Energetics of molecular motor proteins: could it pay to take a free ride?

ABSTRACT

Molecular motor proteins are used in biological systems to generate directed motion. They consist of one end that can bind to and then move along a filament. The other end can then bind to a cargo that needs transporting and the motor then pulls it along. Here, we consider the energetics of this process allowing for the friction force exerted by the surrounding fluid, given that the process takes place in a confined geometry. In nature, not all motor/cargo complexes are bound to the filament, many are in solution. Here, we address the question of whether this can be energetically favourable given that the unbound complexes will be transported by the flow generated by those that are bound. A simple theory suggests that this is the case and that there exists an optimal coverage of bound complexes. Simulations of a model of this system that includes all the relevant hydrodynamic effects confirm that the assumptions in the theory are valid so long as the coverage of bound complexes is not too low. Using realistic values for the parameters involved yields an optimal coverage that is plausible for the biological systems involved.     

Deformation in cooperative molecular motors

We implement a model to represent the effect of the deformation of the backbone of a system of motor proteins while sliding on a track filament. This model incorporates a nearest neighbor interaction term among the motors for the deformation energy. Correlations induced by this term result in increased motor force for inter-particle distances small compared to the ratchet period. Received 20 February 2001 and Received in final form 31 May 2001     

Raman Spectroscopy of Galactosemic Rat Lens Crystalline: Correlation of Microscopic Changes of Lens Proteins at Molecular Levels with Gross Cataractous Alteration

Near‐Infrared Fourier trans form (near‐IR FT) Raman spectros copy has been used to study the structural changes of lens proteins both in cortex and nucleus of galactosemic rat lenses. It was found that tyrosine doublet ratio of Raman bands, I₈₃₂/I₈₅₅, in creased more rapidly in the cortex than in the nucleus during a 5‐week period of galactose feeding, i.e., from 0.86 to 1.1 for the cortex and 0.88 to 0.92 for the nucleus. The ratio obtained for lens nucleus suggests that a lower ratio of less than 1 does not necessarily reflect the apparent transparent state of lens morphology. More over our results for the in crease of tyrosine doubletratio with the extent of cataract formation in galactosemic lens appear to indicate that there is more hydration in crystallins of the cortex than the nucleus since the in creased ratio of tyro sine doublet has been shown to be due to the hydrogen‐bond formation of hydroxyl groups in various tyrosines of proteins with water. The tryptophan band ratio at 880 cm^?1 and 757 cm^? (I₈₈₀/I₇₅₇) under went a precipitous de crease in the cortex and a rather gradual de crease in the nucleus, suggesting buried tryptophan residues become more exposed in the cortex than in the nucleus during galactose‐induced cataractogenesis. Based on the changes of the two ratios, I₈₃₂/I₈₅₅ and I₈₈₀/I₇₅₇, the change of lens protein environment induced by galactosemic feeding appeared to take place in the cortex first, which was consistent with the observation that the development of an opaque lens be gins in the cortex. While no sulfhydryl (‐SH) signal was detected, there was a slow in crease of disulfide (‐S‐S‐) signal in the cortex of galactose‐fed lenses as compared to control lenses with out galactose. This suggested that a loss of lens glutathione occurred early and oxidation of cysteines in crystallins started in the first week, i.e., be fore the onset of cortical cataract. In contrast, for nucleus of galactosemic lenses the signal of the‐SH group was detected and yet the ‐S‐S‐signal of crystallins could not be found. In this study, we have conclusively demonstrated using Raman vibrational band shift that galactosemic cataract be gins in the cortex, and that the lens cortex suffers more structural alteration in crystallins than the nucleus.     

THE ROLE OF FRONTAL NEURONS IN PAIN AND ACUPUNCTURE ANALGESIA

To study the role of frontal neurons in pain and acupuncture analgesia, experiments were carried out on 4 monkeys (Macaca mulatta) during performing two tasks, the Heat Discrimination Response GO/NO-GO Task (Task Ⅰ) and the Heat Delayed Discrimination GO/NO-GO Task (Task Ⅱ). After a criterion of 90% of correct performances over three successive days had been reached, activity of single neurons was recorded from the frontal cortex. Of 276 Task Ⅰ-related neurons, 211 responded to noxious and/or innocuous heat stimuli. Of 73 Task Ⅱ-related neurons, 59 responded to noxious and/or innocuous heat stimuli. During acupuncture, the nociceptive reaction time for lever release to avoid painful stimuli was increased, the percentage of correct performances was lowered, and the neuronal responses to noxious and/or innocuous stimuli were suppressed. These neurons were mainly located in a circumscribed area medial to the superior ramus of the arcuate sulcus in frontal cortex, including the prefrontal and premotor a     

Kinetic distribution of paeoniflorin in cortex of normal and cerebral ischemia-reperfusion rats after intravenous administration of Paeoniae Radix extract

The time course of paeoniflorin in the cortex of normal and cerebral ischemia-reperfusion rats, following intravenous administration of Paeoniae Radix extract at a dose of 60 mg/kg of paeoniflorin, was determined using high-performance liquid chromatographic (HPLC) assay. The results showed that paeoniflorin could penetrate through the blood-brain barrier to reach the cortex, and that the injuries of ischemia-reperfusion could play an important role in pharmacokinetic process of paeoniflorin in the cortex after intravenous administration of Paeoniae Radix extract. The cortex concentrations of paeoniflorin in cerebral ischemia-reperfusion rats were lower 5 min after dosing and declined more slowly than that in normal control.     

气相色谱法测定4种中药材中有机氯农药残留量

建立了气相色谱法同时测定中药材天仙子、半夏、杜仲、吴茱萸中有机氯农药残留量方法。13种有机氯农药的浓度在1~100μg/L内线性关系良好(r>0.995 5),检出限为0.04~0.21μg/L,加标回收率为81.79%~100.50%,测定结果的相对标准偏差为0.28%~0.98%。     

A finite volume method and experimental study of a stator of a piezoelectric traveling wave rotary ultrasonic motor

Piezoelectric traveling wave rotary ultrasonic motors are motors that generate torque by using the friction force between a piezoelectric composite ring (or disk-shaped stator) and a metallic ring (or disk-shaped rotor) when a traveling wave is excited in the stator. The motor speed is proportional to the amplitude of the traveling wave and, in order to obtain large amplitudes, the stator is excited at frequencies close to its resonance frequency. This paper presents a non-empirical partial differential equations model for the stator, which is discretized using the finite volume method. The fundamental frequency of the discretized model is computed and compared to the experimentally-measured operating frequency of the stator of Shinsei USR60 piezoelectric motor.     

The compatibility of six alkaloids in ermiao pill explored by a comparative pharmacokinetic and network pharmacological study

Ermiao Pill (EMW), a traditional Chines medicine (TCM), composed of a two‐herb pair, Phellodendri Cortex (PC) and Atractylodis Rhizome (AR), is used for the treatment of pelvic inflammatory disease and inflammatory‐related diseases. However, the underlying mechanism is still unknown. Compatibility plays a crucial role in the complex drugs such as those used in traditional Chinese medicine. We propose a compositive strategy, which integrated pharmacokinetics and network pharmacology to explore the compatibility in EMW. Firstly, a simple, rapid, and selective method based on UPLC–MS/MS was established and validated for simultaneous qualification of six alkaloids in rat plasma, which was used for a comparative pharmacokinetic study of EMW and its constituent herb PC. The concentration–time profiles suggested that AR might reduce the toxicity of some alkaloids in EMW. Secondly, network pharmacology analysis showed that the key protein PTGS2 was targeted by four alkaloids, and that the competition among them might be allevited by AR. Thirdly, molecular docking exhibited interactions between the alkaloids and PTGS2 through H and π–π bonds, and the same residue formed interactions with different alkaloids, which account for the toxicity of these alkaloids, and these were confirmed by the cell viability assay. The combination of pharmacokinetics and network pharmacology clarified the compatibility in EMW.     

Ocular integrity following manganese labeling of the visual system for MRI

Injection of manganese into the eye will enhance the contrast of visual system neuronal pathways imaged by MRI (MEMRI). The present study was undertaken to determine the effect of a range of MnCl₂ doses upon the integrity of various ocular structures. Anesthetized mice received ocular anterior chamber injections of 50–500 nmol of MnCl₂. One week later, the eyes were fixed, embedded in paraffin, sectioned, and stained with hematoxylin and eosin. Additional animals received 50 nmol of MnCl₂ injected into the anterior chamber and were later imaged using T1-weighted 7 T MRI. Following 500 and 300 nmol MnCl₂, the corneal stroma and endothelium were degenerated, the anterior chamber contained a dense fibrin matrix with extensive inflammatory cell infiltration, a plaque often formed on the anterior lens, and significant retinal degeneration was observed. Following 100 nmol MnCl₂, retinal preservation of ocular structures was significantly better than at higher doses. In addition, there was no difference from vehicle control retina in cell counts within the ganglion cell layer, or in the width of the inner nuclear layer or outer nuclear layer. Also, there was no difference in the thickness of the inner plexiform layer. However, there was thinning of the peripheral outer plexiform layer, as well as in the outer segment layer. Visual system elements labeled in MRI of mice that received 100 nmol MnCl₂ included the retina, optic nerve, lateral geniculate nucleus, and superior colliculus. The preservation of ganglion cell layer cell counts and inner plexiform layer thickness following 100 nmol MnCl₂ suggests there was negligible injury to RGCs following this dose. These results support using 100 nmol MnCl₂ in mouse eyes for in vivo assessment of the integrity of RGC projections to target neurons in the brain.     

Characterization of Motor Oil by Laser-Induced Fluorescence

A new laser-induced fluorescence method is presented to classify brands of motor oil. A 266-nanometer radiation was employed to collect sixty sets of fluorescence spectra for each brand. Cluster analysis and support vector machine were employed to distinguish motor oils with principal component analysis, which was applied to extract spectral characteristics. The recognition accuracy was up to 100 percent. The results demonstrate that laser-induced fluorescence offers rapid response, high recognition, and high sensitivity for the classification of motor oils.