Frequencies of paired open-closed durations of ion channels. Method of evaluation from single-channel recordings.

The probability of the occurrence of consecutive closed-open or open-closed intervals of specified durations in single-channel recordings may be of enormous help in the establishment of the kinetic scheme that describes the behavior of the channel. The relevant probability functions are linear combinations of products of exponential functions of the closed durations and the open durations. A method is presented for the evaluation of the coefficients of the exponential functions using a set of auxiliary functions that are each orthogonal to all but one of the exponential functions. The coefficients in the probability functions may then be obtained from the experimental data by multiplication by the auxiliary functions and subsequent simple integration operations. Furthermore, the variance to be expected in the evaluated numerical magnitude of the parameters, due to the stochastic nature of the transitions in the channel conductance, is also readily estimated by use of the above auxiliary functions. The procedure is illustrated by analysis of synthetic data obtained from computer simulated experiments.     

Tilt aftereffects generated by symmetrical dot patterns with two or four axes of symmetry

This paper follows from studies by Joung, van der Zwan and Latimer (2000) in which symmetrical dot patterns with one axis of symmetry were used to produce tilt aftereffects (TAEs). The present paper investigates TAE functions produced by symmetrical dot patterns with multiple axes of symmetry. In Experiments 1 and 2, TAE functions produced by dot patterns with two axes of symmetry were compared with TAE functions produced by line stimuli arranged in the same orientation and location as the axes of symmetry in the dot patterns. Similar functions were found. In Experiments 3 and 4, functions produced by dot patterns with four axes of symmetry were compared with functions produced by line stimuli arranged in the same orientation and location as the four axes of symmetry. Again, similar functions were found. These experiments demonstrate that line stimuli and dot stimuli produce similar TAE functions. The implications of these results are discussed.     

Space for people,plants, and livestock? Quantifying interactions among multiple landscape functions in a Dutch rural region

Rural landscapes are often multifunctional, meaning that at one single location different goods and services are being provided. Multifunctionality is spatially heterogeneous as not all areas are equally suitable to supply multiple goods and services. This suitability depends on favourable biophysical and socio-economic conditions and interactions among landscape functions. The objective of this paper is to identify and quantify interactions among landscape functions in a diverse and dynamic rural region, the Gelderse Vallei in the Netherlands. To be able to study these interactions first seven landscape functions (residential, intensive livestock, cultural heritage, tourism, plant habitat, arable production, and leisure cycling) are quantified and mapped using landscape indicators. These landscape function maps are subsequently aggregated to identify and quantify multifunctionality. The results of these analyses are used to study three aspects of landscape function interactions (a) influence of landscape characteristics on function interactions, (b) interrelations among landscape functions and (c) effect of multifunctionality on the different landscape functions. Landscape functions do not equally interact with one another, some landscape functions are affected negatively by the presence of other functions while other landscape functions benefit from multifunctionality. At multifunctionality hot spots different landscape functions are present that are enhancing one another. Additionally, in our study area it appears that mainly locations with landscape functions that sub-optimally provide goods and services are strongly multifunctional. Quantification and an improved understanding of landscape interactions will help to design and evaluate spatial policies related to the provision of multiple goods and services by the landscape.     

Cross-validation of Non-linear Growth Functions for Modelling Tree Height–Diameter Relationships

Six non-linear growth functions were fitted to tree height–diameter data of ten conifer species collected in the inland Northwest of the United States. The data sets represented a wide range of tree sizes, especially large-sized trees. According to the model statistics, the six growth functions fitted the data equally well, but resulted in different asymptote estimates. The model prediction performance was evaluated using Monte Carlo cross-validation or data splitting for 25-cm diameter classes. All six growth functions yielded similar mean prediction errors for small- and middle-sized trees. For large-sized trees [e.g. DBH (diameter at breast height)>100 cm], however, five of the six growth functions (except the Gompertz function) overestimated tree heights for western white pine, western larch, Douglas-fir, subalpine fir, and ponderosa pine, but underestimated tree heights for western hemlock and Engelmann spruce. Among these five functions, the Korf/Lundqvist and Exponential functions produced larger overestimations. The Schnute, Weibull, and Richards functions were superior in prediction performance to others. The Gompertz function seemed always to underestimate tree heights for large-sized trees.     

Evaluating CASP4 predictions with physical energy functions

Physical energy scoring functions based on implicit solvation models are tested by evaluating predictions from the most recent CASP4 competition. The best performing scoring functions are identified along with the best protocol for preparing structures before energies are evaluated. Ranking of structures with the best scoring functions is compared across CASP4 targets to establish when physical scoring functions can be expected to reliably distinguish structures that are most similar to the native fold in a set of misfolded or unfolded protein conformations. The results are used to interpret previous studies where scoring functions were tested on the standard decoy sets by Park, Levitt, and Baker. We show that the best physical scoring functions can be applied successfully in automated consensus scoring applications where a single best conformation has to be selected from a set of structures from different sources. Finally, the potential for better protein structure scoring functions is discussed with a suggestion for an empirically parameterized linear combination of energy components.     

Evolutionary innovations and the organization of protein functions in genotype space

The organization of protein structures in protein genotype space is well studied. The same does not hold for protein functions, whose organization is important to understand how novel protein functions can arise through blind evolutionary searches of sequence space. In systems other than proteins, two organizational features of genotype space facilitate phenotypic innovation. The first is that genotypes with the same phenotype form vast and connected genotype networks. The second is that different neighborhoods in this space contain different novel phenotypes. We here characterize the organization of enzymatic functions in protein genotype space, using a data set of more than 30,000 proteins with known structure and function. We show that different neighborhoods of genotype space contain proteins with very different functions. This property both facilitates evolutionary innovation through exploration of a genotype network, and it constrains the evolution of novel phenotypes. The phenotypic diversity of different neighborhoods is caused by the fact that some functions can be carried out by multiple structures. We show that the space of protein functions is not homogeneous, and different genotype neighborhoods tend to contain a different spectrum of functions, whose diversity increases with increasing distance of these neighborhoods in sequence space. Whether a protein with a given function can evolve specific new functions is thus determined by the protein's location in sequence space.     

What controls TOR?

The target of rapamycin (TOR) is a protein kinase with numerous functions in cell growth control. Some of these functions can be potently inhibited by rapamycin, an immunosuppressive and potential anticancer drug. TOR exists as part of two functionally distinct protein complexes. The functions of TOR complex 1 (TORC1) are effectively inhibited by rapamycin, but the mechanism for this inhibition remains elusive. The identification of TORC2 and recent reports that rapamycin can inhibit TORC2 functions, in some cases, challenge current models of TOR regulation. This review discusses the latest findings in yeast and mammals on the possible mechanisms that control TOR activity leading to its many cellular functions     

青藏高原生态系统土壤保持功能及其价值

在 GIS手段支持下 ,运用通用土壤流失方程 ( USLE)研究了青藏高原生态系统土壤保持功能 ,并评价了其经济价值。研究表明 ,在总面积为 1 .49× 1 0 8hm2的青藏高原林地、草地、沼泽和农田生态系统上 ,土壤保持总量为 3.77× 1 0 8t/a,其经济价值总计为 5 .5 9× 1 0 8RMB/a,占西藏和青海两省 (区 ) 2 0 0 0年种植业、林业和牧业收入的 6.1 7%。其中保持土壤养分的经济价值为 3.68× 1 0 8RMB/a,减少废弃土地的经济价值为0 .2 6× 1 0 8RMB/a,减少泥沙淤积的经济价值为 2 .0 0× 1 0 8RMB/a。由此可见 ,青藏高原生态系统服务功能对当地社会和经济发展有着重要的作用     

Expression of fetal and neonatal hepatic functions by mouse hepatoma-rat hepatoma hybrids

In order to analyze the mechanisms implicated in the expression of differentiated functions during development, we have studied ten hybrid clones arising from fusion of cells of a mouse hepatoma characterized by the expression of only fetal hepatic functions with those of a rat hepatoma which express, like adult hepatocytes, a set of neonatal as well as fetal hepatic functions. The cells of most hybrid clones contain one set of chromosomes of each parent and coexpress the hepatic functions common to both parents. Among the hepatic proteins characteristic of only one parental line, some continue to be expressed while others are extinguished. The three functions out of the eight examined which are subject to extinction are expressed uniquely by the rat parental cells and appear only near or at birth during normal liver development. These results suggest that regulatory mechanisms (whose final effect is negative) operate in fetal cells to inhibit the expression of differentiated functions limited to a later stage of development.     

Multiple stressors and multifunctionality: limited effects on an illuminated benthic system

The bulk of experiments that study stressor effects on ecosystem functioning consider only individual functions one at a time, and such narrow focus may well bias our understanding of the overall impact on ecosystem functioning. We used data from six published experiments in which marine illuminated sediment systems were exposed to nutrient enrichment, toxicants, sedimentation and warming, either alone or in combination. Measured functions were primary production, community respiration, inorganic nitrogen and phosphorus fluxes, and autotrophic biomass. We calculated two indices of multifunctionality that simultaneously considered all six functions: (i) a weighted average level of the functions and (ii) the number of functions that simultaneously exceed a critical threshold level. Stressors affected individual functions both positively and negatively, but multifunctionality was generally unaffected by both single and joint stressors. The filtering capacity of coastal illuminated sediment systems thus appears resilient to exposure to moderate levels of multiple stressors, most probably due to the robustness of the benthic microalgal community. We recommend using a multifunctionality approach in future studies on cumulative stressor effects on ecosystem functioning, particularly when considering functions related to ecosystem services.     

京津冀地区县域耕地景观多功能性评价

随着城镇化发展和农业产业化升级,耕地景观功能由单一的生产功能向经济功能、生态功能、文化功能拓展,耕地景观多功能性成为新的学术热点。已有研究往往侧重于探讨耕地功能的多指数耦合,缺乏耕地景观多重功能空间定量化与相互关联的分析。以京津冀地区为研究区,对耕地景观的粮食供给功能、生境维持功能、景观连通功能、土壤保持功能、景观美学功能和人口承载功能六项功能及其冷热点聚集区分别空间定量化,评价县域尺度耕地景观多功能性,并识别耕地景观多种功能的空间关联。研究结果表明,京津冀中部平原地区粮食供给功能显著,南部平原地区景观连通功能突出,燕山与太行山山脉土壤保持功能、维持生境功能最高,山前平原地带人口承载功能相对重要。2010年京津冀地区耕地景观功能总体呈现南高北低的分布格局,但功能高低值分布规律差异明显,各功能全部处于高值或低值的样本极少;耕地景观不同功能间的权衡与协同关系数量相当,景观连通功能与粮食供给功能呈现明显协同关系,而与土壤保持功能呈现较强权衡关联。     

Re-expression of hepatic functions in mouse hepatoma X rat hepatoma hybrids

Abstract. Neonatal hepatic functions are selectively extinguished in hybrids between mouse hepatoma cells, that express only fetal hepatic functions, and rat hepatoma cells expressing neonatal as well as fetal functions. A search for hybrid cells reexpressing these neonatal functions was undertaken to determine; (1) whether the selective extinction of neonatal functions is reversible and at what frequency, and (2) whether the reexpression of neonatal functions would be accompanied by modifications in the expression of fetal functions. The criterion used to obtain hybrids showing reexpression was glucose-free medium (G-) where growth requires the presence of the extinguished gluconeogenic enzymes. Even though the parental cells are of the same histotype it proved difficult to obtain re-expression. Survivors in G- were obtained only from hybrids containing a greater than Is complement of rat chromosomes; they reexpress not only gluconeogenic enzymes but also basal tyrosine aminotransferase activity, and the fetal hepatic function a-fetoprotein continues to be expressed in most of the clones. All survivors in G- display a significant loss of chromosomes and this loss concerns essentially mouse chromosomes.     

Moonlighting is mainstream: paradigm adjustment required

Moonlighting--the performance of more than one function by a single protein--is becoming recognized as a common phenomenon with important implications for systems biology and human health. The different functions of a moonlighting protein may use different regions of the protein structure, or alternative structures that occur due to post-translational modifications and/or differences in binding partners. Often the different functions of moonlighting proteins are used at different times or in different places. The existence of moonlighting functions complicates efforts to understand metabolic and regulatory networks, as well as physiological and pathological processes in organisms. Because moonlighting functions can play important roles in disease processes, an improved understanding of moonlighting proteins will provide new opportunities for pharmacological manipulations that specifically target a function involved in pathology while sparing physiologically important functions.     

Coordinate expression of parietal endodermal functions in hybrids of embryonal carcinoma and endodermal cells.

A derivative, FOT5, of the F9 murine embryonal carcinoma cell line which is resistant to ouabain and thioguanine was fused with a near diploid parietal endodermal cell line, PFHR9, Hybrid clones (ENEC1 to ENEC5) were isolated in HAT Medium containing ouabain at a frequency of approximately 2 x 10(-4). The DNA contents and chromosome number of the ENEC hybrids were approximately the sum of those of the parents. Five hybrid cell lines examined in detail expressed the following parietal endodermal functions: plasminogen activator activity, basement membrane proteins, and endodermal cytoskeletal proteins. Embryonal carcinoma characteristic functions (tumorigenicity, a stage specific embryonic antigen, and high alkaline phosphatase activity) were extinguished in the hybrids. No hybrid clones with embryonal carcinoma morphology were observed among 1,358 hybrid clones examined. Hybrids, propagated for over 100 generations, continued to express endodermal functions and not embryonal carcinoma functions. The coordinate expression of endodermal functions and the extinction of embryonal carcinoma functions in the ENEC hybrids suggest that the parietal endodermal cells contain diffusible activities which extinguish embryonal carcinoma functions and possibly cause the embryonal carcinoma genome to express parietal endodermal characteristics.     

Re-expression of hepatic functions in mouse hepatoma X rat hepatoma hybrids

Neonatal hepatic functions are selectively extinguished in hybrids between mouse hepatoma cells, that express only fetal hepatic functions, and rat hepatoma cells expressing neonatal as well as fetal functions. A search for hybrid cells reexpressing these neonatal functions was undertaken to determine; (1) whether the selective extinction of neonatal functions is reversible and at what frequency, and (2) whether the re-expression of neonatal functions would be accompanied by modifications in the expression of fetal functions. The criterion used to obtain hybrids showing re-expression was glucose-free medium (G) where growth requires the presence of the extinguished gluconeogenic enzymes. Even though the parental cells are of the same histotype it proved difficult to obtain re-expression. Survivors in G- were obtained only from hybrids containing a greater than 1s complement of rat chromosomes; they reexpress not only gluconeogenic enzymes but also basal tyrosine aminotransferase activity, and the fetal hepatic function alpha-fetoprotein continues to be expressed in most of the clones. All survivors in G- display a significant loss of chromosomes and this loss concerns essentially mouse chromosomes.     

Sex assessment on the basis of long bone circumference

Discriminant functions have long been used to classify individuals into groups according to the dimensions of their bones. Although lengths, widths, and diameters have been extensively used, the circumferences have not been adequately validated. In this work, the importance that the circumferences of long bones can have in assigning the sex of ancient human remains is demonstrated. The functions produced by using just one circumference achieved accuracies higher than 80%, and circumference at the radial tuberosity of the radius is able to classify 92.8% of skeletons from the Late Roman site of Mas Rimbau/Mas Mallol (Spain). When functions are produced by using more than one circumference, they can achieve the uppermost classification attained in this sample. The functions also showed that the arm circumference functions are more useful than those of the leg, probably because male individuals of the population had greater mechanical stress than did females. The classification percentages, as well as other statistical values for the functions, demonstrated the great ability of long bone circumferences in helping to classify the sex of individuals of other sites of the Mediterranean area besides the ones examined in this study.     

The Validity of Quasi-Steady-State Approximations in Discrete Stochastic Simulations

In biochemical networks, reactions often occur on disparate timescales and can be characterized as either fast or slow. The quasi-steady-state approximation (QSSA) utilizes timescale separation to project models of biochemical networks onto lower-dimensional slow manifolds. As a result, fast elementary reactions are not modeled explicitly, and their effect is captured by nonelementary reaction-rate functions (e.g., Hill functions). The accuracy of the QSSA applied to deterministic systems depends on how well timescales are separated. Recently, it has been proposed to use the nonelementary rate functions obtained via the deterministic QSSA to define propensity functions in stochastic simulations of biochemical networks. In this approach, termed the stochastic QSSA, fast reactions that are part of nonelementary reactions are not simulated, greatly reducing computation time. However, it is unclear when the stochastic QSSA provides an accurate approximation of the original stochastic simulation. We show that, unlike the deterministic QSSA, the validity of the stochastic QSSA does not follow from timescale separation alone, but also depends on the sensitivity of the nonelementary reaction rate functions to changes in the slow species. The stochastic QSSA becomes more accurate when this sensitivity is small. Different types of QSSAs result in nonelementary functions with different sensitivities, and the total QSSA results in less sensitive functions than the standard or the prefactor QSSA. We prove that, as a result, the stochastic QSSA becomes more accurate when nonelementary reaction functions are obtained using the total QSSA. Our work provides an apparently novel condition for the validity of the QSSA in stochastic simulations of biochemical reaction networks with disparate timescales.     

The Validity of Quasi-Steady-State Approximations in Discrete Stochastic Simulations

In biochemical networks, reactions often occur on disparate timescales and can be characterized as either fast or slow. The quasi-steady-state approximation (QSSA) utilizes timescale separation to project models of biochemical networks onto lower-dimensional slow manifolds. As a result, fast elementary reactions are not modeled explicitly, and their effect is captured by nonelementary reaction-rate functions (e.g., Hill functions). The accuracy of the QSSA applied to deterministic systems depends on how well timescales are separated. Recently, it has been proposed to use the nonelementary rate functions obtained via the deterministic QSSA to define propensity functions in stochastic simulations of biochemical networks. In this approach, termed the stochastic QSSA, fast reactions that are part of nonelementary reactions are not simulated, greatly reducing computation time. However, it is unclear when the stochastic QSSA provides an accurate approximation of the original stochastic simulation. We show that, unlike the deterministic QSSA, the validity of the stochastic QSSA does not follow from timescale separation alone, but also depends on the sensitivity of the nonelementary reaction rate functions to changes in the slow species. The stochastic QSSA becomes more accurate when this sensitivity is small. Different types of QSSAs result in nonelementary functions with different sensitivities, and the total QSSA results in less sensitive functions than the standard or the prefactor QSSA. We prove that, as a result, the stochastic QSSA becomes more accurate when nonelementary reaction functions are obtained using the total QSSA. Our work provides an apparently novel condition for the validity of the QSSA in stochastic simulations of biochemical reaction networks with disparate timescales.