The evolutionary potential of the Drosophila sex determination gene network

The evolution of sex determination mechanisms is known to be relatively rapid, though recent evidence indicates that certain parts of the mechanism may be more highly conserved. These characteristics establish the sex determination mechanism as a good candidate for the theoretical study of gene network evolution, particularly of networks involved in development. We investigate the short-term evolutionary potential of the sex determination mechanism in Drosophila melanogaster with the aid of a synchronous logical model. We introduce general theoretical concepts such as a network-specific form of mutation, and a notion of functional equivalence between networks. We apply this theoretical framework to the sex determination mechanism and compare it to a population of random networks, enabling us to find features both general to sex determination networks, and particular to the Drosophila network. In general, sex determination networks exist within large sets of functionally equivalent networks all of which satisfy the sex determination task. These large sets are in turn composed of subsets which are mutationally related, suggesting a high degree of flexibility is available without compromising the core functionality. Two particular characteristics of the Drosophila network are found: (a) a parsimonious use of gene interactions, and (b) the network structure can produce a relatively large number of dynamical pattern variations through single network mutations.     

Atropisomeric quinazolin-4-one derivatives are potent noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists

Piriqualone (1) was found to be an antagonist of AMPA receptors. Structure activity optimization was conducted on each of the three rings in 1 to afford a series of potent and selective antagonists. The sterically crowded environment surrounding the N-3 aryl group provided sufficient thermal stability for atropisomers to be isolated. Separation of these atropisomers resulted in the identification of (+)-38 (CP-465,022), a compound that binds to the AMPA receptor with high affinity (IC50 = 36 nM) and displays potent anticonvulsant activity.     

Fluorescence lifetime,yield, energy transfer and spectrum in photosynthesis, 1950–1960*

The fluorescence lifetime of chlorophyll agives information about the primary photo-physical events in photosynthesis. Most of the light energy absorbed by chlorophylls is utilized for photochemistry. There are two main additional pathways competing for the absorbed light energy: fluorescence and radiationless internal conversion (heat). Only a few percent of the absorbed energy proceeds along these two pathways. This historical minireview focuses on the first direct measurements of the lifetime of chlorophyll fluorescence, the time it takes to transfer energy from phycoerythrin to chlorophyll a, and the discovery of the fluorescence band at 720 nm (F720; then attributed to a dimer of chlorophyll). These works were carried out during the the late 1950s to the early 1960s in the laboratory of Professor Eugene Rabinowitch at the University of Illinois, Urbana-Champaign [Brody (1995) Photosynth Res 43: 67–74]. This Minireview is dedicated to Professor Eugene Rabinowitch (1901–1973), mentor of the author (Steve Brody) as well as of the editor, and authors classmate (Govindjee). The career and contributions of Eugene Rabinowitch are available in a dedication by Bannister (1972). This revised version was published online in June 2006 with corrections to the Cover Date.     

Oxygen transport capacity in the air-breathing fish,Megalops cyprinoides: compensations for strenuous exercise

Tarpon have high resting or routine hematocrits (Hct) (37.6+/-3.4%) and hemoglobin concentrations (120.6+/-7.3 gl(-1)) that increased significantly following bouts of angling-induced exercise (51.9+/-3.7% and 142.8+/-13.5 gl(-1), respectively). Strenuous exercise was accompanied by an approximately tenfold increase in blood lactate and a muscle metabolite profile indicative of a high energy demand teleost. Routine blood values were quickly restored only when this facultative air-breathing fish was given access to atmospheric air. In vitro studies of oxygen transport capacity, a function of carrying capacity and viscosity, revealed that the optimal Hct range corresponded to that observed in fish under routine behaviour. During strenuous exercise however, further increase in viscosity was largely offset by a pronounced reduction in the shear-dependence of blood which conformed closely to an ideal Newtonian fluid. The mechanism for this behaviour of the erythrocytes appears to involve the activation of surface adrenergic receptors because pre-treatment with propranolol abolished the response. High levels of activity in tarpon living in hypoxic habitats are therefore supported by an elevated Hct with adrenergically mediated viscosity reduction, and air-breathing behaviour that enables rapid metabolic recovery.     

Peptide-mediated RNA delivery: a novel approach for enhanced transfection of primary and post-mitotic cells

Synthetic vectors were evaluated for their ability to mediate efficient mRNA transfection. Initial results indicated that lipoplexes, but not polyplexes based on polyethylenimine (PEI, 25 and 22 kDa), poly(L-lysine) (PLL, 54 kDa) or dendrimers, mediated efficient translation of mRNA in B16-F10 cells. Significant mRNA transfection was achieved by lipoplex delivery in quiescent (passage 0) human umbilical vein endothelial cells (HUVEC), and by passage 4, 10.7% of HUVEC were transfected compared to 0.84% with DNA. Lack of expression with PEI 25 kDa/mRNA or PLL 54 kDa/mRNA in a cell-free translation assay and following cytoplasmic injection into Rat1 cells indicated that these polyplexes were too stable to release mRNA. In contrast, polyplexes formed using smaller PEI 2 kDa and PLL 3.4 kDa gave 5-fold greater expression in B16-F10 cells compared to DOTAP, but were dependent on chloroquine for transfection activity. Endosomolytic activity was incorporated by conjugating PEI 2 kDa to melittin and resulting PEI 2 kDa-melittin/mRNA polyplexes mediated high transfection levels in HeLa cells (31.1 +/- 4.1%) and HUVEC (58.5 +/- 2.9%) in the absence of chloroquine, that was potentiated to 52.2 +/- 2.7 and 71.6 +/- 1.7%, respectively, in the presence of chloroquine. These results demonstrate that mRNA polyplexes based on peptide-modified low molecular weight polycations can possess versatile properties including endosomolysis that should enable efficient non-viral mRNA transfection of quiescent and post-mitotic cells.     

The principle of laplace and scaling of ventricular wall stress and blood pressure in mammals and birds

Maximum left ventricular wall stress is calculated at end-diastolic volume and systemic arterial diastolic blood pressure, according to a thick-walled model for the principle of Laplace. Stress is independent of body mass and averages 13.9 kPa (+/-2.3; 95% confidence interval) in 24 species of mammals weighing 0.025-4,000 kg and 15.5 kPa (+/-4.7) in 12 birds weighing 0.014-110 kg. Birds have higher arterial blood pressures and larger hearts than mammals. Systolic and diastolic arterial blood pressures increase with body mass according to M(0.05) in mammals, and heart mass increases according to M(1.06) in the same species, further supporting the principle. However, blood pressure in birds is independent of body mass, and heart mass scales isometrically. End-diastolic stress values, calculated according to Laplace, are about one-third of peak stresses recorded in isolated mammalian myocardial preparations.     

Dynamics of mitochondrial inheritance in the evolution of binary mating types and two sexes

The uniparental inheritance (UPI) of mitochondria is thought to explain the evolution of two mating types or even true sexes with anisogametes. However, the exact role of UPI is not clearly understood. Here, we develop a new model, which considers the spread of UPI mutants within a biparental inheritance (BPI) population. Our model explicitly considers mitochondrial mutation and selection in parallel with the spread of UPI mutants and self-incompatible mating types. In line with earlier work, we find that UPI improves fitness under mitochondrial mutation accumulation, selfish conflict and mitonuclear coadaptation. However, we find that as UPI increases in the population its relative fitness advantage diminishes in a frequency-dependent manner. The fitness benefits of UPI ‘leak’ into the biparentally reproducing part of the population through successive matings, limiting the spread of UPI. Critically, while this process favours some degree of UPI, it neither leads to the establishment of linked mating types nor the collapse of multiple mating types to two. Only when two mating types exist beforehand can associated UPI mutants spread to fixation under the pressure of high mitochondrial mutation rate, large mitochondrial population size and selfish mutants. Variation in these parameters could account for the range of UPI actually observed in nature, from strict UPI in some Chlamydomonas species to BPI in yeast. We conclude that UPI of mitochondria alone is unlikely to have driven the evolution of two mating types in unicellular eukaryotes.     

13C-nuclear magnetic resonance spectra of compounds containing β-D-fructofuranosyl groups or residues

¹³C-N.m.r. spectra have been recorded for sucrose, melezitose, levan, inulin, palatinose, and D-fructose. Except for the last, each compound contains a different O-substituted D-fructofuranose residue or group, or β-D-fructofuranosyl residue or group. On the basis of chemical-shift displacements, resulting from O-substitution at specific carbon atoms, resonances can be assigned to the carbon atoms of the β-D-fructofuranosyl residue. Fortuitously, the α-D-glucopyranosyl group present in some of these compounds exhibits resonances that do not obscure the β-D-fructofuranosyl resonances. O-Substitution of the β-D-fructofuranosyl residue causes a downfield displacement of the corresponding, linked-C resonance; however, the other major resonances of this residue are not affected by bulky substituents. Members of a series of levan fractions, the products of partial, acid hydrolysis of Streptoccoccus salivarius levan, were then examined for changes in relative degree of branching.