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51.
Spatiotemporal patterns of action potentials are considered to be closely related to information processing in the brain. Auto-generating neurons contributing to these processing tasks are known to cause multifractal behavior in the inter-spike intervals of the output action potentials. In this paper we define a novel relationship between this multifractality and the adaptive Nernst equilibrium in hippocampal neurons. Using this relationship we are able to differentiate between various drugs at varying dosages. Conventional methods limit their ability to account for cellular charge depletion by not including these adaptive Nernst equilibria. Our results provide a new theoretical approach for measuring the effects which drugs have on single-cell dynamics.  相似文献   
52.
HIV infection is one of the most difficult infections to control and manage. The most recent recommendations to control this infection vary according to the guidelines used (US, European, WHO) and are not patient-specific. Unfortunately, no two individuals respond to infection and treatment quite the same way. The purpose of this paper is to make use of the uncertainty and sensitivity analysis to investigate possible short-term treatment options that are patient-specific. We are able to identify the most significant parameters that are responsible for ART outcome and to formulate some insights into the ART success.  相似文献   
53.
Narrowly dispersed, temperature-responsive BAB block copolymers capable of forming physical gels under physiological conditions were synthesized via aqueous reversible addition fragmentation chain transfer (RAFT) polymerization. The use of a difunctional trithiocarbonate facilitates the two-step synthesis of BAB copolymers with symmetrical outer blocks. The outer B blocks of the triblock copolymers consist of poly(N-isopropylacrylamide) (PNIPAM) and the inner A block consists of poly(N,N-dimethylacrylamide). The copolymers form reversible physical gels above the phase transition temperature of PNIPAM at concentrations as low as 7.5 wt % copolymer. Mechanical properties similar to collagen, a naturally occurring polypeptide used as a three-dimensional in vitro cell growth scaffold, have been achieved. Herein, we report the mechanical properties of the gels as a function of solvent, polymer concentration, and inner block length. Structural information about the gels was obtained through pulsed field gradient NMR experiments and confocal microscopy.  相似文献   
54.
Circulating T lymphocytes enter a tissue if they express appropriate chemokine receptors and adhesion molecules to engage ligands presented at this site. To aid rational development of T cell-based therapies for Hodgkin's lymphoma (HL), we have assessed the expression and function of homing receptors on tumour-infiltrating T cells in HL and compared them with T cells from unaffected lymph nodes and colorectal cancer tissue. Chemokine receptors CXCR3, CXCR4 and CCR7 were expressed on a large proportion of T cells within HL tissue and mediated chemotaxis to purified chemokine. The corresponding ligands (CXCL10, CXCL12, CCL21) were expressed on the malignant cells and/or vascular endothelium. Adhesion molecules including CD62L were widely expressed on HL-derived T cells and their corresponding ligands were detected on vessels within the tumour. This homing phenotype was distinct from T cells isolated from colorectal cancer, but matched closely the phenotype of T cells from unaffected lymph nodes. Thus, T cell recruitment to HL resembles entry of na?ve/central memory T cells into normal lymph nodes. This has important implications for current approaches to treat HL using T cells activated and expanded in vitro that lack CCR7 and CD62L expression.  相似文献   
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56.
The functional role of producer diversity in ecosystems   总被引:6,自引:0,他引:6  
Over the past several decades, a rapidly expanding field of research known as biodiversity and ecosystem functioning has begun to quantify how the world's biological diversity can, as an independent variable, control ecological processes that are both essential for, and fundamental to, the functioning of ecosystems. Research in this area has often been justified on grounds that (1) loss of biological diversity ranks among the most pronounced changes to the global environment and that (2) reductions in diversity, and corresponding changes in species composition, could alter important services that ecosystems provide to humanity (e.g., food production, pest/disease control, water purification). Here we review over two decades of experiments that have examined how species richness of primary producers influences the suite of ecological processes that are controlled by plants and algae in terrestrial, marine, and freshwater ecosystems. Using formal meta-analyses, we assess the balance of evidence for eight fundamental questions and corresponding hypotheses about the functional role of producer diversity in ecosystems. These include questions about how primary producer diversity influences the efficiency of resource use and biomass production in ecosystems, how primary producer diversity influences the transfer and recycling of biomass to other trophic groups in a food web, and the number of species and spatial /temporal scales at which diversity effects are most apparent. After summarizing the balance of evidence and stating our own confidence in the conclusions, we outline several new questions that must now be addressed if this field is going to evolve into a predictive science that can help conserve and manage ecological processes in ecosystems.  相似文献   
57.
In numerous cellular studies, cells labeled with radioisotopes have been separated from the labeling medium by an aqueous solution in order to determine the quantity of internalized labels; however, the aqueous wash tends to remove significant labeling from the cells. Therefore, in order to preserve all of the internalized labels, non-aqueous medium such as silicone fluids may be used. The termination of the labeling is achieved in the silicone method when, upon centrifugation, the cells separate from the medium and enter the silicone fluid to sediment to the tube bottom. This sedimentation of cells placed above a layer of silicone fluid exhibits a critical dependence on the centrifugal force, and gives rise to an uncertainty of only 2 s in determining the time of separation of cells from the medium using General Electric F-50 silicone fluid and a modified Beckman J2-21 centrifuge. It is therefore possible to determine the kinetics of incorporation of labeled amino acids into intracellular pools and proteins. In particular, since this silicone wash method determines the size of the total pool and the aqueous wash method determines the size of the acid-extractable pool, the simultaneous measurements of the size of both pools leads to the determination of the kinetics of labeling of the free amino acid pool. Among many possible applications and extensions of these methods, the studies of formation of intracellular pools and relations among different pools of transported molecules, such as water and amino acids, appear promising.  相似文献   
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59.
Yersinia pestis, the agent of plague, is usually transmitted by fleas. To produce a transmissible infection, Y. pestis colonizes the flea midgut and forms a biofilm in the proventricular valve, which blocks normal blood feeding. The enteropathogen Yersinia pseudotuberculosis, from which Y. pestis recently evolved, is not transmitted by fleas. However, both Y. pestis and Y. pseudotuberculosis form biofilms that adhere to the external mouthparts and block feeding of Caenorhabditis elegans nematodes, which has been proposed as a model of Y. pestis-flea interactions. We compared the ability of Y. pestis and Y. pseudotuberculosis to infect the rat flea Xenopsylla cheopis and to produce biofilms in the flea and in vitro. Five of 18 Y. pseudotuberculosis strains, encompassing seven serotypes, including all three serotype O3 strains tested, were unable to stably colonize the flea midgut. The other strains persisted in the flea midgut for 4 weeks but did not increase in numbers, and none of the 18 strains colonized the proventriculus or produced a biofilm in the flea. Y. pseudotuberculosis strains also varied greatly in their ability to produce biofilms in vitro, but there was no correlation between biofilm phenotype in vitro or on the surface of C. elegans and the ability to colonize or block fleas. Our results support a model in which a genetic change in the Y. pseudotuberculosis progenitor of Y. pestis extended its pre-existing ex vivo biofilm-forming ability to the flea gut environment, thus enabling proventricular blockage and efficient flea-borne transmission.  相似文献   
60.
The equilibrium Nernst potential plays a critical role in neural cell dynamics. A common approximation used in studying electrical dynamics of excitable cells is that the ionic concentrations inside and outside the cell membranes act as charge reservoirs and remain effectively constant during excitation events. Research into brain electrical activity suggests that relaxing this assumption may provide a better understanding of normal and pathophysiological functioning of the brain. In this paper we explore time-dependent ionic concentrations by allowing the ion-specific Nernst potentials to vary with developing transmembrane potential. As a specific implementation, we incorporate the potential-dependent Nernst shift into a one-dimensional Morris-Lecar reaction-diffusion model. Our main findings result from a region in parameter space where self-sustaining oscillations occur without external forcing. Studying the system close to the bifurcation boundary, we explore the vulnerability of the system with respect to external stimulations which disrupt these oscillations and send the system to a stable equilibrium. We also present results for an extended, one-dimensional cable of excitable tissue tuned to this parameter regime and stimulated, giving rise to complex spatiotemporal pattern formation. Potential applications to the emergence of neuronal bursting in similar two-variable systems and to pathophysiological seizure-like activity are discussed.  相似文献   
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