On the Use of Bayesian Methods for Evaluating Compartmental Neural Models

Computational modeling is being used increasingly in neuroscience. In deriving such models, inference issues such as model selection, model complexity, and model comparison must be addressed constantly. In this article we present briefly the Bayesian approach to inference. Under a simple set of commonsense axioms, there exists essentially a unique way of reasoning under uncertainty by assigning a degree of confidence to any hypothesis or model, given the available data and prior information. Such degrees of confidence must obey all the rules governing probabilities and can be updated accordingly as more data becomes available. While the Bayesian methodology can be applied to any type of model, as an example we outline its use for an important, and increasingly standard, class of models in computational neuroscience—compartmental models of single neurons. Inference issues are particularly relevant for these models: their parameter spaces are typically very large, neurophysiological and neuroanatomical data are still sparse, and probabilistic aspects are often ignored. As a tutorial, we demonstrate the Bayesian approach on a class of one-compartment models with varying numbers of conductances. We then apply Bayesian methods on a compartmental model of a real neuron to determine the optimal amount of noise to add to the model to give it a level of spike time variability comparable to that found in the real cell.     

Changes of plasma insulin, urea, amino acids and rumen metabolites in somatotropin treated dairy cows

Summary An experiment was performed to evaluate the effects of somatotropin on plasma free amino acid, urea and insulin concentrations and rumen fermentation pattern and to assess their relationships. Four Italian Friesian dairy cows fitted with rumen cannulae were used in a switch-back design. Slow releasing recombinant bovine somatotropin (640 mg/cow) was injected every 28 days for two consecutive periods. Rumen fluid and blood samples were collected before and after feeding at 0, 7 and 21 days after rbST injection. Exogenous rbST increased plasma insulin concentration and the insulin response to feeding, and decreased plasma urea and free essential and branched chain amino acid concentrations. rbST did not affect rumen fermentation pattern. No correlation was found between rumen and plasma parameters measured after feeding. Our results are consistent with the notion that the main effect of somatotropin is post-absorptive.     

Binding of estradiol receptor complexes to isolated human breast chromatin

Summary The interaction of estradiol-receptor complexes and isolated human breast tumor chromatin was studied under equilibrium conditions.The estradiol-receptor complexes bound specifically to the chromatin of hormone dependent tumors and showed a single class of binding sites with a Ka of 0.96 × 10¹⁰ m ^–1 and a binding capacity of 1.5 pmoles/mg DNA. The binding was a temperature-dependent process and involved a transformation of the receptor protein.The heat-activated hormone-receptor com-plex was more active than the 8S form in the binding phenomenon. The specific interaction of estradiol-receptor complex with isolated chromatin was saturable and sensitive to conditions of temperature and ionic strength. Furthermore under optimal conditions no acceptor sites were detected in chromatin of hormone independent tumors.Dedicated to ProfessorLuis F. Leloir on the occasion of his 70th birthday.     

Particulate DNA polymerase from the cytoplasm of Xenopus laevis oocytes

A DNA polymerase has been partially purified and characterized from Xenopus laevis stage 6 oocytes. The enzyme is present only in the cytoplasm and has been shown to be able to copy Poly(A) x oligo(dT), to be sensitive to N-ethylmaleimide, and to sediment faster than 4 S in high salt glycerol gradient. The enzyme can be extracted from particulate material which has a density in sucrose gradient ranging from 1.200 to 1.225 g/cc. This particulate material is identified by its ability to use Poly(A) x oligo(dT) as template in an exogenous DNA polymerase reaction and by its endogenous DNA synthesizing capacity.     

Functional analysis of proteins involved in Plasmodium falciparum merozoite invasion of red blood cells

Plasmodium falciparum causes the most lethal form of malaria in humans and is responsible for over two million deaths per year. The development of a vaccine against this parasite is an urgent priority and potential protein targets include those on the surface of the asexual merozoite stage, the form that invades the host erythrocyte. The development of methods to transfect P. falciparum has enabled the construction of gain-of-function and loss-of-function mutants and provided new strategies to analyse the role of parasite proteins. In this review, we describe the use of this technology to examine the role of merozoite antigens in erythrocyte invasion and to address their potential as vaccine candidates.     

On the convergence of a clustering algorithm for protein-coding regions in microbial genomes

MOTIVATION: As the number of fully sequenced prokaryotic genomes continues to grow rapidly, computational methods for reliably detecting protein-coding regions become even more important. Audic and Claverie (1998) Proc. Natl Acad. Sci. USA, 95, 10026-10031, have proposed a clustering algorithm for protein-coding regions in microbial genomes. The algorithm is based on three Markov models of order k associated with subsequences extracted from a given genome. The parameters of the three Markov models are recursively updated by the algorithm which, in simulations, always appear to converge to a unique stable partition of the genome. The partition corresponds to three kinds of regions: (1) coding on the direct strand, (2) coding on the complementary strand, (3) non-coding. RESULTS: Here we provide an explanation for the convergence of the algorithm by observing that it is essentially a form of the expectation maximization (EM) algorithm applied to the corresponding mixture model. We also provide a partial justification for the uniqueness of the partition based on identifiability. Other possible variations and improvements are briefly discussed.     

A case of granulomatous skin lesions caused by Mycobacterium marinum in the Campania region

The diagnosis of cutaneous Mycobacterium marinum infection is frequently presumptive, as detection by conventional methods is difficult. We describe a patient with granulomatous skin lesions on the right dorsal hand and forearm. Histological examinations were presumptive for mycobacterium lesions. We identified Mycobacterium marinum directly in the patient's lesional skin biopsy combining polymerase chain reaction (PCR) amplification using Mycobacterium genus-specific primers, and subsequent restriction enzyme analysis enabling identification to the species level. The symptoms were no longer present after specific therapy, thereby confirming the initial diagnosis.     

ChemDB: a public database of small molecules and related chemoinformatics resources

MOTIVATION: The development of chemoinformatics has been hampered by the lack of large, publicly available, comprehensive repositories of molecules, in particular of small molecules. Small molecules play a fundamental role in organic chemistry and biology. They can be used as combinatorial building blocks for chemical synthesis, as molecular probes in chemical genomics and systems biology, and for the screening and discovery of new drugs and other useful compounds. RESULTS: We describe ChemDB, a public database of small molecules available on the Web. ChemDB is built using the digital catalogs of over a hundred vendors and other public sources and is annotated with information derived from these sources as well as from computational methods, such as predicted solubility and three-dimensional structure. It supports multiple molecular formats and is periodically updated, automatically whenever possible. The current version of the database contains approximately 4.1 million commercially available compounds and 8.2 million counting isomers. The database includes a user-friendly graphical interface, chemical reactions capabilities, as well as unique search capabilities. AVAILABILITY: Database and datasets are available on http://cdb.ics.uci.edu.     

Iron deficiency-induced changes in carbon fixation and leaf elemental composition of sugar beet (Beta vulgaris) plants

In this experiment we (i) tested the hypothesis that, besides decreasing leaf C fixation, lime induced iron (Fe) deficiency increases root C fixation via PEP carboxylase and (ii) assessed the Fe-induced modifications in the elemental composition of plant tissues. Sugar beet plants were grown in nutrient solutions with Fe (45 M Fe-EDTA; +Fe control) or in a similar nutrient solution without Fe (–Fe) and in presence of CaCO₃ (1.0 gL^–1), either labelled with ¹³C (20 at. %) or unlabelled. After 7 and 17 days from treatment imposition, plants were harvested and single organs analysed for total O, C, H, macro and micronutrients. ¹³C abundance was also assessed in control, unlabelled and labelled –Fe plants. Iron deficiency caused significant growth reductions; chlorophyll and net photosynthesis decreased markedly in Fe-deficient plants when compared to the controls, whereas leaf transpiration rates and stomatal conductance were not affected by Fe deficiency. Iron deficient plants had leaf biomass with lower C (2 to 4%) and higher O (3 to 5%) concentrations than +Fe plants. The ¹³C was higher (less negative) in +Fe than in –Fe unlabelled plants. Iron deficient plants grown in the nutrient solution enriched with labelled CaCO₃ absorbed a relatively small amount of labelled C, which was mainly recovered in the fine roots and accounted for less than 2% of total C gain in the 10 d treatment period. Evidences suggest that iron deficient sugar beets grown in the presence of CaCO₃ do not markedly shift their C fixation from leaf RuBP to root PEPC.