Diversity in enoyl-acyl carrier protein reductases

The enoyl-acyl carrier protein reductase (ENR) is the last enzyme in the fatty acid elongation cycle. Unlike most enzymes in this essential pathway, ENR displays an unusual diversity among organisms. The growing interest in ENRs is mainly due to the fact that a variety of both synthetic and natural antibacterial compounds are shown to specifically target their activity. The primary anti-tuberculosis drug, isoniazid, and the broadly used antibacterial compound, triclosan, both target this enzyme. In this review, we discuss the diversity of ENRs, and their inhibitors in the light of current research progress. Received 3 November 2008; received after revision 5 December 2008; accepted 8 December 2008     

Functions and pathologies of BiP and its interaction partners

The endoplasmic reticulum (ER) is involved in a variety of essential and interconnected processes in human cells, including protein biogenesis, signal transduction, and calcium homeostasis. The central player in all these processes is the ER-lumenal polypeptide chain binding protein BiP that acts as a molecular chaperone. BiP belongs to the heat shock protein 70 (Hsp70) family and crucially depends on a number of interaction partners, including co-chaperones, nucleotide exchange factors, and signaling molecules. In the course of the last five years, several diseases have been linked to BiP and its interaction partners, such as a group of infectious diseases that are caused by Shigella toxin producing E. coli. Furthermore, the inherited diseases Marinesco-Sj?gren syndrome, autosomal dominant polycystic liver disease, Wolcott-Rallison syndrome, and several cancer types can be considered BiP-related diseases. This review summarizes the physiological and pathophysiological characteristics of BiP and its interaction partners. Received 20 November 2008; received after revision 09 December 2008; accepted 12 December 2008     

Breaking biological symmetry in membrane proteins: The asymmetrical orientation of PsaC on the pseudo-C2 symmetric Photosystem I core

The elucidation of assembly pathways of multi-subunit membrane proteins is of growing interest in structural biology. In this study, we provide an analysis of the assembly of the asymmetrically oriented PsaC subunit on the pseudo C₂-symmetric Photosystem I core. Based on a comparison of the differences in the NMR solution structure of unbound PsaC with that of the X-ray crystal structure of bound PsaC, and on a detailed analysis of the PsaC binding site surrounding the F_X iron-sulfur cluster, two models can be envisioned for what are likely the last steps in the assembly of Photosystem I. Here, we dissect both models and attempt to address heretofore unrecognized issues by proposing a mechanism that includes a thermodynamic perspective. Experimental strategies to verify the models are proposed. In closing, the evolutionary aspects of the assembly process will be considered, with special reference to the structural arrangement of the PsaC binding surface. Received 22 October 2008; received after revision 17 November 2008; accepted 05 December 2008     

基于拉格朗日系统中约束力思想的编队卫星构形非线性控制方法

借鉴经典动力学中约束力的思想,提出了一种编队卫星构形精确保持的非线性控制方法．该方法首先将非线性和摄动条件下编队卫星构形保持问题转换为带有完整约束的拉格朗日动力学系统,然后将问题转换为一组微分代数方程,通过求解微分代数方程,确定编队卫星构形保持的非线性控制律．由于借鉴了约束力的思想,该方法自然地利用了编队卫星动力学系统的力学特性,具有节省能量和高精度的特点．通过对线性和非线性条件下空间圆编队卫星构形保持问题的仿真,验证了提出的非线性控制方法的这些特性．     

Direct inhibition of phospholipid scrambling activity in erythrocytes by potassium ions

The exposure of phosphatidylserine (PS) at the cell surface plays a critical role in blood coagulation and serves as a macrophage recognition moiety for the engulfment of apoptotic cells. Previous observations have shown that a high extracellular [K⁺] and selective K⁺ channel blockers inhibit PS exposure in platelets and erythrocytes. Here we show that the rate of PS exposure in erythrocytes decreases by ~50% when the intracellular [K⁺] increases from 0 to physiological concentrations. Using resealed erythrocyte membranes, we further show that lipid scrambling is inducible by raising the intracellular [Ca²⁺] and that K⁺ ions have a direct inhibitory effect on this process. Lipid scrambling in resealed ghosts occurs in the absence of cell shrinkage and microvesicle formation, processes that are generally attributed to Ca²⁺-induced lipid scrambling in intact erythrocytes. Thus, opening of Ca²⁺-sensitive K⁺ channels causes loss of intracellular K⁺ that results in reduced intrinsic inhibitory effect of these ions on scramblase activity. Received 11 September 2008; received after revision 17 October 2008; accepted 27 October 2008     

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     

Operationalising “Double-Loop” Learning in Service Organisations: A Systems Approach for Creating Knowledge

Learning organisation literature has widely discussed the connections between “double-loop” learning and its significance to organisational performance, but paying little attention to tools and systems that can operationalise “double-loop” learning in organisations. This paper investigates the impact of applying a systems approach for service operations design, expressed as the Vanguard Method (Seddon, Freedom from command and control: a better way to make the work work, 2003), in order to activate “double-loop” learning in service organisations. Two case studies were conducted in the banking mortgage operations and adults’ social care services in the UK, using the dimensions of the learning organisation questionnaire (DLOQ), semi-structured interviews, observations, and documents. The findings of the cross-case analysis support the link of applying the Vanguard Method with operationalising “double-loop” learning through three main factors, namely systematic-operations improvement, organisational capacity development, and outside-in mode of work; that are all embedded into the seven dimensions of the DLOQ. The value of this paper is the introduction of a service operations design tool that can activate “double-loop” learning performance in the fast changing knowledge era. It also provides an impetus for service organisations to creatively influence employees’ competencies to effectively improve internal systems.