Orientation to sex pheromone in the American cockroach: Analysis of chemo-orientation mechanisms

Male Periplaneta americana were photographed in a 2.4 m diameter arena containing a female sex pheromone source in the centre. Orientation pathways were digitized and analysed with regard to chemo-orientation mechanisms employed. Indirect components of chemo-orientation include arrestment near the pheromone source owing to an increase in turning rate and decrease in rate of locomotion, and zig-zag motor patterns that facilitate localization of the source. Most males were successful in locating the source if they moved to within 30 cm. Direct components of chemo-orientation include looping and relatively sharp correcting turns.No significant differences in orientation were observed between intact and unilaterally-antennectomized males, except that correcting turns close to the pheromone source were significantly less precise in males with one antenna. These results indicate that males with two antennae have an advantage over males with one antenna in being able to employ simultaneous information processing close to the pheromone source. Males with crossed antennae were unable to locate the pheromone source, suggesting that the fixed position of their antennae interfered with sensory information input.     

Linking genes to brain,behavior and neurological diseases: what can we learn from zebrafish?

How our brain is wired and subsequently generates functional output, ranging from sensing and locomotion to emotion, decision-making and learning and memory, remains poorly understood. Dys-regulation of these processes can lead to neurodegenerative, as well as neuro-psychiatric, disorders. Molecular genetic together with behavioral analyses in model organisms identify genes involved in the formation of neuronal circuits, the execution of behavior and mechanisms involved in neuro-pathogenesis. In this review I will discuss the current progress and future potential for study in a newly established vertebrate model organism for genetics, the zebrafish Danio rerio . Where available, schemes and results of genetic screens will be reviewed concerning the sensory, motor and neuromodulatory monoamine systems. Genetic analyses in zebrafish have the potential to provide important insights into the relationship between genes, neuronal circuits and behavior in normal as well as diseased states.     

Optimal isn’t good enough

The notion that biological systems come to embody optimal solutions seems consistent with the competitive drive of evolution. It has been used to interpret many examples of sensorimotor behavior. It is attractive from the viewpoint of control engineers because it solves the redundancy problem by identifying the one optimal motor strategy out of many similarly acceptable possibilities. This perspective examines whether there is sufficient basis to apply the formal engineering tools of optimal control to a reductionist understanding of biological systems. For an experimental biologist, this translates into whether the theory of optimal control generates nontrivial and testable hypotheses that accurately predict novel phenomena, ideally at deeper levels of structure than the observable behavior. The methodology of optimal control is applicable when there is (i) a single, known cost function to be optimized, (ii) an invertible model of the plant, and (iii) simple noise interfering with optimal performance. None of these is likely to be true for biological organisms. Furthermore, their motivation is usually good-enough rather than globally optimal behavior. Even then, the performance of a biological organism is often much farther from optimal than the physical limits of its hardware because the brain is continuously testing the acceptable limits of performance as well as just performing the task. This perspective considers an alternative strategy called ??good-enough?? control, in which the organism uses trial-and-error learning to acquire a repertoire of sensorimotor behaviors that are known to be useful, but not necessarily optimal. This leads to a diversity of solutions that tends to confer robustness on the individual organism and its evolution. It is also more consistent with the capabilities of higher sensorimotor structures, such as cerebral cortex, which seems to be designed to classify and recall complex sets of information, thereby allowing the organism to learn from experience, rather than to compute new strategies online. Optimal control has been a useful metaphor for understanding some superficial aspects of motor psychophysics. Reductionists who want to understand the underlying neural mechanisms need to move on.     

Keep Your Options Open: An Information-Based Driving Principle for Sensorimotor Systems

The central resource processed by the sensorimotor system of an organism is information. We propose an information-based quantity that allows one to characterize the efficiency of the perception-action loop of an abstract organism model. It measures the potential of the organism to imprint information on the environment via its actuators in a way that can be recaptured by its sensors, essentially quantifying the options available and visible to the organism. Various scenarios suggest that such a quantity could identify the preferred direction of evolution or adaptation of the sensorimotor loop of organisms.     

Cadmium transport, resistance, and toxicity in bacteria, algae, and fungi

Cadmium is an important environmental pollutant and a potent toxicant to bacteria, algae, and fungi. Mechanisms of Cd toxicity and resistance are variable, depending on the organism. It is very clear that the form of the metal and the environment it is studied in, play an important role in how Cd exerts its effect and how the organism(s) responds. A wide range of Cd concentrations have been used to designate resistance in organisms. To date, no concentration has been specified that is applicable to all species studied under standardized conditions. Cadmium exerts its toxic effect(s) over a wide range of concentrations. In most cases, algae and cyanobacteria are the most sensitive organisms, whereas bacteria and fungi appear to be more resistant. In some bacteria, plasmid-encoded resistance can lead to reduced Cd2+ uptake. However, some Gram-negative bacteria without plasmids are just as resistant to Cd as are bacteria containing plasmids encoding for Cd resistance. According to Silver and Misra (1984), there is no evidence for enzymatic or chemical transformations associated with Cd resistance. Insufficient information is available on the genetics of Cd uptake and resistance in cyanobacteria and algae. Mechanisms remain largely unknown at this point in time. Cadmium is toxic to these organisms, causing severe inhibition of such physiological processes as growth, photosynthesis, and nitrogen fixation at concentrations less than 2 ppm, and often in the ppb range (Tables 2 and 3). Cadmium also causes pronounced morphological aberrations in these organisms, which are probably related to deleterious effects on cell division. This may be direct or indirect, as a result of Cd effects on protein synthesis and cellular organelles such as mitochondria and chloroplasts. Cadmium is accumulated internally in algae (Table 4) as a result of a two-phase uptake process. The first phase involves a rapid physicochemical adsorption of Cd onto cell wall binding sites, which are probably proteins and (or) polysaccharides. This is followed by a lag period and then a slow, steady intracellular uptake. This latter phase is energy dependent and may involve transport systems used to accumulate other divalent cations, such as Mn2+ and Ca2+. Some data indicate that Cd resistance, and possibly uptake, in algae and cyanobacteria is controlled by a plasmid-encoded gene(s). Although considerable information is available on Cd toxicity to, and uptake in fungi, further work is clearly needed in several areas. There is little information about Cd uptake by filamentous fungi, and even in yeasts, information on the specificity, kinetics, and mechanisms of Cd uptake is limited.(ABSTRACT TRUNCATED AT 400 WORDS)     

NCBI Reference Sequence project: update and current status

The goal of the NCBI Reference Sequence (RefSeq) project is to provide the single best non-redundant and comprehensive collection of naturally occurring biological molecules, representing the central dogma. Nucleotide and protein sequences are explicitly linked on a residue-by-residue basis in this collection. Ideally all molecule types will be available for each well-studied organism, but the initial database collection pragmatically includes only those molecules and organisms that are most readily identified. Thus different amounts of information are available for different organisms at any given time. Furthermore, for some organisms additional intermediate records are provided when the genome sequence is not yet finished. The collection is supplied by NCBI through three distinct pipelines in addition to collaborations with community groups. The collection is curated on an ongoing basis. Additional information about the NCBI RefSeq project is available at http://www.ncbi.nih.gov/RefSeq/.     

Stages in the development of a model organism as a platform for mechanistic models in developmental biology: Zebrafish, 1970-2000

Model organisms became an indispensable part of experimental systems in molecular developmental and cell biology, constructed to investigate physiological and pathological processes. They are thought to play a crucial role for the elucidation of gene function, complementing the sequencing of the genomes of humans and other organisms. Accordingly, historians and philosophers paid considerable attention to various issues concerning this aspect of experimental biology. With respect to the representational features of model organisms, that is, their status as models, the main focus was on generalization of phenomena investigated in such experimental systems. Model organisms have been said to be models for other organisms or a higher taxon. This, however, presupposes a representation of the phenomenon in question. I will argue that prior to generalization, model organisms allow researchers to built generative material models of phenomena - structures, processes or the mechanisms that explain them - through their integration in experimental set-ups that carve out the phenomena from the whole organism and thus represent them. I will use the history of zebrafish biology to show how model organism systems, from around 1970 on, were developed to construct material models of molecular mechanisms explaining developmental or physiological processes.     

From the sequence to cell modeling: comprehensive functional genomics in Escherichia coli

As a result of the enormous amount of information that has been collected with E. coli over the past half century (e.g. genome sequence, mutant phenotypes, metabolic and regulatory networks, etc.), we now have detailed knowledge about gene regulation, protein activity, several hundred enzyme reactions, metabolic pathways, macromolecular machines, and regulatory interactions for this model organism. However, understanding how all these processes interact to form a living cell will require further characterization, quantification, data integration, and mathematical modeling, systems biology. No organism can rival E. coli with respect to the amount of available basic information and experimental tractability for the technologies needed for this undertaking. A focused, systematic effort to understand the E. coli cell will accelerate the development of new post-genomic technologies, including both experimental and computational tools. It will also lead to new technologies that will be applicable to other organisms, from microbes to plants, animals, and humans. E. coli is not only the best studied free-living model organism, but is also an extensively used microbe for industrial applications, especially for the production of small molecules of interest. It is an excellent representative of Gram-negative commensal bacteria. E. coli may represent a perfect model organism for systems biology that is aimed at elucidating both its free-living and commensal life-styles, which should open the door to whole-cell modeling and simulation.     

Fundamental taboos of biology

This paper formulates some taboos relating to living systems and cognition of these systems: in nature, there exist no two identical living complex multicellular organisms; there is no way to create an exact copy of a multicellular organism; there is no way to obtain two identical clones of a unicellular organism if they contain a sufficiently large number of cells; based on comparing present-day organisms, it is impossible to restore the structure of the first living cell and the processes that have led to its emergence; it is impossible to create a living cell from its separate simple constituents; the mechanisms determining cell vitality are essentially incognizable.     

Computational inference of the molecular logic for synaptic connectivity in C. elegans

MOTIVATION: The nematode C. elegans is an ideal model organism in which to investigate the biomolecular mechanisms underlying the connectivity of neurons, because synaptic connections are described in a comprehensive wiring diagram and methods for defining gene expression profiles of individual neurons are now available. RESULTS: Here we present computational techniques linking these two types of information. A systems-based approach (EMBP: Entropy Minimization and Boolean Parsimony) identifies sets of synergistically interacting genes whose joint expression predicts neural connectivity. We introduce an information theoretic measure of the multivariate synergy, a fundamental concept in systems biology, connecting the members of these gene sets. We present and validate our preliminary results based on publicly available information, and demonstrate that their synergy is exceptionally high indicating joint involvement in pathways. Our strategy provides a robust methodology that will yield increasingly more accurate results as more neuron-specific gene expression data emerge. Ultimately, we expect our approach to provide important clues for universal mechanisms of neural interconnectivity.     

Assays optimized for detection and quantification of antibacterial activity in shark cell lysates under high salt conditions

To assess non-cellular innate immune mechanisms that play a role in the antimicrobial defense of an organism several assay systems have been devised to screen for such factors. Most assays, however, have been developed to measure activity against clinical isolates of medical importance. There is scant information on methods optimal for assaying material from sharks and other marine fish for antimicrobial activity particularly against salt tolerant organisms that are likely to be encountered in the marine environment. We have modified and optimized agar diffusion and broth dilution assays for detection and quantification of antibacterial activity of shark leukocyte lysates. By replacing marine agar, typically used for marine organisms, with artificial sea water complete medium (SCM) enriched with tryptone and yeast extract has resulted in an improved inhibition zone assay that uses Planococcus citreus, a salt-tolerant organism as the target organism. Antibacterial activity is correlated to the size of zone of no bacterial growth around wells containing bioactive test sample. An alternative broth based microdilution growth assay uses the 96 well format and the antibacterial effect of the sample on growth of P. citreus, the target organism, is measured spectrophotometrically as percent inhibition of bacterial growth when compared to the growth of P. citreus grown in medium alone that represents 100% growth. The assay can also be used to titrate antibacterial activity and express the level of growth inhibition as a titer.     

Directional Hydrodynamic Sensing by Free-Swimming Organisms

Many aquatic organisms detect the presence of moving objects in their environment, such as predators, by sensing the hydrodynamic disturbances the movements produce. The resultant water flow is readily detectable by stationary organisms, but free-swimming organisms are carried with the surrounding water and may not detect the bulk surrounding flow, which limits the available information about the source. We have developed a theory that clarifies what information is contained in disturbances generated by an attacking predator that is available to a free-swimming organism and might be extracted from local flow deformations alone. The theory shows that, depending on how well the deformations can be measured in space and time, an organism can reduce the range of possible locations, speeds, sizes, and arrival times of the predator. We apply the theory to planktonic copepods that have mechanosensory hairs along a pair of antennules. The study reveals the presence of “blind spots,” potential ambiguities in resolving from which of two sides a predator attacks, and whether it generates a bow wave or suction. Our findings lead to specific testable hypotheses concerning optimal escape strategies, which are helpful for interpreting the behavior of evasive prey and designing free-swimming robots with sensory capabilities.     

Illuminating drug discovery with biological pathways

Systems biology promises to impact significantly on the drug discovery process. One of its ultimate goals is to provide an understanding of the complete set of molecular mechanisms describing an organism. Although this goal is a long way off, many useful insights can already come from currently available information and technology. One of the biggest challenges in drug discovery today is the high attrition rate: many promising candidates prove ineffective or toxic owing to a poor understanding of the molecular mechanisms of biological systems they target. A "systems" approach can help identify pathways related to a disease and can suggest secondary effects of drugs that might cause these problems and thus ultimately improve the drug discovery pipeline.     

Mass spectrometric approaches for characterizing bacterial proteomes

The emergence of advanced liquid chromatography mass spectrometry technologies for characterizing very complex mixtures of proteins has greatly propelled the field of proteomics, the goal of which is the simultaneous examination of all the proteins expressed by an organism. This research area represents a paradigm shift in molecular biology by attempting to provide a top-down qualitative and quantitative view of all the proteins (including their modifications and interactions) that are essential for an organism's life cycle, rather than targeting a particular protein family. This level of global protein information about an organism such as a bacterium can be combined with genomic and metabolomic data to enable a systems biology approach for understanding how these organisms live and function.     

The neural circuits and synaptic mechanisms underlying motor initiation in C. elegans

C. elegans is widely used to dissect how neural circuits and genes generate behavior. During locomotion, worms initiate backward movement to change locomotion direction spontaneously or in response to sensory cues; however, the underlying neural circuits are not well defined. We applied a multidisciplinary approach to map neural circuits in freely behaving worms by integrating functional imaging, optogenetic interrogation, genetic manipulation, laser ablation, and electrophysiology. We found that a disinhibitory circuit and a stimulatory circuit together promote initiation of backward movement and that circuitry dynamics is differentially regulated by sensory cues. Both circuits require glutamatergic transmission but depend on distinct glutamate receptors. This dual mode of motor initiation control is found in mammals, suggesting that distantly related organisms with anatomically distinct nervous systems may adopt similar strategies for motor control. Additionally, our studies illustrate how a multidisciplinary approach facilitates dissection of circuit and synaptic mechanisms underlying behavior in a genetic model organism.     

Evolution in biological and nonbiological systems under different mechanisms of generation and inheritance

The majority of definitions of life and evolution include the notion that part of an organism has to be copied to its offspring and that this includes some form of coded information. This article presents the thesis that this conception is too restrictive and that evolution can occur in systems in which there is no copy of information between generations. For that purpose, this article introduces a new set of concepts and a theoretical framework that is designed to be equally applicable to the study of the evolution of biological and nonbiological systems. In contrast to some theoretical approaches in evolution, like neo-Darwinism, the approach presented here is not focused on the transmission and change of hereditary information that can be copied (like in the case of DNA). Instead, multiple mechanisms by which a system can generate offspring (with and without copying) and by which information in it affects the structure and evolution of its offspring are considered. The first part of this article describes in detail these new concepts. The second part of this article discusses how these concepts are directly applicable to the diversity of systems that can evolve. The third part introduces hypotheses concerning (1) how different mechanisms of generation and inheritance can arise from each other during evolution, and (2) how the existence of several inheritance mechanisms in an organism can affect its evolution.     

New model systems for studying the evolutionary biology of aging: Crustacea

Progress in any area of biology has generally required work on a variety of organisms. This is true because particular species often have characteristics that make them especially useful for addressing specific questions. Recent progress in studying the evolutionary biology of senescence has been made through the use of new species, such asCaenorhabditis elegans andDrosophila melanogaster, because of the ease of working with them in the laboratory and because investigators have used theories for the evolution of aging as a basis for discovering the underlying mechanisms.I describe ways of finding new model systems for studying the evolutionary mechanisms of aging by combining the predictions of theory with existing information about the natural history of organisms that are well-suited to laboratory studies. Properties that make organisms favorable for laboratory studies include having a short generation time, high fecundity, small body size, and being easily cultured in a laboratory environment. It is also desirable to begin with natural populations that differ in their rate of aging. I present three scenarios and four groups of organisms which fulfill these requirements. The first two scenarios apply to well-documented differences in age/size specific predation among populations of guppies and microcrustacea. The third is differences among populations of fairy shrimp (anostraca) in habitat permanence. In all cases, there is an environmentla factor that is likely to select for changes in the life history, including aging, plus a target organism which is well-suited for laboratory studies of aging.