Bcl-2-independent Bcr-Abl-mediated resistance to apoptosis: protection is correlated with up regulation of Bcl-xL

Bcr - Abl is the molecule responsible for both the transformation phenotype and the resistance to chemotherapeutic drugs found in chronic myelogenous leukemia (CML) cells. Wild-type HL-60, a transformed pro-myelocytic cell line, is very susceptible to apoptosis-inducing agents. We show here that expression of Bcr - Abl in HL-60 cells rendered them extremely resistant to apoptosis induced by a wide variety of agents. The anti-apoptotic effect of Bcr - Abl was found to be independent of the phase of the cell cycle. Treatment with antisense oligonucleotides directed to bcr decreased the expression of the ectopic bcr - abl and restored susceptibility to apoptosis. Double mutations affecting the autophosphorylation site and the phosphotyrosine-binding motif (FLVRES) have been previously shown to impair the transforming activity of Bcr - Abl in fibroblasts and hematopoietic cells, however HL-60 cells expressing this double mutant molecule exhibited the same level of resistance to apoptosis as those expressing the wild-type Bcr - Abl. Interestingly, wild type and mutant Bcr - Abl induced in HL-60 cells a dramatic down regulation of Bcl-2 and increased the levels of Bcl-xL. The level of Bax did not change in response to the presence of Bcr - Abl. Antisense oligonucleotides targeted to bcl-x downregulated the expression of Bcl-x, and increased the susceptibility of HL-60. Bcr - Abl cells to staurosporine. Importantly, HL-60 cells overexpressing Bcl-xL showed higher expression of Bcl-xL but lower resistance to apoptosis when compared to HL-60. Bcr - Abl cells. The results described here show that Bcr - Abl is a powerful mammalian anti-apoptotic molecule and can act independently of Bcl-2. Bcl-xL, however, seems to participate in part in Bcr - Abl-mediated resistance to apoptosis in HL-60 cells.     

Effect of frozen storage on protein denaturation in bovine muscle 1. Myofibrillar ATPase activity and differential scanning calorimetric studies

The effect of frozen storage on myofibrillar ATPase activity and thermal transitions in bovine muscle was investigated. Myofibrillar ATPase activity and total enthalpy of denaturation (ΔH) decreased with time of storage. The rate of decrease was lower at −20°C than at −5°C or −10°C. Differences in behaviour during storage of muscle after fast or slow freezing could be attributed to differences in ice recrystallization. The observed decreases in area of the first peak seen in the thermograms and Ca²⁺-myo-fibrillar ATPase activity show that the myosin head denaturated progressively during storage. The myosin tail also denaturated during storage but the thin filament remained unaltered. Kinetic analysis suggested that the denaturation of the myofibrillar proteins took place through two consecutive first order reactions; an initial rapid reaction followed by a slower one.     

316Ti不锈钢环境敏感断裂起裂时间研究

采用慢应变速率和恒载荷试验方法,研究在压水堆一次侧工况下氯离子浓度,氧浓度,加载应力和应速率对ＰＷＲ压力边界材料３１６Ｔｉ不锈钢环境促进起裂时间的影响。     

The effect of occlusion of the better seeing eye on the function of the visual system in children with unilateral amblyopia

Vision acuity and visual evoked potentials (VEP) to a homogeneous light field and chess field reversion were studied in children aged 5-6 years with unilateral amblyopia before and after 3-month direct total occlusion of the intact eye. Occlusion of the intact eye resulted in improvement of the vision acuity and VEP of the amblyopic eye, that correlated with the degree of amblyopia. At the same time examinations of the intact eyes revealed reduced amplitude of VEP to large and increased latency to small chess pattern cells but no changes of the vision acuity. The results evidence the necessity of monitoring the occlusion by VEP recording to prevent the detrimental effects of visual deprivation on the development of the system of vision in a child.     

Gramicidin channel kinetics under tension

We have measured the effect of tension on dimerization kinetics of the channel-forming peptide gramicidin A. By aspirating large unilamellar vesicles into a micropipette electrode, we are able to simultaneously monitor membrane tension and electrical activity. We find that the dimer formation rate increases by a factor of 5 as tension ranges from 0 to 4 dyn/cm. The dimer lifetime also increases with tension. This behavior is well described by a phenomenological model of membrane elasticity in which tension modulates the mismatch in thickness between the gramicidin dimer and membrane.