Characterization of the human SDHC gene encoding of the integral membrane proteins of succinate-quinone oxidoreductase in mitochondria

The neurological manifestations of multiple sclerosis (MS) have been considered to result from demyelination of axons with relative preservation of axonal integrity. This concept has been challenged recently by a landmark pathological study, published in the New England Journal of Medicine, which has demonstrated that axonal degeneration is also present. The authors of the study hypothesized that axonal degeneration is the pathological correlate of the irreversible neurological impairment in this disease. However, this hypothesis cannot be reconciled with the clinical results obtained with transcranial applications of AC pulsed electromagnetic fields (EMFs) of picotesla flux density which have shown rapid and sustained improvement of symptoms including normalization of evoked potential responses in patients with chronic progressive or secondary progressive MS without demyelinated areas first undergoing remyelination or transected axons undergoing regeneration. Biochemical studies have shown that MS patients are serotonergically depleted with the extent of cerebral depletion correlating with the degree of motor disability and a chronic progressive course. It is believed that progressive serotonergic neuronal atrophy with synaptic inactivation, not axonal degeneration, are the hallmarks of the disease and that administration of AC pulsed magnetic fields improves symptoms of MS partly through reactivation of serotonergic neurons and amplification of synaptic serotonergic transmission.     

执行器失效不确定时滞系统的指定衰减度鲁棒可靠控制

针对一类含有时变时滞的不确定参数线性系统,研究了在执行器发生故障情况下的鲁棒可靠控制器设计问题.系统中的参数不确定性满足广义匹配条件,时变时滞的大小及其变化率有界,并假设故障执行器元件的输出为零.经过适当的模型变换,将原系统的鲁棒指数镇定问题转化为另一个等价系统的鲁棒镇定问题.根据Lyapunov稳定性理论和线性矩阵不等式(LMI)方法,分别给出了鲁棒可靠控制器存在的时滞无关和时滞相关充分条件.仿真结果表明了该控制器设计方法的有效性.     

ATP-dependent proteolysis in mitochondria. m-AAA protease and PIM1 protease exert overlapping substrate specificities and cooperate with the mtHsp70 system

To analyze protein degradation in mitochondria and the role of molecular chaperone proteins in this process, bovine apocytochrome P450scc was employed as a model protein. When imported into isolated yeast mitochondria, P450scc was mislocalized to the matrix and rapidly degraded. This proteolytic breakdown was mediated by the ATP-dependent PIM1 protease, a Lon-like protease in the mitochondrial matrix, in cooperation with the mtHsp70 system. In addition, a derivative of P450scc was studied to which a heterologous transmembrane region was fused at the amino terminus. This protein became anchored to the inner membrane upon import and was degraded by the membrane-embedded, ATP-dependent m-AAA protease. Again, degradation depended on the mtHsp70 system; it was inhibited at non-permissive temperature in mitochondria carrying temperature-sensitive mutant forms of Ssc1p, Mdj1p, or Mge1p. These results demonstrate overlapping substrate specificities of PIM1 and the m-AAA protease, and they assign a central role to the mtHsp70 system during the degradation of misfolded polypeptides by both proteases.     

Success rates with gamete intrafallopian transfer and in vitro fertilization in women of advanced maternal age

OBJECTIVE: To evaluate the effect of maternal age on outcomes for IVF and GIFT in women 40 to 45 years of age. DESIGN: Retrospective. SETTING: Boston IVF, a free-standing university-affiliated IVF and GIFT unit. PATIENTS: A total of 2,931 cycles of IVF and 1,826 cycles of GIFT were analyzed in women undergoing assisted reproductive technologies (IVF or GIFT) using autologous eggs. INTERVENTIONS: Medical records of patient outcomes were reviewed. RESULTS: For patients undergoing IVF, the cancellation rate for initiated cycles showed significant differences in women aged 25 to 39 (38.3%), women aged 40 to 43 (49.5%), and women aged 44 to 45 years (69.5%). A significantly lower delivery rate per stimulation and delivery rate per retrieval was found in women aged 40 to 43 years when compared with women aged 25 to 39 years. No deliveries occurred in 59 cycles in women aged 44 to 45 years, thereby representing a significant difference when compared with both women aged 25 to 39 years and women aged 40 to 43 years. For patients undergoing GIFT, the cancellation rate for initiated cycles was significantly higher in women aged 40 to 43 (25.0%) and 44 to 45 years (31.0%) when compared with women aged 25 to 39 years (15.1%). A significantly lower delivery rate per stimulation and delivery rate per retrieval was found in women aged 40 to 43 and 44 to 45 years when compared with women aged 25 to 39 years. CONCLUSIONS: Success rates for IVF and GIFT decline significantly in women > 40 years old. Women aged > or = 44 years are unlikely to benefit from the use of IVF and GIFT.