Drop In Tension Research Articles

Cross-Bridge Populations and the Biphasic Time Course of Muscle Relaxation

A biphasic time course of relaxation follows Ca2+ removal from a contracting muscle fiber--a small linear decline is followed by a faster large exponential drop in tension to the relaxed state. Our aim is to see if recent insights into tension generation and the cross-bridge cycle can shed light on these kinetics (Davis and Epstein, 2009). In fully activated isometric rabbit psoas fibers two distinct and roughly equal populations of myosin heads are attached to actin. Half are termed “competent” and are capable of generating tension, while the other half are termed “noncompetent” and serve to “buffer” tension. For example, a step-decrease in fiber length releases a steric constraint on noncompetent cross-bridges thereby triggering tension recovery. We investigate whether the “buffer” of noncompetent AMD bridges might support the linear phase, with the exponential decline (kREL FAST) mediated by the decay of the remaining competent cross-bridge population. To do this, the linear phase was treated as a steady-state reaction with duration and not slope used to determine kREL SS. We found kREL SS normalized to kCAT (fiber ATPase) if a reasonable ∼21% of myosin heads constitute the noncompetent buffer. This leaves the final exponential decline to the relaxed state governed by the discharge of tension generating competent cross-bridges on exhaustion of the noncompetent buffer population. Additional support comes from the observations that added Pi decreases the duration and increases the slope of the linear phase with virtually no effect on kREL FAST (Tesi et al, 2002), and that a slow Tn Ca2+ off switch prolongs the linear phase (Kreutziger et al, 2008). Arrhenius plots of kCAT, kREL SS and kREL FAST are similar in slope, suggesting a common rate-limiting step of strain-sensitive ADP cross-bridge dissociation for all processes.

Dynamic Adaption of Actin Stress Fibers in Response to Stretch

Actin stress fibers are mechanosensitive structural elements that respond to stretching to regulate cell morphology, stress fiber alignment, signal transduction and cell function. Adherent cells maintain a level of prestress largely dependent on myosin contractility, suggesting that stress fibers self-adjust to an equilibrium level of stress. Here a quantitative model is developed to describe a potential mechanism for fibers to re-establish stress equilibrum in response to changes in fiber length. The model involves dynamic changes in fiber reference length regulated by myosin-actin cross bridging, where the force-velocity relationship for individual sarcomeres is expressed as a hyperbolic Hill-type model. Under static conditions, the basal level of fiber tension and pre-extension are determined by the number of sarcomeres bundled together in the fiber and the stall force of the constituent myosin filaments. Following a step increase in fiber length, tension initially increases elastically, but then relaxes with a characteristic time constant dependent on the rate of myosin cross bridge dynamics. Returning the fiber to the original length results in a drop in tension below equilibrium, followed by a relatively rapid return to equilibrium.The model predicts that stress fibers respond to cyclic stretch in a manner dependent on frequency, ATP concentration, equilibrium sarcomere length, and sarcomere stiffness with relaxation times ranging from 0.02 to 0.8 sec based on model parameter values extracted from the literature. The modeling results are consistent with various experimental findings and provide molecular insight into how stress fibers determine and maintain mechanical equilibrium in response to changes in length.

Mechanical Unfolding of a Homopolymer Globule Studied by Self-Consistent Field Modeling

We present results of numerical self-consistent field (SCF) calculations for the equilibrium mechanical unfolding of a globule formed by a single flexible polymer chain collapsed in a poor solvent. In accordance with earlier scaling theory and stochastic dynamics simulations findings we have identified three regimes of extensional deformation: (i) a linear response regime characterized by a weakly elongated (ellipsoidal) shape of the globule at small deformations, (ii) a tadpole structure with a globular “head” coexisting with a stretched “tail” at intermediate ranges of deformations, and (iii) an uniformly stretched chain at strong extensions. The conformational transition from the tadpole to the stretched chain is accompanied by an abrupt unfolding of the depleted globular head and a corresponding jump-wise drop in the intrachain tension. The unfolding-refolding cycle demonstrates a hysteresis loop in the vicinity of the transition point. These three regimes of deformation, as well as the first-order li...

Tuning of mitochondrial pathways by muscle work: from triggers to sensors and expression signaturesThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

Performance of striated muscle relies on the nerve-driven activation of the sarcomeric motor and coupled energy supply lines. This biological engine is unique; its mechanical and metabolic characteristics are not fixed, but are tailored by functional demand with exercise. This remodelling is specific for the imposed muscle stimulus. This is illustrated by the increase in local oxidative capacity with highly repetitive endurance training vs. the preferential initiation of sarcomerogenesis with strength training regimes, where high-loading increments are imposed. The application of molecular biology has provided unprecedented insight into the pathways that govern muscle plasticity. Time-course analysis indicates that the adjustments to muscle work involve a broad regulation of transcript expression during the recovery phase from a single bout of exercise. Highly resolving microarray analysis demonstrates that the specificity of an endurance-exercise stimulus is reflected by the signature of the transcriptome response after muscle work. A quantitative match in mitochondrial transcript adjustments and mitochondrial volume density after endurance training suggests that the gradual accumulation of expressional microadaptations underlies the promotion of fatigue resistance with training. This regulation is distinguished from control of muscle growth via the load-dependent activation of sarcomerogenesis. Discrete biochemical signalling systems have evolved that sense metabolic perturbations during exercise and trigger a specific expression program, which instructs the remodelling of muscle makeup. A drop in muscle oxygen tension and metabolite perturbations with exercise are recognized as important signals in the genome-mediated remodelling of the metabolic muscle phenotype in humans.

Increased cloud activation potential of secondary organic aerosol for atmospheric mass loadings

Abstract. The effect of organic particle mass loading from 1 to ≥100 μg m−3 on the cloud condensation nuclei (CCN) properties of mixed organic-sulfate particles was investigated in the Harvard Environmental Chamber. Mixed particles were produced by the condensation of organic molecules onto ammonium sulfate particles during the dark ozonolysis of α-pinene. A continuous-flow mode of the chamber provided stable conditions over long time periods, allowing for signal integration and hence increased measurement precision at low organic mass loadings representative of atmospheric conditions. CCN activity was measured at eight mass loadings for 80- and 100-nm particles grown on 50-nm sulfate seeds. A two-component (organic/sulfate) Köhler model, which included the particle heterogeneity arising from DMA size selection and from organic volume fraction for the selected 80- and 100-nm particles, was used to predict CCN activity. For organic mass loadings of 2.9 μg m−3 and greater, the observed activation curves were well predicted using a single set of physicochemical parameters for the organic component. For mass loadings of 1.74 μg m−3 and less, the observed CCN activity increased beyond predicted values using the same parameters, implying changed physicochemical properties of the organic component. A sensitivity analysis suggests that a drop in surface tension must be invoked to explain quantitatively the CCN observations at low SOA particle mass loadings. Other factors, such as decreased molecular weight, increased density, or increased van't Hoff factor, can contribute to the explanation but are quantitatively insufficient as the full explanation.

Model Compounds for Asphaltenes and C80 Isoprenoid Tetraacids. Part I: Synthesis and Interfacial Activities

Three model compounds for asphaltenes and two model compounds for the C80 isoprenoid tetraacids (ARN) have been synthesized and their interfacial and solubility properties were investigated. All compounds exhibit high interfacial activities. The asphaltene models lowered the interfacial tension between toluene and pH 9 to around 5 mN/m at 12.5–35 μM and the tetraacid models gave a drop in the interfacial tension between chloroform and pH 9 to 13 mN/m at only 5 μM, which is consistent with previous findings for the natural occurring C80 tetraacids. A sudden drop in the IFT over a very narrow concentration range was observed for two of three asphaltene models. NIR spectroscopy studies indicated an aggregation most likely a result of polar and hydrogen bond interactions. The IFT results also showed different behavior with only small changes in chemical structure. The tetraacid models have similar interfacial behavior as the C80 tetraacids and will thus be suitable model compounds with their highly UV active and fluorescent properties.

Mapping Cell-Matrix Stresses during Stretch Reveals Inelastic Reorganization of the Cytoskeleton

The mechanical properties of the living cell are intimately related to cell signaling biology through cytoskeletal tension. The tension borne by the cytoskeleton (CSK) is in part generated internally by the actomyosin machinery and externally by stretch. Here we studied how cytoskeletal tension is modified during stretch and the tensional changes undergone by the sites of cell-matrix interaction. To this end we developed a novel technique to map cell-matrix stresses during application of stretch. We found that cell-matrix stresses increased with imposition of stretch but dropped below baseline levels on stretch release. Inhibition of the actomyosin machinery resulted in a larger relative increase in CSK tension with stretch and in a smaller drop in tension after stretch release. Cell-matrix stress maps showed that the loci of cell adhesion initially bearing greater stress also exhibited larger drops in traction forces after stretch removal. Our results suggest that stretch partially disrupts the actin-myosin apparatus and the cytoskeletal structures that support the largest CSK tension. These findings indicate that cells use the mechanical energy injected by stretch to rapidly reorganize their structure and redistribute tension.

Ensaios de tração uniaxial com variação de temperatura em adesivo utilizado em juntas coladas de tubulações de PRFV aplicado em plataformas marítimas

O objetivo deste trabalho é avaliar o comportamento termo-mecânico de adesivos usados em juntas coladas de tubos de plástico reforçado com fibras de vidro (PRFV). Inicialmente usados em instalações de dessalinização e tratamento de efluentes, hoje são aplicados na indústria do petróleo, tanto em plataformas de perfuração quanto de produção, devido à necessidade do uso de materiais mais leves e com alta resistência à corrosão. Destaca-se que no Brasil estas tubulações estão submetidas a temperaturas de serviço da ordem 85ºC, com transientes térmicos de até 115ºC, enquanto as demais aplicações destes tubos são projetadas para operar à temperatura ambiente. O adesivo foi avaliado por meio de ensaios uniaxiais de tração realizados às temperaturas de 25, 55, 85 e 115ºC, tendo sido determinado a tensão de escoamento, a tensão de ruptura, a deformação associada a estas tensões e o módulo de elasticidade. Os resultados obtidos mostram que, com o aumento da temperatura, há uma elevada queda na tensão de escoamento, na tensão de ruptura e no módulo de elasticidade do adesivo, ao mesmo tempo em que aumenta a deformação associada a estas tensões. Pode-se também concluir que o adesivo opera com segurança até a temperatura de 55ºC. Acima desta temperatura as juntas produzidas com este adesivo estariam sujeitas a falhas como o aparecimento de trincas e deformação excessiva, o que pode vir a trazer como conseqüência o colapso da estrutura.

Characterization of a Globin-coupled Oxygen Sensor with a Gene-regulating Function

Globin-coupled sensors (GCSs) are multiple-domain transducers, consisting of a regulatory globin-like heme-binding domain and a linked transducer domain(s). GCSs have been described in both Archaea and bacteria. They are generally assumed to bind O(2) (and perhaps other gaseous ligands) and to transmit a conformational change signal through the transducer domain in response to fluctuating O(2) levels. In this study, the heme-binding domain, AvGReg178, and the full protein, AvGReg of the Azotobacter vinelandii GCS, were cloned, expressed, and purified. After purification, the heme iron of AvGReg178 was found to bind O(2). This form was stable over many hours. In contrast, the predominant presence of a bis-histidine coordinate heme in ferric AvGReg was revealed. Differences in the heme pocket structure were also observed for the deoxygenated ferrous state of these proteins. The spectra showed that the deoxygenated ferrous derivatives of AvGReg178 and AvGReg are characterized by a penta-coordinate and hexa-coordinate heme iron, respectively. O(2) binding isotherms indicate that AvGReg178 and AvGReg show a high affinity for O(2) with P(50) values at 20 degrees C of 0.04 and 0.15 torr, respectively. Kinetics of CO binding indicate that AvGReg178 carbonylation conforms to a monophasic process, comparable with that of myoglobin, whereas AvGReg carbonylation conforms to a three-phasic reaction, as observed for several proteins with bis-histidine heme iron coordination. Besides sensing ligands, in vitro data suggest that AvGReg(178) may have a role in O(2)-mediated NO-detoxification, yielding metAvGReg(178) and nitrate.

Force generation examined by laser temperature‐jumps in shortening and lengthening mammalian (rabbit psoas) muscle fibres

We examined the tension change induced by a rapid temperature jump (T-jump) in shortening and lengthening active muscle fibres. Experiments were done on segments of permeabilized single fibres (length (L0) ∼2 mm, sarcomere length 2.5 μm) from rabbit psoas muscle; [MgATP] was 4.6 mm, pH 7.1, ionic strength 200 mm and temperature ∼9°C. A fibre was maximally Ca2+-activated in the isometric state and a ∼3°C, rapid (< 0.2 ms), laser T-jump applied when the tension was approximately steady in the isometric state, or during ramp shortening or ramp lengthening at a limited range of velocities (0–0.2 L0 s−1). The tension increased to 2- to 3 × P0 (isometric force) during ramp lengthening at velocities > 0.05 L0 s−1, whereas the tension decreased to about < 0.5 × P0 during shortening at 0.1–0.2 L0 s−1; the unloaded shortening velocity was ∼1 L0 s−1 and the curvature of the force–shortening velocity relation was high (a/P0 ratio from Hill's equation of ∼0.05). In isometric state, a T-jump induced a tension rise of 15–20% to a new steady state; by curve fitting, the tension rise could be resolved into a fast (phase 2b, 40–50 s−1) and a slow (phase 3, 5–10 s−1) exponential component (as previously reported). During steady lengthening, a T-jump induced a small instantaneous drop in tension, followed by recovery, so that the final tension recorded with and without a T-jump was not significantly different; thus, a T-jump did not lead to a net increase of tension. During steady shortening, the T-jump induced a pronounced tension rise and both its amplitude and the rate (from a single exponential fit) increased with shortening velocity; at 0.1–0.2 L0 s−1, the extent of fibre shortening during the T-jump tension rise was estimated to be ∼1.2% L0 and it was shorter at lower velocities. At a given shortening velocity and over the temperature range of 8–30°C, the rate of T-jump tension rise increased with warming (Q10 ≈ 2.7), similar to phase 2b (endothermic force generation) in isometric muscle. Results are discussed in relation to the previous findings in isometric muscle fibres which showed that a T-jump promotes an early step in the crossbridge–ATPase cycle that generates force. In general, the finding that the T-jump effect on active muscle tension is pronounced during shortening, but is depressed/inhibited during lengthening, is consistent with the expectations from the Fenn effect that energy liberation (and acto-myosin ATPase rate) in muscle are increased during shortening and depressed/inhibited during lengthening.

The effect of filamentous bacteria on foam production and stability

Bacteria have been implicated in the formation of viscous brown foams that can appear suddenly on wastewater treatment plants. Three strains of the filamentous bacterium Gordonia amarae, isolated from wastewater treatment plants, were investigated to determine their effect on foam formation and stabilisation. During the exponential phase of the bacterial growth a biosurfactant was formed, causing a significant drop in the surface tension of the filtered medium and the formation of persistent foam. Foaming tests in the presence and absence of bacteria showed that bacteria increased foam persistence, most probably by reducing the drainage from the lamellae between bubbles. Experiments showed that ≥55% of the three bacterial strains partitioned into the foam produced by the biosurfactant, indicating that their surfaces were hydrophobic. The extent of partitioning was independent of the growth stage, suggesting that the cell surface hydrophobicity did not change with age, or with cell viability. This work shows that, although the G. amarae cells themselves do not cause foaming, they do produce biosurfactant, which aids foam formation, and they stabilise the foam by reducing the rate of drainage from the foam lamellae.

Oily sludge degradation by bacteria from Ankleshwar, India

Abstract Three bacterial strains, Bacillus sp. SV9, Acinetobacter sp. SV4 and Pseudomonas sp., SV17 from contaminated soil in Ankleshwar, India were tested for their ability to degrade the complex mixture of petroleum hydrocarbons (such as alkanes, aromatics, resins and asphaltenes), sediments, heavy metals and water known as oily sludge. Gravimetric analysis showed that Bacillus sp. SV9 degraded approx. 59% of the oily sludge in 5 days at 30 °C whereas Acinetobacter sp. SV4 and Pseudomonas sp. SV17 degraded 37% and 35%. Capillary gas chromatographic analysis revealed that after 5 days the Bacillus strain was able to degrade oily sludge components of chain length C 12 –C 30 and aromatics more effectively than the other two strains. Maximum drop in surface tension (from 70 to 28.4 mN/m) was accompanied by maximum biosurfactant production (6.7 g l −1 ) in Bacillus sp. SV9 after 72 h, these results collectively indicating that this bacterial strain has considerable potential for bioremediation of oily sludge.

Myosin Phosphatase and Cofilin Mediate cAMP/cAMP-dependent Protein Kinase-induced Decline in Endothelial Cell Isometric Tension and Myosin II Regulatory Light Chain Phosphorylation

This study determined the effects of increased intracellular cAMP and cAMP-dependent protein kinase activation on endothelial cell basal and thrombin-induced isometric tension development. Elevation of cAMP and maximal cAMP-dependent protein kinase activation induced by 10 microm forskolin, 40 microm 3-isobutyl-1-methylxanthine caused a 50% reduction in myosin II regulatory light chain (RLC) phosphorylation and a 35% drop in isometric tension, but it did not inhibit thrombin-stimulated increases in RLC phosphorylation and isometric tension. Elevation of cAMP did not alter myosin light chain kinase catalytic activity. However, direct inhibition of myosin light chain kinase with KT5926 resulted in a 90% decrease in RLC phosphorylation and only a minimal decrease in isometric tension, but it prevented thrombin-induced increases in RLC phosphorylation and isometric tension development. We showed that elevated cAMP increases phosphorylation of RhoA 10-fold, and this is accompanied by a 60% decrease in RhoA activity and a 78% increase in RLC phosphatase activity. Evidence is presented that it is this inactivation of RhoA that regulates the decrease in isometric tension through a pathway involving cofilin. Activated cofilin correlates with increased F-actin severing activity in cell extracts from monolayers treated with forskolin/3-isobutyl-1-methylxanthine. Pretreatment of cultures with tautomycin, a protein phosphatase type 1 inhibitor, blocked the effect of cAMP on 1) the dephosphorylation of cofilin, 2) the decrease in RLC phosphorylation, and 3) the decrease in isometric tension. Together, these data provide in vivo evidence that elevated intracellular cAMP regulates endothelial cell isometric tension and RLC phosphorylation through inhibition of RhoA signaling and its downstream pathways that regulate myosin II activity and actin reorganization.

Characterization of the Aggregates Made by Short Poly(ethylene oxide) Chains Labeled at One End with Pyrene

The association of a monodisperse poly(ethylene oxide) 53 ethylene oxide units long and labeled at one end with pyrene (Py-PEO) was monitored as a function of Py-PEO concentration by steady-state and time-resolved fluorescence, surface tension, static (SLS), and dynamic (DLS) light scattering. The excimer fluorescence decays exhibit no rise time for any polymer concentration investigated in this study (>0.5 g/L), indicating that pyrene aggregates are present in solution and confirming the existence of Py-PEO micelles. No excimer emission could be detected for Py-PEO concentration smaller than 0.1 g/L. The first critical aggregation concentration (CAC1) for the formation of Py-PEO micelles was estimated to equal 0.003 g/L by SLS. The Py-PEO micelles are surface active above a Py-PEO concentration larger than 0.001 g/L (0.4 μM) where a clear drop in surface tension is observed at concentrations slightly lower than CAC1. At a Py-PEO concentration of 10 g/L, the surface tension plateaus due to the aggregation...

Towards optimization of selective photothermolysis: prothrombotic pharmaceutical agents as potential adjuvants in laser treatment of port wine stains

For the past two decades much research on selective photothermolysis of port wine stain vasculature has been devoted to optimizing laser parameters. Unfortunately, 60% of patients still respond suboptimally to laser therapy, despite significant innovations in treatment strategies and laser technology. Here we present a novel treatment approach based on combining selective photothermolysis with the administration of prothrombotic and/or anti-fibrinolytic pharmaceutical agents, with the aim of enhancing vaso-occlusion and post-treatment remodelling in difficult-to-target vessels. A hypercoagulable state of blood will instill laser-induced occlusive thrombosis in a wider array of vessel diameters at greater dermal depths, whereby larger vascular segments will ultimately undergo the chronic inflammatory processes that result in blood volume reduction, and thus lesional blanching. With thrombosis as a primary trigger for these inflammatory processes, we have extrapolated the threshold damage profile that is required for clinically relevant thrombus formation. Consequently, a recently proposed model of thrombus organization, in which recanalization is associated with endothelial progenitor cell-mediated neovasculogenesis, is elaborated in the framework of lesional blanching and juxtaposed to angiogenic reconstruction of affected dermal vasculature. Since neovasculogenesis and angiogenesis are regulated by the degree of vaso-occlusion and corollary drop in local oxygen tension, both can be manipulated by the administration of procoagulant pharmaceuticals. Lastly, in an effort to optimally balance selective photothermolysis with pharmacokinetics and clinical safety, the use of a gold nanoshell drug delivery system, in which the procoagulant drugs are encapsulated by a wavelength-modulated, gold-coated polymer matrix, is proposed. We have termed this modality site-specific pharmaco-laser therapy.

A role for rhamnolipid in biofilm dispersion

Biofilms are often considered as localized zones of high cell density. Quorum sensing provides a means for control of population processes and has been implicated in the regulation of biofilm activities. We present a role for quorum sensing in programmed detachment and dispersal processes. Biofilms of Pseudomonas aeruginosa PAO1 and its isogenic homoserine lactone (HSL) mutant P. aeruginosa PAO-JP2 were grown in batch culture on glass substrata; differences were found in the rate and extent of formation of biofilm. Climax communities were observed for PAO1 at 24 h. These were later accompanied by foaming, a drop in the surface tension of culture media and dispersal of the biofilm, after which no subsequent biofilm accretion occurred. PAO-JP2 cultures reformed biofilm post-detachment and did not foam. Prevention of biofilm reformation in the wild type was related to some component excreted into the culture medium. Rhamnolipid, a biosurfactant regulated by quorum sensing, was detected in PAO1 cultures. When rhamnolipid was added to freshly inoculated substrata, biofilm formation was inhibited. At 20 h, PAO1 biofilms were transferred to medium with added rhamnolipid: biofilm was relatively unaffected. Biofilm events were also studied in medium supplemented with N-butyryl-L-homoserine lactone, which is involved in the regulation of rhamnolipid synthesis. Both strains exhibited similar trends of rapid biofilm formation and dramatic changes in the rate and extent of biofilm accretion. In both cases, there was premature foaming, lowered surface tension and elevated rhamnolipid levels. A role for HSLs in maintenance of biofilm and events leading to dispersion of cells is proposed. This role would encompass dispersion but not necessarily detachment of cells from biofilm and supports a new function for rhamnolipid in pathogenesis, whereby rhamnolipid would promote the dissemination of cells from a nidus of infection.

Age-Related Peculiarities of the Control of Respiration and Their Correlation with the Intensity of Free-Radical Processes

We describe the results of a study of the relations between the control of the respiratory function in isocapnic increasing hypoxia and the intensity of free-radical processes in groups of healthy young and aged subjects. It is known that aging is accompanied by some weakening of the response of the respiratory system to hypoxia with no considerable changes in the indices of ventilation in the resting state. Aged subjects, as compared with young tested persons, are characterized by a decrease in the activity of catalase, the absence of significant differences in the activity of superoxide dismutase, and a trend toward an increase in the content of products of lipid peroxidation in the blood. We discuss possible mechanisms mediating age-related modifications in the system of control of respiration and consider shifts in the system of pro/antioxidant balance and intensification of peroxidation processes against the background of a decreased activity of catalase primary changes responsible for the above modifications. These effects lead to modifications of the sensitivity of chemoreceptors responding to a drop in O2 tension in the blood.

Effect of dimethyl sulfoxide on excitation-contraction coupling in chicken slow skeletal muscle.

To evaluate the suitability of dimethyl sulfoxide (DMSO) as a solvent for muscle-contraction studies in the chicken, its effect on the slow muscle contracture induced by high-K(+) solution was explored using the anterior latissimus dorsi (ALD) muscle from one-week-old chicks. Measurements were made of isometric tension and various characteristics of the contractures [peak tension, total tension (area under the curve), duration of contraction, drop in tension from peak to plateau, and resting tension], in the presence and absence of DMSO (20 mM). Exposure to DMSO led to a concentration-dependent reduction in resting tension of up to 9 +/- 1.8% (n = 4) with respect to the control. The threshold concentration was 10 mM, and the maximum effect was reached between 20 and 30 mM. The drop in tension from peak to plateau was three times larger in the presence of DMSO (20 mM) than in its absence. At the same concentration, there was a 10 +/- 2.3% increase in the time constant of activation. No significant changes were observed in peak tension or in total tension in the presence of 20 mM DMSO. As a consequence, this type of biological preparation is not suitable for research on muscle contractures involving drugs that must be dissolved in DMSO (at the DMSO concentrations tested here).

Human unilateral lower limb suspension as a model for spaceflight effects on skeletal muscle

To the Editor: Widrick et al. ([18][1]) have published data from a 12-day unilateral lower limb suspension (ULLS) study conducted in 1994 using the methods originally published by Berg et al. in 1991 ([3][2]). Analyses included the morphology and contractile behavior of skinned skeletal muscle

Signaling cross-talk between hypoxia and glucose via hypoxia-inducible factor 1 and glucose response elements

The substrates oxygen and glucose are important for the appropriate regulation of metabolism, angiogenesis, tumorigenesis and embryonic development. The knowledge about an interaction between these two signals is limited. We demonstrated that the regulation of glucagon receptor, insulin receptor and L-type pyruvate kinase (L-PK) gene expression in liver is dependent upon a cross-talk between oxygen and glucose. The periportal to perivenous drop in O2 tension was proposed to be an endocrine key regulator for the zonated gene expression in liver. In primary rat hepatocyte cultures, the expression of the glucagon receptor and the L-PK mRNA was maximally induced by glucose under arterial pO2 whereas the insulin receptor was maximally induced under perivenous pO2. It was demonstrated for the L-PK gene that the modulation by O2 of the glucose-dependent induction occured at the glucose-responsive element (GlcPKRE) in the L-PK gene promoter. The reduction of the glucose-dependent induction of the L-PK gene expression under venous pO2 appeared to be mediated via an interference between hypoxia-inducible factor 1 (HIF-1) and the glucose-responsive transcription factors at the GlcPKRE. The glucose response element (GlcRE) also functioned as a hypoxia response element and, vice versa, a hypoxia-responsive element was functioning as a GlcRE. Thus, our findings implicate that the cross-talk between oxygen and glucose might have a fundamental role in the regulation of several physiological and pathophysiological processes.