bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of genetic variability in populations of two chromosomal races of Dichroplus pratensis (Melanoplinae, Acrididae) and their hybrid zone
Authors: Chiappero M. B. , Parise C. , Martí D. A. , Bidau C. J. , Gardenal C. N.
Published: January 2004

We examined, through allozyme electrophoresis, the genetic structure of populations of the acridid grasshopper Dichroplus pratensis from two chromosomal races (Northern and Southern) and their hybrid zone in Argentina. No fixed alleles for any particular race were found, although genetic differentiation among parental races was significant (θ = 0.044, 95% CI: 0.004–0.068). Hybrid populations are genetically more similar to the Southern race (θ = 0.008, 95% CI: −0.005–0.018) than to Northern ones (θ = 0.018, 95% CI: 0.002–0.030). Differential viability or fertility of hybrids, or asymmetry in mating preferences in favour of one particular cross would cause a higher proportion of matings between hybrid individuals and those from the Southern race. This would explain the high genetic similarity between those groups, in spite of their geographical vicinity with northern race populations.
Homology, behaviour and spider webs: web construction behaviour of Linyphia hortensis and L. triangularis (Araneae: Linyphiidae) and its evolutionary significance
Authors: Benjamin S. P. , Zschokke S.
Published: January 2004

Linyphiidae is the second largest family of spiders. Using Linyphia hortensis and L. triangularis, we describe linyphiid sheet-web construction behaviour. Orb-web construction behaviour is reviewed and compared with that of nonorb-weaving orbicularians. Phylogenetic comparisons and the biogenetic law are applied to deduce behavioural homology. Linyphia webs were constructed gradually and in segments over a period of many days and had a long lifespan. Two construction behaviours, supporting structure and sticky thread (ST) (within the sheet) were observed. ST construction behaviour in linyphiids is considered homologous to sticky spiral construction in orb-weavers. Overall web construction conformed to the pattern of alternate construction of sticky and nonsticky parts as observed in theridiids. Linyphiids had no problem in switching between structure construction and ST construction even during a single behavioural bout. Both web construction behaviours in linyphiids were nonstereotypic, which is unusual in orbicularians. This might be due to the loss of control mechanisms at genetic level, probably by macro mutation. Lack of stereotypic behaviour might have played a substantial role in the origin of the diverse web forms seen in nonorb-weaving orbicularians. This hypothesis is consistent with patterns observed in the orbicularian phylogeny.
MHC-linked susceptibility to a bacterial infection, but no MHC-linked cryptic female choice in whitefish
Authors: Wedekind C. , Walker M. , Portmann J. , Cenni B. , Müller R. , Binz T.
Published: January 2004

Non-random gamete fusion is one of several potential cryptic female choice mechanisms that have been postulated and that may enhance the survival probability of the offspring. Previous studies have found that gamete fusion in mice is influenced by genes of the major histocompatibility complex (MHC) region. Here we test (i) whether there is MHC-dependent gamete fusion in whitefish (Coregonus sp.) and (ii) whether there is a link between the MHC and embryo susceptibility to an infection by the bacterium Pseudomonas fluorescens. We experimentally bred whitefish and reared sibships in several batches that either experienced or did not experience strong selection by P. fluorescens. We then determined the MHC class II B1 genotype of 1016 surviving larvae of several full sibships. We found no evidence for MHC-linked gamete fusion. However, in one of seven sibships we found a strong connection between the MHC class II genotype and embryo susceptibility to P. fluorescens. This connection was still significant after correcting for multiple testing. Hence, the MHC class II genotype can considerably influence embryo survival in whitefish, but gamete fusion seems to be random with respect to the MHC.
Predicting shielding constants in solution using gauge invariant atomic orbital theory and the effective fragment potential method
Authors: Freitag Mark A. , Hillman Brandon , Agrawal Anubhav , Gordon Mark S.
Published: January 2004

A method to approximate ab initio shielding constants is presented, in which the ab initio density matrix is replaced in the gauge invariant atomic orbital formalism with the density matrix resulting from an effective fragment potential calculation. The resulting first-order density matrix is then iterated to self-consistency. The method is compared with fully ab initio gauge invariant atomic orbital restricted Hartree–Fock calculations on hydrogen chloride, water, and ammonia solutes with up to nine solvent water molecules using the 6-31G, 6-31G(d,p), and 6-31+G(d,p) basis sets. Using the 6-31G(d,p) basis sets, the average of the average absolute deviations for the three environments tested is 0.34 ppm. This is sufficiently accurate to allow for the identification of specific H1 nuclei in a solvated molecule when the chemical shift between nuclei is not less than 1 ppm. The success of the method at this level of approximation is due to a cancellation of errors between the paramagnetic and diamagnetic terms of the shielding constant: the diamagnetic term is underestimated by roughly the same amount that the paramagnetic term is overestimated.
Surface-plasmon-resonance-enhanced cavity ring-down detection
Authors: Pipino Andrew C. R. , Woodward John T. , Meuse Curtis W. , Silin Vitalii
Published: January 2004

The cavity ring-down technique is used to probe the absolute optical response of the localized surface plasmon resonance (SPR) of a gold nanoparticle distribution to adsorption of trichloroethylene (TCE) and perchloroethylene (PCE) from the gas phase. Extended Mie theory for a coated sphere with a particle-size-dependent dielectric function is used to elucidate size-dispersion effects, the size-dependence of the SPR sensitivity to adsorption, and the kinetics of adsorption. An approximate Gaussian distribution of nanospheres with a mean diameter of 4.5 nm and a standard deviation of 1.1 nm, as determined by atomic force microscopy, is provided by the intrinsic granularity of an ultrathin, gold film, having a nominal thickness of ≈0.18 nm. The cavity ring-down measurements employ a linear resonator with an intracavity flow cell, which is formed by a pair of ultrasmooth, fused-silica optical flats at Brewster’s angle, where the Au film is present on a single flat. The total system intrinsic loss is dominated by the film extinction, while the angled flats alone contribute only ≈5×10−5/flat to the total loss. Based on a relative ring-down time precision of 0.1% for ensembles averages of 25 laser shots from a pulsed optical parametric oscillator, the minimum detectable concentrations of PCE and TCE obtained by probing the SPR response are found to be 2 and 7×10−8 mol/L, respectively, based on a 30 s integration time.
Electron and nuclear dynamics of molecular clusters in ultraintense laser fields. I. Extreme multielectron ionization
Authors: Last Isidore , Jortner Joshua
Published: January 2004

In this paper we present a theoretical and computational study of extreme multielectron ionization (involving the stripping of all the electrons from light, first-row atoms, and the production of heavily charged ions, e.g., Xe+q (q⩽36) from heavy atoms) in elemental and molecular clusters of Xen,(D2)n, and (CD4)n (n=55–1061) in ultraintense (intensity I=1015–1019 W cm−2) laser fields. Single atom or molecule multielectron ionization can be adequately described by the semiclassical barrier suppression ionization (BSI) mechanism. Extreme cluster multielectron ionization is distinct from that of a single atomic or molecular species in terms of the mechanisms, the ionization level and the time scales for electron dynamics and for nuclear motion. The novel compound mechanism of cluster multielectron ionization, which applies when the cluster size (radius R0) considerably exceeds the barrier distance for the BSI of a single constituent, involves a sequential-parallel, inner-outer ionization. The cluster inner ionization driven by the BSI for the constituents is induced by a composite field consisting of the laser field and inner fields. The energetics and dynamics of the system consisting of high energy (⩽3 keV) electrons and of ≲100 keV ions in the laser field was treated by molecular dynamics simulations, which incorporate electron–electron, electron–ion, ion–ion, and charge-laser interactions. High-energy electron dynamics also incorporates relativistic effects and includes magnetic field effects. We treat inner ionization considering inner field ignition, screening and fluctuation contributions as well as small [(⩽13%)] impact ionization contributions. Subsequent to inner ionization a charged nanoplasma is contained within the cluster, whose response to the composite (laser+inner) field results in outer ionization, which can be approximately described by an entire cluster barrier suppression ionization mechanism.
A fully self-consistent treatment of collective fluctuations in quantum liquids
Authors: Rabani Eran , Reichman David R.
Published: January 2004

The problem of calculating collective density fluctuations in quantum liquids is revisited. A fully quantum mechanical self-consistent treatment based on a quantum mode-coupling theory [E. Rabani and D.R. Reichman, J. Chem. Phys. 116, 6271 (2002)] is presented. The theory is compared with the maximum entropy analytic continuation approach and with available experimental results. The quantum mode-coupling theory provides semiquantitative results for both short and long time dynamics. The proper description of long time phenomena is important in future study of problems related to the physics of glassy quantum systems, and to the study of collective fluctuations in Bose fluids.
DFT:B3LYPab initiomolecular dynamics study of the Zundel and Eigen proton complexes, H5O2+ and H9O4+, in the triplet state in gas phase and solution
Authors: Tulub Alexander A.
Published: January 2004

DFT:B3LYP ab initio molecular dynamics (MD) approach is used to elucidate the properties of the Zundel and Eigen, H5O2+ and H9O4+, proton complexes in the triplet state. The simulation considers the complexes in the gas phase (isolated complexes) and inside the clusters composed of 32, 64, and 128 water molecules, mimicking the behavior of aqueous solutions. MD simulations reveal three distinct periods. For the complex in solutions, the periods are smoothed out. The H5O2+ and H9O4+ complexes in the triplet state undergo structural rearrangements, which eventually result in hydrogen elimination. For the H5O2+, the hydrogen is eliminated from the center of the water cluster, whereas for the H9O4+ it is removed from a near-surface water molecule. The rate of hydrogen elimination decreases with increasing the number of water molecules surrounding the complex.
The dynamics of endohedral complex formation in surface pick-up scattering as probed by kinetic energy distributions: Experiment and model calculation for Cs@C60+
Authors: Kaplan A. , Manor Y. , Bekkerman A. , Tsipinyuk B. , Kolodney E.
Published: January 2004

Endohedral Cs@C60 molecules were formed by implanting low energy (E0=30–220 eV) Cs+ ions into C60 molecules adsorbed on gold. Both growth and etching experiments of the surface deposited C60 layer provide clear evidence for a submonolayer coverage. The Cs+ penetration and Cs@C60 ejection stages are shown to be a combined, single collision event. Thermal desorption measurements did not reveal any Cs@C60 left on the surface following the Cs+ impact. The Cs@C60 formation/ejection event therefore constitutes a unique example of a pick-up scattering by endocomplex formation. Kinetic energy distributions (KEDs) of the outgoing Cs@C60+ were measured for two different Cs+ impact energies under field-free conditions. The most striking observation is the near independence of the KEDs on the Cs+ impact energy. Both KEDs peak around 1.2 eV with similar line shapes. A simple model for the formation/ejection/fragmentation dynamics of the endohedral complex is proposed. The model leads to a strong correlation between the vibrational and kinetic energy of the outgoing Cs@C60. The KEDs are calculated taking into account the competition between the various decay processes: fragmentation and delayed ionization of the neutral Cs@C60 emitted from the surface, fragmentation of the Cs@C60+ ion, and radiative cooling. It is concluded that the measured KEDs are heavily biased by the experimental breakdown function. Good agreement between experimental and calculated KEDs is obtained.
The chemical shifts of Xe in the cages of clathrate hydrate Structures I and II
Authors: Stueber Dirk , Jameson Cynthia J.
Published: January 2004

We report, for the first time, a calculation of the isotropic NMR chemical shift of Xe129 in the cages of clathrate hydrates Structures I and II. We generate a shielding surface for Xe in the clathrate cages by quantum mechanical calculations. Subsequently this shielding surface is employed in canonical Monte Carlo simulations to find the average isotropic Xe shielding values in the various cages. For the two types of cages in clathrate hydrate Structure I, we find the intermolecular shielding values [σ(Xe@512 cage)−σ(Xe atom)]=−214.0 ppm, and [σ(Xe@51262 cage)−σ(Xe atom)]=−146.9 ppm, in reasonable agreement with the values −242 and −152 ppm, respectively, observed experimentally by Ripmeester and co-workers between 263 and 293 K. For the 512 and 51264 cages of Structure II we find [σ(Xe@512 cage)−σ(Xe atom)]=−206.7 ppm, and [σ(Xe@51264 cage)−σ(Xe atom)]=−104.7 ppm, also in reasonable agreement with the values −225 and −80 ppm, respectively, measured in a Xe-propane type II mixed clathrate hydrate at 77 and 220–240 K by Ripmeester et al.
Spatial regimes in the dynamics of polyolefins: Collective motion
Authors: Neelakantan Arun , Maranas Janna K.
Published: January 2004

Molecular simulation is used to characterize the spatial dependence of collective motion in four saturated hydrocarbon polymers. The observable is the distinct intermediate scattering function, as measured in coherent quasielastic neutron scattering experiments. Ranges of 0.01–1000 ps in time and 2–14 Å in spatial scale are covered. In this time range, a two-step relaxation, consisting of a fast exponential decay and a slower stretched decay, is observed for all spatial scales. The relaxation times for the fast process are very similar to those obtained by following self motion, with a small modulation of relaxation times near the peak in the static structure factor which is well described by the narrowing picture suggested by de Gennes. For the slow process, self and collective relaxation times have larger numerical differences and follow different scaling with spatial scale. The modulation of slow relaxation times is larger than that observed for the fast process, but is overestimated by the de Gennes prediction, which only works qualitatively.
Environmental swap energy and role of configurational entropy in transfer of small molecules from water into alkanes
Authors: Smejtek Pavel , Word Robert C.
Published: January 2004

We studied the effect of segmented solvent molecules on the free energy of transfer of small molecules from water into alkanes (hexane, heptane, octane, decane, dodecane, tetradecane, and hexadecane). For these alkanes we measured partition coefficients of benzene, 3-methylindole (3MI), 2,3,4,6-tetrachlorophenol (TeCP), and 2,4,6-tribromophenol (TriBP) at 3, 11, 20, 3, and 47 °C. For 3MI, TeCP, and TriBP the dependence of free energy of transfer on length of alkane chains was found to be very different from that for benzene. In contrast to benzene, the energy of transfer for 3MI, TeCP, and TriBP was independent of the number of carbons in alkanes. To interpret data, we used the classic Flory–Huggins (FH) theory of concentrated polymer solutions for the alkane phase. For benzene, the measured dependence of energy of transfer on the number of carbons in alkanes agreed well with predictions based on FH model in which the size of alkane segments was obtained from the ratio of molar volumes of alkanes and the solute. We show that for benzene, the energy of transfer can be divided into two components, one called environmental swap energy (ESE), and one representing the contribution of configurational entropy of alkane chains. For 3MI, TeCP, and TriBP the contribution of configurational entropy was not measurable even though the magnitude of the effect predicted from the FH model for short chain alkanes was as much as 20 times greater than experimental uncertainties. From the temperature dependence of ESE we obtained enthalpy and entropy of transfer for benzene, 3MI, TeCP, and TriBP. Experimental results are discussed in terms of a thermodynamic cycle considering creation of cavity, insertion of solute, and activation of solute-medium attractive interactions. Our results suggest that correcting experimental free energy of transfer by Flory–Huggins configurational entropy term is not generally appropriate and cannot be applied indiscriminately.
Energy conserving approximations to the quantum potential: Dynamics with linearized quantum force
Authors: Garashchuk Sophya , Rassolov Vitaly A.
Published: January 2004

Solution of the Schrödinger equation within the de Broglie–Bohm formulation is based on propagation of trajectories in the presence of a nonlocal quantum potential. We present a new strategy for defining approximate quantum potentials within a restricted trial function by performing the optimal fit to the log-derivatives of the wave function density. This procedure results in the energy-conserving dynamics for a closed system. For one particular form of the trial function leading to the linear quantum force, the optimization problem is solved analytically in terms of the first and second moments of the weighted trajectory distribution. This approach gives exact time-evolution of a correlated Gaussian wave function in a locally quadratic potential. The method is computationally cheap in many dimensions, conserves total energy and satisfies the criterion on the average quantum force. Expectation values are readily found by summing over trajectory weights. Efficient extraction of the phase-dependent quantities is discussed. We illustrate the efficiency and accuracy of the linear quantum force approximation by examining a one-dimensional scattering problem and by computing the wavepacket reaction probability for the hydrogen exchange reaction and the photodissociation spectrum of ICN in two dimensions.
Non-Gaussian statistics of amide I mode frequency fluctuation of N-methylacetamide in methanol solution: Linear and nonlinear vibrational spectra
Authors: Kwac Kijeong , Lee Hochan , Cho Minhaeng
Published: January 2004

By carrying out molecular dynamics simulations of an N-methylacetamide (NMA) in methanol solution, the amide I mode frequency fluctuation and hydrogen bonding dynamics were theoretically investigated. Combining an extrapolation formula developed from systematic ab initio calculation studies of NMA–(CH3OH)n clusters with a classical molecular dynamics simulation method, we were able to quantitatively describe the solvatochromic vibrational frequency shift induced by the hydrogen-bonding interaction between NMA and solvent methanol. It was found that the fluctuating amide I mode frequency distribution is notably non-Gaussian and it can be decomposed into two Gaussian peaks that are associated with two distinctively different solvation structures. The ensemble-average-calculated linear response function associated with the IR absorption is found to be oscillating, which is in turn related to the doublet amide I band shape. Numerically calculated infrared absorption spectra are directly compared with experiment and the agreement was found to be excellent. By using the Onsager’s regression hypothesis, the rate constants of the interconversion process between the two solvation structures were obtained. Then, the nonlinear response functions associated with two-dimensional infrared pump–probe spectroscopy were simulated. The physics behind the two-dimensional line shape and origin of the cross peaks in the time-resolved pump–probe spectra is explained and the result is compared with 2D spectra experimentally measured recently by Woutersen et al. [S. Woutersen, Y. Mu, G. Stock, and P. Hamm, Chem. Phys. 266, 137 (2001)].
Adsorption, desorption, and clustering of H2O on Pt(111)
Authors: Daschbach John L. , Peden Brandon M. , Smith R. Scott , Kay Bruce D.
Published: January 2004

The adsorption, desorption, and clustering behavior of H2O on Pt(111) has been investigated by specular He scattering. The data show that water adsorbed on a clean Pt(111) surface undergoes a structural transition from a random distribution to clustered islands near 60 K. The initial helium scattering cross sections as a function of temperature are found to be insensitive to the incident H2O flux over a range of 0.005 monolayers (ML)/s–0.55 ML/s indicating that the clustering process is more complex than simple surface diffusion. The coarsening process of an initially random distribution of water deposited at 25 K is found to occur over a broad temperature range, 60<T<140 K, during thermal annealing. The desorption kinetics for submonolayer water are determined to be zero order for surface coverages greater than 0.05 ML and temperatures between 145 and 172 K. The zero-order desorption kinetics are consistent with a two-dimensional two-phase coexistence between a high-density H2O condensed phase (islands) and a low-density two-dimensional gaslike phase on the Pt surface.
Wavelet treatment of structure and thermodynamics of simple liquids
Authors: Chuev G. N. , Fedorov M. V.
Published: January 2004

A new algorithm is developed to solve integral equations for simple liquids. The algorithm is based on the discrete wavelet transform of radial distribution functions. The Coifman 2 basis set is employed for the wavelet treatment. To solve integral equations we have applied the combined scheme in which the coarse part of the solution is calculated by wavelets, while the fine part by the direct iterations. Tests on the PY and HNC approximations have indicated that the proposed procedure is more effective than the conventional method based on the hybrid algorithm. Possibilities for application of the method to molecular liquids and mixed quantum-classical systems are discussed.
Experimental CC stretching phonon dispersion curves and electron phonon coupling in polyene derivatives
Authors: Bianco A. , Del Zoppo M. , Zerbi G.
Published: January 2004

We analyze the infrared and Raman spectra (both experimentally and with the aid of quantum chemical calculations) of a series of polyenals which provide us with the fortunate case of a set of polyene chains with one of the end groups consisting of a C=O group which not only does take part in the conjugation but also pulls electrons from the chain making the whole system highly polar, thus affecting the vibrational transition moments. In the following we show, for the first time, that it is possible to derive experimental phonon dispersion curves and these prove to be different for each chain length. We support our experimental findings with Density Functional Theory quantum chemical calculations which reproduce with sufficient accuracy the IR and Raman spectral pattern and at the same time help in disentangling the assignment of the fine structure observed in the experimental spectra.
Comment on “An interpretation of the low-frequency spectrum of liquid water” [J. Chem. Phys. 118, 452 (2003)]
Authors: De Santis Alberto , Ercoli Alessandro , Rocca Dario
Published: January 2004

The comparison between the translational densities of states of water and argon suggests that the water bands at about 60 and 240 cm−1 reflect the transverse and longitudinal dynamics, respectively. The water–argon similarity and the role of the hydrogen bonds in producing more intense and sharp bands are highlighted. Our interpretation partially contradicts that of the authors of the title article.
Response to “Comment on ‘An interpretation of the low-frequency spectrum of liquid water’ ” [J. Chem. Phys. 118, 452 (2003)]
Authors: Padró Joań Àngel , Martı́ Jordi
Published: January 2004

We remark the fact that even if the frequency peak around 60 cm−1 in the low-frequency spectrum of liquid water at room temperature can have a transversal component, it is a general feature of all sorts of liquids at ambient conditions. Conversely, the frequency around 170 cm−1 is only present in the spectra of associated liquids at ambient conditions, since although this mode is seen in the spectra of simple nonassociated liquids at supercooled states, it vanishes as temperature rises.
Interfacial statistical geometry: Fluids adsorbed in wedges and at edges
Authors: Henderson J. R.
Published: January 2004

An exact sum rule is derived that links the structure of fluids adsorbed in wedges and at edges to the interfacial free energy far from the wedge apex. By focusing on hard-wall models, one observes a correspondence between interfacial statistical mechanics and geometry. The physical necessity of this correspondence can be argued from the presence of complete drying at a hard wall. Invoking the potential distribution theorem generates yet another class of geometric results, this time concerning the excluded volume generated by a sphere rolling along the surface of the wedge. Direct proof of these latter geometric theorems is straightforward in two-dimensions. Acute wedges and the right-angled wedge, provide examples of models for which comparison with simulation data and density functional theory are available.
Isotropic-liquid crystalline phase diagram of a CdSe nanorod solution
Authors: Li Liang-shi , Marjanska Malgorzata , Park Gregory H. J. , Pines Alexander , Alivisatos A. Paul
Published: January 2004

We report the isotropic-liquid crystalline phase diagram of 3.0 nm×60 nm CdSe nanorods dispersed in anhydrous cyclohexane. The coexistence concentrations of both phases are found to be lower and the biphasic region wider than the results predicted by the hard rod model, indicating that the attractive interaction between the nanorods may be important in the formation of the liquid crystalline phase in this system.
Capillary force in atomic force microscopy
Authors: Jang Joonkyung , Schatz George C. , Ratner Mark A.
Published: January 2004

Under ambient conditions, a water meniscus generally forms between a nanoscale atomic force microscope tip and a hydrophilic surface. Using a lattice gas model for water and thermodynamic integration methods, we calculate the capillary force due to the water meniscus for both hydrophobic and hydrophilic tips at various humidities. As humidity rises, the pull-off force rapidly reaches a plateau value for a hydrophobic tip but monotonically increases for a weakly hydrophilic tip. For a strongly hydrophilic tip, the force increases at low humidities (<30%) and then decreases. We show that mean-field density functional theory reproduces the simulated pull-off force very well.
Rules for minimal atomic multipole expansion of molecular fields
Authors: Tsiper E. V. , Burke K.
Published: January 2004

A nonempirical minimal atomic multipole expansion (MAME) defines atomic charges or higher multipoles that reproduce electrostatic potential outside molecules. MAME eliminates problems associated with redundancy and with statistical sampling, and produces atomic multipoles in line with chemical intuition.
Triplet Lifetimes, Solvent, and Intramolecular Capture of Isoxazolones
Authors: Ang Kiah H. , Cox Matthew , Lawrance Warren D. , Prager Rolf , Smith Jason A. , Staker Warren
Published: January 2004

The first step in the photochemical decarboxylation of isoxazolones is the formation of the triplet state of the isoxazolone. We present evidence for the first time from flash laser photolysis of the lifetime of such species, and examples of their capture by solvent and by intramolecular cycloaddition.
Taxane Diterpene Synthesis Studies. Part 2: Towards Taxinine—Enantiospecific Construction of an AB-ring Substructure Incorporating both Quaternary Carbon Centres and Attempts to Annulate the C-ring
Authors: Banwell Martin G. , McLeod Malcolm D. , Riches Andrew G.
Published: January 2004

In connection with efforts to develop an efficient total synthesis of the biologically active natural product taxinine 1, the enzymatically-derived and monochiral cis-1,2-dihydrocatechol 7 was converted, over several steps including a Diels–Alder cycloaddition reaction, into the bicyclo[2.2.2]octan-2-one 18. Reaction of the last compound with the organocerium reagent 22 afforded the 1,5-diene 23 which engaged in an anionic oxy-Cope rearrangement reaction to give, after C-methylation of the product enolate 25, bicyclo[5.3.1]undecenone 27 embodying the AB-ring system of target 1. Two methods for allylic oxidation of such products were developed and several unsuccessful attempts to effect a cyclization reaction so as to establish the taxane C-ring are described.
Molecular Modelling and Design of Radiolabelled Complexes for Melanoma Diagnosis
Authors: Tuttle C. T. Tell , Seabrook Shane A. , Wise Lauren E. , Katsifis Andrew , Knott Robert B. , Yates Brian F.
Published: January 2004

Molecular modelling has been used to analyze a database of compounds with known binding affinities for the integrin receptors αVβ3 and αIIbβ3. We describe how a variety of novel radiolabelled compounds (specifically 131I labelled) were designed and how the binding affinity of these compounds to the two integrin receptors was predicted. The selectivity for the αVβ3 receptor has also been predicted and a summary of some of the best candidates for positron emission tomography (PET) imaging is provided. This work will have significant implications for the development of diagnostic (and possibly therapeutic) drugs for melanomas.
A Three Component Metalloporphyrin Assembly
Authors: Langford Steven J. , Lau Vei-Lin
Published: January 2004

A novel dialkylammonium salt 1 · PF6, bearing a pyridyl group, has been employed as a structural motif for the efficient one-pot self-assembly of a three-component system comprising dibenzo-[24]crown-8, 1 · PF6, and zinc(II) 5,10,15,20-tetraphenylporphyrin. The resulting metalloporphyrin assembly has been characterized in solution by 1H NMR spectroscopy and ESIMS and serves as a model to more elaborate multichromophoric systems.
Cell swelling, heat, and chemical agonists use distinct pathways for the activation of the cation channel TRPV4
Authors: Vriens J. , Watanabe H. , Janssens A. , Droogmans G. , Voets T. , Nilius B.
Published: January 2004

TRPV4 is a Ca
2+
- and Mg
2+
-permeable cation channel within the vanilloid receptor subgroup of the transient receptor potential (TRP) family, and it has been implicated in Ca
2+
-dependent signal transduction in several tissues, including brain and vascular endothelium. TRPV4-activating stimuli include osmotic cell swelling, heat, phorbol ester compounds, and 5′,6′-epoxyeicosatrienoic acid, a cytochrome P450 epoxygenase metabolite of arachidonic acid (AA). It is presently unknown how these distinct activators converge on opening of the channel. Here, we demonstrate that blockers of phospholipase A
2
(PLA
2
) and cytochrome P450 epoxygenase inhibit activation of TRPV4 by osmotic cell swelling but not by heat and 4α-phorbol 12,13-didecanoate. Mutating a tyrosine residue (Tyr-555) in the N-terminal part of the third transmembrane domain to an alanine strongly impairs activation of TRPV4 by 4α-phorbol 12,13-didecanoate and heat but has no effect on activation by cell swelling or AA. We conclude that TRPV4-activating stimuli promote channel opening by means of distinct pathways. Cell swelling activates TRPV4 by means of the PLA
2
-dependent formation of AA, and its subsequent metabolization to 5′,6′-epoxyeicosatrienoic acid by means of a cytochrome P450 epoxygenase-dependent pathway. Phorbol esters and heat operate by means of a distinct, PLA
2
- and cytochrome P450 epoxygenase-independent pathway, which critically depends on an aromatic residue at the N terminus of the third transmembrane domain.
Stimulatory and inhibitory protein kinase C consensus sequences regulate the cystic fibrosis transmembrane conductance regulator
Authors: Chappe Valerie , Hinkson Deborah A. , Howell L. Daniel , Evagelidis Alexandra , Liao Jie , Chang Xiu-Bao , Riordan John R. , Hanrahan John W.
Published: January 2004

Protein kinase C (PKC) phosphorylation stimulates the cystic fibrosis transmembrane conductance regulator (CFTR) channel and enhances its activation by protein kinase A (PKA) through mechanisms that remain poorly understood. We have examined the effects of mutating consensus sequences for PKC phosphorylation and report here evidence for both stimulatory and inhibitory sites. Sequences were mutated in subsets and the mutants characterized by patch clamping. Activation of a 4CA mutant (S707A/S790A/T791A/S809A) by PKA was similar to that of wild-type CFTR and was enhanced by PKC, whereas responses of 3CA (T582A/T604A/S641A) and 2CA (T682A/S686A) channels to PKA were both drastically reduced (>90%). When each mutation in the 3CA and 2CA constructs was studied individually in a wild-type background, T582, T604, and S686 were found to be essential for PKA activation. Responses were restored when these three residues were reintroduced simultaneously into a 9CA mutant lacking all nine PKC consensus sequences (R6CA revertant); however, PKC phosphorylation was not required for this rescue. Nevertheless, two of the sites (T604 and S686) were phosphorylated
in vitro
, and PKC alone partially activated wild-type CFTR, the 4CA mutant, and the point mutants T582A and T604A, but not S686A channels, indicating that PKC does act at S686. The region encompassing S641 and T682 is inhibitory, because S641A enhanced activation by PKA, and T682A channels had 4-fold larger responses to PKC compared to wild-type channels. These results identify functionally important PKC consensus sequences on CFTR and will facilitate studies of its convergent regulation by PKC and PKA.
Neurotoxic effects of polymorphonuclear granulocytes on hippocampal primary cultures
Authors: Dinkel Klaus , Dhabhar Firdaus S. , Sapolsky Robert M.
Published: January 2004

Many neurological insults and neurodegenerative disorders are accompanied by an acute inflammatory reaction that can contribute to neuronal damage. This inflammation involves infiltration of bloodborne polymorphonuclear leukocytes (PMNs) into the injured brain area. The role of inflammation in brain injury, however, is controversial, because recent studies suggest that inflammation may actually be beneficial in the recovery from brain damage. Therefore, we investigated the effects of pathophysiologically relevant concentrations of PMNsin vitroon mixed hippocampal primary cultures. Rat PMNs and peripheral blood lymphocytes were isolated by density centrifugation and cocultured with hippocampal cells for 24-72 h plus or minus an excitotoxic insult (50 μM kainic acid) or 6-h oxygen glucose deprivation. Cell death was analyzed by immunocytochemistry, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and neuron-specific [2,2′-azino-bis(ethylbenzothiazoline-6-sulfonic acid)] assay. After 3 days of coculture in the absence of insult, PMNs caused massive neuron loss and dramatic morphological changes in glial cells (astrocyte detachment, aggregation). Furthermore PMNs exacerbated kainic acid- and oxygen glucose deprivation-induced neuron death by 20-30%. The cytotoxic effect of PMNs required heterocellular contact and were ameliorated by protease inhibitors. Lymphocytes, on the other hand, were not neurotoxic, but, instead, increased astrocyte proliferation. These findings suggest that PMN might represent a harmful part of inflammation after brain injury that can contribute to secondary damage.
The genomic arrangement of T cell receptor variable genes is a determinant of the developmental rearrangement pattern
Authors: Xiong Na , Baker Jeanne E. , Kang Chulho , Raulet David H.
Published: January 2004

Developmentally regulated V(D)J recombination profoundly influences immune repertoires, but the underlying mechanisms are poorly understood. In the endogenous T cell receptor Cγ1 cluster, the 3′ Vγ3 gene (closest to Jγ1) rearranges preferentially in the fetal period whereas rearrangement of the 5′ Vγ2 gene predominates in the adult. Reversing the positions of the Vγ2 and Vγ3 genes in a genomic transgene resulted in decreased rearrangement of the now 5′ Vγ3 gene in the fetal thymus and increased rearrangement of the now 3′ Vγ2 gene. The reversed rearrangement pattern was not accompanied by significant changes in chromatin accessibility of the relocated Vγ genes. The results support a model in which the 3′ location is the key determinant of rearrangement in the fetus, after which there is a promoter-dependent inactivation of Vγ3 rearrangement in favor of Vγ2 rearrangement.
Dynamic alterations in the conformation of the
Ifng
gene region during T helper cell differentiation
Authors: Eivazova Elvira R. , Aune Thomas M.
Published: January 2004

Gene expression and silencing in eukaryotic systems can be controlled by regulatory elements acting over a distance. Here, we analyze chromatin conformation of the 24-kb region of the
Ifng
gene during CD4
+
T helper (Th) cell differentiation. We find that chromatin within this region is a highly flexible structure that undergoes dynamic changes during the course of transcriptional activation and silencing of the
Ifng
gene. Each Th subset displays a common core conformation in this gene region and unique features that distinguish neutral and effector Th1 and Th2 lineages. This chromatin configuration brings distal regions into close proximity to the gene. Th1 cells that produce high levels of IFN-γ display the most open conformation. In contrast, IFN-γ silent Th2 cells have a tightly closed conformation. Therefore, we postulate that there is a direct structure–function relationship between the spatial organization of the chromatin around the
Ifng
gene and its transcriptional potential.
Chronic exposure to nitric oxide alters the free iron pool in endothelial cells: Role of mitochondrial respiratory complexes and heat shock proteins
Authors: Ramachandran Anup , Ceaser Erin , Darley-Usmar Victor M.
Published: January 2004

The mechanisms of nitric oxide (NO) signaling include binding to the iron centers in soluble guanylate cyclase and cytochromecoxidase and posttranslational modification of proteins by S-nitrosation. Low levels of NO control mitochondrial number in cells, but little is known of the impact of chronic exposure to high levels of NO on mitochondrial function in endothelial cells. The focus of this study is the interaction of NO with mitochondrial respiratory complexes in cell culture and the effect this has on iron homeostasis. We demonstrate that chronic exposure of endothelial cells to NO decreased activity and protein levels of complexes I, II, and IV, whereas citrate synthase and ATP synthase were unaffected. Inhibition of these respiratory complexes was accompanied by an increase in cellularS-nitrosothiol levels, modification of cysteines residues, and an increase in the labile iron pool. The NO-dependent increase in the free iron pool and inhibition of complex II was prevented by inhibition of mitochondrial protein synthesis, consistent with a major contribution of the organelle to iron homeostasis. In addition, inhibition of mitochondrial protein synthesis was associated with an increase in heat shock protein 60 levels, which may be an additional mechanism leading to preservation of complex II activity.
Heptahelical domain of metabotropic glutamate receptor 5 behaves like rhodopsin-like receptors
Authors: Goudet Cyril , Gaven Florence , Kniazeff Julie , Vol Claire , Liu Jiangfeng , Cohen-Gonsaud Martin , Acher Francine , Prézeau Laurent , Pin Jean Philippe
Published: January 2004

Although agonists bind directly in the heptahelical domain (HD) of most class-I rhodopsin-like G protein coupled receptors (GPCRs), class-III agonists bind in the extracellular domain of their receptors. Indeed, the latter possess a large extracellular domain composed of a cysteine-rich domain and a Venus flytrap module. Both the low sequence homology and the structural organization of class-III GPCRs raised the question of whether or not the HD of these receptors functions the same way as rhodopsin-like GPCRs. Here, we show that the HD of metabotropic glutamate receptor 5 (mGlu
5
) displays the same agonist-independent constitutive activity as the wild-type receptor. Moreover, we show that the noncompetitive antagonist MPEP [2-methyl-6-(phenylethynyl)-pyridine hydrochloride] and the positive allosteric modulator DFB (3,3′-difluorobenzaldazine) act as inverse agonist and full agonist, respectively, on the mGlu
5
HD in the absence of the extracellular domain. This finding illustrates that, like rhodopsin-like receptors, the HD of mGluRs can constitutively couple to G proteins and be negatively and positively regulated by ligands. These data show that the HD of mGluRs behave like any other class-I GPCRs in terms of G protein coupling and regulation by various types of ligands.
Guanylyl cyclase is an ATP sensor coupling nitric oxide signaling to cell metabolism
Authors: Ruiz-Stewart I. , Tiyyagura S. R. , Lin J. E. , Kazerounian S. , Pitari G. M. , Schulz S. , Martin E. , Murad F. , Waldman S. A.
Published: January 2004

Defending cellular integrity against disturbances in intracellular concentrations of ATP ([ATP]i) is predicated on coordinating the selection of substrates and their flux through metabolic pathways (metabolic signaling), ATP transfer from sites of production to utilization (energetic signaling), and the regulation of processes consuming energy (cell signaling). Whereas NO and its receptor, soluble guanylyl cyclase (sGC), are emerging as key mediators coordinating ATP supply and demand, mechanisms coupling this pathway with metabolic and energetic signaling remain undefined. Here, we demonstrate that sGC is a nucleotide sensor whose responsiveness to NO is regulated by [ATP]i. Indeed, ATP inhibits purified sGC with aKipredicting >60% inhibition of NO signaling in cells maintaining physiological [nucleotide]i. ATP inhibits sGC by interacting with a regulatory site that prefers ATP > GTP. Moreover, alterations in [ATP]i, by permeabilization and nucleotide clamping or inhibition of mitochondrial ATP synthase, regulate NO signaling by sGC. Thus, [ATP]iserves as a “gain control” for NO signaling by sGC. At homeostatic [ATP]i, NO activation of sGC is repressed, whereas insults that reduce [ATP]i,derepress sGC and amplify responses to NO. Hence, sGC forms a key synapse integrating metabolic, energetic, and cell signaling, wherein ATP is the transmitter, allosteric inhibition the coupling mechanism, and regulated accumulation of cGMP the response.
A deoxyribozyme that harnesses light to repair thymine dimers in DNA
Authors: Chinnapen Daniel J.-F. , Sen Dipankar
Published: January 2004

In vitro
selection was used to investigate whether nucleic acid enzymes are capable of catalyzing photochemical reactions. The reaction chosen was photoreactivation of thymine cyclobutane dimers in DNA by using serotonin as cofactor and light of wavelengths longer than the absorption spectrum of DNA. Curiously, the dominant single-stranded DNA sequence selected, UV1A, was found to repair its internal thymine dimer substrate efficiently even in the absence of serotonin or any other cofactor. UV1C, a 42-nucleotide fragment of UV1A, repaired the thymine dimer substrate
in trans
(
k
cat
/
k
uncat
= 2.5 × 10
4
), showing optimal activity with 305 nm light and thus resembling naturally occurring photolyase enzymes. Mechanistic investigation of UV1C indicated that its catalytic role likely exceeded the mere positioning of the substrate in a conformation favorable for photoreactivation. A higher-order structure, likely a quadruplex, formed by specific guanine bases within the deoxyribozyme, was implicated as serving as a light-harvesting antenna, with photoreactivation of the thymine dimer proceeding possibly via electron donation from an excited guanine base. In a primordial “RNA world,” self-replicating nucleic acid populations may have been vulnerable to deactivation via UV light-mediated pyrimidine dimer formation. Photolyase nucleic acid enzymes such as the one described here could thus have played a role in preserving the integrity of such an RNA world.
Motor training compensates for cerebellar dysfunctions caused by oligodendrocyte ablation
Authors: Collin Ludovic , Usiello Alessandro , Erbs Eric , Mathis Carole , Borrelli Emiliana
Published: January 2004

The role played by oligodendrocytes (OLs), the myelinating cells of the CNS, during brain development has not been fully explored. We have addressed this question by inducing a temporal and reversible ablation of OLs on postnatal CNS development. OL ablation in newborn mice leads to a profound alteration in the structure of the cerebellar cortex, which can be progressively rescued by newly generated cells, leading to a delayed myelination. Nevertheless, the temporal shift of the OL proliferation and myelinating program cannot completely compensate for developmental defects, resulting in impaired motor functions in the adult. Strikingly, we show that, despite these abnormalities, epigenetic factors, such as motor training, are able to fully rescue cerebellar-directed motor skills.
Pharmacogenetic rescue in time and space of the
rutabaga
memory impairment by using Gene-Switch
Authors: Mao Zhengmei , Roman Gregg , Zong Lin , Davis Ronald L.
Published: January 2004

The GAL4-based Gene-Switch system has been engineered to regulate transgene expression in
Drosophila
in both time and space. We constructed a Gene-Switch transgene in which Gene-Switch expression is restricted spatially by a defined mushroom body enhancer. This system allows Gene-Switch to be active only in the mushroom bodies and only on administration of the pharmacological Gene-Switch ligand RU486. This line was used to drive the expression of a
rutabaga
cDNA in otherwise
rutabaga
mutant flies. Induction of the
rutabaga
cDNA in the mushroom bodies only during adulthood, or during adulthood along with the larval and pupal developmental stages, corrects the olfactory memory impairment found in
rutabaga
mutants. Induction of the cDNA only during the larval and pupal stages was inconsequential to performance in olfactory memory tasks. These data indicate that normal
rutabaga
function must be expressed in adulthood for normal memory and conclusively delimit the time and space expression requirements for correcting the
rutabaga
memory impairment. Such combined pharmacogenetic regulation of transgene expression now allows this time and space dissection to be made for other behavioral mutants.