一个可能引起歧义的概念——“条件致病菌”辨析

"条件致病菌"是国内医学微生物学教材中普遍应用的一个基本概念,但此概念在建立与应用中都存在明显缺陷,其使用可能对医学学生理解"人体共生微生物群落"与"机会性感染"等重要的医学基础理念造成误解与歧义。谨就此提出一些粗浅的认识与观点,希望通过同行间切磋,就此建立更完善的概念与更合理的表述。     

Bystander effects in unicellular organisms

Radiation-induced bystander effects have been seen in mammalian cells from diverse origins. These effects can be transmitted through the medium to cells not present at the time of irradiation. We have developed an assay for detecting bystander effects in the unicellular eukaryote, the fission yeast Schizosaccharomyces pombe. This assay allows maximal exposure of unirradiated cells to cells that have received electron beam irradiation. S. pombe cells were irradiated with 16-18 MeV electrons from a pulsed electron LINAC. When survival of the irradiated cells decreased to approximately 50%, forward-mutation to 2-deoxy-d-glucose resistance increased in the unirradiated bystander cells. Further increase in dose had no additional effect on this increase. In order to detect this response, it was necessary for the irradiated cell/unirradiated cell ratio to be high. Other cellular stresses, such as heat treatment, UV irradiation, and bleomycin exposure, also caused a detectable response in untreated cells grown with the treated cells. We discuss evolutionary implications of these results.     

Bystander effects and radiotherapy

Radiation-induced bystander effects are defined as biological effects expressed after irradiation by cells whose nuclei have not been directly irradiated. These effects include DNA damage, chromosomal instability, mutation, and apoptosis. There is considerable evidence that ionizing radiation affects cells located near the site of irradiation, which respond individually and collectively as part of a large interconnected web. These bystander signals can alter the dynamic equilibrium between proliferation, apoptosis, quiescence or differentiation. The aim of this review is to examine the most important biological effects of this phenomenon with regard to areas of major interest in radiotherapy. Such aspects include radiation-induced bystander effects during the cell cycle under hypoxic conditions when administering fractionated modalities or combined radio-chemotherapy. Other relevant aspects include individual variation and genetics in toxicity of bystander factors and normal tissue collateral damage. In advanced radiotherapy techniques, such as intensity-modulated radiation therapy (IMRT), the high degree of dose conformity to the target volume reduces the dose and, therefore, the risk of complications, to normal tissues. However, significant doses can accumulate out-of-field due to photon scattering and this may impact cellular response in these regions. Protons may offer a solution to reduce out-of-field doses. The bystander effect has numerous associated phenomena, including adaptive response, genomic instability, and abscopal effects. Also, the bystander effect can influence radiation protection and oxidative stress. It is essential that we understand the mechanisms underlying the bystander effect in order to more accurately assess radiation risk and to evaluate protocols for cancer radiotherapy.     

Bystander effects in radiation-induced genomic instability

Exposure of GM10115 hamster-human hybrid cells to X-rays can result in the induction of chromosomal instability in the progeny of surviving cells. This instability manifests as the dynamic production of novel sub-populations of cells with unique cytogenetic rearrangements involving the "marker" human chromosome. We have used the comet assay to investigate whether there was an elevated level of endogenous DNA breaks in chromosomally unstable clones that could provide a source for the chromosomal rearrangements and thus account for the persistent instability observed. Our results indicate no significant difference in comet tail measurement between non-irradiated and radiation-induced chromosomally unstable clones. Using two-color fluorescence in situ hybridization we also investigated whether recombinational events involving the interstitial telomere repeat-like sequences in GM10115 cells were involved at frequencies higher than random processes would otherwise predict. Nine of 11 clones demonstrated a significantly higher than expected involvement of these interstitial telomere repeat-like sequences at the recombination junction between the human and hamster chromosomes. Since elevated levels of endogenous breaks were not detected in unstable clones we propose that epigenetic or bystander effects (BSEs) lead to the activation of recombinational pathways that perpetuate the unstable phenotype. Specifically, we expand upon the hypothesis that radiation induces conditions and/or factors that stimulate the production of reactive oxygen species (ROS). These reactive intermediates then contribute to a chronic pro-oxidant environment that cycles over multiple generations, promoting chromosomal recombination and other phenotypes associated with genomic instability.     

Bystander effects in repair-deficient cell lines

One of the current hypotheses concerning the role of bystander effects in biological systems is that they are protective because they terminate division in cells with collateral or possibly pre-existing DNA damage that is not properly repaired. Following the logic of this hypothesis led us to consider that cell lines that are repair deficient should have larger than usual bystander effects. To test this, several different "repair- deficient" cell lines were used for bystander experiments. Response was monitored by determining the cloning efficiency or, in the case of non-adherent cell lines, the cell number. The results show that the repair-deficient human cell lines and surviving progeny produced moderate to severe bystander- induced death effects in either autologous cells or a reporter cell line. Normal "repair-proficient" lines, which were matched as far as possible, have very much less severe or absent bystander-inducible effects on cloning efficiency. Cells of hamster cell lines derived from CHO-K1 cells did not produce similar severe effects. The results suggest that repair- deficient human cell lines, irrespective of the actual repair defect, may respond to the occurrence of DNA damage in the population by removing large numbers of cells from the proliferating pool.     

Intraspecies variation in bacterial genomes: the need for a species genome concept

Bacterial populations are clonal. Their evolution involves not only divergence between orthologous genes but also gain of genes from other clones or species, which has only recently been widely appreciated through macrorestriction mapping, genomic subtraction and complete genome sequencing. Genes can also be lost in response to selection or by random mutation after becoming redundant. The bacterial genome is a dynamic structure and intraspecies variation needs to be included in genome analysis if we are to gain insight into the full species genome.     

Evolution,actuality and species concept: a need for a palaeontological tool

Species concept was developed to fit neontological necessities in ordering biological variability. Transversal (horizontal, synchronic) taxonomy shows hierarchical requirements quite different from those involved in longitudinal (vertical, diachronic) classifications. Furthermore, limitations within the species concept itself make it scarcely available in many paleontological contexts. Classical species definitions are often limited by theoretic and logic constraints, that are seldom available to describe practical situations. Morphology is an uncertain source of phylogenetic information, but it is still the main ground of biological comparison for extinct populations. Therefore, efforts in species recognition should be devoted to making taxonomy a useful tool for communication. First, inferences in systematics have to be led upon the available information about characters and processes. If this information is missing or not developed, no detailed conclusions can be supported. Secondly, definitions should be sufficiently elastic and generalised to allow an adaptation to each different case-study. The final target is to synthesise actual evolutionary histories, and not biological potentialities.     

景观多功能性:概念辨析、近今进展与前沿议题

景观多功能性是指景观同时提供多种功能,且不同功能间存在相互作用的特性。良好的景观多功能性可以有效提升区域人类福祉,使景观多功能性成为一项典型的人地耦合研究议题。然而,概念不明确、计量方法粗略、实践应用较少是当前制约景观多功能性研究继续深化的重要障碍。通过明晰景观多功能性与生态系统功能、生态系统服务、土地功能、景观服务、景观可持续性等近似概念的逻辑关系,梳理近年来国际上农业景观多功能性、城市景观多功能性以及其他具有区域特色的景观多功能性研究进展,发现格局-过程-服务-可持续性的级联研究链条已逐渐显现。未来景观多功能性研究有待基于供需原理优化景观功能评估指标与方法,正确认知景观功能主导性与多样性的关系,探究可持续发展目标达成的多目标协同途径,为国土空间优化提供理论、方法与实践指引。     

生物多样性事业需要科学、可操作的物种概念

物种概念(species concept)是生物学家们持续关注的中心问题。物种概念决定物种划分, 而物种划分的合理性关系到生物多样性的研究、保护和可持续利用。本文把现有较流行的物种概念分为6类, 并对它们予以述评后指出: 虽然生物学物种概念、遗传学物种概念、进化物种概念、系统发生物种概念等从不同方面认识了物种的客观真实性和物种的本质, 但在实践中都难以操作。绝大多数物种是由分类学家划分的, 但目前所有的分类学物种概念都包含有不同程度的主观因素, 从而造成物种划分的人为性, 对生物多样性研究造成负面影响。因此, 生物多样性事业需要科学、可操作的物种概念。本文在吸收了生物学物种概念、遗传学物种概念、进化物种概念以及系统发生物种概念等的长处, 也分析了它们的不足和问题的基础上提出一个新的物种概念, 即形态-生物学物种概念。最后, 以芍药属(Paeonia)几个物种的处理为例, 说明这一新的物种概念是可操作的, 划分的物种在形态上区别分明, 易于鉴别。更重要的是, 其结果得到基于25或26个单拷贝或寡拷贝核基因DNA序列所作的系统发生分析的强有力支持。各个物种在系统发生树上形成单系和独立的谱系, 表明其间各自形成独立的基因库, 没有基因交换, 它们独立进化, 有各自的生态位和独立的分布区。因此, 利用这一新的物种概念能够达到预期目标。     

Bystander effects and the structure of dominance hierarchies

Prior modeling work has found that pure winner and loser effects(i.e., changing the estimation of your own fighting abilityas a function of direct prior experience) can have importantconsequences for hierarchy formation. Here these models areextended to incorporate "bystander effects." When bystandereffects are in operation, observers (i.e., bystanders) of aggressiveinteractions change their assessment of the protagonists' fighting abilities (depending on who wins and who loses). Computer simulations demonstrate that when bystander winner effects alone are atplay, groups have a clear omega (bottom-ranking individual),while the relative position of other group members remainsdifficult to determine. When only bystander loser effects arein operation, wins and losses are randomly distributed throughout a group (i.e., no discernible hierarchy). When pure and bystanderwinner effects are jointly in place, a linear hierarchy, inwhich all positions (i.e., to when N = 4) are clearly defined,emerges. Joint pure and bystander loser effects produce thesame result. In principle one could test the predictions fromthe models developed here in a straightforward comparativestudy. Hopefully, the results of this model will spur on suchstudies in the future.     

企业生态创新的研究脉络、内涵澄清与测量

生态创新因具有"双重正外部性"而得到实践界和理论界的双重青睐,与此形成鲜明对照的是,现有研究对生态创新概念的适用层次、理论定位、内涵与测量等基本理论问题的理解模糊而缺乏一致性。回顾了企业社会责任、环境管理和创新管理三大领域的相关研究成果,辨析了企业生态创新的内涵特征与外延,进一步梳理了企业生态创新的维度划分与测量,对企业生态创新的未来研究给出了展望。     

The hologenome concept: we need to incorporate function

Are we in the midst of a paradigm change in biology and have animals and plants lost their individuality, i.e., are even so-called ‘typical’ organisms no longer organisms in their own right? Is the study of the holobiont—host plus its symbiotic microorganisms—no longer optional, but rather an obligatory path that must be taken for a comprehensive understanding of the ecology and evolution of the individual components that make up a holobiont? Or are associated microbes merely a component of their host’s environment, and the holobiont concept is just a beautiful idea that does not add much or anything to our understanding of evolution? This article explores different aspects of the concept of the holobiont. We focus on the aspect of functional integration, a central holobiont property, which is only rarely considered thoroughly. We conclude that the holobiont comes in degrees, i.e., we regard the property of being a holobiont as a continuous trait that we term holobiontness, and that holobiontness is differentiated in several dimensions. Although the holobiont represents yet another level of selection (different from classical individual or group selection because it acts on a system that is composed of multiple species), it depends on the grade of functional integration whether or not the holobiont concept helps to cast light on the various degrees of interactions between symbiotic partners.     

Biotic indirect effects: a neglected concept in invasion biology

Indirect effects involve more than two species and are defined as how one species alters the effect that another species has on a third. These complex interactions are often overlooked in studies of interactions between alien and native species, and their role in influencing biological invasions has been rarely considered. Based on a comprehensive review of the invasion biology literature, we examine the evidence for the occurrence of four of the most commonly documented indirect effects (apparent competition, indirect mutualism/commensalism, exploitative competition, and trophic cascades) in the invasion process. Studies investigating indirect effects in the context of invasion biology are relatively rare, but have been increasing in recent years, and there are sufficient examples to indicate that this kind of interaction is likely to be more common than is currently recognized. Whether indirect interactions are mediated by an alien or a native species, and whether they occur between ecologically similar or dissimilar alien and native species, depends in part on the type of interaction considered and no predictable patterns were detected in the literature. Further empirical studies will help to elucidate such patterns. At this stage, the inherent unpredictability of indirect interactions means that their impacts in relation to invasions are particularly challenging for land managers to deal with, and their role in invasions is a complex, but is a valuable area of investigation for researchers.     

Bystander and delayed effects after fractionated radiation exposure

Human immortalized keratinocytes were exposed to a range of single or fractionated doses of gamma rays from (60)Co, to medium harvested from donor cells exposed to these protocols, or to a combination of radiation and irradiated cell conditioned medium (ICCM). The surviving fractions after direct irradiation or exposure to ICCM were determined using a clonogenic assay. The results show that medium harvested from cultures receiving fractionated irradiation gave lower "recovery factors" than direct fractionated irradiation, where normal split-dose recovery occurred. The recovery factor is defined here as the surviving fraction of the cells receiving two doses (direct or ICCM) separated by an interval of 2 h divided by the surviving fraction of cells receiving the same dose in one exposure. After treatment with ICCM, the recovery factors were less than 1 over a range of total doses from 5 mGy-5 Gy. Varying the time between doses from 10 min to 180 min did not alter the effect of ICCM, suggesting that two exposures to ICCM are more toxic than one irrespective of the dose used to generate the response. In certain protocols using mixtures of direct irradiation and ICCM, it was possible to eliminate the bystander effect. If bystander factors are produced in vivo, then they may reduce the sparing effect of the dose fractionation.     

Bystander effects of nucleoside analogs phosphorylated in the cytosol or mitochondria

The efficiency of nucleoside kinase suicide gene therapy for cancer is highly dependent on "bystander" cell killing, i.e., the transfer of cytotoxic phosphorylated nucleoside analogs to cells adjacent to those expressing the suicide enzyme. We have recently studied the possible use of mitochondrial nucleoside kinases as suicide genes. In the present study, we investigated if nucleoside analogs phosphorylated in the mitochondrial matrix cause bystander killing. We used deoxycytidine kinase-deficient Chinese hamster ovary cells reconstituted with deoxycytidine kinase targeted to either the cytosol or mitochondria matrix and determined the bystander cell killing when these cells were incubated with the nucleoside analogs 1-beta-D-arabinofuranosylcytosine and 2',2'-difluorodeoxycytidine. A bystander effect occurred when nucleoside analogs were phosphorylated in the cytosol, but not when these compounds were phosphorylated in the mitochondria. These findings suggest that nucleoside kinases targeted to the mitochondrial matrix have limited use in suicide gene therapy when efficient bystander cell killing is required.     

Homozygous haemoglobin constant spring: A need for revision of concept

Summary Twenty-two patients with mild haemolytic anaemia and haemoglobin (Hb) Constant Spring (CS) of around 6% were studied because they were suspected of having homozygous Hb CS. Family studies revealed Hb CS trait in both parents of eight patients, supporting that they were homozygous for Hb CS. The other patients were included because they had clinical and haematological features similar to the diagnosed cases of homozygous Hb CS. Heterozygosity and homozygosity for Hb CS are clearly distinguishable in that the former is asymptomatic but the latter is associated with overt haemolytic anaemia, and the levels of Hb CS in the two conditions of less than 1% and around 6%, respectively, do not overlap. The findings in homozygous Hb CS contracdict prediction. There are four a-structural genes per normal human diploid genome. Hb CS trait is believed to be almost equivalent to a-thalassaemia 2 or a loss of one a-gene because HB CS, an a-variant, is barely or not detectable. Homozygosity for Hb CS has thus been predicted to be equivalent to a-thalassaemia 1 or a loss of two genes. The latter is asymptomatic and associated with microcytic-hypochromic red cells. However, Hb CS homozygosity presents with mild overt haemolytic anaemia and normal sized red cells. Pathogenesis associated with Hb CS inheritance is more complex than originally believed. There is a possibility that the unstable a ^CS mRNAs precipitate and aggregate leading to pathology of red cells and to the basophilic stippling appearance, so striking in this syndrome.