SHARPIN is a component of the NF-κB-activating linear ubiquitin chain assembly complex

Cpdm (chronic proliferative dermatitis) mice develop chronic dermatitis and an immunodeficiency with increased serum IgM, symptoms that resemble those of patients with X-linked hyper-IgM syndrome and hypohydrotic ectodermal dysplasia (XHM-ED), which is caused by mutations in NEMO (NF-κB essential modulator; also known as IKBKG). Spontaneous null mutations in the Sharpin (SHANK-associated RH domain interacting protein in postsynaptic density) gene are responsible for the cpdm phenotype in mice. SHARPIN shows significant similarity to HOIL-1L (also known as RBCK1), a component of linear ubiquitin chain assembly complex (LUBAC), which induces NF-κB activation through conjugation of linear polyubiquitin chains to NEMO. Here, we identify SHARPIN as an additional component of LUBAC. SHARPIN-containing complexes can linearly ubiquitinate NEMO and activated NF-κB. Thus, we re-define LUBAC as a complex containing SHARPIN, HOIL-1L, and HOIP (also known as RNF31). Deletion of SHARPIN drastically reduced the amount of LUBAC, which resulted in attenuated TNF-α- and CD40-mediated activation of NF-κB in mouse embryonic fibroblasts (MEFs) or B cells from cpdm mice. Considering the pleomorphic phenotype of cpdm mice, these results confirm the predicted role of LUBAC-mediated linear polyubiquitination in NF-κB activation induced by various stimuli, and strongly suggest the involvement of LUBAC-induced NF-κB activation in various disorders.     

E3 ubiquitin ligase that recognizes sugar chains

N-glycosylation of proteins in the endoplasmic reticulum (ER) has a central role in protein quality control. Here we report that N-glycan serves as a signal for degradation by the Skp1-Cullin1-Fbx2-Roc1 (SCF(Fbx2)) ubiquitin ligase complex. The F-box protein Fbx2 (ref. 4) binds specifically to proteins attached to N-linked high-mannose oligosaccharides and subsequently contributes to ubiquitination of N-glycosylated proteins. Pre-integrin beta 1 is a target of Fbx2; these two proteins interact in the cytosol after inhibition of the proteasome. In addition, expression of the mutant Fbx2 Delta F, which lacks the F-box domain that is essential for forming the SCF complex, appreciably blocks degradation of typical substrates of the ER-associated degradation pathway. Our results indicate that SCF(Fbx2) ubiquitinates N-glycosylated proteins that are translocated from the ER to the cytosol by the quality control mechanism.     

昆虫翅膀的运动参数测量研究

研究可用于精确测量昆虫运动参数的条纹投影法.应用具有高衍射效率的声光调制器(AOD)生成投影条纹,通过调整各衍射光束的角度获得不同角间距的条纹,可用来测量反射比较低的昆虫翅膀.结合AOD和光栅,从两个相互垂直的方向投射条纹,可以在>90°的测量范围内测量蜜蜂的拍打翅膀.结果表明,在蜜蜂的一个拍打周期内,用该方法可以有效地测量其拍打角、滞后角,扭转角和扭转变形,相对测量误差<2%.     

日本传统“诗吟”中单个反射声优选时延与自相关函数的关系

研究在日本传统“诗吟”表演中，在干信号中加上适当时延的单个反射声是否更为有利．专业“诗吟”表演者嗓音中对典型的“节”的吟唱是该种表演艺术的一种独特的吟咏方式．对此及对“节”外内容的吟唱都在消音室中加以录音．文中通过成对比较法试验得出了主观优选的标度值．结果表明，在聆听对“节”的吟唱时，听者更喜欢在干信号中加上延时为10～30ms的单个反射声，而在聆听对“节”外内容的吟唱时，加上单个反射声与否对听者而言并无显著的差别．文中对此项发现从吟唱“节”的声源信号的自相关函数的包络特征上加以讨论．     

ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation

Malnutrition affects up to one billion people in the world and is a major cause of mortality. In many cases, malnutrition is associated with diarrhoea and intestinal inflammation, further contributing to morbidity and death. The mechanisms by which unbalanced dietary nutrients affect intestinal homeostasis are largely unknown. Here we report that deficiency in murine angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (Ace2), which encodes a key regulatory enzyme of the renin-angiotensin system (RAS), results in highly increased susceptibility to intestinal inflammation induced by epithelial damage. The RAS is known to be involved in acute lung failure, cardiovascular functions and SARS infections. Mechanistically, ACE2 has a RAS-independent function, regulating intestinal amino acid homeostasis, expression of antimicrobial peptides, and the ecology of the gut microbiome. Transplantation of the altered microbiota from Ace2 mutant mice into germ-free wild-type hosts was able to transmit the increased propensity to develop severe colitis. ACE2-dependent changes in epithelial immunity and the gut microbiota can be directly regulated by the dietary amino acid tryptophan. Our results identify ACE2 as a key regulator of dietary amino acid homeostasis, innate immunity, gut microbial ecology, and transmissible susceptibility to colitis. These results provide a molecular explanation for how amino acid malnutrition can cause intestinal inflammation and diarrhoea.     

钢箱梁斜拉桥等效疲劳车辆荷载模型分析

为了调查长江中下游地区跨江大桥的车辆荷载运行特性,首先,以某一钢箱梁斜拉桥为例,分析大桥1 a实测交通流特性,得到相关轴型车辆的轴距、车辆质量及轴重分布;其次,基于损伤等效原则计算大桥各轴型车的等效疲劳车辆荷载模型;最后,对我国钢桥规范提供的疲劳荷载模型III进行修正,提出适用于同区域类型桥梁的标准疲劳车。研究结果表明：大桥呈现交通流量大、货车载重高及超载现象普遍的特征;等效疲劳车辆荷载模型可简化为6种车型,等效车辆质量大于10 t的疲劳车辆占比高达85.9%,其中6轴车在疲劳损伤中占主导地位;提出的疲劳标准车是1辆质量为64 t的4轴车,单轴重为16 t;国外规范疲劳标准车引起的疲劳损伤均低于本文实际疲劳标准车引起的疲劳损伤;对于顶板U肋连接细节,顶板厚度增加2 mm可至少降低疲劳损伤46.4%。     

电吉他增加畸变后的音色研究

声音畸变是电吉他音乐最重要的特性之一，对电吉他增加畸变后的音色的描述是目前的研究热点．笔者利用实验手段研究了不同畸变后得到的音色差别与从震源信号的自相关函数中提取出来的物理因子的关系，并利用自相关函数Φ（0）定义了一个因子WΦ（0）在利用模拟声音畸变进行的实验中，发现形WΦ（0）因子可以较好地描述声音的畸变，同时，音色的差别与WΦ（0）的平均值有较强的相关关系．另一项采用商业化效应器进行的实验也得到了类似的结果，这表明音色差异与WΦ（。0）的均值之间也有强的相关关系．