Muscle active force-length curve explained by an electrophysical model of interfilament spacing

The active isometric force-length relation (FLR) of striated muscle sarcomeres is central to understanding and modeling muscle function. The mechanistic basis of the descending arm of the FLR is well explained by the decreasing thin:thick filament overlap that occurs at long sarcomere lengths. The mechanistic basis of the ascending arm of the FLR (the decrease in force that occurs at short sarcomere lengths), alternatively, has never been well explained. Because muscle is a constant-volume system, interfilament lattice distances must increase as sarcomere length shortens. This increase would decrease thin and thick-filament electrostatic interactions independently of thin:thick filament overlap. To examine this effect, we present here a fundamental, physics-based model of the sarcomere that includes filament molecular properties, calcium binding, sarcomere geometry including both thin:thick filament overlap and interfilament radial distance, and electrostatics. The model gives extremely good fits to existing FLR data from a large number of different muscles across their entire range of measured activity levels, with the optimized parameter values in all cases lying within anatomically and physically reasonable ranges. A local first-order sensitivity analysis (varying individual parameters while holding the values of all others constant) shows that model output is most sensitive to a subset of model parameters, most of which are related to sarcomere geometry, with model output being most sensitive to interfilament radial distance. This conclusion is supported by re-running the fits with only this parameter subset being allowed to vary, which increases fit errors only moderately. These results show that the model well reproduces existing experimental data, and indicate that changes in interfilament spacing play as central a role as changes in filament overlap in determining the FLR, particularly on its ascending arm.     

Rigidity loss of protein macromolecule induced by force—Effective field theory

In the framework of the effective field theory for the order parameter, which characterizes the degree of deviating the protein globule structure from its native state, the phase transition of the protein macromolecule from the elastic state into the plastic one under its mechanical stretching is considered. Elastic properties of a protein are studied as a function of the applied force, temperature, and the mean coordination number of the protein “network.” Proteins 2014; 82:966–974. © 2013 Wiley Periodicals, Inc.     

Whisking mechanics and active sensing

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Rigidity sensing at the leading edge through alphavbeta3 integrins and RPTPalpha

Cells require optimal substrate stiffness for normal function and differentiation. The mechanisms for sensing matrix rigidity and durotaxis, however, are not clear. Here we showed that control, Shp2-/-, integrin beta1-/-, and talin1-/- cell lines all spread to a threefold greater area on fibronectin (FN)-coated rigid polyacrylamide surfaces than soft. In contrast, RPTPalpha-/- cells spread to the same area irrespective of rigidity on FN surfaces but spread 3x greater on rigid collagen IV-coated surfaces than soft. RPTPalpha and alphavbeta3 integrins were shown previously to be colocalized at leading edges and antibodies to alphavbeta3 blocked FN rigidity sensing. When FN beads were held with a rigid laser trap at the leading edge, stronger bonds to the cytoskeleton formed than when held with a soft trap; whereas back from the leading edge and in RPTPalpha-/- cells, weaker bonds were formed with both rigid and soft laser traps. From the rigidity of the trap, we calculate that a force of 10 pN generated in 1 s is sufficient to activate the rigidity response. We suggest that RPTPalpha and alphavbeta3 at the leading edge are critical elements for sensing FN matrix rigidity possibly through SFK activation at the edge and downstream signaling.     

Sensory acquisition in active sensing systems

A defining feature of active sensing is the use of self-generated energy to probe the environment. Familiar biological examples include echolocation in bats and dolphins and active electrolocation in weakly electric fish. Organisms that utilize active sensing systems can potentially exert control over the characteristics of the probe energy, such as its intensity, direction, timing, and spectral characteristics. This is in contrast to passive sensing systems, which rely on extrinsic energy sources that are not directly controllable by the organism. The ability to control the probe energy adds a new dimension to the task of acquiring relevant information about the environment. Physical and ecological constraints confronted by active sensing systems include issues of signal propagation, attenuation, speed, energetics, and conspicuousness. These constraints influence the type of energy that organisms use to probe the environment, the amount of energy devoted to the process, and the way in which the nervous system integrates sensory and motor functions for optimizing sensory acquisition performance.     

Modification of sodium channel gating by lanthanum. Some effects that cannot be explained by surface charge theory

In clonal pituitary (GH3) cells we studied the changes in sodium channel gating caused by substitution of La3+ for Ca2+ ion. Gating of sodium channels was simplified by using intracellular papain to remove inactivation. To quantify La effects, we empirically fitted closing and the late phase of opening of the channels with single exponentials, determined the opening (a) and closing (b) rate, and plotted these rates as a function of Vm (membrane voltage). The midpoint of the fraction open-Vm curve was also determined. Changing from Ca to La shifted the curves for these three measures of Na channel gating along the voltage axis and changed their shape somewhat. Surface charge theory, in the form usually presented, predicts equal shifts of all three curves, with no change in shape. We found, however, that the shift for each of the measurements was different. 2 mM La, for example, shifted opening kinetics by +52 mV (i.e., 52 mV must be added to the depolarization to make activation in 2 mM La as fast as in 2 mM Ca), the fraction open voltage curve by +42.5 mV, and the closing rate curve by +28 mV. The shift was an almost linear function of log [La] for each of the measures. The main finding is that changing from 2 mM Ca to 10 microM La causes a positive shift of the opening rate and fraction open curves, but a negative shift of the closing rate curve. The opposite signs of the two effects cannot be explained in terms of surface charge theory. We briefly discuss some alternatives to this theory.     

Thirty-five years of synchrony in the organic matter concentrations of Swedish rivers explained by variation in flow and sulphate

Increasing concentrations of organic matter (OM) in surface waters have been noted over large parts of the boreal/nemoral zone in Europe and North America. This has raised questions about the causes and the likelihood of further increases. A number of drivers have been proposed, including temperature, hydrology, as well as ‐ and Cl^? deposition. The data reported so far, however, have been insufficient to define the relative importance of different drivers in landscapes where they interact. Thirty‐five years of monthly measurements of absorbance and chemical oxygen demand (COD), two common proxies for OM, from 28 large Scandinavian catchments provide an unprecedented opportunity to resolve the importance of hypothesized drivers. For 21 of the catchments, there are 18 years of total organic carbon (TOC) measurements as well. Despite the heterogeneity of the catchments with regards to climate, size and land use, there is a high degree of synchronicity in OM across the entire region. Rivers go from widespread trends of decreasing OM to increasing trends and back again three times in the 35‐year record. This synchronicity in decadal scale oscillations and long‐term trends suggest a common set of dominant OM drivers in these landscapes. Here, we use regression models to test the importance of different potential drivers. We show that flow and together can predict most of the interannual variability in OM proxies, up to 88% for absorbance, up to 78% for COD. Two other candidate drivers, air temperature and Cl^?, add little explanatory value. Declines in anthropogenic since the mid‐1970s are thus related to the observed OM increases in Scandinavia, but, in contrast to many recent studies, flow emerges as an even more important driver of OM variability. Stabilizing levels also mean that hydrology is likely to be the major driver of future variability and trends in OM.     

70% efficiency of bistate molecular machines explained by information theory,high dimensional geometry and evolutionary convergence

The relationship between information and energy is key to understanding biological systems. We can display the information in DNA sequences specifically bound by proteins by using sequence logos, and we can measure the corresponding binding energy. These can be compared by noting that one of the forms of the second law of thermodynamics defines the minimum energy dissipation required to gain one bit of information. Under the isothermal conditions that molecular machines function this is joules per bit ( is Boltzmann''s constant and T is the absolute temperature). Then an efficiency of binding can be computed by dividing the information in a logo by the free energy of binding after it has been converted to bits. The isothermal efficiencies of not only genetic control systems, but also visual pigments are near 70%. From information and coding theory, the theoretical efficiency limit for bistate molecular machines is ln 2 = 0.6931. Evolutionary convergence to maximum efficiency is limited by the constraint that molecular states must be distinct from each other. The result indicates that natural molecular machines operate close to their information processing maximum (the channel capacity), and implies that nanotechnology can attain this goal.     

Delayed-relaxed response explained by hyperactivation of RelE

Escherichia coli encodes two rel loci, both of which contribute to the control of synthesis of macromolecules during amino acid starvation. The product of relA (ppGpp synthetase I) is responsible for the synthesis of guanosine tetraphosphate, ppGpp, the signal molecule that exerts stringent control of stable RNA synthesis. The second rel locus, relBE, was identified by mutations in relB that confer a so-called 'delayed-relaxed response' characterized by continued RNA synthesis after a lag period of approximately 10 min after the onset of amino acid starvation. We show here that the delayed-relaxed response is a consequence of hyperactivation of RelE. As in wild-type cells, [ppGpp] increased sharply in relB101 relE cells after the onset of starvation, but returned rapidly to the prestarvation level. RelE is a global inhibitor of translation that is neutralized by RelB by direct protein-protein interaction. Lon protease activates RelE during amino acid starvation by degradation of RelB. We found that mutations in relB that conferred the delayed-relaxed phenotype destabilized RelB. Such mutations confer severe RelE-dependent inhibition of translation during amino acid starvation, indicating hyperactivation of RelE. Hyperactivation of RelE during amino acid starvation was shown directly by measurement of RelE-mediated cleavage of tmRNA. The RelE-mediated shutdown of translation terminated amino acid consumption and explains the rapid restoration of the ppGpp level observed in relB mutant cells. Restoration of the prestarvation level of ppGpp, in turn, allows for the resumption of stable RNA synthesis seen during the delayed-relaxed response.     

Daphnia revisited: local stability and bifurcation theory for physiologically structured population models explained by way of an example

We consider the interaction between a general size-structured consumer population and an unstructured resource. We show that stability properties and bifurcation phenomena can be understood in terms of solutions of a system of two delay equations (a renewal equation for the consumer population birth rate coupled to a delay differential equation for the resource concentration). As many results for such systems are available (Diekmann et al. in SIAM J Math Anal 39:1023–1069, 2007), we can draw rigorous conclusions concerning dynamical behaviour from an analysis of a characteristic equation. We derive the characteristic equation for a fairly general class of population models, including those based on the Kooijman–Metz Daphnia model (Kooijman and Metz in Ecotox Env Saf 8:254–274, 1984; de Roos et al. in J Math Biol 28:609–643, 1990) and a model introduced by Gurney–Nisbet (Theor Popul Biol 28:150–180, 1985) and Jones et al. (J Math Anal Appl 135:354–368, 1988), and next obtain various ecological insights by analytical or numerical studies of special cases.     

Feedback control in active sensing: rat exploratory whisking is modulated by environmental contact

Rats sweep their facial whiskers back and forth to generate tactile sensory information through contact with environmental structure. The neural processes operating on the signals arising from these whisker contacts are widely studied as a model of sensing in general, even though detailed knowledge of the natural circumstances under which such signals are generated is lacking. We used digital video tracking and wireless recording of mystacial electromyogram signals to assess the effects of whisker-object contact on whisking in freely moving animals exploring simple environments. Our results show that contact leads to reduced protraction (forward whisker motion) on the side of the animal ipsilateral to an obstruction and increased protraction on the contralateral side. Reduced ipsilateral protraction occurs rapidly and in the same whisk cycle as the initial contact. We conclude that whisker movements are actively controlled so as to increase the likelihood of environmental contacts while constraining such interactions to involve a gentle touch. That whisking pattern generation is under strong feedback control has important implications for understanding the nature of the signals reaching upstream neural processes.     

The concept of matter in modern atomic theory

In biology the idea of matter as something passive has been abandoned in favour of the idea that matter has the capacity of self-activity. In modern physics too matter functions more as an agent, with which the experimenter has a relation, than as passive material which he can handle as he likes. So in both fields of study the antithesis between idealism and materialism has been given up, so that the relation instead of the difference between man and nature became the starting point of scientific inquiry.     

Cell formation by myxozoan species is not explained by dogma

Eukaryotes form new cells through the replication of nuclei followed by cytokinesis. A notable exception is reported from the class Myxosporea of the phylum Myxozoa. This assemblage of approximately 2310 species is regarded as either basal bilaterian or cnidarian, depending on the phylogenetic analysis employed. For myxosporeans, cells have long been regarded as forming within other cells by a process referred to as endogenous budding. This would involve a nucleus forming endoplasmic reticulum around it, which transforms into a new plasma membrane, thus enclosing and separating it from the surrounding cell. This remarkable process, unique within the Metazoa, is accepted as occurring within stages found in vertebrate hosts, but has only been inferred from those stages observed within invertebrate hosts. Therefore, I conducted an ultrastructural study to examine how internal cells are formed by a myxosporean parasitizing an annelid. In this case, actinospore parasite stages clearly internalized existing cells; a process with analogies to the acquisition of endosymbiotic algae by cnidarian species. A subsequent examination of the myxozoan literature did not support endogenous budding, indicating that this process, which has been a central tenet of myxozoan developmental biology for over a century, is dogma.     

Enantioselective sensing of chiral amino acids by potentiometric sensors based on optical active polyaniline films

A novel enantioselective potentiometric sensor was constructed based on optical active polyaniline (PAn) films. The sensor with high stability showed discrimination behavior toward one isomer of racemic phenylalanine (Phe). The (-) or (+) PAn-based electrodes exhibited an excellent Nernstian slope of approximately 60 mV per decade for L-Phe or D-Phe, respectively. In addition, when the sensor was exposed to the mixture of enantiomers, the slope of the response changed along with their proportions, which would be employed as an index of the enantiomeric purity of the mixture. At last, the mechanism of chiral discrimination for Phe was discussed.     

Contributions to the theory of active transport

A system consisting of two solutions separated by a membrane may be in one of four possible states: (1) transient, (2) steady, (3) equilibrium, or (4) pseudo-equilibrium. The latter state denotes that in the solutions the net flow of all components is zero but at least one of the components is not in thermodynamic equilibrium. Transient and steady-state systems may or may not have active transport. Thus only systems in either equilibrium or pseudo-equilibrium are considered in this paper, since the former indicates that there is no active transport, whereas in the latter case there always is active transport. This simplifies the problem of finding whether a system does or does not have an active transport mechanism, since it is frequently fairly easy to determine experimentally whether a system is in equilibrium or pseudo-equilibrium. The assumption that electric neutrality exists within very thin membranes is shown not to be valid. However, electric neutrality does exist in the solutions in a system in a pseudo-equilibrium state with fixed charges and impermeative ions. It is then shown how the presence and sign of an electric potential may be found by use of electroneutrality. The mechanism of active transport may be due to a general force acting on all particles of a particular component or to an individual force acting on the individual particles of a particular component. A general solvent flow or a diffusion drag force illustrates the first mechanism while the second is accomplished by either a carrier or a Maxwell Demon. The general type of active transport has been extensively treated in the literature, while the individual type has not been treated in a generalized form. Therefore, the individual type of active transport is discussed at length, and a simple illustrative model is intensively analyzed. Following this, there is a discossion of the Maxwell Demon and some models of it are presented. This research was supported by the United States Air Force through the Air Force Office of Scientific Research of the Air Research and Development Command under contract No. AF 18(600) 1454.     

广西中南部耕地土壤有机质和全氮变化的遥感监测

以1981年、2011年土壤数据为基础,以AVHRR和MODIS遥感影像为数据源,通过研究广西中南部土壤有机质、全氮及其变化与归一化差异植被指数(NDVI)、植被覆盖度、植被净初级生产力(NPP)等遥感因子之间的耦合关系,建立表层土壤有机质、全氮含量变化的遥感监测模型。研究表明:近30年来,研究区土壤有机质、全氮变化均呈极显著上升趋势,分别增加了5.43g/kg和0.21g/kg;1981—2011年间,NDVI、植被覆盖度和NPP 3个遥感因子变化趋势一致,均呈现缓慢上升趋势,且遥感因子变化与有机质、全氮变化均具有显著正相关关系;利用逐步线性回归方法,建立土壤有机质、全氮变化的遥感监测模型,分别能够解释有机质、全氮变化的16.9%和20.3%;根据所建模型对研究区耕地土壤有机质、全氮变化可进行空间预测制图。结果表明,研究区内耕地土壤表层有机质、全氮分别上升了6.65g/kg和0.31g/kg,验证结果显示遥感模型能够反映出不同区域土壤有机质和全氮长期变化的空间特征。     

Rigidity of microtubules is increased by stabilizing agents

Microtubules are rigid polymers that contribute to the static mechanical properties of cells. Because microtubules are dynamic structures whose polymerization is regulated during changes in cell shape, we have asked whether the mechanical properties of microtubules might also be modulated. We measured the flexural rigidity, or bending stiffness, of individual microtubules under a number of different conditions that affect the stability of microtubules against depolymerization. The flexural rigidity of microtubules polymerized with the slowly hydrolyzable nucleotide analogue guanylyl-(alpha, beta)- methylene-diphosphonate was 62 +/- 9 x 10(-24) Nm2 (weighted mean +/- SEM); that of microtubules stabilized with tau protein was 34 +/- 3 x 10(-24) Nm2; and that of microtubules stabilized with the antimitotic drug taxol was 32 +/- 2 x 10(-24) Nm2. For comparison, microtubules that were capped to prevent depolymerization, but were not otherwise stabilized, had a flexural rigidity of 26 +/- 2 x 10(-24) Nm2. Decreasing the temperature from 37 degrees C to approximately 25 degrees C, a condition that makes microtubules less stable, decreased the stiffness of taxol-stabilized microtubules by one-third. We thus find that the more stable a microtubule, the higher its flexural rigidity. This raises the possibility that microtubule rigidity may be regulated in vivo. In addition, the high rigidity of an unstabilized, GDP-containing microtubule suggests that a large amount of energy could be stored as mechanical strain energy in the protein lattice for subsequent force generation during microtubule depolymerization.