Diketopiperazines in peptide and combinatorial chemistry.

Diketopiperazines (DKPs), the smallest cyclic peptides, represent an important class of biologically active natural products and their research has been fundamental to many aspects of peptide chemistry. The advent of combinatorial chemistry has revived interest in DKPs for two reasons: firstly, they are simple heterocyclic scaffolds in which diversity can be introduced and stereochemically controlled at up to four positions; secondly, they can be prepared from readily available alpha-amino acids using very robust chemistry. Here synthetic methods, conformation, as well as applications of DKPs are summarized and discussed critically.     

Contractile system of muscle as an auto-oscillator

It is widely known that the contractile system of muscle takes on either the state of contraction (force-generating) or the state of relaxation (non-force-generating), which is known as the "all-or-nothing" principle. However, it is important to note that under intermediate activation conditions there exists a third state, which demonstrates auto-oscillatory properties and is termed SPOC (SPontaneous Oscillatory Contraction) state. We present a phase diagram, in which the states of the contractile system of muscle are divided into three regions consisting of contraction, relaxation and SPOC states. In the present review, experimental data related to the characteristics of SPOC are summarized and the mechanism of SPOC is described. We propose that the bio-motile system itself is an auto-oscillator, even in a membrane-less supra-molecular structure composed of an assembly of molecular motors and cytoskeletons (actin filaments and microtubules). Finally, the physiological significance of SPOC is discussed.     

微生物学“小规模限制性在线开放课程+对分课堂”混合教学模式的探索与实践

互联网时代下新兴技术推陈出新，传统讲授型课堂面临诸多挑战。秉承“教”与“学”并重的理念，深圳大学微生物学课程探索并初步实践了“小规模限制性在线开放课程(small private online course，SPOC)+对分课堂”混合教学模式。综合两种教学方法的优势，对微生物学课程的教学内容按照“课前、课中、课后”三大模块进行了系统重构，将每个教学单元设计为讲授(presentation，P)-内化吸收(assimilation，A)-温故知新(review，R)-讨论(discussion，D)-讲授(presentation，P)，即P-A-R-D-P这5个环节，其中课前P-A环节采用线上SPOC、课中R-D-P采用对分课堂形式。这样的混合教学模式既不忽视传统课堂中教师系统传授知识的重要性，也不完全让学生自学，打造了教师充分设计、学生充分参与的良性互动课堂氛围，有利于实现教师与学生两个主体达到“教”与“学”及“权”与“责”上的动态平衡，获得了学生的充分肯定，达到了较高的教学满意度。     

SPontaneous Oscillatory Contraction (SPOC): auto-oscillations observed in striated muscle at partial activation

Striated muscle is well known to exist in either of two states—contraction or relaxation—under the regulation of Ca²⁺ concentration. Described here is a less well-known third, intermediate state induced under conditions of partial activation, known as SPOC (SPontaneous Oscillatory Contraction). This state is characterised by auto-oscillation between rapid-lengthening and slow-shortening phases. Notably, SPOC occurs in skinned muscle fibres and is therefore not the result of fluctuating Ca²⁺ levels, but is rather an intrinsic and fundamental phenomenon of the actomyosin motor. Summarised in this review are the experimental data on SPOC and its fundamental mechanism. SPOC presents a novel technique for studying independent communication and coordination between sarcomeres. In cardiac muscle, this auto-oscillatory property may work in concert with electro-chemical signalling to coordinate the heartbeat. Further, SPOC may represent a new way of demonstrating functional defects of sarcomeres in human heart failure.     

基于SPOC+Problem orientation的环境微生物学混合式教学设计与初探

环境微生物学是高校本科环境类专业的重要专业课程,针对该课程在传统教学中存在的问题,以智慧教学工具雨课堂为平台,将小规模限制性在线课程(Small private online course,SPOC)和问题导向(Problemorientation)引入到环境微生物学课程教学,构建线上和线下相结合的混合式教学模式。该教学模式主要由线上和线下教学内容制订、线上和线下教学实施和教学效果考核、评价及反馈3部分组成。该教学模式以学生为主体,以问题为导向,充分激发学生的学习兴趣,赋予学生更多的个性化体验,增强理论课程教学的互动性。初步教学实践表明,SPOC和Problem orientation的有机结合行之有效,能有效提高教学质量和教学效果。该混合式教学模式有助于培养具备环境微生物专业知识和技能的环保领域创新型人才,也可为其它课程教学质量的提高提供参考。     

A theory on auto-oscillation and contraction in striated muscle

It is widely accepted that muscle cells take either force-generating or relaxing state in an all-or-none fashion through the so-called excitation–contraction coupling. On the other hand, the membrane-less contractile apparatus takes the third state, i.e., the auto-oscillation (SPOC) state, at the activation level that is intermediate between full activation and relaxation. Here, to explain the dynamics of all three states of muscle, we construct a novel theoretical model based on the balance of forces not only parallel but also perpendicular to the long axis of myofibrils, taking into account the experimental fact that the spacing of myofilament lattice changes with sarcomere length and upon contraction. This theory presents a phase diagram composed of several states of the contractile apparatus and explains the dynamic behavior of SPOC, e.g., periodical changes in sarcomere length with the saw-tooth waveform. The appropriate selection of the constant of the molecular friction due to the cross-bridge formation can explain the difference in the SPOC periods observed under various activating conditions and in different muscle types, i.e., skeletal and cardiac. The theory also predicts the existence of a weak oscillation state at the boundary between SPOC and relaxation regions in the phase diagram. Thus, the present theory comprehensively explains the characteristics of auto-oscillation and contraction in the contractile system of striated muscle.     

Facile Synthesis of Orthogonally Protected Optically Pure Keto- and Diketopiperazine Building Blocks for Combinatorial Chemistry

A simple and convenient synthesis of orthogonally protected multi-tethered, optically pure 2-ketopiperazine and 2,5-diketopiperazine scaffolds for Fmoc and Boc combinatorial chemistry was achieved, starting from accessible chiral amino acid precursors, by sequentially utilizing reductive alkylation, dipeptide coupling and ketopiperazine ring formation as key steps. These scaffolds can introduce valuable drug-like properties in three independent directions to any medicinally relevant piperazine-based motif by “around the scaffold” drug optimization. In addition, these building blocks have a wide application scope in managing fast and efficient multi-cyclic optimization processes in the combinatorial chemistry and drug design fields.     

植物化学全线上轻翻转教学实践探索

为响应教育部"停课不停学"的号召,我校积极开展线上教学。以植物化学为例,经教学结构重组、教学内容筛选、教学活动设计,结合任务式分组讨论、嵌套慕课堂等教学方式开展课堂教学。通过模块规划、重难点剖析,设计翻转环节,构建了基于ZOOM嵌套慕课的全线上轻翻转教学模式,突出了对学生能力的培养,教学效果良好。本文就相关教学方法与成效进行了总结,为网络教学、线上线下混合信息化创新教学积累经验。     

Myocardial sarcomeres spontaneously oscillate with the period of heartbeat under physiological conditions

During heartbeat, the repeated contractions of myocardium are induced by the oscillation of intracellular Ca(2+) concentration. On the other hand, when intermediately activated at a certain Ca(2+) concentration, cardiac myofibrils exhibit the spontaneous sarcomeric oscillation (Ca-SPOC) under steady ionic conditions. In the present study, we found that Ca-SPOC occurred over a wide range of Ca(2+) concentrations, including physiological contractile conditions, in skinned myocardium prepared from various animal species (rat, rabbit, pig, and cow). The period of sarcomeric oscillation fell within the same range as the period of heartbeat of each animal species. On the basis of these results we propose that the intrinsic auto-oscillatory property of sarcomeres (myofibrils) significantly contributes to myocardial beating in vivo.