Degradation of the mitochondrial complex I assembly factor TMEM126B under chronic hypoxia

Cell stress such as hypoxia elicits adaptive responses, also on the level of mitochondria, and in part is mediated by the hypoxia-inducible factor (HIF) 1α. Adaptation of mitochondria towards acute hypoxic conditions is reasonably well understood, while regulatory mechanisms, especially of respiratory chain assembly factors, under chronic hypoxia remains elusive. One of these assembly factors is transmembrane protein 126B (TMEM126B). This protein is part of the mitochondrial complex I assembly machinery. We identified changes in complex I abundance under chronic hypoxia, in association with impaired substrate-specific mitochondrial respiration. Complexome profiling of isolated mitochondria of the human leukemia monocytic cell line THP-1 revealed HIF-1α-dependent deficits in complex I assembly and mitochondrial complex I assembly complex (MCIA) abundance. Of all mitochondrial MCIA members, we proved a selective HIF-1-dependent decrease of TMEM126B under chronic hypoxia. Mechanistically, HIF-1α induces the E3-ubiquitin ligase F-box/WD repeat-containing protein 1A (β-TrCP1), which in turn facilitates the proteolytic degradation of TMEM126B. Attenuating a functional complex I assembly appears critical for cellular adaptation towards chronic hypoxia and is linked to destruction of the mitochondrial assembly factor TMEM126B.     

Evidence of G-protein-coupled receptor and substrate transporter heteromerization at a single molecule level

G-protein-coupled receptors (GPCRs) can constitute complexes with non-GPCR integral membrane proteins, while such interaction has not been demonstrated at a single molecule level so far. We here investigated the potential interaction between the thyrotropin receptor (TSHR) and the monocarboxylate transporter 8 (MCT8), a member of the major facilitator superfamily (MFS), using fluorescence cross-correlation spectroscopy (FCCS). Both the proteins are expressed endogenously on the basolateral plasma membrane of the thyrocytes and are involved in stimulation of thyroid hormone production and release. Indeed, we demonstrate strong interaction between both the proteins which causes a suppressed activation of G_q/11 by TSH-stimulated TSHR. Thus, we provide not only evidence for a novel interaction between the TSHR and MCT8, but could also prove this interaction on a single molecule level. Moreover, this interaction forces biased signaling at the TSHR. These results are of general interest for both the GPCR and the MFS research fields.     

Impact of biofilm matrix components on interaction of commensal Escherichia coli with the gastrointestinal cell line HT-29

Commensal Escherichia coli form biofilms at body temperature by expressing the extracellular matrix components curli fimbriae and cellulose. The role of curli fimbriae and cellulose in the interaction of commensal E. coli with the intestinal epithelial cell line HT-29 was investigated. Expression of curli fimbriae by the typical commensal isolate E. coli TOB1 caused adherence and internalization of the bacteria and triggered IL-8 production in HT-29 cells. In particular, induction of IL-8 production was complex and involved curli-bound flagellin. While cellulose alone had no effect on the interaction of TOB1 with HT-29 cells, co-expression of cellulose with curli fimbriae decreased adherence to, internalization and IL-8 induction of HT-29 cells. Investigation of a panel of commensal isolates showed a partial correlation between expression of curli fimbriae and enhanced internalization and IL-8 production. In addition, a high immunostimulatory flagellin was identified. Thus, the consequences of expression of extracellular matrix components on commensal bacterial-host interactions are complex.     

战区物资调运数学模型研究

如何优化分配,合理调运,及时准确地完成后勤保障任务,是现代战争中战区物资调运面临的重要问题之一.基于运输问题,就现代战争条件下战区物资调运问题的各种情况建立了数学模型.该模型可用于后勤物资保障的决策支持系统及指挥自动化系统,为解决战时后勤保障供应问题提供了新的理论方法和思路.     

一种采用混合进制的算术编码

针对许多实际应用中需要同时编码压缩来自多种不同符号集的数据,提出一种采用混合进制的算术编码,提高编码效率的同时增强了算术编码的抗误码扩散能力.从理论上分析了该算法并给出了实现过程.处理小波零树系数以及随机混合数据的实验结果表明,该算法明显优于单一进制的编码算法.     

非基线对称类信号的基线扣除新算法

在分析了现有基线扣除算法的基础上,根据非基线对称类基线信号的特征提出了一种新的基线扣除算法--基于小波滤波和梯度直方图最佳分割的非基线对称类信号基线扣除新算法.考虑到信号总是存在着噪声,含噪的基线信号梯度值也较大,并且分布无规律,采用了多分辨率小波变换滤波技术.通过合理选择最佳分割阈值门限,算法可精确提取出该类信号的基线.     

引信全电子安全系统程序控制组件设计

全电子安全系统是引信设计的发展方向,程序控制组件是实现引信安全控制的重要部件.介绍了一种引信全电子安全系统程序控制组件的技术要求、基本功能和工作顺序及原理,提出了提高系统可靠性的电路模式和设计原则,同时对程序控制组件的软件设计方法进行了介绍.采用先进的在系统可编程器件,实现系统逻辑功能的集成化、小型化,且具有易于功能扩展、设计升级等优点.     

一种基于串行总线的智能容错飞控计算机系统

从工程技术角度出发,讨论了适用于无人驾驶飞行器的容错飞控计算机系统的实现,给出了基于串行总线的智能容错飞控计算机系统结构,将工作状态检测系统和故障预测技术应用到容错计算机系统中,可在故障发生前采取容错措施,避免故障发生和故障造成的系统失效.给出了总线接口、运算控制单元、A/D转换单元、通讯模块的结构和实现方法,指出利用CPLD和HDL语言进行电路综合具有效率高、测试方便、易修改的特点,应在实践中广泛推广.     

电梯上高峰模式下动态分区算法的研究

研究了电梯群控系统(EGCS)上行高峰时期的动态分区群控方法.动态分区是根据大楼乘客流量的大小和分布情况动态地调整楼层区域的划分;同时提出了一致的UPPINT的目标函数,将动态分区问题归结为一个最优化问题,用直接搜索法对其进行求解;并对群控的几种算法进行了仿真比较,验证了动态分区算法的良好效果.