Introduction to the Symposium: What is Computational Neurobiology?

SYNOPSIS. Current advances in computational biology are derivedfrom two sets of ideas established in the work of Santiago Ramóny Cajal. One is the neuron doctrine, which holds that neuronsare the functional units of the nervous system, and has ledto detailed models of neuronal properties based on increasinginformation on the physical and chemical properties of neurons.The second is the idea of networks of neurons with specificpatterns of interconnections that has led to a variety of mathematicalmethods of analyzing such networks. Future work in computationalneurobiology promises to be a blend of these two modeling approaches.     

What is happening to the monocotyledons?

An attempt is made to elucidate some of the more pronounced departures from traditional classifications in the book The families of the monocotyledons byDahlgren and collaborators, which embodies the latest opinions of the lateRolf Dahlgren on the subject. Consideration is given to the treatment of theLiliiflorae (especiallyLiliales andAsparagales) andBromeliiflorae, and to the theory offered for the origin of the monocots which identifies theDioscoreales as the most primitive order of the subclass.Dahlgren aimed at an eclectic classification (one based on a combination of similarity criteria and phylogenetic criteria) and the results of his use of cladistic methods (in association withF. N. Rasumssen) to supply the phylogenetic input are assessed. The resulting system itself is considered in the light of the distinction drawn byJ. S. L. Gilmour between natural and artificial classifications and their respective uses.Dedicated to the memory of JohnS. L. Gilmour.     

Somatic recombination in adult tissues: What is there to learn?

Somatic recombination is essential to protect genomes of somatic cells from DNA damage but it also has important clinical implications, as it is a driving force of tumorigenesis leading to inactivation of tumor suppressor genes. Despite this importance, our knowledge about somatic recombination in adult tissues remains very limited. Our recent work, using the Drosophila adult midgut has demonstrated that spontaneous events of mitotic recombination accumulate in aging adult intestinal stem cells and result in frequent loss of heterozygosity (LOH). In this Extra View article, we provide further data supporting long-track chromosome LOH and discuss potential mechanisms involved in the process. In addition, we further discuss relevant questions surrounding somatic recombination and how the mechanisms and factors influencing somatic recombination in adult tissues can be explored using the Drosophila midgut model.     

Multidrug resistant to extensively drug resistant tuberculosis: What is next?

Drug resistant tuberculosis is a man made problem. While tuberculosis is hundred percent curable, multidrug resistant tuberculosis (MDR-TB) is difficult to treat. Inadequate and incomplete treatment and poor treatment adherence has led to a newer form of drug resistance known as extensively drug resistant tuberculosis (XDR-TB). XDR-TB is defined as tuberculosis caused by Mycobacterium tuberculosis strain, which is resistant to at least rifampicin and isoniazid among the first line anti tubercular drugs (MDR-TB) in addition to resistance to any fluroquinolones and at least one of three injectable second line anti tubercular drugs i.e. amikacin, kanamycin and/or capreomycin. Mismanagement of tuberculosis paves the way to drug resistant tuberculosis. Emergence of XDR-TB is reported world wide. Reported prevalence rates of XDR-TB of total MDR cases are; 6.6% overall worldwide, 6.5% in industrialized countries, 13.6% in Russia and Eastern Europe, 1.5% in Asia, 0.6% in Africa and Middle East and 15.4% in Republic of Korea. Better management and control of tuberculosis specially drug resistant TB by experienced and qualified doctors, access to standard microbiology laboratory, co-morbitidy of HIV and tuberculosis, new anti-TB drug regimens, better diagnostic tests, international standards for second line drugs (SLD)-susceptibility testing, invention of newer antitubercular molecules and vaccines and knowing the real magnitude of XDR-TB are some of the important issues to be addressed for effective prevention and management of XDR-TB.     

To fuse or not to fuse: What is your purpose?

Since the dawn of time, or at least the dawn of recombinant DNA technology (which for many of today''s scientists is the same thing), investigators have been cloning and expressing heterologous proteins in a variety of different cells for a variety of different reasons. These range from cell biological studies looking at protein-protein interactions, post-translational modifications, and regulation, to laboratory-scale production in support of biochemical, biophysical, and structural studies, to large scale production of potential biotherapeutics. In parallel, fusion-tag technology has grown-up to facilitate microscale purification (pull-downs), protein visualization (epitope tags), enhanced expression and solubility (protein partners, e.g., GST, MBP, TRX, and SUMO), and generic purification (e.g., His-tags, streptag, and FLAG™-tag). Frequently, these latter two goals are combined in a single fusion partner. In this review, we examine the most commonly used fusion methodologies from the perspective of the ultimate use of the tagged protein. That is, what are the most commonly used fusion partners for pull-downs, for structural studies, for production of active proteins, or for large-scale purification? What are the advantages and limitations of each? This review is not meant to be exhaustive and the approach undoubtedly reflects the experiences and interests of the authors. For the sake of brevity, we have largely ignored epitope tags although they receive wide use in cell biology for immunopreciptation.     

From Metaphor to Measurement: Resilience of What to What?

Resilience is the magnitude of disturbance that can be tolerated before a socioecological system (SES) moves to a different region of state space controlled by a different set of processes. Resilience has multiple levels of meaning: as a metaphor related to sustainability, as a property of dynamic models, and as a measurable quantity that can be assessed in field studies of SES. The operational indicators of resilience have, however, received little attention in the literature. To assess a system's resilience, one must specify which system configuration and which disturbances are of interest. This paper compares resilience properties in two contrasting SES, lake districts and rangelands, with respect to the following three general features: (a) The ability of an SES to stay in the domain of attraction is related to slowly changing variables, or slowly changing disturbance regimes, which control the boundaries of the domain of attraction or the frequency of events that could push the system across the boundaries. Examples are soil phosphorus content in lake districts woody vegetation cover in rangelands, and property rights systems that affect land use in both lake districts and rangelands. (b) The ability of an SES to self-organize is related to the extent to which reorganization is endogenous rather than forced by external drivers. Self-organization is enhanced by coevolved ecosystem components and the presence of social networks that facilitate innovative problem solving. (c) The adaptive capacity of an SES is related to the existence of mechanisms for the evolution of novelty or learning. Examples include biodiversity at multiple scales and the existence of institutions that facilitate experimentation, discovery, and innovation. Received 20 March 2001; accepted 6 June 2001.