A New Implementation and Detailed Study of Breakpoint Analysis

Phylogenies derived from gene order data may prove crucial in answering some fundamental open questions in biomolecular evolution. Yet very few techniques are available for such phylogenetic reconstructions. One method is breakpoint analysis, developed by Blanchette and Sankoff 2 for solving the breakpoint phylogeny.\u27 Our earlier studies 5;6 confirmed the usefulness of this approach, but also found that BPAnalysis, the implementation developed by Sankoff and Blanchette, was too slow to use on all but very small datasets. We report here on a reimplementation of BPAnalysis using the principles of algorithmic engineering. Our faster (by 2 to 3 orders of magnitude) and flexible implementation allowed us to conduct studies on the characteristics of breakpoint analysis, in terms of running time, quality, and robustness, as well as to analyze datasets that had so far been considered out of reach. We report on these findings and also discuss future directions for our new implementation.\u2

Metabolic Futile Cycles and Their Functions: A Systems Analysis of Energy and Control

It has long been hypothesized that futile cycles in cellular metabolism are involved in the regulation of biochemical pathways. Following the work of Newsholme and Crabtree, we develop a quantitative theory for this idea based on open-system thermodynamics and metabolic control analysis. It is shown that the {\it stoichiometric sensitivity} of an intermediary metabolite concentration with respect to changes in steady-state flux is governed by the effective equilibrium constant of the intermediate formation, and the equilibrium can be regulated by a futile cycle. The direction of the shift in the effective equilibrium constant depends on the direction of operation of the futile cycle. High stoichiometric sensitivity corresponds to ultrasensitivity of an intermediate concentration to net flow through a pathway; low stoichiometric sensitivity corresponds to super-robustness of concentration with respect to changes in flux. Both cases potentially play important roles in metabolic regulation. Futile cycles actively shift the effective equilibrium by expending energy; the magnitude of changes in effective equilibria and sensitivities is a function of the amount of energy used by a futile cycle. This proposed mechanism for control by futile cycles works remarkably similarly to kinetic proofreading in biosynthesis. The sensitivity of the system is also intimately related to the rate of concentration fluctuations of intermediate metabolites. The possibly different roles of the two major mechanisms for cellular biochemical regulation, namely reversible chemical modifications via futile cycles and shifting equilibrium by macromolecular binding, are discussed.Comment: 11 pages, 5 figure

Effects of Intermittent IL-2 Alone or with Peri-Cycle Antiretroviral Therapy in Early HIV Infection: The STALWART Study

The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4+ counts compared to no therapy

Molecular and physiological responses of two classes of marine chromophytic phytoplankton (diatoms and prymnesiophytes) during the development of nutrient-stimulated blooms

Generic taxon-specific DNA probes that target an internal region of the gene (rbcL) encoding the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) were developed for two groups of marine phytoplankton (diatoms and prymnesiophytes). The specificity and utility of the probes were evaluated in the laboratory and also during a 1-month mesocosm experiment in which we investigated the temporal variability in RubisCO gene expression and primary production in response to inorganic nutrient enrichment. We found that the onset of successive bloom events dominated by each of the two classes of chromophyte algae was associated with marked taxon-specific increases in rbcL transcription rates. These observations suggest that measurements of RubisCO gene expression can provide an early indicator of the development of phytoplankton blooms and may also be useful in predicting which taxa are likely to dominate a bloom

Dynamics of ribulose 1,5-bisphosphate carboxylase/xxygenase gene expression in the coccolithophorid Coccolithus pelagicus during a tracer release experiment in the northeast Atlantic

We report a pronounced diel rhythm in ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO) gene expression in a natural population of the coccolithophorid Coccolithus pelagicus sampled during a Lagrangian experiment in the Northeast Atlantic. Our observations show that there is greater heterogeneity in the temporal regulation of RubisCO expression among planktonic chromophytes than has been reported hitherto