The molecular interaction of Fas and FAP-1. A tripeptide blocker of human Fas interaction with FAP-1 promotes Fas-induced apoptosis

Fas (APO-1/CD95), which is a member of the tumor necrosis factor receptor superfamily, is a cell surface receptor that induces apoptosis. A protein tyrosine phosphatase, Fas-associated phosphatase-1 (FAP-1), that was previously identified as a Fas binding protein interacts with the C-terminal 15 amino acids of the regulatory domain of the Fas receptor. To identify the minimal region of the Fas C-terminal necessary for binding to FAP-1, we employed an in vitro inhibition assay of Fas/FAP-1 binding using a series of synthetic peptides as well as a screen of random peptide libraries by the yeast two-hybrid system. The results showed that the C-terminal three amino acids (SLV) of human Fas were necessary and sufficient for its interaction with the third PDZ (GLGF) domain of FAP-1. Furthermore, the direct cytoplasmic microinjection of this tripeptide (Ac-SLV) resulted in the induction of Fas-mediated apoptosis in a colon cancer cell line that expresses both Fas and FAP-1. Since t(S/T)X(V/L/I) motifs in the C termini of several other receptors have been shown to interact with PDZ domain in signal transducing molecules, this may represent a general motif for protein-protein interactions with important biological functions.     

Effects of short- and long-term dexamethasone treatment on growth and growth hormone (GH)-releasing hormone (GRH)-GH-insulin-like growth factor-I axis in conscious rats

Although the inhibitory effects of a chronic excess of glucocorticoids (GC) on body growth and GH secretion are well established, the mechanisms involved remain unclear. In this study, we examined the chronic effects of a high dose of dexamethasone (DEX) on spontaneous GH secretion and insulin-like growth factor (IGF)-I in conscious rats. The animals were given daily i.p. injections of DEX (200 microg/day) for either one or four weeks. Body growth assessed by tibia length and serum IGF-I levels was significantly inhibited 1 week after treatment. By contrast, spontaneous GH secretion was not altered 1 week after the treatment. Neither hypothalamic GRH and somtatostain mRNA levels nor GH responses to GRH from single somatotropes were affected 1 week after the treatment. Four weeks after DEX treatment, body growth of the rats was noticeably suppressed. Interestingly, spontaneous GH secretion, hypothalamic GRH mRNA levels and GH responses to GRH were all inhibited 4 weeks after treatment. Pituitary GRH receptor mRNA levels were not altered 1 week after treatment, but increased after 4 weeks. These results indicate that a high dose of DEX initially impairs IGF-I production and subsequently inhibits spontaneous GH secretion in rats. Inhibition of spontaneous GH secretion resulting from chronic GC excess is due, at least in part, to the impairment of hypothalamic GRH synthesis and pituitary GH responsiveness. An increase in the pituitary GRH receptor may be caused by decreased GRH secretion.     

Developmental changes in enzyme activities and in structural features of rat masticatory muscle mitochondria

The functional ability of a muscle is closely related to the activities of the mitochondria, which are energy-producing organelles in muscle cells. The development of the mammalian masticatory muscle progresses dramatically when feeding behavior changes from suckling to mastication, but it is unclear how the energy-producing systems of the mitochondria change. In this paper, the development of rat masticatory muscle mitochondria was investigated in terms of enzyme activities of the mitochondrial respiratory chain and the structural and numerical development of mitochondria, especially regarding the change in feeding behavior from suckling to mastication. Using isolated mitochondria from the masticatory muscle, we measured succinate dehydrogenase, NADH dehydrogenase, succinate-O2 oxidoreductase, and NADH-O2 oxidoreductase. These were found to be increased in the 15-day postnatal rat compared with the 0- to 10-day postnatal rat. The structural development of mitochondria was gradual in the 0- to 15-day postnatal rat. However, a notable increase was found in the cross-sectional area of mitochondria between 10 and 15 days postnatally. The number of mitochondria per muscle fiber was apparently constant during the same period. We demonstrated that the change in feeding behavior was well-correlated with an increase in mitochondrial enzyme activity, also supported by the early structural development of mitochondria.     

Transcutaneous measurement and spectrum analysis of heart wallvibrations

For the noninvasive diagnosis of heart disease based on the acoustic and elastic characteristics of the heart muscle, it is necessary to transcutaneously measure small vibration signals, including components with an amplitude of less than 100 μm, from various parts of the heart wall continuously for periods of more than several heartbeats in a wide frequency range up to 1 kHz. Such measurement, however, has not been realized by any ultrasonic diagnostic methods or systems to date. By introducing the constraint least-square approach, this paper proposes a new method for accurately tracking the movement of the heart wall based on both the phase and magnitude of the demodulated signal to determine the instantaneous position of the object so that the vibration velocity of the moving object can be accurately estimated. By this method, small vibrations of the heart wall with small amplitudes less than 100 μm on the motion resulting from a heartbeat with large amplitude of 10 mm can be successfully detected with sufficient reproducibility in the frequency range up to several hundred Hertz continuously for periods of about 10 heartbeats. The resultant small vibration is analyzed not only in the time domain, but also in the frequency domain. As confirmed by the preliminary experiments herein reported, the new method offers potential for research in acoustical diagnosis of heart disease     

Measurements ofPVTx properties of refrigerant mixture HFC-32+HFC-125 in the gaseous phase

The experimental 156PVTx properties of an important binary refrigerant mixture, HFC-32 (difluoromethane)+HFC-125 (pentafluorethane), have been measured for three compositions, i.e., 50, 60, and 80 wt% HFC-32, by a constant-mass-method coupled with expansion procedure in an extensive range of temperaturesT from 320 to 440 K, of pressuresP from 1.8 to 5.3 M Pa, and of densities p from 50 to 124 kg · m^–3. The experimental uncertainties of the present measurements are estimated to be within ±7 mK in temperature, ±2 kPa in pressure, ±0.2% in density and ±0.02 wt% of HFC-32. The sample purities are 99.998 wt% for HFC-32 and 99.99 wt% for HFC-125. Seventy-eight second and third virial coeflicients for temperatures from 320 to 440 K have been determined by the present measurements.Paper presented at the Twelfth Symposium on Thermophysical Properties, June 19–24, 1994, Boulder, Colorado, U.S.A.     

Lipopolysaccharide primes human alveolar macrophages for enhanced release of superoxide anion and leukotriene B4: self-limitations of the priming response with protein synthesis

Human alveolar macrophages (AM) can produce potent reactive oxygen intermediates (ROI) and arachidonic acid metabolites (eicosanoids), which have important roles in host defense and the pathogenesis of some diseases of the lung. Bacterial lipopolysaccharide (LPS) is believed to cause profound lung injury and can prime mouse peritoneal macrophages for the enhanced secretion of ROI and eicosanoids. Therefore, we investigated the effect of LPS pretreatment on the ability of AM to release superoxide anions (O2-) and leukotriene B4 (LTB4). LPS can prime AM for the enhanced secretion of O2- and LTB4, regardless of whether they are derived from nonsmokers or smokers. Moreover, judging from the time-response characteristics, this priming for LTB4 release could be inhibited in the later stages of pretreatment, when the O2(-)-releasing capacity was enhanced. The priming inhibition was prevented, at least in part, by cycloheximide, but not by SOD and/or catalase. In addition, cycloheximide also inhibited the priming for O2- release. Hence, protein synthesis might be necessary for the priming for O2- release and for inhibiting the priming for LTB4 release. This phenomenon of self-limiting the priming response with LPS seems to be very important when we consider the high oxygen tension in the lungs and the many bacterial substances inspired into alveoli.     

An automatic torque ripple compensation system for direct drive motors

A serious problem in motion control is the occurrence of torque ripple. Since a direct drive (DD) motor with a magnet rotor uses a rare-earth magnet, the torque ripple is more serious than that of conventional servomotors. This paper presents an auto-compensation of torque ripple using a software-implemented torque observer. The frequency and amplitude of torque ripple can be obtained in the controller by using the estimated torque from an observer, and the autonomous generation of a compensating current component for a torque ripple is possible. The proposed algorithm has been verified by experiments.     

An equation of state for 1,1-difluroethane (HFC 152a)

An equation of state for 1,1-difluoroethane (HFC 152a, CH₃CHF₂) has been developed on the basis of reliable experimental data including PVT, liquid C_p, and saturated-liquid-density data measured by our group. It is a non-dimensionalized virial equation whose functional form is the same as that originally developed for 1,1,1,2-tetrafluoroethane (HFC 134a) in our group. The effective range is for pressures up to 15 MPa, temperatures from 230 to 450 K, and densities to 1000 kg m⁻³. The equation represents reliable PVT measurements within ± 1% in pressure for the superheated vapour and supercritical fluid, while within ±0.5% in density for the compressed liquid. In addition, it should be noted that the equation represents the other essential thermodynamic properties including vapour pressures, saturated-liquid/ vapour densities, isobaric/isochoric specific heats and sound velocity in both the liquid and gaseous phase of HFC 152a.     

Regenerating-mode low-speed operation of sensorless induction motor drive with adaptive observer

Speed estimation methods for sensorless induction motor drives can be divided into two groups. One is based on information about fundamental components of stator currents and voltages. The other is based on high-frequency components injection in stator voltages or currents. The latter may operate stably under zero frequency, which occurs in regenerating mode at low speeds. It, however, causes loss increasing and torque ripple. The former is difficult to operate under zero frequency. The authors propose a stable method categorized in the former group even in regenerating mode at low speeds. The proposed method is based on an adaptive flux observer. First, a new observer gain design is shown. Next, a method avoiding zero-frequency operation with controlling a rotor flux level is proposed.     

Heat Capacity of 3He Solid Film on Graphite in Magnetic Fields

Heat capacities of a submonolayer ³He solid film adsorbed on a graphite surface are measured in magnetic fields up to 400 Oe. The measured heat capacity shifts to higher temperatures with an increasing magnetic field. The amplitudes of the shifts are twenty times larger than the magnitude of the Zeeman energy, which is anomalously large. With regard to the origin of these large shifts, the reduction of frustrations and the weakening of the competition between multiple spin exchange interactions are discussed.