Mechanism of transport and storage of neurotransmitters

This review will focus on the bioenergetics, mechanism, and molecular basis of neurotransmitter transport. As indicated in the next section, these processes play an important role in the overall process of synaptic transmission. During the last few years, direct evidence has been obtained that these processes are coupled chemiosmotically, i.e., the accumulation of neurotransmitters is driven by ion gradients. Two types of neurotransmitter transport systems have been identified: sodium-coupled systems located in the synaptic plasma membrane of nerves (and sometimes in the plasma membrane of glial cells) and proton-coupled systems which are part of the membrane of intracellular storage organelles. From a bioenergetic point of view, the sodium-coupled systems are especially interesting, since it has recently been discovered that many systems require other ions in addition to sodium. It has now been demonstrated in several cases that, besides sodium ions, these additional ions, such as chloride and potassium, serve as additional coupling ions. These systems will be reviewed here in considerable detail with emphasis on the role of the additional ions. In the second part of the review we shall focus on neurotransmitter transport into storage organelles. Although both sodium and proton coupled systems have been reviewed in the past, there has been a shift from a kinetic and thermodynamic to a biochemical approach. In fact, a few transporters have been identified and functionally reconstituted. These developments have of course been incorporated in this review.     

A review of the influence of biogeography,riverine linkages,and marine connectivity on fish assemblages in evolving lagoons and lakes of coastal southern Africa

The Holocene evolution of eight South African coastal lakes and lagoons is examined and related to changes in fish composition over that period. Historical and current connectivity with riverine and marine environments are the primary determinants of present‐day fish assemblages in these systems. A small and remarkably consistent group of relict estuarine species have persisted in these coastal lakes and lagoons. The loss or reduction of connectivity with the sea has impacted on the diversity of marine fishes in all eight study systems, with no marine fishes occurring in those water bodies where connectivity has been completely broken (e.g. Sibaya, Groenvlei). In systems that have retained tenuous linkages with the sea (e.g., Verlorenvlei, Wilderness lakes), elements of the marine fish assemblage have persisted, especially the presence of facultative catadromous species. Freshwater fish diversity in coastal lakes and lagoons is a function of historical and present biogeography and salinity. From a freshwater biogeography perspective, the inflowing rivers of the four temperate systems reviewed here contain three or fewer native freshwater fishes, while the subtropical lakes that are fed by river systems contain up to 40 freshwater fish species. Thus, the significantly higher fish species diversity in subtropical versus temperate coastal lakes and lagoons comes as no surprise. Fish species diversity has been increased further in some systems (e.g., Groenvlei) by alien fish introductions. However, the impacts of fish introductions and translocations have not been studied in the coastal lakes and lagoons of South Africa. In these closed systems, it is probable that predation impacts on small estuarine fishes are significant. The recent alien fish introductions is an example of the growing threats to these systems during the Anthropocene, a period when human activities have had significant negative impacts and show potential to match the changes recorded during the entire Holocene.     

El tacto,un sentido crucial en las interacciones sociales para mejorar la homeostasis en el envejecimiento y promover una longevidad saludable

Aging is associated with the generalized deterioration of the organism, being of great relevance experienced by homeostatic systems such as the nervous, immune, and endocrine systems, which increases the risk of morbidity and mortality. Among the lifestyle strategies that have been researched to improve these systems and achieve greater healthy longevity, this review will focus on the social environment. In order to verify the effectiveness of these both in the improvement of homeostasis and in life expectancy, the research carried out with experimental animals that have allowed this to be done will be discussed. In addition, as it has been observed that physical contact is crucial for the positive outcomes of social interaction on homeostatic systems and longevity to occur, we will focus on that mechanism, as well as some of the possible molecular pathways underlying the effects found.     

Artificial activation of toxin-antitoxin systems as an antibacterial strategy

Toxin-antitoxin (TA) systems are unique modules that effect plasmid stabilization via post-segregational killing of the bacterial host. The genes encoding TA systems also exist on bacterial chromosomes, and it has been speculated that these are involved in a variety of cellular processes. Interest in TA systems has increased dramatically over the past 5 years as the ubiquitous nature of TA genes on bacterial genomes has been revealed. The exploitation of TA systems as an antibacterial strategy via artificial activation of the toxin has been proposed and has considerable potential; however, efforts in this area remain in the early stages and several major questions remain. This review investigates the tractability of targeting TA systems to kill bacteria, including fundamental requirements for success, recent advances, and challenges associated with artificial toxin activation.     

Surface plasmon resonance spectroscopy: an emerging tool for the study of peptide-membrane interactions

The interactions between peptides and membranes mediate a wide variety of biological processes, and characterization of the molecular details of these interactions is central to our understanding of cellular events such as protein trafficking, cellular signaling and ion-channel formation. A wide variety of biophysical techniques have been combined with the use of model membrane systems to study peptide-membrane interactions, and have provided important information on the relationship between membrane-active peptide structure and their biological function. However, what has generally not been reported is a detailed analysis of the affinity of peptide for different membrane systems, which has largely been due to the difficulty in obtaining this information. To address this issue, surface plasmon resonance (SPR) spectroscopy has recently been applied to the study of biomembrane-based systems using both planar mono- or bilayers or liposomes. This article provides an overview of these recent applications that demonstrate the potential of SPR to enhance our molecular understanding of membrane-mediated peptide function.     

Effect of low-level alpha-radiation on bioluminescent assay systems of various complexity.

This study addresses the effects of low-level alpha-radiation on bioluminescent assay systems of different levels of organization: in vivo and in vitro. Three bioluminescent assay systems are used: intact bacteria, lyophilized bacteria, and bioluminescent system of coupled enzyme reactions. Solutions of 241Am(NO3)3 are used as a source of alpha-radiation. It has been shown that activation processes predominate in all the three bioluminescent assay systems subjected to short-term exposure (20-55 h) and inhibition processes in the systems subjected to longer-term exposure to radiation. It has been found that these effects are caused by the radiation component of 241Am3+ impact. The intensity of the 241Am3+ effect on the bioluminescent assay systems has been shown to depend on the 241Am3+ concentration, level of organization and integrity of the bioluminescent assay system. The bioluminescent assay systems in vivo have been found to be highly sensitive to 241Am3+ (up to 10(-17) M).     

A framework for evaluating sustainability indicators in the real estate industry

The growth in the use of sustainability indicators and ratings in the real estate industry has been accompanied by strong criticism of the most commonly used rating systems designed to evaluate the sustainability performance of real estate developments. Most of these criticisms focus on the content of the different rating systems. A systematic evaluation of the methodologies of sustainability ratings is lacking. This article builds a framework that can be used to evaluate the methodologies of sustainability ratings and applies the evaluation framework to five widely used sustainability ratings for homes and communities (BREAAM, CASBEE, Estidama, Green Star, LEED). The evaluation results highlight three major shortcomings in the rating systems that have been evaluated. First, the systems lack unambiguous definitions of sustainability. They give insufficient explanation of why certain components are included in the ratings and on what basis these components have been accorded their weights. Second, the rating systems put more emphasis on sustainable design than performance, especially for the ratings for communities. Finally, the ratings are generally not responsive to local conditions of a project. Each rating system has its particular strengths and weaknesses and no system is superior on all dimensions. The proposed evaluation framework can be applied to sustainability ratings in different industries and is adaptable depending on stakeholder requirements.     

镰刀菌属分类进展

镰刀菌是真菌中最难鉴定和最具经济价值的属之一。自从1935年德国的Wollen-weber & Reinking发表了第一个以16组65种为内容的分类系统以来,人们对该属的分类展开了长期的研究和讨论,在国际上陆续出现了10种以此系统为基础的,而又各具特色的分类系统。它们是Snyder & Hansen(1940s,美国)的9种系统;Paйлло(1950,苏联)的55种系统;Gordon(1952,加拿大)的26种系统;Билай(1955,苏联)的26种系统;Messiaen & Cassini(1968,法国)的9种和9变种系统;Booth(1971,英国)的44种系统;松尾卓见(Matuo,1972,日本)的10种系统;Joffe(1974,以色列)的33种系统;Gerlach& Nirenberg(1982,德国)的90多种和变种的系统;Nelson等(1983,美国)的30种系统。本文重点论述了其中5种在国际上颇具影响的系统,并列表加以详细比较。     

Recombinant DNA approaches for the development of metabolic systems used in in vitro toxicology.

In the past few years there has been considerable progress in the development of mammalian cell systems for use in genetic toxicology by the stable transfer of genes/cDNAs coding for drug metabolizing enzymes directly into the target cell. Alternative approaches have also been developed in which mammalian cells are transiently transfected with cDNAs coding for drug-metabolizing enzymes and S9 preparations expressing a single metabolizing enzyme isolated and used for metabolic activation. Progress in these areas is reviewed here and the relative merits of the different approaches are discussed. Work to date has focused primarily on the cytochrome P450 family of enzymes, although other enzyme systems involved in xenobiotic metabolism have been used. The central theme of this review is the transfer of genetic information to improve the metabolic capability of cell systems used in genetic toxicology. However, a basic philosophy of the review is that genetic manipulation of cultured mammalian cells has the potential for developing systems to be used to better understand chemically induced toxicological effects.     

Olfactory memory: the long and short of it

It has been proposed that memory for odors does not have a short-term (or working) memory system. The distinction between short- and long- term memory in other sensory modalities has been generally supported by three main lines of evidence: capacity differences between the proposed systems, evidence of differential coding, and differential memory losses in neuropsychological patients. The present paper examines these issues in an effort to establish a similar distinction for the memory of olfactory stimuli. Each of these lines of evidence is examined in relation to the literature on olfactory memory. Based on this examination, it seems that there is at least preliminary support from each of these lines of evidence to advocate a distinction between a long- and short-term memory for olfactory stimuli. Emphasis is placed upon the qualitative similarity of olfactory memory to other memory systems. This similarity is further highlighted through an examination of the literature pertinent to serial position effects in memory for olfactory stimuli.      

Secretion systems for secondary metabolites: how producer cells send out messages of intercellular communication

Many secondary metabolites (e.g. antibiotics and mycotoxins) are toxic to the microorganisms that produce them. The clusters of genes that are responsible for the biosynthesis of secondary metabolites frequently contain genes for resistance to these toxic metabolites, such as different types of multiple drug resistance systems, to avoid suicide of the producer strains. Recently there has been research into the efflux systems of secondary metabolites in bacteria and in filamentous fungi, such as the large number of ATP-binding cassette transporters found in antibiotic-producing Streptomyces species and that are involved in penicillin secretion in Penicillium chrysogenum. A different group of efflux systems, the major facilitator superfamily exporters, occur very frequently in a variety of bacteria that produce pigments or antibiotics (e.g. the cephamycin and thienamycin producers) and in filamentous fungi that produce mycotoxins. Such efflux systems include the CefT exporters that mediate cephalosporin secretion in Acremonium chrysogenum. The evolutionary origin of these efflux systems and their relationship with current resistance determinants in pathogenic bacteria has been analyzed. Genetic improvement of the secretion systems of secondary metabolites in the producer strain has important industrial applications.     

Extrachromosomal systems and gene transmission in anaerobic bacteria

Obligately anaerobic bacteria are important in terms of their role as medical pathogens as well as their degradative capacities in a variety of natural ecosystems. Two major anaerobic genera, Bacteroides and Clostridium, are examined in this review. Plasmid elements in both genera are reviewed within the context of conjugal transfer and drug resistance. Genetic systems that facilitate the study of these anaerobic bacteria have emerged during the past several years. In large part, these developments have been linked to work centered on extrachromosomal genetic systems in these organisms. Conjugal transfer of antibiotic resistance has been a central focus in this regard. Transposable genetic elements in the Bacteroides are discussed and the evolution and spread of resistance to lincosamide antibiotics are considered at the molecular level. Recombinant DNA systems that employ shuttle vectors which are mobilized by conjugative plasmids have been developed for use in Bacteroides and Clostridium. The application of transmission and recombinant DNA genetic systems to study these anaerobes is under way and is likely to lead to an increased understanding of this important group of procaryotes.     

Biochemical systems theory: operational differences among variant representations and their significance

An appropriate language or formalism for the analysis of complex biochemical systems has been sought for several decades. The necessity for such a formalism results from the large number of interacting components in biochemical systems and the complex non-linear character of these interactions. The Power-Law Formalism, an example of such a language, underlies several recent attempts to develop an understanding of integrated biochemical systems. It is the simplest representation of integrated biochemical systems that has been shown to be consistent with well-known growth laws and allometric relationships--the most regular, quantitative features that have been observed among the systemic variables of complex biochemical systems. The Power-Law Formalism provides the basis for Biochemical Systems Theory, which includes several different strategies of representation. Among these, the synergistic-system (S-system) representation is the most useful, as judged by a variety of objective criteria. This paper first describes the predominant features of the S-system representation. It then presents detailed comparisons between the S-system representation and other variants within Biochemical Systems Theory. These comparisons are made on the basis of objective criteria that characterize the efficiency, power, clarity and scope of each representation. Two of the variants within Biochemical Systems Theory are intimately related to other approaches for analyzing biochemical systems, namely Metabolic Control Theory and Flux-Oriented Theory. It is hoped that the comparisons presented here will result in a deeper understanding of the relationships among these variants. Finally, some recent developments are described that demonstrate the potential for further growth of Biochemical Systems Theory and the underlying Power-Law Formalism on which it is based.     

Hacking the Code of Amyloid Formation

Many research efforts in the last years have been directed towards understanding the factors determining protein misfolding and amyloid formation. Protein stability and amino acid composition have been identified as the two major factors in vitro. The research of our group has been focused on understanding the relationship between amino acid sequence and amyloid formation. Our approach has been the design of simple model systems that reproduce the biophysical properties of natural amyloids. An amyloid sequence pattern was extracted that can be used to detect amyloidogenic hexapeptide stretches in proteins. We have added evidence supporting that these amyloidogenic stretches can trigger amyloid formation by non-amyloidogenic proteins. Some experimental results in other amyloid proteins will be analyzed under the conclusions obtained in these studies. Our studies together with evidences from other groups suggest that amyloid formation is the result of the interplay between a decrease of protein stability, and the presence of highly amyloidogenic regions in proteins. As many of these results have been obtained in vitro, the challenge for the next years will be to demonstrate their validity in in vivo systems.     

Electrokinetic energy conversion studies of urine-oxalic acid systems across urinary bladder membrane.

Electrokinetic studies of urine-oxalic acid systems with increasing concentration of oxalic acid in urine have been carried out across urinary bladder membranes. It has been found that electro-osmotic flux and streaming current decrease with increase in concentration of oxalic acid in urine while hydrodynamic flux and streaming potential increase with increase in concentration. Kinetic energy term (alpha 1) and polarizability term (alpha 2) have been computed for these systems and it has been found that polarizability decreases much faster with increase in concentration of oxalic acid in urine. Electrokinetic energy conversion of these systems have been computed and it has been found that electrokinetic energy conversion is maximum for urine and it decreases with increase in concentration of oxalic acid in urine. Poor energy conversion may lead to sluggish flushing action which may ultimately lead to formation of urinary calculi in the bladder and so present study may be of some use in predicting electrophysiology of the bladder.     

Standardisation of DNA quantitation by image analysis: quality control of instrumentation.

BACKGROUND: DNA image analysis is frequently performed in clinical practice as a prognostic tool and to improve diagnosis. The precision of prognosis and diagnosis depends on the accuracy of analysis and particularly on the quality of image analysis systems. It has been reported that image analysis systems used for DNA quantification differ widely in their characteristics (Thunissen et al.: Cytometry 27: 21-25, 1997). This induces inter-laboratory variations when the same sample is analysed in different laboratories. In microscopic image analysis, the principal instrumentation errors arise from the optical and electronic parts of systems. They bring about problems of instability, non-linearity, and shading and glare phenomena. METHODS: The aim of this study is to establish tools and standardised quality control procedures for microscopic image analysis systems. Specific reference standard slides have been developed to control instability, non-linearity, shading and glare phenomena and segmentation efficiency. RESULTS: Some systems have been controlled with these tools and these quality control procedures. Interpretation criteria and accuracy limits of these quality control procedures are proposed according to the conclusions of a European project called PRESS project (Prototype Reference Standard Slide). Beyond these limits, tested image analysis systems are not qualified to realise precise DNA analysis. CONCLUSIONS: The different procedures presented in this work determine if an image analysis system is qualified to deliver sufficiently precise DNA measurements for cancer case analysis. If the controlled systems are beyond the defined limits, some recommendations are given to find a solution to the problem.     

Human welfare and its connection to nature: What have we learned from crop pollination studies?

Human welfare depends on the function of natural systems. This idea is paradigmatic to ecologists and has been the theme of a growing branch of applied ecology. I examine the narrative of human dependence on nature by considering the literature on crop pollination by animals and its importance for food production. Making the connections between human welfare and natural systems is seen as a way to better motivate society to make better decisions, but the debate around crop pollination has been surprisingly contentious. There have been confusing messages, disagreements on the facts, an unfortunate focus on dire projections for the future and a lesser focus on solutions. Most of these problems arise not from poor science but instead from poor communication of complex ideas and differences in perspective, such as the deep disciplinary gap between agricultural scientists and ecologists. By understanding these problems, we can improve the way we do our science and communicate our ideas. I argue that ecologists should continue to communicate the principle that human welfare depends on the function of natural systems and discuss how we can do so in a way that is more genuinely connected to society's needs, such as growing food. If we succeed, we will be changing an intellectually interesting conversation into a dialogue that influences how society interacts with nature.     

Protected amino acids as novel low-molecular-weight displacers in cation-exchange displacement chromatography

Although the ability to carry out simultaneous concentration and purification in a single displacement step has significant advantages for downstream processing of pharmaceuticals, a major impediment to the implementation of displacement chromatography has been the lack of suitable displacer compounds. An important recent advance in the state of the art of displacement chromatography has been the discovery that low-molecular-weight dendritic polymers can be successfully employed as displacers for protein purification in ion-exchange systems. In this article, protected amino acid esters (based on arginine and lysine) are shown to be useful displacers for protein purification in cation-exchange systems. A dynamic affinity plot is employed to evaluate the affinity of these low-molecular-weight compounds under dis-placement conditions. In contrast to large polyelectroyte displacers, the efficacy of these low-molecular-weight displacers was shown to be dependent on both the initial carrier salt concentration and the displacer concentration. In addition to the funcamental interest generated by low-molecular-weight displacers, it is likely that these displacers will have significant operatioal advantages as compared with large polyelectrolyte displacers. (c) 1995 John Wiley & Sons, Inc.