Prebiotic Microreactors: A Synthesis of Purines and Dihydroxy Compounds in Aqueous Aerosol

We report the synthesis of purine bases and other heterocycles and the formation of amino acids, hydroxy acids and dihydroxy compounds by the spark activation of an atmosphere of methane, nitrogen and hydrogen, in the presence of an aqueous aerosol. With the aid of the interface air–water, the organic material obtained shows greater amounts and diversity of molecules with biological interest than the products obtained in the absence of an aerosol. Our results support the suggestion that aerosols may have played a significant role in the prebiotic origin of molecular diversity and evolution.     

The 1953 Stanley L. Miller Experiment: Fifty Years of Prebiotic Organic Chemistry

The field of prebiotic chemistry effectively began with a publicationin Science 50 years ago by Stanley L. Miller on the spark discharge synthesis of amino acids and other compounds using a mixture of reduced gases that were thought to represent the components of the atmosphere on the primitive Earth. On the anniversary of this landmark publication, weprovide here an accounting of the events leading to the publication of the paper. We also discuss the historical aspects that lead up to the landmark Miller experiment.     

Prebiotic Chemistry and the Origin of the RNA World

The demonstration that ribosomal peptide synthesis is a ribozyme-catalyzed reaction makes it almost certain that there was once an RNA World. The central problem for origin-of-life studies, therefore, is to understand how a protein-free RNA World became established on the primitive Earth. We first review the literature on the prebiotic synthesis of the nucleotides, the nonenzymatic synthesis and copying of polynucleotides, and the selection of ribozyme catalysts of a kind that might have facilitated polynucleotide replication. This leads to a brief outline of the Molecular Biologists' Dream, an optimistic scenario for the origin of the RNA World. In the second part of the review we point out the many unresolved problems presented by the Molecular Biologists' Dream. This in turn leads to a discussion of genetic systems simpler than RNA that might have “invented” RNA. Finally, we review studies of prebiotic membrane formation.     

Hydrothermal Circulation of Seawater through Hot Vents and Contribution of Interface Chemistry to Prebiotic Synthesis

Synthesizing oligopeptides from glycine andalanine in a flow reactor, which stimulates constanthydrothermal circulation of seawater through hot vents onthe primitive Earth, demonstrated that an exponential growthof the products is possible. The initial rapid growth of the product is a consequence of using the products formed inone cycle as the starting materials for the cycle of synthesis.     

Asymmetric Spatiotemporal Evolution of Prebiotic Homochirality

The role of asymmetry on the evolution of prebiotic homochirality is investigated in the context of autocatalytic polymerization reaction networks. A model featuring enantiometric cross-inhibition and chiral bias is used to study the diffusion equations controlling the spatiotemporal development of left and right-handed domains. Bounds on the chiral bias are obtained based on present-day constraints on the emergence of life on early Earth. The viability of biasing mechanisms such as weak neutral currents and circularly polarized UV light is discussed. The results can be applied to any hypothetical planetary platform.     

Prebiotic Adenine Revisited: Eutectics and Photochemistry

Recent studies support an earlier suggestion that, if adenine was formed prebiotically on the primitive earth, eutectic freezing of hydrogen cyanide solutions is likely to have been important. Here we revisit the suggestion that the synthesis of adenine may have involved the photochemical conversion of the tetramer of hydrogen cyanide in eutectic solution to 4-amino-5-cyano-imidazole. This would make possible a reaction sequence that does not require the presence of free ammonia. It is further suggested that the reaction of cyanoacetylene with cyanate in eutectic solution to give cytosine might have proceeded in parallel with adenine synthesis.     

Prebiotic Methylation and the Evolution of Methyl Transfer Reactions in Living Cells

An hypothesis is presented for theprebiotic origin of methyl groups and the evolution ofmethyl transfer reactions in living cells. This hypothesis,described in terms of prebiotic and early biotic chemicalevolution, is based on experimental observations in our laband in those of others, and on the mechanisms of enzymaticmethyl transfer reactions that occur in living cells. Ofparticular interest is our demonstration of the reductivemethylation of ethanolamine and glycine in aqueous solutionby excess formaldehyde. These reactions, involving prebioticcompounds and conditions, are mechanistically analogous tothe de novo origin of methyl groups in modern cellsby reduction of methylene tetrahydrofolate. Furthermore,modern cellular methyl transfers from S-adenosylmethionineto amine nitrogen may involve formaldehyde as anintermediate and subsequent reductive methylation, analogousto the prebiotic chemistry observed herein.     

Concentration by Evaporation and the Prebiotic Synthesis of Cytosine

The efficient prebiotic synthesis of cytosine from urea andcyanoacetaldehyde (CA) has recently been claimed to be invalidon the basis of possible side reactions of the starting materials and the inapplicability of prebiotic syntheses usingdrying beach conditions. We therefore have investigated the synthesis of cytosine and uracil from urea and cyanoacetaldehydeat 100 °C under dry-down conditions, and in solution at 4 °C and -20 °C. We find that cytosine isproduced from the low temperature experiments more efficientlythan calculated from the Arrhenius extrapolation from highertemperatures, i.e., 60-120 °C. In addition, we findthat CA dimer is as efficient as the monomer in cytosine synthesis. We also studied whether evaporating very dilutesolutions of nonvolatile organic compounds will concentrateaccording to theory. Solutions as dilute as 10^-4 M concentrate from pure water approximately according to theory.Similar solutions in 0.5 M NaCl have less than theoreticalconcentrations due to absorption, but concentrations neardryness were very high.     

Prebiotic Synthesis of Nucleotides

If an RNA-only world preceded more complex forms oflife, then it is essential that the process wherebythe first nucleotides were made be considered. Presumably there were no enzymes and no templates tofacilitate the synthesis of the first nucleotides soanother form of chemical evolution must have beeninvolved. Answers to problems of this sort weresought vigorously in the 1960s and the early 1970s butmany issues were left unresolved. Progress made inthe last few years has added to this early work andbrings us closer to a satisfactory solution. In thisarticle key results, old and new, and some ideas as tohow further progress is likely to be made are discussed.There are reasons for optimism. Substantial progresshas been made on the synthesis of purines and ribose,phosphorylation and polyphosphorylation. Theoutstanding problems at this juncture relate to thesynthesis of ribose to the exclusion of the otheraldopentoses and to the problem of linking ribose tothe purine bases.     

The Fission Yeast php2 Mutant Displays a Lengthened Chronological Lifespan

The Schizosaccharomyces pombe php2 ⁺ gene encodes a subunit of the CCAAT-binding factor complex. We found that disruption of the php2 ⁺ gene extended the chronological lifespan of the fission yeast. Moreover, the lifespan of the Δphp2 mutant was barely extended under calorie restricted (CR) conditions. Many other phenotypes of the Δphp2 mutant resembled those of wild-type cells grown under CR conditions, suggesting that the Δphp2 mutant might undergo CR. The mutant also showed low respiratory activity concomitant with decreased expression of the cyc1 ⁺ and rip1 ⁺ genes, both of which are involved in mitochondrial electron transport. On the basis of a chromatin immunoprecipitation assay, we determined that Php2 binds to a DNA region upstream of cyc1 ⁺ and rip1 ⁺ in S. pombe. Here we discuss the possible mechanisms by which the chronological lifespan of Δphp2 mutant is extended.     

Comments on `Concentration by Evaporation and the Prebiotic Synthesis of Cytosine'

The claim by Nelson et al. (2001) that the reactionof cyanoacetaldehyde and urea provides `an efficient prebioticsynthesis' of cytosine is disputed. The authors have not dealt withthe important points presented in a criticism of this reaction(Shapiro, 1999): (1) The reactants undergo side reactions with commonnucleophiles that appear to proceed more rapidly than cytosineformation, and (2) No reactions have been described thus far thatwould produce cytosine at a rate sufficient to compensate for itsdecomposition by deamination, and permit accumulation over extendedperiods of time. Instead, Nelson et al. have conducted `drying-down' experiments, inan effort to simulate evaporations on the early Earth, but thedesign of these experiments is flawed. The initial reactantconcentrations are much higher than might be expected in a naturalsetting, and potentially interfering substances such as glycine,cyanide and thiols have been excluded. `Drying beaches and dryinglagoons' have been invoked as sites for such a reaction but noeffort has been made to describe the characteristics of such sitesor to estimate their frequency with reference to the present Earth.In the absence of contradictory data, the conclusion put forward inShapiro (1999) remains valid: `It was quite unlikely that cytosineplayed a role in the origin of life'.     

线粒体融合/分裂对线粒体的质量控制作用

线粒体是一种结构和功能复杂而敏感的细胞器,拥有独立于细胞核的基因组,在细胞的不同时相,生理过程和环境条件下,线粒体的形态,数量和质量,具有高度的可塑性。线粒体是细胞和生物体内最主要的能量供应场所,几乎存在于所有种类的细胞中,是一种动态变化的细胞器。正常情况下,线粒体的数量、形态以及功能维持相对稳定的状态,称之为线粒体稳态。当上述状态发生紊乱时,细胞乃至生物体形态、功能也将受到影响甚至死亡。线粒体质量控制是在细胞中维持正常状态的关键机制,决定着线粒体的命运。近年,随着线粒体研究的深入和具体,逐渐发现融合/分裂在其形态、数量、遗传物质等质量控制相关的方面挥了重要作用。本文通过探讨融合/分裂对线粒体质量控制的作用机制,总结和讨论相关前沿研究,为后期研究提供一定的理论依据。     

检测病毒气溶胶存活的方法学研究

以钝齿棒状杆菌噬菌体B271血清型为病毒等小颗粒生物粒子的模拟剂,建立了一种适合这类小颗粒生物粒子气溶胶存活研究的方法。本文从该噬菌体耐气溶胶化特性、气溶胶粒谱、用气溶胶示踪剂求算物理衰亡的方法和气溶胶采样回收技术等方面探讨了病毒气溶胶存活研究中的几个关键技术问题,为病毒气溶胶存活研究提供了参考。     

线粒体融合、分裂与神经变性疾病

线粒体是一种处于高度运动状态的频繁地进行融合与分裂的细胞器.在生理状态下,线粒体的融合与分裂处于一种平衡的状态,这种平衡受线粒体融合蛋白1/2（Mfn1/2）、视神经萎缩蛋白1（OPA1）和动力相关蛋白1（Drp1）的调节. Mfn1/2介导线粒体外膜的融合,而OPA1则参与线粒体内膜的融合,这些蛋白受泛素化和蛋白水解的调控. Drp1参与线粒体的分裂过程,受多种翻译后修饰的调节,如磷酸化、泛素化、SUMO化和S 硝基化.对于神经元来说,线粒体融合分裂的动态平衡对保证神经元末梢长距离运输和能量平均分布是非常重要的.因此,线粒体融合分裂异常可能是许多神经变性疾病的致病因素之一.对线粒体融合而言,Mfn2错义突变将导致遗传性运动感觉神经病2型（CMT2A）;OPA1错义突变将引起显性遗传性视神经萎缩(ADOA),而就线粒体分裂而言,Drp1突变与多系统功能障碍的新生儿致死性相关.     

The Spontaneous Mutation Rate in the Fission Yeast Schizosaccharomyces pombe

The rate at which new mutations arise in the genome is a key factor in the evolution and adaptation of species. Here we describe the rate and spectrum of spontaneous mutations for the fission yeast Schizosaccharomyces pombe, a key model organism with many similarities to higher eukaryotes. We undertook an ∼1700-generation mutation accumulation (MA) experiment with a haploid S. pombe, generating 422 single-base substitutions and 119 insertion-deletion mutations (indels) across the 96 replicates. This equates to a base-substitution mutation rate of 2.00 × 10⁻¹⁰ mutations per site per generation, similar to that reported for the distantly related budding yeast Saccharomyces cerevisiae. However, these two yeast species differ dramatically in their spectrum of base substitutions, the types of indels (S. pombe is more prone to insertions), and the pattern of selection required to counteract a strong AT-biased mutation rate. Overall, our results indicate that GC-biased gene conversion does not play a major role in shaping the nucleotide composition of the S. pombe genome and suggest that the mechanisms of DNA maintenance may have diverged significantly between fission and budding yeasts. Unexpectedly, CpG sites appear to be excessively liable to mutation in both species despite the likely absence of DNA methylation.     

Insight into Actin Organization and Function in Cytokinesis from Analysis of Fission Yeast Mutants

Actin is a key cytoskeletal protein with multiple roles in cellular processes such as polarized growth, cytokinesis, endocytosis, and cell migration. Actin is present in all eukaryotes as highly dynamic filamentous structures, such as linear cables and branched filaments. Detailed investigation of the molecular role of actin in various processes has been hampered due to the multifunctionality of the protein and the lack of alleles defective in specific processes. The actin cytoskeleton of the fission yeast, Schizosaccharomyces pombe, has been extensively characterized and contains structures analogous to those in other cell types. In this study, primarily with the view to uncover actin function in cytokinesis, we generated a large bank of fission yeast actin mutants that affect the organization of distinct actin structures and/or discrete physiological functions of actin. Our screen identified 17 mutants with specific defects in cytokinesis. Some of these cytokinesis mutants helped in dissecting the function of specific actin structures during ring assembly. Further genetic analysis of some of these actin mutants revealed multiple genetic interactions with mutants previously known to affect the actomyosin ring assembly. We also characterize a mutant allele of actin that is suppressed upon overexpression of Cdc8p-tropomyosin, underscoring the utility of this mutant bank. Another 22 mutant alleles, defective in polarized growth and/or other functions of actin obtained from this screen, are also described in this article. This mutant bank should be a valuable resource to study the physiological and biochemical functions of actin.     

人体上呼吸道口喉呼吸流涡结构演化对病毒气溶胶扩散的影响研究

揭示涡结构演化对病毒气溶胶扩散的影响作用,对于有效防治呼吸道疾病具有非常重要的意义.本文运用大涡模拟的方法,对人体在循环呼吸模式下口喉模型内的涡结构演化及气溶胶扩散进行了数值仿真研究,分析了口喉模型内涡结构演化过程以及气溶胶扩散状态.结果表明：受呼吸流涡结构演化的影响,颗粒轨迹主要分布在上气道内涡量集中的区域;受横向涡结构和纵向涡结构的共同影响,部分病毒气溶胶颗粒具备了混合有环状轨迹和波状轨迹的螺旋状轨迹.本研究从微观角度揭示了涡结构演化与气溶胶扩散行为的关系,为深入认识病毒气溶胶上呼吸道传播特点提供了新的途径.