Ankle torque control that shifts the center of pressure from heel to toe contributes non-zero sagittal plane angular momentum during human walking

A principle objective of human walking is controlling angular motion of the body as a whole to remain upright. The force of the ground on each foot (F) reflects that control, and recent studies show that in the sagittal plane F exhibits a specific coordination between F direction and center-of-pressure (CP) that is conducive to remaining upright. Typical walking involves the CP shifting relative to the body due to two factors: posterior motion of the foot with respect to the hip (stepping) and motion of the CP relative to the foot (foot roll-over). Recent research has also shown how adjusting ankle torque alone to shift CP relative to the foot systematically alters the direction of F, and thus, could play a key role in upright posture and the F measured during walking. This study explores how the CP shifts due to stepping and foot roll-over contribute to the observed F and its role in maintaining upright posture. Experimental walking kinetics and kinematics were combined with a mechanical model of the human to show that variation in F that was not attributable to foot roll-over had systematic correlation between direction and CP that could be described by an intersection point located near the center-of-mass. The findings characterize a component of walking motor control, describe how typical foot roll-over contributes to postural control, and provide a rationale for the increased fall risk observed in individuals with atypical ankle muscle function.     

Theoretical aspects of specific and non-specific equilibrium binding of proteins to DNA as studied by the nitrocellulose filter binding assay. Co-operative and non-co-operative binding to a one-dimensional lattice

The analysis of equilibrium binding isotherms obtained by methods such as the nitrocellulose filter binding assay, which measure the fraction. θ, of DNA to which at least one protein molecule is bound, as a function of the free protein concentration (L_F) require a different type of theoretical framework from that required for analysis of conventional equilibrium binding data, in which the number of moles of protein bound per mole of DNA, θ_c is measured as a function of L_F. The theoretical framework required to analyse equilibrium binding data generated by measuring θ(L_F) is developed for co-operative and non-co-operative binding of a protein to a large number of non-specific sites and to a specific sites(s) in the presence of a large number of non-specific sites on a DNA molecule. The theory is simple to apply, equations for θ(L_F) being easy to derive and evaluate, and is suitable for least-squares analysis. Two examples of the application of the theory to the analysis of experimental data are provided for the specific and non-specific binding of the EcoRI restriction endonuclease to bacteriophage λ DNA, and for the specific and non-specific binding of the enzyme dihydrofolate reductase from Lactobacillus casei to pBR322 and pWDLcB1 DNA, the latter differing from the former only in a 2.9 × 10³ base-pair insert containing the L. casei dihydrofolate reductase structural gene. The theoretical and experimental advantages and disadvantages of measuring θ(L_F) rather than θ_c(L_F) are discussed.     

Frequency — dependent advantage in wheat

Summary The effect of frequency-dependent advantage in wheat was investigated by growing F₁. hybrid seeds of the crosses (Warimek X Halberd) and (Wariquam x Halberd) in a stand of Halberd at 5 frequencies: 4 %, 6.25 %, 11.11 %, 25 % and 50 %. A reduction of 35 % to 40 % in grain yield of individual plants was observed with both hybrids as their frequencies changed from 4% to 50 %. A similar trend with frequency was noted for several other plant characteristics, including total grain number, particularly with those measured towards the end of the growing season. Halberd plants did not show a corresponding increase as their frequency declined from 96 % to 50%. — The following season, 76 F₄ lines from the cross (Warimek X Halberd) and 70 F₄ lines from (Wariquam x Gabo) were grown at frequencies of 6.25% and 18.75% in machine sown stands of Wariquam and Halberd, respectively. Again grain yield decreased as genotypic frequency increased. Furthermore, there was a positive correlation between frequency-dependent advantage and relative grain yield, suggesting that high yielding genotypes show a greater advantage at low frequencies than lower yielding ones.     

REPRODUCTIVE ISOLATION AND INTROGRESSION BETWEEN NOTROPIS CORNUTUS AND NOTROPIS CHRYSOCEPHALUS (FAMILY CYPRINIDAE): COMPARISON OF MORPHOLOGY,ALLOZYMES, AND MITOCHONDRIAL DNA

Hybrid zones in fluvial fishes may be heterogeneous from drainage to drainage. The comparison of data from morphology, allozymes, and mitochondrial DNA (mtDNA) indicates variability in the causes and degree of restriction of gene flow between Notropis cornutus and Notropis chrysocephalus. Allozyme marker loci show frequency-dependent introgression; i.e., the rarer species, whichever it is at a particular locality, tends to exhibit a higher proportion of introgressed alleles. Unlike allozymes, introgression of mtDNA haplotypes varies geographically. In westward-flowing Michigan drainages, N. cornutus mtDNA haplotypes are more common in F₁ hybrids and backcrosses, independent of parental frequencies. In eastward-flowing Michigan drainages, N. chrysocephalus mtDNA is more common in F₁ hybrids and backcrosses; this pattern may be due to local ecological effects or frequency-dependent introgression. Morphological data alone are not sufficient to distinguish all classes of hybrids. The lack of concordance of morphological, allozymic, and mtDNA introgression patterns implies operation of one or two factors: 1) geographically variable patterns of selection against different hybrid and backcross combinations or 2) genetic differences between Michigan populations inhabiting eastward- and westward-flowing drainage systems accumulated during historical isolation.     

T-cell neoplasm induced by subcutaneous transplantation of a plasmacytoma: characterization of tumor cells.

Thymocytes, isolated 6 days following subcutaneous (sc) transplantation of BALB/c MOPC-315 plasmacytoma into F₁ (BALB/c × C57BL) hybrid mice, when injected sc into normal syngeneic mice, caused the development of a solid sc tumor. The cells of the newly developed tumor were of a mixed population of θ⁺F₁ (BALB/c × C57BL) and θ^? BALB/c cells (approximately 1:1), which represents a new type of mixed T cell-plasma cell neoplasm. Efforts were made to isolate the transformed thymocytes (θ⁺) from the plasmacytoma (θ^?) cells in the new tumor, exploiting differences in their surface properties. Treatment of the mixed tumor cell population with peanut agglutinin (PNA) revealed that only the T tumor cells were agglutinated. The agglutinated cells were recovered after dispersing the clumps with d-galactose (0.15 M) and consisted of 95% θ⁺ cells. The PNA-agglutinated cells were found to induce a similar tumor (85% θ⁺ cells) when injected sc into F₁ (BALB/c × C57BL) mice.     

Interactions of DNA with a new electron-deficient tentacle porphyrin: meso-Tetrakis[2,3,5,6-tetrafluoro-4-(2-trimethylammoniumethylamine)phenyl]porphyrin

A new electron-deficient tentacle porphyrin meso-tetrakis[2,3,5,6-tetrafluoro-4-(2-trimethylammoniumethylamine)phenyl]porphyrin (TθF₄TAP) has been synthesized. The binding interactions of TθF₄TAP with DNA polymers were studied for comparison to those of an electron-deficient tentacle porphyrin and an electron-rich tentacle porphyrin; these previously studied porphyrins bind to DNA primarily by intercalative and outside-binding modes, respectively. The three tentacle porphyrins have similar size and shape. The basicity of TθF₄TAP indicated that it has electronic characteristics similar to those of the intercalating electron-deficient tentacle porphyrin. However, TθF₄TAP binds to calf thymus DNA, [poly(dA-dT)]₂, and [poly(dG-dC)]₂ in a self-stacking, outside-binding manner under all conditions. Evidence for this binding mode included a significant hypochromicity of the Soret band, a conservative induced CD spectrum, and the absence of an increase in DNA solution viscosity. As found previously for the electron-rich porphyrin, the results suggest that combinations of closely related self-stacked forms coexist. The mix of forms depended on the DNA and the solution conditions. There are probably differences in the detailed features of the self-stacking adducts for the two types of tentacle porphyrins, especially at high R (ratio of porphyrin to DNA). At low R values, the induced CD signal of TθF₄TAP/CT DNA resembled that of TθF₄TAP/[poly(dA-dT)]₂, suggesting that TθF₄TAP binds preferentially at AT regions. Competitive binding experiments gave evidence that TθF₄TAP binds preferentially to [poly(dA-dT)]₂ over [poly(dG-dC)]₂. Thus, despite the long, positively charged, flexible substituents on the porphyrin, the binding of TθF₄TAP is significantly affected by base-pair composition. Similar characteristics were found previously for the electron-rich tentacle porphyrin. Thus, significant changes in electron richness have relatively minor effects on this outside binding selectivity for AT regions. TθF₄TAP is the first porphyrin with electron deficiency and shape similar to intercalating porphyrins that does not appear to intercalate. All porphyrins reported to intercalate have had pyridinium substituents. Thus, the electronic distribution in the porphyrin ring, not just the overall electron richness, may play a role in facilitating intercalation. © 1997 John Wiley & Sons, Inc. Biopoly 42: 203–217, 1997     

Micro- and Macro-Geographic Scale Effect on the Molecular Imprint of Selection and Adaptation in Norway Spruce

Forest tree species of temperate and boreal regions have undergone a long history of demographic changes and evolutionary adaptations. The main objective of this study was to detect signals of selection in Norway spruce (Picea abies [L.] Karst), at different sampling-scales and to investigate, accounting for population structure, the effect of environment on species genetic diversity. A total of 384 single nucleotide polymorphisms (SNPs) representing 290 genes were genotyped at two geographic scales: across 12 populations distributed along two altitudinal-transects in the Alps (micro-geographic scale), and across 27 populations belonging to the range of Norway spruce in central and south-east Europe (macro-geographic scale). At the macrogeographic scale, principal component analysis combined with Bayesian clustering revealed three major clusters, corresponding to the main areas of southern spruce occurrence, i.e. the Alps, Carpathians, and Hercynia. The populations along the altitudinal transects were not differentiated. To assess the role of selection in structuring genetic variation, we applied a Bayesian and coalescent-based F _ST-outlier method and tested for correlations between allele frequencies and climatic variables using regression analyses. At the macro-geographic scale, the F _ST-outlier methods detected together 11 F _ST-outliers. Six outliers were detected when the same analyses were carried out taking into account the genetic structure. Regression analyses with population structure correction resulted in the identification of two (micro-geographic scale) and 38 SNPs (macro-geographic scale) significantly correlated with temperature and/or precipitation. Six of these loci overlapped with F _ST-outliers, among them two loci encoding an enzyme involved in riboflavin biosynthesis and a sucrose synthase. The results of this study indicate a strong relationship between genetic and environmental variation at both geographic scales. It also suggests that an integrative approach combining different outlier detection methods and population sampling at different geographic scales is useful to identify loci potentially involved in adaptation.     

Conformational changes in erythrocyte membranes by prostaglandins as measured by circular dichroism

Membranes were prepared from fresh, washed human erythrocytes by hemolysis and washing with 5 mm sodium phosphate buffer (pH 7.4). The mean residue ellipticity, [θ], of erythrocyte membrane circular dichroism was altered by prostaglandin E₁ or prostaglandin F_2α at 37 °C when observed from 250 nm to 190 nm. The decrease in negativity of [θ] with 10^?6m prostaglandin E₁ was 12.7% at 222 nm and 17.7% at 208 nm, and with 10^?6m prostaglandin F_2α 22.5% and 34.2%, respectively (P < 0.01). Similar changes in [θ] were observed at lower concentrations of prostaglandins. No strict relationship between amount of change of [θ] and prostaglandin concentrations of 3 × 10^?5m to 3 × 10^?12m was evident. A persistent alteration of [θ] with prostaglandin was observed at 37 °C. Transient change of [θ] occurred at 25 °C with prostaglandin. No change of [θ] was observed at 15 or 20 °C. Buffer or palmitic acid were without effect on membrane [θ]. Phosphatidyl inositol or methyl arachidonate caused an increase in negativity of membrane spectra. The observed alterations of membrane [θ] did not arise from changes in light scattering as the OD₇₀₀–OD₂₀₀ of membranes was not changed by prostaglandin. Effects of prostaglandin were not dependent on light path length. The prostaglandin E₁ antagonist, 7-oxa-13-prostynoic acid, at 10^?7m produced no change of [θ] of membrane spectra and prevented the otherwise demonstrable effects of 10^?10m prostaglandin E₁ on [θ]. The decrease in negativity of [θ] at 222 nm is indicative of a decrease in ellipticity of membrane protein. These studies suggest that prostaglandins may act by inducing a conformational change in membrane protein.     

Identification of an Intragenic Ribosome Binding Site That Affects Expression of the uncB Gene of the Escherichia coli Proton-Translocating ATPase (unc) Operon

The uncB gene codes for the a subunit of the F_o proton channel sector of the Escherichia coli F₁ F_o ATPase. Control of expression of uncB appears to be exerted at some step after translational initiation. Sequence analysis by the perceptron matrices (G. D. Stormo, T. D. Schneider, L. Gold, and A. Ehrenfeucht, Nucleic Acids Res. 10:2997–3011, 1982) identified a potential ribosome binding site within the uncB reading frame preceding a five-codon reading frame which is shifted one base relative to the uncB reading frame. Elimination of this binding site by mutagenesis resulted in a four- to fivefold increase in expression of an uncB′-′lacZ fusion gene containing most of uncB. Primer extension inhibition (toeprint) analysis to measure ribosome binding demonstrated that ribosomes could form an initiation complex at this alternative start site. Two fusions of lacZ to the alternative reading frame demonstrated that this site is recognized by ribosomes in vivo. The results suggest that expression of uncB is reduced by translational frameshifting and/or a translational false start at this site within the uncB reading frame.     

Empirical Distributions of F ST from Large-Scale Human Polymorphism Data

Studies of the apportionment of human genetic variation have long established that most human variation is within population groups and that the additional variation between population groups is small but greatest when comparing different continental populations. These studies often used Wright’s F _ST that apportions the standardized variance in allele frequencies within and between population groups. Because local adaptations increase population differentiation, high-F _ST may be found at closely linked loci under selection and used to identify genes undergoing directional or heterotic selection. We re-examined these processes using HapMap data. We analyzed 3 million SNPs on 602 samples from eight worldwide populations and a consensus subset of 1 million SNPs found in all populations. We identified four major features of the data: First, a hierarchically F _ST analysis showed that only a paucity (12%) of the total genetic variation is distributed between continental populations and even a lesser genetic variation (1%) is found between intra-continental populations. Second, the global F _ST distribution closely follows an exponential distribution. Third, although the overall F _ST distribution is similarly shaped (inverse J), F _ST distributions varies markedly by allele frequency when divided into non-overlapping groups by allele frequency range. Because the mean allele frequency is a crude indicator of allele age, these distributions mark the time-dependent change in genetic differentiation. Finally, the change in mean-F _ST of these groups is linear in allele frequency. These results suggest that investigating the extremes of the F _ST distribution for each allele frequency group is more efficient for detecting selection. Consequently, we demonstrate that such extreme SNPs are more clustered along the chromosomes than expected from linkage disequilibrium for each allele frequency group. These genomic regions are therefore likely candidates for natural selection.     

Nonequilibrium Dissipation-free Transport in F1-ATPase and the Thermodynamic Role of Asymmetric Allosterism

F₁-ATPase (or F₁), the highly efficient and reversible biochemical engine, has motivated physicists as well as biologists to imagine the design principles governing machines in the fluctuating world. Recent experiments have clarified yet another interesting property of F₁; the dissipative heat inside the motor is very small, irrespective of the velocity of rotation and energy transport. Conceptual interest is devoted to the fact that the amount of internal dissipation is not simply determined by the sequence of equilibrium pictures, but also relies on the rotational-angular dependence of nucleotide affinity, which is a truly nonequilibrium aspect. We propose that the totally asymmetric allosteric model (TASAM), where adenosine triphosphate (ATP) binding to F₁ is assumed to have low dependence on the angle of the rotating shaft, produces results that are most consistent with the experiments. Theoretical analysis proves the crucial role of two time scales in the model, which explains the universal mechanism to produce the internal dissipation-free feature. The model reproduces the characteristic torque dependence of the rotational velocity of F₁ and predicts that the internal dissipation upon the ATP synthesis direction rotation becomes large at the low nucleotide condition.     

Leg stiffness and joint stiffness while running to and jumping over an obstacle

During running, muscles of the lower limb act like a linear spring bouncing on the ground. When approaching an obstacle, the overall stiffness of this leg-spring system (k_leg) is modified during the two steps preceding the jump to enhance the movement of the center of mass of the body while leaping the obstacle. The aim of the present study is to understand how k_leg is modified during the running steps preceding the jump. Since k_leg depends on the joint torsional stiffness and on the leg geometry, we analyzed the changes in these two parameters in eight subjects approaching and leaping a 0.65 m-high barrier at 15 km h⁻¹. Ground reaction force (F) was measured during 5–6 steps preceding the obstacle using force platform and the lower limb movements were recorded by camera. From these data, the net muscular moment (M_j), the angular displacement (θ_j) and the lever arm of F were evaluated at the hip, knee and ankle. At the level of the hip, the M_j–θ_j relation shows that muscles are not acting like torsional springs. At the level of the knee and ankle, the M_j–θ_j relation shows that muscles are acting like torsional springs: as compared to steady-state running, the torsional stiffness k_j decreases from ~1/3 two contacts before the obstacle, and increases from ~2/3 during the last contact. These modifications in k_j reflect in changes in the magnitude of F but also to changes in the leg geometry, i.e. in the lever arms of F.     

Nonequilibrium Dissipation-free Transport in F1-ATPase and the Thermodynamic Role of Asymmetric Allosterism

F₁-ATPase (or F₁), the highly efficient and reversible biochemical engine, has motivated physicists as well as biologists to imagine the design principles governing machines in the fluctuating world. Recent experiments have clarified yet another interesting property of F₁; the dissipative heat inside the motor is very small, irrespective of the velocity of rotation and energy transport. Conceptual interest is devoted to the fact that the amount of internal dissipation is not simply determined by the sequence of equilibrium pictures, but also relies on the rotational-angular dependence of nucleotide affinity, which is a truly nonequilibrium aspect. We propose that the totally asymmetric allosteric model (TASAM), where adenosine triphosphate (ATP) binding to F₁ is assumed to have low dependence on the angle of the rotating shaft, produces results that are most consistent with the experiments. Theoretical analysis proves the crucial role of two time scales in the model, which explains the universal mechanism to produce the internal dissipation-free feature. The model reproduces the characteristic torque dependence of the rotational velocity of F₁ and predicts that the internal dissipation upon the ATP synthesis direction rotation becomes large at the low nucleotide condition.     

Carbon Sequestration in Fine Roots and Foliage Biomass Offsets Soil CO2 Effluxes along a 19-year Chronosequence of Shrub Willow (Salix x dasyclados) Biomass Crops

Previous greenhouse gas (GHG) assessments for the shrub willow biomass crops (SWBC) production system lacked quantitative data on the soil CO₂ efflux (F_c). This study quantifies the mean annual cumulative F_c, the C sequestration in the above- and belowground biomass, and the carbon balance of the production system. We utilized four SWBC fields, which have been in production for 5, 12, 14, and 19 years. Two treatments were applied: continuous production (CP)—shrub willows were harvested, and stools were allowed to regrow, and tear-out (TO) (crop removal)—shrub willows were harvested, and stools were sprayed with herbicide following spring, crushed, and mixed into the soil. Mean annual cumulative F_c were measured using dynamic closed chambers (LI-8100A and LI-8150). Across different age classes, the mean cumulative F_c ranged from 27.2 to 35.5 Mg CO₂ ha^?1 year^?1 for CP and 26.5 to 29.3 Mg CO₂ ha^?1 year^?1 for TO. The combined carbon (C) sequestration of the standing above- and belowground biomass, excluding stems, ranged from 50.6 to 94.8 Mg CO₂ eqv. ha^?1. In the CP treatment, the annual C sequestration in the fine roots and foliage offsets the annual cumulative F_c. Across different age classes, C balances ranged from ?21.5 to ?59.3 Mg CO₂ ha^?1 for CP and 26.5 to 29.3 Mg CO₂ ha^?1 for TO. The GHG potential of SWBC is about ?36.3 Mg CO₂ eqv. ha^?1 at the end of 19 years, suggesting that the SWBC system sequesters C until termination of the crop.     

The nonlinear chemo-mechanic coupled dynamics of the F 1 -ATPase molecular motor

The ATP synthase consists of two opposing rotary motors, F₀ and F₁, coupled to each other. When the F₁ motor is not coupled to the F₀ motor, it can work in the direction hydrolyzing ATP, as a nanomotor called F₁-ATPase. It has been reported that the stiffness of the protein varies nonlinearly with increasing load. The nonlinearity has an important effect on the rotating rate of the F₁-ATPase. Here, considering the nonlinearity of the γ shaft stiffness for the F₁-ATPase, a nonlinear chemo-mechanical coupled dynamic model of F₁ motor is proposed. Nonlinear vibration frequencies of the γ shaft and their changes along with the system parameters are investigated. The nonlinear stochastic response of the elastic γ shaft to thermal excitation is analyzed. The results show that the stiffness nonlinearity of the γ shaft causes an increase of the vibration frequency for the F₁ motor, which increases the motor’s rotation rate. When the concentration of ATP is relatively high and the load torque is small, the effects of the stiffness nonlinearity on the rotating rates of the F₁ motor are obvious and should be considered. These results are useful for improving calculation of the rotating rate for the F₁ motor and provide insight about the stochastic wave mechanics of F₁-ATPase.     

An evaluation of inbreeding measures using a whole-genome sequenced cattle pedigree

The estimation of the inbreeding coefficient (F) is essential for the study of inbreeding depression (ID) or for the management of populations under conservation. Several methods have been proposed to estimate the realized F using genetic markers, but it remains unclear which one should be used. Here we used whole-genome sequence data for 245 individuals from a Holstein cattle pedigree to empirically evaluate which estimators best capture homozygosity at variants causing ID, such as rare deleterious alleles or loci presenting heterozygote advantage and segregating at intermediate frequency. Estimators relying on the correlation between uniting gametes (F_UNI) or on the genomic relationships (F_GRM) presented the highest correlations with these variants. However, homozygosity at rare alleles remained poorly captured. A second group of estimators relying on excess homozygosity (F_HOM), homozygous-by-descent segments (F_HBD), runs-of-homozygosity (F_ROH) or on the known genealogy (F_PED) was better at capturing whole-genome homozygosity, reflecting the consequences of inbreeding on all variants, and for young alleles with low to moderate frequencies (0.10 < . < 0.25). The results indicate that F_UNI and F_GRM might present a stronger association with ID. However, the situation might be different when recessive deleterious alleles reach higher frequencies, such as in populations with a small effective population size. For locus-specific inbreeding measures or at low marker density, the ranking of the methods can also change as F_HBD makes better use of the information from neighboring markers. Finally, we confirmed that genomic measures are in general superior to pedigree-based estimates. In particular, F_PED was uncorrelated with locus-specific homozygosity.Subject terms: Conservation genomics, Animal breeding, Inbreeding     

The effect of phonation into a straw on the vocal tract adjustments and formant frequencies. A preliminary MRI study on a single subject completed with acoustic results

Phonation into a straw is used in voice training and therapy. This study investigated its’ effects on the vocal tract adjustments.Magnetic resonance images were taken from one female phonating first on [a:], then into a plastic drinking straw and then again on [a:]. Acoustic samples were recorded from her and 10 other females. The samples were analyzed for fundamental frequency, sound pressure level (SPL), five lowest formant frequencies (F₁–F₅) and SPL of the speaker's formant cluster range (2.5–4.5 kHz).During and after phonation into a straw, the midsagittal area of the vocal tract increased and the velar closure improved. The ratio of the transversal area of the lower pharynx over that of the epilarynx increased both during (27%) and after the straw (20%). The overall SPL and the SPL of the speaker's formant cluster increased. The frequencies of F₂, F₄ and F₅ decreased, while F₃ increased. The distances between F₄ and F₃ and F₅ and F₄ decreased by 49%. For the 10 subjects, F₃ increased, F₄ decreased and the distance between F₃ and F₄ decreased significantly.The results suggest that exercising with a straw helps establishing a speaker's formant cluster, which increases loudness and thus improves vocal economy.