PPAR γ partial agonist, KR-62776, inhibits adipocyte differentiation via activation of ERK

Indenone KR-62776 acts as an agonist of PPARγ without inducing obesity in animal models and cells. X-ray crystallography reveals that the indenone occupies the binding pocket in a different manner than rosiglitazone. 2-Dimensional gel-electrophoresis showed that the expression of 42 proteins was altered more than 2.0-fold between KR-62776- or rosiglitazone-treated adipocyte cells and control cells. Rosiglitazone down-regulated the expression of ERK1/2 and suppressed the phosphorylation of ERK1/2 in these cells. However, the expression of ERK1/2 was up-regulated in KR-62776-treated cells. Phosphorylated ERK1/2, activated by indenone, affects the localization of PPARγ, suggesting a mechanism for indenone-inhibition of adipogenesis in 3T3-L1 preadipocyte cells. The preadipocyte cells are treated with ERK1/2 inhibitor PD98059, a large amount of the cells are converted to adipocyte cells. These results support the conclusion that the localization of PPARγ is one of the key factors explaining the biological responses of the ligands. Received 04 March 2009; received after revision 13 March 2009; accepted 17 March 2009     

Molecular mechanisms of BK channel activation

Large conductance, Ca²⁺-activated potassium (BK) channels are widely expressed throughout the animal kingdom and play important roles in many physiological processes, such as muscle contraction, neural transmission and hearing. These physiological roles derive from the ability of BK channels to be synergistically activated by membrane voltage, intracellular Ca²⁺ and other ligands. Similar to voltage-gated K⁺ channels, BK channels possess a pore-gate domain (S5–S6 transmembrane segments) and a voltage-sensor domain (S1–S4). In addition, BK channels contain a large cytoplasmic C-terminal domain that serves as the primary ligand sensor. The voltage sensor and the ligand sensor allosterically control K⁺ flux through the pore-gate domain in response to various stimuli, thereby linking cellular metabolism and membrane excitability. This review summarizes the current understanding of these structural domains and their mutual interactions in voltage-, Ca²⁺ - and Mg²⁺ -dependent activation of the channel. Received 25 September 2008; received after revision 23 October 2008; accepted 24 October 2008     

Bitter peptides and bitter taste receptors

Bitter peptides are a structurally diverse group of oligopeptides often generated in fermented, aged, and hydrolyzed food products that make them unfavorable for consumption. Humans perceive bitterness by a repertoire of 25 human bitter receptors, termed T2Rs. Knowledge of the structural features of bitter receptors and of the factors that stimulate bitter receptors will aid in understanding the mechanism responsible for bitter taste perception. This article reviews the current knowledge regarding structural features of bitter peptides and bitter taste receptors. Received 24 November 2008; received after revision 11 December 2008; accepted 16 December 2008     

具有常余维数2k+2l不动点集的(Z2)k作用

设(Z₂)^k作用作用于光滑闭流形Mⁿ, 其不动点集具有常余维数r, J^r_n,k是具有上述性质的未定向n维上协边类［Mⁿ］构成的 集合.J^r_*,k为未定向上协边环MO_*的理想. 通过构造MO_*的一组生成元证明由所有维数大于2^k+2^l的上协边类及分解式中每个因子的维数都小于2^k的2^k+2^l维可分解上协边类构成.     

基于网络考试系统的UML建模

通过统一建模语言(UML)对网络考试系统进行了分析和建模,建立了系统用例图,并结合主要用例-学生考试模块,建立了类图、顺序图、活动图.描述了系统的功能需求、功能流程、类的结构与关系、对象之间的交互.最终采用面向对象语言实现在线考试系统.使用这种方法对系统进行建模,优化了开发过程,并有利于提高系统的稳定性、可维护性和可重用性.     

基于多元共生遗传神经网络的藻类预测仿真

提出一种多元共生遗传神经网络(PGANN),从遗传算法和神经网络——进化和学习两方面及其相互关系着手完善进化过程,以提高优化效果和泛化能力。该算法包括一个共生平衡交叉算子,一种多元选择策略和一种神经网络的分级优化策略,其中共生平衡算子能够兼顾进化过程中的方向性、多样性和自适应性;多元选择策略能够适应进化过程不同时段对选择压力不同的需求;而分级优化使运算规模和运算速度之间的矛盾得到缓解。将该改进的遗传神经网络PGANN应用于水库和湖泊有毒的优势蓝绿藻爆发预测,取得了满意的效果。     

Highly homologous HERC proteins localize to endosomes and exhibit specific interactions with hPLIC and Nm23B

Small HERC proteins are defined by the presence of one RCC1-like domain and a HECT domain. Having evolved out of one common ancestor, the four members of the family exhibit a high degree of homology in genomic organization and amino acid sequence, thus it seems possible that they might accomplish similar functions. Here we show that small HERC proteins interact with each other and localize to the same cellular structures, which we identify as late endosomes and lysosomes. We demonstrate interaction of HERC3 with the ubiquitin-like proteins hPLIC-1 and hPLIC-2 and we establish interaction of HERC5 with the metastasis suppressor Nm23B. While hPLIC proteins are not ubiquitinated by HERC3, HERC5 plays an important role in ubiquitination of Nm23B. In summary, although small HERC proteins are highly homologous showing the same subcellular distribution, they undergo different molecular interactions.     

Bile Acids: Chemistry, Pathochemistry, Biology, Pathobiology, and Therapeutics

Bile acids and bile alcohols in the form of their conjugates are amphipathic end products of cholesterol metabolism with multiple physiological functions. The great variety of bile acids and bile alcohols that are present in vertebrates are tabulated. Bile salts have an enterohepatic circulation resulting from efficient vectorial transport of bile salts through the hepatocyte and the ileal enterocyte; such transport leads to the accumulation of a pool of bile salts that cycles between the liver and intestine. Bile salt anions promote lipid absorption, enhance tryptic cleavage of dietary proteins, and have antimicrobial effects. Bile salts are signaling molecules, activating nuclear receptors in the hepatocyte and ileal enterocyte, as well as an increasing number of G-protein coupled receptors. Bile acids are used therapeutically to correct deficiency states, to decrease the cholesterol saturation of bile, or to decrease the cytotoxicity of retained bile acids in cholestatic liver disease.     

The utility F-box for protein destruction

A signature feature of all living organisms is their utilization of proteins to construct molecular machineries that undertake the complex network of cellular activities. The abundance of a protein element is temporally and spatially regulated in two opposing aspects: de novo synthesis to manufacture the required amount of the protein, and destruction of the protein when it is in excess or no longer needed. One major route of protein destruction is coordinated by a set of conserved molecules, the F-box proteins, which promote ubiquitination in the ubiquitin-proteasome pathway. Here we discuss the functions of F-box proteins in several cellular scenarios including cell cycle progression, synapse formation, plant hormone responses, and the circadian clock. We particularly emphasize the mechanisms whereby F-box proteins recruit specific substrates and regulate their abundance in the context of SCF E3 ligases. For some exceptions, we also review how F-box proteins function through non-SCF mechanisms.