the effects on receptor number, coupling with G proteins, and activation of the cyclic AMP (cAMP) cascade. Chronic treatment of rats with anandamide (20 mg/kg i.p. for 15 days) resulted in behavioral tolerance without any change in cannabinoid receptor binding in the brain regions studied (striatum, cortex, hippocampus, and cerebellum), suggesting that receptor down-regulation was not involved in the development of anandamide behavioral tolerance. In contrast, prolonged exposure to anandamide significantly reduced agonist-stimulated guanosine 5'-O:-(3-[(35)S]thiotriphosphate) binding in the same areas, with losses of >50%, suggesting that receptor desensitization may be part of the molecular mechanism underlying this tolerance. Finally, concerning the cAMP cascade-the most well-known intracellular signaling pathways activated by CB(1) receptors-in the brain regions from rats tolerant to anandamide, we found no alteration in cAMP levels or in protein kinase A activity. We propose that anandamide, unlike Delta(9)-tetrahydrocannabinol and other cannabinoids, does not alter the receptor system at multiple levels but that desensitization of the CB(1) receptor might account for behavioral tolerance to the drug.     

真核生物的MAPK级联信号传递途径

MAPK级联途径在真核生物细胞的信号传递过程中起着重要的作用.MAPK级联途径由MAPK、MAPKK和MAPKKK三类酶蛋白组成.这三类蛋白质的结构非常保守,通过磷酸化作用传递各种信号.在酵母和动、植物细胞中已经发现了一系列的MAPK级联途径成员,使真核生物的信号传递途径逐渐得到阐明.     

Effects of environmental stress cascade up through four trophic levels in a salt marsh study system

1. Although in recent years there have been a number of studies demonstrating trophic cascades in terrestrial systems, it is still unclear what environmental conditions enable or enhance such cascades, especially among four trophic levels. 2. In this study, the influence of environmental stress (increased soil pore water salinity) on a four trophic level study system in a Florida salt marsh was examined by experimentally increasing soil pore water salinity. Effects of increased salinity on the quality of the host plant, Batis maritima, were assessed, as were resulting effects on the lepidopteran herbivore Ascia monuste, and the primary parasitoids and hyperparasitoids of its caterpillars. 3. Increased salinity altered host‐plant quality, which subsequently affected the consumer species. These effects of altered plant quality cascaded up through the herbivore and primary parasitoid to the hyperparasitoid Hypopteromalus inimicus, influencing its density, sex ratio, body size, and initial egg load. 4. These results demonstrate how heterogeneity in environmental stress can result in effects that cascade up through four trophic levels. We suggest that such strong effects at higher trophic levels may be more likely in systems in which relationships are more specific and intimate such as those among hosts, parasitoids, and hyperparasitoids.     

Antitcoagulant and antiplatelet activities of scolymoside

Cyclopia subternata is a medicinal plant commonly used in traditional medicine to relieve pain. Here, the anticoagulant effects of scolymoside, an active compound in C. subternata, were examined by monitoring activated partial thromboplastin time (aPTT), prothrombin time (PT), and the activities of thrombin and activated factor X (FXa). The effects of scolymoside on plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) expression were evaluated in tumor necrosis factor (TNF)-α-activated human endothelial cells. Treatment with scolymoside resulted in prolonged aPTT and PT and the inhibition of thrombin and FXa activities and production. In addition, scolymoside inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. Scolymoside also elicited anticoagulant effects in mice, including a significant reduction in the PAI-1 to t-PA ratio. Collectively, these findings indicate that scolymoside possesses anticoagulant activities and could be developed as a novel anticoagulant. [BMB Reports 2015; 48(10): 577-582]