Predictability and hierarchy in Drosophila behavior

Even the simplest of animals exhibit behavioral sequences with complex temporal dynamics. Prominent amongst the proposed organizing principles for these dynamics has been the idea of a hierarchy, wherein the movements an animal makes can be understood as a set of nested sub-clusters. Although this type of organization holds potential advantages in terms of motion control and neural circuitry, measurements demonstrating this for an animal's entire behavioral repertoire have been limited in scope and temporal complexity. Here, we use a recently developed unsupervised technique to discover and track the occurrence of all stereotyped behaviors performed by fruit flies moving in a shallow arena. Calculating the optimally predictive representation of the fly's future behaviors, we show that fly behavior exhibits multiple time scales and is organized into a hierarchical structure that is indicative of its underlying behavioral programs and its changing internal states

Potential implications of coronary artery calcium testing for guiding aspirin use among asymptomatic individuals with diabetes.

ObjectiveIt is unclear whether coronary artery calcium (CAC) is effective for risk stratifying patients with diabetes in whom treatment decisions are uncertain.Research design and methodsOf 44,052 asymptomatic individuals referred for CAC testing, we studied 2,384 individuals with diabetes. Subjects were followed for a mean of 5.6 ± 2.6 years for the end point of all-cause mortality.ResultsThere were 162 deaths (6.8%) in the population. CAC was a strong predictor of mortality across age-groups (age <50, 50-59, ≥60), sex, and risk factor burden (0 vs. ≥1 additional risk factor). In individuals without a clear indication for aspirin per current guidelines, CAC stratified risk, identifying patients above and below the 10% risk threshold of presumed aspirin benefit.ConclusionsCAC can help risk stratify individuals with diabetes and may aid in selection of patients who may benefit from therapies such as low-dose aspirin for primary prevention

Measuring the repertoire of age-related behavioral changes in Drosophila melanogaster

Aging affects almost all aspects of an organism -- its morphology, its physiology, its behavior. Isolating which biological mechanisms are regulating these changes, however, has proven difficult, potentially due to our inability to characterize the full repertoire of an animal's behavior across the lifespan. Using data from fruit flies (D. melanogaster) we measure the full repertoire of behaviors as a function of age. We observe a sexually dimorphic pattern of changes in the behavioral repertoire during aging. Although the stereotypy of the behaviors and the complexity of the repertoire overall remains relatively unchanged, we find evidence that the observed alterations in behavior can be explained by changing the fly's overall energy budget, suggesting potential connections between metabolism, aging, and behavior

A framework for studying behavioral evolution by reconstructing ancestral repertoires

Although extensive behavioral changes often exist between closely related animal species, our understanding of the genetic basis underlying the evolution of behavior has remained limited. Here, we propose a new framework to study behavioral evolution by computational estimation of ancestral behavioral repertoires. We measured the behaviors of individuals from six species of fruit flies using unsupervised techniques and identified suites of stereotyped movements exhibited by each species. We then fit a Generalized Linear Mixed Model to estimate the suites of behaviors exhibited by ancestral species, as well as the intra- and inter-species behavioral covariances. We found that much of intraspecific behavioral variation is explained by differences between individuals in the status of their behavioral hidden states, what might be called their "mood." Lastly, we propose a method to identify groups of behaviors that appear to have evolved together, illustrating how sets of behaviors, rather than individual behaviors, likely evolved. Our approach provides a new framework for identifying co-evolving behaviors and may provide new opportunities to study the genetic basis of behavioral evolution

A framework for studying behavioral evolution by reconstructing ancestral repertoires

Although different animal species often exhibit extensive variation in many behaviors, typically scientists examine one or a small number of behaviors in any single study. Here, we propose a new framework to simultaneously study the evolution of many behaviors. We measured the behavioral repertoire of individuals from six species of fruit flies using unsupervised techniques and identified all stereotyped movements exhibited by each species. We then fit a Generalized Linear Mixed Model to estimate the intra-and inter-species behavioral covariances, and, by using the known phylogenetic relationships among species, we estimated the (unobserved) behaviors exhibited by ancestral species. We found that much of intra-specific behavioral variation has a similar covariance structure to previously described long-time scale variation in an individual’s behavior, suggesting that much of the measured variation between individuals of a single species in our assay reflects differences in the status of neural networks, rather than genetic or developmental differences between individuals. We then propose a method to identify groups of behaviors that appear to have evolved in a correlated manner, illustrating how sets of behaviors, rather than individual behaviors, likely evolved. Our approach provides a new framework for identifying co-evolving behaviors and may provide new opportunities to study the mechanistic basis of behavioral evolution.Fil: Hernández Lahme, Damián Gabriel. University of Emory; Estados Unidos. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Rivera, Catalina. University of Emory; Estados UnidosFil: Cande, Jessica. Howard Hughes Medical Institute; Estados UnidosFil: Zhou, Baohua. University of Yale; Estados Unidos. University of Emory; Estados UnidosFil: Stern, David L.. Howard Hughes Medical Institute; Estados UnidosFil: Berman, Gordon J.. University of Emory; Estados Unido

Driving calmodulin protein towards conformational shift by changing ionization states of select residues

Proteins are complex systems made up of many conformational sub-states which are mainly determined by the folded structure. External factors such as solvent type, temperature, pH and ionic strength play a very important role in the conformations sampled by proteins. Here we study the conformational multiplicity of calmodulin (CaM) which is a protein that plays an important role in calcium signaling pathways in the eukaryotic cells. CaM can bind to a variety of other proteins or small organic compounds, and mediates different physiological processes by activating various enzymes. Binding of calcium ions and proteins or small organic molecules to CaM induces large conformational changes that are distinct to each interacting partner. In particular, we discuss the effect of pH variation on the conformations of CaM. By using the pKa values of the charged residues as a basis to assign protonation states, the conformational changes induced in CaM by reducing the pH are studied by molecular dynamics simulations. Our current view suggests that at high pH, barrier crossing to the compact form is prevented by repulsive electrostatic interactions between the two lobes. At reduced pH, not only is barrier crossing facilitated by protonation of residues, but also conformations which are on average more compact are attained. The latter are in accordance with the fluorescence resonance energy transfer experiment results of other workers. The key events leading to the conformational change from the open to the compact conformation are (i) formation of a salt bridge between the N-lobe and the linker, stabilizing their relative motions, (ii) bending of the C-lobe towards the N-lobe, leading to a lowering of the interaction energy between the two-lobes, (iii) formation of a hydrophobic patch between the two lobes, further stabilizing the bent conformation by reducing the entropic cost of the compact form, (iv) sharing of a Ca+2 ion between the two lobes

Quantum cellular automata quantum computing with endohedral fullerenes

We present a scheme to perform universal quantum computation using global addressing techniques as applied to a physical system of endohedrally doped fullerenes. The system consists of an ABAB linear array of Group V endohedrally doped fullerenes. Each molecule spin site consists of a nuclear spin coupled via a Hyperfine interaction to an electron spin. The electron spin of each molecule is in a quartet ground state $S=3/2$. Neighboring molecular electron spins are coupled via a magnetic dipole interaction. We find that an all-electron construction of a quantum cellular automata is frustrated due to the degeneracy of the electronic transitions. However, we can construct a quantum celluar automata quantum computing architecture using these molecules by encoding the quantum information on the nuclear spins while using the electron spins as a local bus. We deduce the NMR and ESR pulses required to execute the basic cellular automata operation and obtain a rough figure of merit for the the number of gate operations per decoherence time. We find that this figure of merit compares well with other physical quantum computer proposals. We argue that the proposed architecture meets well the first four DiVincenzo criteria and we outline various routes towards meeting the fifth criteria: qubit readout.Comment: 16 pages, Latex, 5 figures, See http://planck.thphys.may.ie/QIPDDF/ submitted to Phys. Rev.

An Approach to the Cosmological Constant Problem(s)

We propose an approach to explaining why naive large quantum fluctuations are not the right estimate for the cosmological constant. We argue that the universe is in a superposition of many vacua, in such a way that the resulting fluctuations are suppressed by level repulsion to a very small value. The approach combines several aspects of string theory and the early history of the universe, and is only valid if several assumptions hold true. The approach may also explain why the effective cosmological constant reamins small as the universe evolves though several phase transitions. It provides a non-anthropic mechansim leading to a small, non-zero cosmological constant.Comment: Talk given at Rencontres de Moriond, 2004 by G.L. Kan

Physicochemical study of spiropyran-terthiophene derivatives: photochemistry and thermodynamics

The photochemistry and thermodynamics of two terthiophene (TTh) derivatives bearing benzospiropyran (BSP) moieties, 1-(3,3’’-dimethylindoline-6’-nitrobenzospiropyranyl)-2-ethyl 4,4’’-didecyloxy-2,2’:5’,2’’-terthiophene-3’-acetate (BSP-2) and 1-(3,3’’-dimethylindoline-6’-nitrobenzospiropyranyl)-2-10 ethyl 4,4’’-didecyloxy-2,2’:5’,2’’-terthiophene-3’-carboxylate (BSP-3), differing only by a single methylene spacer unit, have been studied. The kinetics of photogeneration of the equivalent merocyanine (MC) isomers (MC-2 and MC-3, respectively), the isomerisation properties of MC-2 and MC-3, and the thermodynamic parameters have been studied in cetonitrile, and compared to the parent, non-TThfunctionalised, benzospiropyran derivative, BSP-1. Despite the close structural similarity of BSP-2 and 15 BSP-3, their physicochemical properties were found to differ significantly; examples include activation energies (Ea(MC-2) = 75.05 KJ mol-1, Ea(MC-3) = 100.39 kJ mol-1) and entropies of activation (S‡ MC-2 = - 43.38 J K-1 mol-1, S‡ MC-3 = 37.78 J K-1 mol-1) for the thermal relaxation from MC to BSP, with the MC-3 value much closer to the unmodified MC-1 value (46.48 J K -1 mol-1) for this latter quantity. The thermal relaxation kinetics and solvatochromic behaviour of the derivatives in a range of solvents of 20 differing polarity (ethanol, dichloromethane, acetone, toluene and diethyl ether) are also presented. Differences in the estimated values of these thermodynamic and kinetic parameters are discussed with reference to the molecular structure of the derivatives