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71.
Marcus T. Wilson Melissa Barry John N. J. Reynolds William P. Crump D. Alistair Steyn-Ross Moira L. Steyn-Ross James W. Sleigh 《Journal of biological physics》2010,36(3):245-259
We study the dynamics of the transition between the low- and high-firing states of the cortical slow oscillation by using
intracellular recordings of the membrane potential from cortical neurons of rats. We investigate the evidence for a bistability
in assemblies of cortical neurons playing a major role in the maintenance of this oscillation. We show that the trajectory
of a typical transition takes an approximately exponential form, equivalent to the response of a resistor–capacitor circuit
to a step-change in input. The time constant for the transition is negatively correlated with the membrane potential of the
low-firing state, and values are broadly equivalent to neural time constants measured elsewhere. Overall, the results do not
strongly support the hypothesis of a bistability in cortical neurons; rather, they suggest the cortical manifestation of the
oscillation is a result of a step-change in input to the cortical neurons. Since there is evidence from previous work that
a phase transition exists, we speculate that the step-change may be a result of a bistability within other brain areas, such
as the thalamus, or a bistability among only a small subset of cortical neurons, or as a result of more complicated brain
dynamics. 相似文献
72.
Zhongcai Ma Kenny Y.C. Kwong David Paek 《Biochemical and biophysical research communications》2010,400(4):569-574
Plaminogen activator inhibitor-1 (PAI-1), the key physiological inhibitor of the plasmin fibrinolytic system, plays important roles in the pathogenesis of asthma. Mast cells (MCs) are crucial effector cells and a major source of PAI-1 for asthma. Cyclic adenosine monophosphate (cAMP) is the important regulator of MCs; however, its effects on PAI-1 expression in MCs remain unknown. We reported cAMP/protein kinase A pathway positively regulates PAI-1 expression through cAMP-response element binding protein binding to hypoxia response element-1 at −158 to −153 bp of human PAI-1 promoter in human MCs. Moreover, cAMP synergistically augments PAI-1 expression with ionomycin- or IgE receptor cross-linking-mediated stimulation. 相似文献
73.
74.
Robin G. Crump Michael F. Barker 《Journal of experimental marine biology and ecology》1985,88(2):109-127
Sexual reproduction and asexual reproduction by fission were studied in four populations of Coscinasterias calamaria (Gray), two in Otago Harbour in the South Island of New Zealand and two in the North Island near Auckland. The annual reproductive cycle in both islands of New Zealand is clearly defined with a spawning season between November and January. In both sites the pyloric caeca index was approximately inverse to the gonad index cycle as found in other forcipulate asteroids. There are substantial differences in the sex ratios of mature starfish at each site studied, with 1:1 ratios in two populations, one population heavily biased towards females and the fourth consisting almost entirely of males. Morphometric variation in arm number due to splitting was studied and the frequency of splitting varied considerably between the four populations. Generally speaking sublittoral C. calamaria divide less frequently than intertidal starfish and populations in which food is less abundant or of poorer quality are more fissiparous and put less energy into sexual reproduction, than populations with plentiful readily available food in the form of mussels. The significance of the different reproductive patterns in C. calamaria is discussed. 相似文献
75.
Salmonella induces a switched antibody response without germinal centers that impedes the extracellular spread of infection 总被引:1,自引:0,他引:1
Cunningham AF Gaspal F Serre K Mohr E Henderson IR Scott-Tucker A Kenny SM Khan M Toellner KM Lane PJ MacLennan IC 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(10):6200-6207
T-dependent Ab responses are characterized by parallel extrafollicular plasmablast growth and germinal center (GC) formation. This study identifies that, in mice, the Ab response against Salmonella is novel in its kinetics and its regulation. It demonstrates that viable, attenuated Salmonella induce a massive early T-dependent extrafollicular response, whereas GC formation is delayed until 1 mo after infection. The extrafollicular Ab response with switching to IgG2c, the IgG2a equivalent in C57BL/6 mice, is well established by day 3 and persists through 5 wk. Switching is strongly T dependent, and the outer membrane proteins are shown to be major targets of the early switched IgG2c response, whereas flagellin and LPS are not. GC responses are associated with affinity maturation of IgG2c, and their induction is associated with bacterial burden because GC could be induced earlier by treating with antibiotics. Clearance of these bacteria is not a consequence of high-affinity Ab production, for clearance occurs equally in CD154-deficient mice, which do not develop GC, and wild-type mice. Nevertheless, transferred low- and high-affinity IgG2c and less efficiently IgM were shown to impede Salmonella colonization of splenic macrophages. Furthermore, Ab induced during the infection markedly reduces bacteremia. Thus, although Ab does not prevent the progress of established splenic infection, it can prevent primary infection and impedes secondary hemogenous spread of the disease. These results may explain why attenuated Salmonella-induced B cell responses are protective in secondary, but not primary infections. 相似文献
76.
Herpes simplex virus type 1 cytoplasmic envelopment requires functional Vps4 总被引:6,自引:3,他引:3
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The assembly and egress of herpesviruses are complex processes that require the budding of viral nucleocapsids into the lumen of cytoplasmic compartments to form mature infectious virus. This envelopment stage shares many characteristics with the formation of luminal vesicles in multivesicular endosomes. Through expression of dominant-negative Vps4, an enzyme that is essential for the formation of luminal vesicles in multivesicular endosomes, we now show that Vps4 function is required for the cytoplasmic envelopment of herpes simplex virus type 1. This is the first example of a large enveloped DNA virus engaging the multivesicular endosome sorting machinery to enable infectious virus production. 相似文献
77.
Ruffolo SC Forsell PK Yuan X Desmarais S Himms-Hagen J Cromlish W Wong KK Kennedy BP 《The Journal of biological chemistry》2007,282(42):30423-30433
Although protein-tyrosine phosphatase 1B (PTP-1B) is a negative regulator of insulin action, adipose tissue from PTP-1B-/- mice does not show enhanced insulin-stimulated insulin receptor phosphorylation. Investigation of glucose uptake in isolated adipocytes revealed that the adipocytes from PTP-1B-/- mice have a significantly attenuated insulin response as compared with PTP-1B+/+ adipocytes. This insulin resistance manifests in PTP-1B-/- animals older than 16 weeks of age and could be partially rescued by adenoviral expression of PTP-1B in null adipocytes. Examination of adipose signaling pathways found that the basal p70S6K activity was at least 50% higher in adipose from PTP-1B-/- mice compared with wild type animals. The increased basal activity of p70S6K in PTP-1B-/- adipose correlated with decreases in IR substrate-1 protein levels and insulin-stimulated Akt/protein kinase B activity, explaining the decrease in insulin sensitivity even as insulin receptor phosphorylation was unaffected. The insulin resistance of the of the PTP-1B-/- adipocytes could also be rescued by treatment with rapamycin, suggesting that in adipose the loss of PTP-1B results in basal activation of mTOR (mammalian target of rapamycin) complex 1 leading to a tissue-specific insulin resistance. 相似文献
78.
Birch AM Kenny PW Oikonomakos NG Otterbein L Schofield P Whittamore PR Whalley DP 《Bioorganic & medicinal chemistry letters》2007,17(2):394-399
A series of substituted 3,4-dihydro-2-quinolone glycogen phosphorylase inhibitors, which have potential as antidiabetic agents, is described. Initial members of the series showed good enzyme inhibitory potency but poor physical properties. Optimisation of the 1-substituent led to 2,3-dihydroxypropyl compounds which showed good in vitro potency and improved physical properties, together with good DMPK profiles and acute in vivo efficacy in a rat model. X-ray crystallographic data are presented, showing an unexpected variety of binding orientations at the dimer interface site. 相似文献
79.
The Toll/IL-1 receptor (TIR) domain plays a central role in Toll-like receptor (TLR) signalling. All TLRs contain a cytoplasmic TIR domain, which, upon activation, acts as a scaffold to recruit adaptor proteins. The adaptor proteins MyD88, Mal, TRIF, TRAM and SARM are also characterized by the presence of a TIR domain. MyD88, Mal, TRIF and TRAM associate with the TLRs via homophilic TIR domain interactions whereas SARM utilizes its TIR domain to negatively regulate TRIF. It is well established that the differential recruitment of adaptors to TLRs provides a significant amount of specificity to the TLR-signalling pathways. Despite this, the TIR-TIR interface has not been well defined. However, structural studies have indicated the importance of TIR domain surfaces in mediating specific TIR-TIR interactions. Furthermore, recent findings regarding the regulation of adaptors provide further insight into the crucial role of the TIR domain in TLR signalling. 相似文献
80.