bluuebunny/crossref_metadata_2025 huggingface dataset:
A Guide to Publishing Your First Book: The Ins and Outs
of Obtaining a Book Contract
Authors: Jeydel Alana S. , Dolan Julie
Published: November 2005

As part of its mission to address issues of recruitment, retention,
and integration of women and people of color in the profession, the
APSA Task Force on Mentoring periodically publishes articles on some
aspect of mentoring that will help political scientists move
successfully through the profession. This brief symposium on
“Publishing Your First Book” is just one such example of this
initiative. For more information about the Task Force and its
ongoing projects, contact Linda Lopez, APSA Director of Education
and Professional Development Programs, at llopez@apsanet.org.

The right contract can make or break tenure and promotion. The
following article presents pearls of wisdom from David Meyer, Clyde
Wilcox, Susan Clarke, Terri Givens, Carol Swain, Robert Spitzer, and
Peter Labella. We divide these suggestions into two parts—those on
obtaining and those on negotiating a contract.
The Frontrunners—2008
Authors: Panagopoulos Costas
Published: November 2005

The final chapter on the 2004 presidential election may not yet be
written, but it is not too soon to look ahead to the 2008 contest.
Public pollsters have been assessing opinions about the 2008
campaign for months already. Given the importance of frontrunner
status in an increasingly frontloaded presidential primary system
(Mayer 2004), the 2008 race has
already begun for many prospective candidates, parties, and voters.
In this article I analyze early public opinion polling data
available from the Roper Center's IPOLL database about the 2008 race
to determine the frontrunning candidates (at least through June
2005) and to reflect on the preliminary dynamics of the next
presidential race.
Exploring Competition and Bargaining among Interest Group
Lobbyists in Washington
Authors: Holyoke Thomas T.
Published: November 2005

In 1997, lobbyists for the Independent Insurance Agents of America,
under pressure from then Senate Banking Committee Chair Alfonse
D'Amato (R-NY), threw in the towel and agreed to negotiate with
their long time enemies, the banking and Wall Street investment
industries, on new laws structuring the financial industry for the
21st century. Their compromise removed a major
legislative barrier to facilitating the emergence of large, one-stop
shopping financial corporations. More surprisingly, the Consumer
Federation of America and other public interest groups also started
bargaining over the shape of the consumer protection laws governing
these new institutions. Getting something through bargaining, they
believed, was better than letting the financial industry write these
laws themselves. Not all consumer groups participated in these
negotiations or gave support to the final bill; there were just not
enough consumer protection provisions included to please their
ideologically motivated members. Nor did every banking and insurance
agent organization support the final deal, largely because their
members felt threatened by the prospect of an industry dominated by
a few financial behemoths. Yet the final interest group coalition
that drove the Gramm-Leach-Bliley Act of 1999 across President Bill
Clinton's desk was truly surprising in its ideological breadth.
INTERNATIONAL RESERVES CRISES, MONETARY INTEGRATION, AND THE PAYMENTS SYSTEM DURING THE INTERNATIONAL GOLD STANDARD
Authors: HERNÁNDEZ-VERME PAULA
Published: November 2005

I model an international payments system with a financial center and periphery to reproduce various aspects of the International Gold Standard. This period was characterized by frequent crises associated with scarce stocks of reserves, high short-term interest rates with subsequent gold inflows, and transmission of output contractions across countries. I find that a common international currency and no legal restrictions on exchange help the periphery share reserves with the financial center, improving the world's welfare and mitigating output losses due to reserve crises. Also, the center has incentives for restrictive rediscounting while the periphery has motives for developing central banking.
Functional elements residing within satellite DNAs
Authors: Ugarkovic Durdica
Published: November 2005

Satellite DNAs represent a fast‐evolving portion of the eukaryotic genome whose evolution is proposed to be driven by the stochastic process of molecular drive. Recent results indicate that satellite DNAs are subject to certain structural constraints, which are probably related to their interaction with proteins involved in the establishment of specific chromatin structures. The evolutionary persistence and high sequence conservation of some satellites, as well as the presence of stage‐ or tissue‐specific, differentially expressed transcripts in several species, are consistent with the hypothesis that satellite DNA could have a regulatory role in eukaryotic organisms. Although the role of most transcripts is not known, some act as precursors of small interfering RNAs, which are now recognized as having an important role in chromatin modulation and the control of gene expression. Furthermore, some transcripts are involved in the cellular response to stress.
Oxygen loss, semiconductivity, and positive temperature coefficient of resistance behavior in undoped cation-stoichiometric BaTiO3 ceramics
Authors: Beltrán H. , Cordoncillo E. , Escribano P. , Sinclair D. C. , West A. R.
Published: November 2005

Stoichiometric BaTiO3 ceramics fabricated from sol-gel-derived powders and sintered at temperatures ⩽1100°C are highly insulating and electrically homogeneous. At higher sintering temperatures, samples gradually lose oxygen and the conductivity increases as a consequence. The latter phenomena are very sensitive to the furnace atmosphere and are partially reversible during cooling when partial reoxidation can occur. This results in ceramics that are often electrically heterogeneous with insulating surfaces or grain boundaries but semiconducting grain cores. In samples that were heated at 1450°C in N2 and quenched, a positive temperature coefficient of resistance (PTCR) effect was observed, associated with an additional impedance arising from space-charge effects. These results demonstrate that, depending on sample processing, insulating cation-stoichiometric BaTiO3 can instead be semiconducting and under certain circumstances, exhibit a PTCR effect, without the need for donor dopant additives.
Are azobenzenophanes rotation-restricted?
Authors: Ciminelli Cosimo , Granucci Giovanni , Persico Maurizio
Published: November 2005

We simulated the photoisomerization dynamics of an azobenzenophane with a semiclassical surface hopping approach and a semiempirical reparametrized quantum mechanics/molecular mechanics Hamiltonian. Only one of the two azobenzene chromophores in the molecule is taken into account quantum mechanically: the other one is treated by molecular mechanics. Both n→π* and π→π* excitations are considered. Our results show that the photoisomerization reaction mainly involves the rotation around the NN double bond. The excited state relaxation features are in qualitative agreement with experimental time-resolved fluorescence results.
Energy transfer in near-field optics
Authors: Colas des Francs Gérard , Girard Christian , Juan Mathieu , Dereux Alain
Published: November 2005

When the probe tip of a near-field optical microscope illuminates nanoparticles with marked absorption bands, a large number of photons are absorbed before reaching the detector. These energy losses enhance the dark contrast usually observed in the vicinity of metallic nanoparticles. We demonstrate theoretically that this phenomenon can be exploited to image, in the optical frequency range, dissipative domains with a nanometer scale resolution. Simulations performed with noble-metal particles indicate that the detected signal significantly drops down when the excitation frequency is approaching the plasmon resonance of the particles.
Mode coupling behavior of a Lennard-Jones binary mixture: A comparison between bulk and confined phases
Authors: Attili A. , Gallo P. , Rovere M.
Published: November 2005

We present a quantitative comparison at equivalent thermodynamical conditions of bulk and confined dynamical properties of a Lennard-Jones binary mixture upon supercooling. Both systems had been previously found to display a behavior in agreement with the mode coupling theory of the evolution of glassy dynamics. Differences and analogies of behavior are discussed focusing, in particular, on the role of hopping in reducing spatially correlated dynamics in the confined system with respect to the bulk.
Pair potentials from diffraction data on liquids: A neural network solution
Authors: Tóth Gergely , Király Norbert , Vrabecz Attila
Published: November 2005

The inverse theorem of liquids states a one to one correspondence between classical mechanical pair potentials and structural functions. Molecular-dynamics and Monte Carlo simulations provide exact structural functions for known pair interactions. There is no exact or widespread method in the opposite direction, where the pair interactions are to be determined from a priori known pair-correlation functions or structure factors. The methods based on the integral equation theories of liquids are approximate and the iterative refinements of pair potentials with simulations take a long time. We applied artificial neural networks to get pair interactions from known structure factors in this study. We performed molecular-dynamics simulations on one-component systems with different pair potentials and the structure factors were calculated. To optimize (train) the weights of neural networks 2000 pair interaction-structure factor pairs were used. The performance of the method was tested on further 200 data pairs. The method provided reasonable potentials for the majority of the systems opening a “quick and dirty” method to determine pair interactions.
Liquid-vapor interfacial properties of water-ammonia mixtures: Dependence on ammonia concentration
Authors: Paul Sandip , Chandra Amalendu
Published: November 2005

The equilibrium and dynamical properties of the liquid-vapor interfaces of water-ammonia mixtures are investigated by means of molecular-dynamics simulations. Altogether, we have simulated seven different systems of different concentration of ammonia. The inhomogeneous density, anisotropic orientational profiles, surface tension, and the pattern of hydrogen bonding are calculated for both water and ammonia molecules in order to characterize the location, width, thermodynamic aspects, and microscopic structure of the liquid-vapor interfaces of each of the water-ammonia systems. The dynamical aspects of the interfaces are investigated in terms of the anisotropic diffusion and dipole orientational relaxation of water and ammonia molecules. The properties of the interfaces are compared with those of the corresponding bulk phases. The present theoretical results are also compared with experimental findings wherever available.
General expression of the gyroviscous force
Authors: Ramos J. J.
Published: November 2005

Assuming only small gyromotion periods and Larmor radii compared to any other time and length scales, and retaining the lowest significant order in δ=ρi∕L⪡1, the general expression of the ion gyroviscous stress tensor is presented. This expression covers both the “fast dynamics” (or “magnetohydrodynamic”) ordering, where the time derivative and ion gyroviscous stress are first order in δ relative to the ion gyrofrequency and scalar pressure, respectively, and the “slow dynamics” (or “drift”) ordering, where the time derivative and ion gyroviscous stress are, respectively, second order in δ. This general stress tensor applies to arbitrary collisionality and does not require the distribution function to be close to a Maxwellian. Its exact divergence (gyroviscous force) is written in a closed vector form, allowing for arbitrary magnetic geometry, parallel gradients, and flow velocities. Considering, in particular, the contribution from the velocity gradient (rate of strain) term, the final form of the momentum conservation equation after the “gyroviscous cancellation” and the “effective renormalization of the perpendicular pressure by the parallel vorticity” is precisely established.
Information entropy, information distances, and complexity in atoms
Authors: Chatzisavvas K. Ch. , Moustakidis Ch. C. , Panos C. P.
Published: November 2005

Shannon information entropies in position and momentum spaces and their sum are calculated as functions of Z(2⩽Z⩽54) in atoms. Roothaan-Hartree-Fock electron wave functions are used. The universal property S=a+blnZ is verified. In addition, we calculate the Kullback-Leibler relative entropy, the Jensen-Shannon divergence, Onicescu’s information energy, and a complexity measure recently proposed. Shell effects at closed-shell atoms are observed. The complexity measure shows local minima at the closed-shell atoms indicating that for the above atoms complexity decreases with respect to neighboring atoms. It is seen that complexity fluctuates around an average value, indicating that the atom cannot grow in complexity as Z increases. Onicescu’s information energy is correlated with the ionization potential. Kullback distance and Jensen-Shannon distance are employed to compare Roothaan-Hartree-Fock density distributions with other densities of previous works.
Saturation of power transfer between two copropagating laser beams by ion-wave scattering in a single-species plasma
Authors: Kirkwood R. K. , Williams E. A. , Cohen B. I. , Divol L. , Dorr M. R. , Hittinger J. A. , Langdon A. B. , Niemann C. , Moody J. , Suter L. J. , Landen O. L.
Published: November 2005

Experiments show that power is transferred between two copropagating 351nm laser beams crossing in an Al plasma when the frequency of the driven ion wave is shifted by a Mach 1 flow. The resonant amplification of a low-intensity (⩽2.5×1014W∕cm2) beam intersected by a high-intensity (7.0×1014W∕cm2) pump beam is determined by comparing the transmitted beam power to that measured in experiments where the plasma flow direction is reversed and the ion wave is evidently detuned. The polarization of the amplified light is also observed to align to the pump polarization consistent with ion-wave scattering. The amplification is found to reduce with probe-beam intensity demonstrating a nonlinear saturation mechanism that is effective when the ion-wave damping is weak, which is modeled with a calculation including both the nonlinear ion-wave frequency shifts due to ion trapping and whole-beam pump depletion.
Magnetic patterning of Fe∕Cr∕Fe(001) trilayers by Ga+ ion irradiation
Authors: Blomeier S. , Hillebrands B. , Demidov V. E. , Demokritov S. O. , Reuscher B. , Brodyanski A. , Kopnarski M.
Published: November 2005

Magnetic patterning of antiferromagnetically coupled epitaxial Fe(10nm)∕Cr(0.7nm)∕Fe(10nm)(001) trilayers by irradiation with 30keV Ga+ ions was studied by means of atomic force microscopy, magnetic force microscopy, and Kerr magnetometry. It was found that within a fluence range of (1.25−5)×1016ions∕cm2 a complete transition from antiferromagnetic to ferromagnetic coupling between the two Fe layers can be achieved. The magnetization reversal processes of the nonirradiated, antiferromagnetically coupled areas situated close to the irradiated areas were studied with lateral resolution. Evidence for a lateral coupling mechanism between the magnetic moments of the irradiated and nonirradiated areas was found. Special attention was paid to preserve the flatness of the irradiated samples. Depending on the fluence, topographic steps ranging from +1.5to−2nm between the nonirradiated and irradiated areas were observed. At lower fluences the irradiation causes an increase of the surface height, while for higher fluences the height decreases. It was found that for the particular fluence of 2.7×1016ions∕cm2 no height difference between the irradiated and nonirradiated areas occurs. The results suggest that the irradiation of Fe∕Cr∕Fe trilayers with midenergy ions is an innovative method for magnetic patterning, preserving the initial smoothness of the sample.
Enhanced modulation rate in platinum-diffused resonant-cavity light-emitting diodes
Authors: Chang L. B. , Yeh D. H. , Hsieh L. Z. , Zeng S. H.
Published: November 2005

This study is focused on the modulation response of resonant-cavity light-emitting diodes (RCLEDs). Platinum (Pt) atoms are diffused into the 660nm RCLED epitaxial layers to increase the concentration of recombination centers and to improve the modulation speed. The RCLED has an AlInGaP multi-quantum-well active layer which was embedded into AlGaAs-distributed Bragg reflectors to form a one-wavelength (1-λ) optical resonator. Afterwards, the deep-level Pt impurity was diffused into the RCLED and an improved average rise time, from 18.07to12.21ns, was obtained. The corresponding modulation frequency can be increased from 19.54to30.21MHz.
Carbon-nanotube tips with edge made of a transition metal
Authors: Mpourmpakis Giannis , Froudakis George E. , Andriotis Antonis N. , Menon Madhu
Published: November 2005

We show that transition metal atoms, when in contact with the open ends of single-wall carbon nanotubes can form stable tip structures. This allows one to combine the superior elastic and mechanical behavior of the nanotubes with the excellent electronic and electrical properties of transition metal systems to make high quality atomistic scanning probes for various nanotechnological applications. The geometry of the tip as well as the nature of the electronic states at the tip are found to be determined by the type of the transition metal atoms. We propose optimal tip materials for efficient probes based on a detailed electronic structure analysis using ab initio methods.
Hydrogen implantation into ZnO for n+-layer formation
Authors: Monakhov E. V. , Christensen J. S. , Maknys K. , Svensson B. G. , Kuznetsov A. Yu.
Published: November 2005

Bulk ZnO crystals were implanted using 100keV H+ ions with doses 5×1016 and 2×1017cm−2 and subsequently annealed at 200–600°C to study the evolution of the implanted H by employing secondary ion mass spectrometry and scanning spreading resistance microscopy. It is shown that the heat treatment results in a decrease of H concentration in the implanted region, while no significant broadening of the H profiles is observed. This suggests that the implanted H is trapped in immobile complexes which dissociate during annealing with subsequent outdiffusion of H from the implanted region. The formation of a highly conductive n+-layer is observed in the implanted region, and the n+-layer is found to be stable up to 600°C. A correlation between electrical activity of H and presence of radiation damage is discussed.
High-contrast vertical alignment of lateral difluoro-terphenyl liquid crystals
Authors: Wen Chien-Hui , Gauza Sebastian , Wu Shin-Tson
Published: November 2005

A simple method for achieving high-contrast vertical alignment of lateral difluoro-terphenyl liquid crystals using buffed polyimide substrates is demonstrated. By doping a positive, nonpolar or negative dielectric anisotropic compound or mixture to the host terphenyl liquid crystals, an excellent vertical alignment is obtained. This alignment is stable throughout the entire nematic range. The selected dopants not only improve the contrast ratio but enhance the figure-of-merit of the host terphenyl mixture as well. This alignment method is particularly useful for high-contrast liquid crystal televisions.
Multiparticle dispersion in fully developed turbulence
Authors: Biferale L. , Boffetta G. , Celani A. , Devenish B. J. , Lanotte A. , Toschi F.
Published: November 2005

The statistical geometry of dispersing Lagrangian clusters of four particles (tetrahedra) is studied by means of high-resolution direct numerical simulations of three-dimensional homogeneous isotropic turbulence. We give evidence of a self-similar regime of shape dynamics characterized by almost two-dimensional, strongly elongated geometries. The analysis of four-point velocity-difference statistics and orientation shows that inertial-range eddies typically generate a straining field with a strong extensional component aligned with the elongation direction and weak extensional/compressional components in the orthogonal plane.
Modeled regional climate change and California endemic oak ranges
Authors: Kueppers Lara M. , Snyder Mark A. , Sloan Lisa C. , Zavaleta Erika S. , Fulfrost Brian
Published: November 2005

In the coming century, anthropogenic climate change will threaten the persistence of restricted endemic species, complicating conservation planning. Although most efforts to quantify potential shifts in species' ranges use global climate model (GCM) output, regional climate model (RCM) output may be better suited to predicting shifts by restricted species, particularly in regions with complex topography or other regionally important climate-forcing factors. Using a RCM-based future climate scenario, we found that potential ranges of two California endemic oaks,Quercus douglasiiandQuercus lobata, shrink considerably (to 59% and 54% of modern potential range sizes, respectively) and shift northward. This result is markedly different from that obtained by using a comparable GCM-based scenario, under which these species retain 81% and 73% of their modern potential range sizes, respectively. The difference between RCM- and GCM-based scenarios is due to greater warming and larger precipitation decreases during the growing season predicted by the RCM in these species' potential ranges. Based on the modeled regional climate change, <50% of protected land area currently containing these species is expected to contain them under a future midrange “business-as-usual” path of greenhouse gas emissions.
Direct interaction of the human I-mfa domain-containing protein, HIC, with HIV-1 Tat results in cytoplasmic sequestration and control of Tat activity
Authors: Gautier Virginie W. , Sheehy Noreen , Duffy Margaret , Hashimoto Kenichi , Hall William W.
Published: November 2005

The primary function of the HIV-1 regulatory protein Tat, activation of transcription from the viral LTR, is highly regulated by complex interactions between Tat and a number of host cell proteins. Tat nuclear import, a process mediated by importin β, is a prerequisite for its activity. Here, we report and characterize the interaction of the human inhibitor of MyoD family domain-containing protein (I-mfa), HIC, with Tat at a biochemical and a functional level. This interaction was shown to occur
in vivo
and
in vitro
and to involve the nuclear localization signal and the transactivation responsive element-binding domains of Tat and the I-mfa domain of HIC. Coexpression of HIC and Tat resulted in the down-regulation of transactivation of the HIV-1 LTR, and colocalization studies revealed the cytoplasmic sequestration of Tat by HIC. Functionally this sequestration appears to be the underlying mechanism of LTR transcriptional repression by HIC and represents a unique mechanism for the control of Tat activity and regulation of HIV-1 replication.
Diversity and functional plasticity of eukaryotic selenoproteins: Identification and characterization of the SelJ family
Authors: Castellano Sergi , Lobanov Alexey V. , Chapple Charles , Novoselov Sergey V. , Albrecht Mario , Hua Deame , Lescure Alain , Lengauer Thomas , Krol Alain , Gladyshev Vadim N. , Guigó Roderic
Published: November 2005

Selenoproteins are a diverse group of proteins that contain selenocysteine (Sec), the 21st amino acid. In the genetic code, UGA serves as a termination signal and a Sec codon. This dual role has precluded the automatic annotation of selenoproteins. Recent advances in the computational identification of selenoprotein genes have provided a first glimpse of the size, functions, and phylogenetic diversity of eukaryotic selenoproteomes. Here, we describe the identification of a selenoprotein family named SelJ. In contrast to known selenoproteins, SelJ appears to be restricted to actinopterygian fishes and sea urchin, with Cys homologues only found in cnidarians. SelJ shows significant similarity to the jellyfish J1-crystallins and with them constitutes a distinct subfamily within the large family of ADP-ribosylation enzymes. Consistent with its potential role as a structural crystallin,
SelJ
has preferential and homogeneous expression in the eye lens in early stages of zebrafish development. A structural role for SelJ would be in contrast to the majority of known selenoenzymes. The unusually highly restricted phylogenetic distribution of SelJ, its specialization, and the comparative analysis of eukaryotic selenoproteomes reveal the diversity and functional plasticity of selenoproteins and point to a mosaic evolution of the use of Sec in proteins.
Site-specific recombinase and integrase activities of a conjugative relaxase in recipient cells
Authors: Draper Olga , César Carolina Elvira , Machón Cristina , de la Cruz Fernando , Llosa Matxalen
Published: November 2005

Conjugative relaxases are the proteins that initiate bacterial conjugation by a site-specific cleavage of the transferred DNA strand.
In vitro
, they show strand-transferase activity on single-stranded DNA, which suggests they may also be responsible for recircularization of the transferred DNA. In this work, we show that TrwC, the relaxase of plasmid R388, is fully functional in the recipient cell, as shown by complementation of an R388
trwC
mutant in the recipient. TrwC transport to the recipient is also observed in the absence of DNA transfer, although it still requires the conjugative coupling protein. In addition to its role in conjugation, TrwC is able to catalyze site-specific recombination between two origin of transfer (
oriT
) copies. Mutations that abolish TrwC DNA strand-transferase activity also abolish
oriT
-specific recombination. A plasmid containing two
oriT
copies resident in the recipient cell undergoes recombination when a TrwC-piloted DNA is conjugatively transferred into it. Finally, we show TrwC-dependent integration of the transferred DNA into a resident
oriT
copy in the recipient cell. Our results indicate that a conjugative relaxase is active once in the recipient cell, where it performs the nicking and strand-transfer reactions that would be required to recircularize the transferred DNA. This TrwC site-specific integration activity in recipient cells may lead to future biotechnological applications.
Innate control of adaptive immunity via remodeling of lymph node feed arteriole
Authors: Soderberg Kelly A. , Payne Geoffrey W. , Sato Ayuko , Medzhitov Ruslan , Segal Steven S. , Iwasaki Akiko
Published: November 2005

The adaptive immune system relies on rare cognate lymphocytes to detect pathogen-derived antigens. Naïve lymphocytes recirculate through secondary lymphoid organs in search of cognate antigen. Here, we show that the naïve-lymphocyte recirculation pattern is controlled at the level of innate immune recognition, independent of antigen-specific stimulation. We demonstrate that inflammation-induced lymphocyte recruitment to the lymph node is mediated by the remodeling of the primary feed arteriole, and that its physiological role is to increase the efficiency of screening for rare antigen-specific lymphocytes. Our data reveal a mechanism of innate control of adaptive immunity: by increasing the pool of naïve lymphocytes for detection of foreign antigens via regulation of vascular input to the local lymph node.
Pharmacological induction of heat-shock proteins alleviates polyglutamine-mediated motor neuron disease
Authors: Katsuno Masahisa , Sang Chen , Adachi Hiroaki , Minamiyama Makoto , Waza Masahiro , Tanaka Fumiaki , Doyu Manabu , Sobue Gen
Published: November 2005

Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motor neuron disease caused by the expansion of a trinucleotide CAG repeat encoding the polyglutamine tract in the first exon of the androgen receptor gene (
AR
). The pathogenic, polyglutamine-expanded AR protein accumulates in the cell nucleus in a ligand-dependent manner and inhibits transcription by interfering with transcriptional factors and coactivators. Heat-shock proteins (HSPs) are stress-induced chaperones that facilitate the refolding and, thus, the degradation of abnormal proteins. Geranylgeranylacetone (GGA), a nontoxic antiulcer drug, has been shown to potently induce HSP expression in various tissues, including the central nervous system. In a cell model of SBMA, GGA increased the levels of Hsp70, Hsp90, and Hsp105 and inhibited cell death and the accumulation of pathogenic AR. Oral administration of GGA also up-regulated the expression of HSPs in the central nervous system of SBMA-transgenic mice and suppressed nuclear accumulation of the pathogenic AR protein, resulting in amelioration of polyglutamine-dependent neuromuscular phenotypes. These observations suggest that, although a high dose appears to be needed for clinical effects, oral GGA administration is a safe and promising therapeutic candidate for polyglutamine-mediated neurodegenerative diseases, including SBMA.
Evidence for capillarity contributions to gecko adhesion from single spatula nanomechanical measurements
Authors: Huber Gerrit , Mantz Hubert , Spolenak Ralph , Mecke Klaus , Jacobs Karin , Gorb Stanislav N. , Arzt Eduard
Published: November 2005

The hairy attachment system on a gecko's toes, consisting of one billion spatulae in the case of
Gekko gecko
[Ruibal, R. & Ernst, V. (1965)
J. Morphol.
117, 271–294], allows it to adhere to nearly all surface topographies. The mechanistic basis for gecko adhesion has been intensely investigated, but the lowest hierarchical level, that of the spatula, has become experimentally accessible only recently. This report details measurements of the adhesion force exerted by a single gecko spatula for various atmospheric conditions and surface chemistries. Through judicious choice and modification of substrates, the short- and long-range adhesive forces are separated. In contrast to previous work [Autumn, K., Sitti, M., Liang, Y. C. A., Peattie, A. M., Hansen, W. R., Sponberg, S., Kenny, T. W., Fearing, R., Israelachvili, J. N. & Full, R. J. (2002)
Proc. Natl. Acad. Sci. USA
99,
12252–12256
], our measurements clearly show that humidity contributes significantly to gecko adhesion on a nanoscopic level. These findings are crucial for the development of artificial biomimetic attachment systems.
A persistent pesticide residue and the unusual catalytic proficiency of a dehalogenating enzyme
Authors: Horvat Christopher M. , Wolfenden Richard V.
Published: November 2005

The soil of potato fields in The Netherlands harbors bacteria with the ability to metabolize 3-chloroacrylic acid, generated by the degradation of a pesticide (1,3-dichloropropene) that entered the environment in 1946. From examination of rate constants at elevated temperatures, we infer that the half-time at 25°C for spontaneous hydrolytic dechlorination oftrans-3-chloroacrylic acid is 10,000 years, several orders of magnitude longer than half-times for spontaneous decomposition of other environmental pollutants such as 1,2-dichloroethane (72 years), paraoxon (13 months), atrazine (5 months), and aziridine (52 h). With thermodynamic parameters for activation similar to those for the spontaneous hydration of fumarate at pH 6.8, this slow reaction proceeds at a constant rate through the pH range between 2 and 12. However, at the active site of the enzyme 3-chloroacrylate dehalogenase (CaaD), isolated from a pseudomonad growing in these soils, hydrolytic dechlorination proceeds with a half-time of 0.18 s. Neitherkcatnorkcat/Kmis reduced by increasing solvent viscosity with trehalose, implying that the rate of enzymatic dechlorination is controlled by chemical events in catalysis rather than by diffusion-limited substrate binding or product release. CaaD achieves an ≈1012-fold rate enhancement, matching or surpassing the rate enhancements produced by many enzymes that act on more conventional biological substrates. One of those enzymes is 4-oxalocrotonate tautomerase, with which CaaD seems to share a common evolutionary origin.
Ocular dominance plasticity is stably maintained in the absence of α calcium calmodulin kinase II (αCaMKII) autophosphorylation
Authors: Taha Sharif A. , Stryker Michael P.
Published: November 2005

The molecule α calcium calmodulin kinase II (αCaMKII) is known to play a fundamental role in the induction of many forms of synaptic plasticity. A major theory of αCaMKII function proposes that autophosphorylation of the molecule mediates not only the induction but also the maintenance of synaptic plasticity. To test this hypothesis, we assessed ocular dominance plasticity in genetically engineered mice that carry a mutation preventing autophosphorylation of αCaMKII. These mutant mice are deficient in plasticity after monocular deprivation, but a sufficiently long period of monocular deprivation will induce ocular dominance plasticity. After induction of ocular dominance plasticity, the stability of the induced changes was assayed after binocular deprivation. Plasticity in homozygous mutant animals was as stable as that measured in WT littermates; also, response characteristics did not differ between the two groups. Our results suggest that αCaMKII autophosphorylation is required for the induction of ocular dominance plasticity but is not needed for its stable maintenance thereafter.
IL-32 synergizes with nucleotide oligomerization domain (NOD) 1 and NOD2 ligands for IL-1β and IL-6 production through a caspase 1-dependent mechanism
Authors: Netea Mihai G. , Azam Tania , Ferwerda Gerben , Girardin Stephen E. , Walsh Mark , Park Jong-Sung , Abraham Edward , Kim Jin-Man , Yoon Do-Young , Dinarello Charles A. , Kim Soo-Hyun
Published: November 2005

The activation of innate immunity requires the amplification of signals induced by pattern-recognition receptors for bacterial products. We have investigated the role of the newly described cytokine IL-32 in the amplification of cytokine production induced by the two most clinically relevant families of microbial receptors, the cell-surface Toll-like receptors (TLRs) and the intracellular nuclear oligomerization domain (NOD) receptor family. IL-32 synergized with the NOD1- and NOD2-specific muropeptides of peptidoglycans for the release of IL-1β and IL-6 (a 3- to 10-fold increase). In contrast, IL-32 did not influence the cytokine production induced via TLRs. The synergistic effect of IL-32 and synthetic muramyl dipeptide (MDP) on cytokine production was absent in the cells of patients with Crohn's disease bearing the NOD2 frameshift mutation 3020insC, demonstrating that the IL-32/MDP synergism depends on NOD2. This
in vitro
synergism between IL-32 and NOD2 ligands was consistent with a marked constitutive expression of IL-32 in human colon epithelial tissue. In addition, the potentiating effect of IL-32 on the cytokine production induced by the synthetic muropeptide FK-156 was absent in NOD1-deficient macrophages, supporting the interaction between IL-32 and NOD1 pathways. When specific caspase inhibitors were used, the synergism between IL-32 and MDP/NOD2 depended on the activation of caspase 1. Only additive effects of IL-32 and muropeptides were observed for TNF-α production. The modulation of intracellular NOD2 pathways by IL-32, but not cell-surface TLRs, and the marked expression of IL-32 in colon mucosa suggest a role of IL-32 in the pathogenesis of Crohn's disease.
Fate of dietary perchlorate in lactating dairy cows: Relevance to animal health and levels in the milk supply
Authors: Capuco A. V. , Rice C. P. , Baldwin R. L. , Bannerman D. D. , Paape M. J. , Hare W. R. , Kauf A. C. W. , McCarty G. W. , Hapeman C. J. , Sadeghi A. M. , Starr J. L. , McConnell L. L. , Van Tassell C. P.
Published: November 2005

Perchlorate is a goitrogenic anion that competitively inhibits the sodium iodide transporter and has been detected in forages and in commercial milk throughout the U.S. The fate of perchlorate and its effect on animal health were studied in lactating cows, ruminally infused with perchlorate for 5 weeks. Milk perchlorate levels were highly correlated with perchlorate intake, but milk iodine was unaffected, and there were no demonstrable health effects. We provide evidence that up to 80% of dietary perchlorate was metabolized, most likely in the rumen, which would provide cattle with a degree of refractoriness to perchlorate. Data presented are important for assessing the environmental impact on perchlorate concentrations in milk and potential for relevance to human health.
Dental senescence in a long-lived primate links infant survival to rainfall
Authors: King Stephen J. , Arrigo-Nelson Summer J. , Pochron Sharon T. , Semprebon Gina M. , Godfrey Laurie R. , Wright Patricia C. , Jernvall Jukka
Published: November 2005

Primates tend to be long-lived, and, except for humans, most primate females are able to reproduce into old age. Although aging in most mammals is accompanied by dental senescence due to advanced wear, primates have low-crowned teeth that wear down before old age. Because tooth wear alters crown features gradually, testing whether early dental senescence causes reproductive senescence has been difficult. To identify whether and when low-crowned teeth compromise reproductive success, we used a 20-year field study of
Propithecus edwardsi
, a rainforest lemur from Madagascar with a maximum lifespan of >27 years. We analyzed tooth wear in three dimensions with dental topographic analysis by using Geographical Information Systems (GIS) technology. We report that tooth wear exposes compensatory shearing blades that maintain dental function for 18 years. Beyond this age, female fertility remains high; however infants survive only if lactation seasons have elevated rainfall. Therefore, low-crowned teeth accommodate wear to a point, after which reproductive success closely tracks environmental fluctuations. These results suggest a tooth wear-determined, but rainfall-mediated, onset of reproductive senescence. Additionally, our study indicates that even subtle changes in climate may affect reproductive success of rainforest species.
Carbonic anhydrase IV and XIV knockout mice: Roles of the respective carbonic anhydrases in buffering the extracellular space in brain
Authors: Shah Gul N. , Ulmasov Barbara , Waheed Abdul , Becker Timothy , Makani Sachin , Svichar Nataliya , Chesler Mitchell , Sly William S.
Published: November 2005

Previous studies have implicated extracellular carbonic anhydrases (CAs) in buffering the alkaline pH shifts that accompany neuronal activity in the rat and mouse hippocampus. CAs IV and XIV both have been proposed to mediate this extracellular buffering. To examine the relative importance of these two isozymes in this and other physiological functions attributed to extracellular CAs, we produced CA IV and CA XIV knockout (KO) mice by targeted mutagenesis and the doubly deficient CA IV/XIV KO mice by intercrossing the individual null mice. Although CA IV and CA XIV null mice both are viable, the CA IV nulls are produced in smaller numbers than predicted, indicating either fetal or postnatal losses, which preferentially affect females. CA IV/XIV double KO mice are also produced in fewer numbers than predicted and are smaller than WT mice, and many females die prematurely before and after weaning. Electrophysiological studies on hippocampal slices on these KO mice showed that either CA can mediate buffering after synaptic transmission in hippocampal slices in the absence of the other, but that eliminating both is nearly as effective as the CA inhibitor, benzolamide, in blocking the buffering seen in the WT mice. Thus, both CA IV and CA XIV contribute to extracellular buffering in the central nervous system, although CA IV appears to be more important in the hippocampus. These individual and double KO mice should be valuable tools in clarifying the relative contributions of each CA to other physiological functions where extracellular CAs have been implicated.
The architecture of pre-mRNAs affects mechanisms of splice-site pairing
Authors: Fox-Walsh Kristi L. , Dou Yimeng , Lam Bianca J. , Hung She-pin , Baldi Pierre F. , Hertel Klemens J.
Published: November 2005

The exon/intron architecture of genes determines whether components of the spliceosome recognize splice sites across the intron or across the exon. Using
in vitro
splicing assays, we demonstrate that splice-site recognition across introns ceases when intron size is between 200 and 250 nucleotides. Beyond this threshold, splice sites are recognized across the exon. Splice-site recognition across the intron is significantly more efficient than splice-site recognition across the exon, resulting in enhanced inclusion of exons with weak splice sites. Thus, intron size can profoundly influence the likelihood that an exon is constitutively or alternatively spliced. An EST-based alternative-splicing database was used to determine whether the exon/intron architecture influences the probability of alternative splicing in the
Drosophila
and human genomes.
Drosophila
exons flanked by long introns display an up to 90-fold-higher probability of being alternatively spliced compared with exons flanked by two short introns, demonstrating that the exon/intron architecture in
Drosophila
is a major determinant in governing the frequency of alternative splicing. Exon skipping is also more likely to occur when exons are flanked by long introns in the human genome. Interestingly, experimental and computational analyses show that the length of the upstream intron is more influential in inducing alternative splicing than is the length of the downstream intron. We conclude that the size and location of the flanking introns control the mechanism of splice-site recognition and influence the frequency and the type of alternative splicing that a pre-mRNA transcript undergoes.
Thyroid hormone receptor β mutants: Dominant negative regulators of peroxisome proliferator-activated receptor γ action
Authors: Araki Osamu , Ying Hao , Furuya Fumihiko , Zhu Xuguang , Cheng Sheue-yann
Published: November 2005

Thyroid hormone (T3) and peroxisome proliferators have overlapping metabolic effects in the maintenance of lipid homeostasis. Their actions are mediated by their respective receptors: thyroid hormone receptors (TR) and peroxisome proliferator-activated receptors (PPAR). We recently found that a dominantly negative TRβ mutant (PV) that causes a genetic disease, resistance to thyroid hormone, acts to repress the ligand (troglitazone)-mediated transcriptional activity of PPARγ in cultured thyroid cells. This finding suggests that TRβ mutants could crosstalk with PPARγ-signaling pathways. The present study explored the molecular mechanisms by which PV represses the PPARγ transcriptional activity. Gel-shift assays show that the PV, similar to wild-type TRβ, bound to the peroxisome proliferator response element (PPRE) as homodimers and heterodimers with PPARγ or the retinoid X receptor (RXR), thereby competing with PPARγ for binding to PPRE and for sequestering RXR. Association of PPRE-bound PV with corepressors [e.g., nuclear receptor corepressor (NCoR)] that led to transcriptional repression was independent of T3 and troglitazone. Chromatin immunoprecipitation assay further demonstrated that, despite the presence of ligands, NCoR was recruited to PPRE-bound PV on a PPARγ-target gene, the lipoprotein lipase,
in vivo
, suggesting the dominant action of PV on PPARγ-mediated transcriptional activity. Thus, the dominant negative action of PV is not limited on the wild-type TRs. The findings that TRβ mutants affect PPARγ functions through dominant negative action provide insights into the molecular mechanisms by which TR regulates the PPARγ-target genes involved in metabolic pathways, lipid homeostasis, and carcinogenesis.
Phosphorylation by Cdk1 induces Plk1-mediated vimentin phosphorylation during mitosis
Authors: Yamaguchi Tomoya , Goto Hidemasa , Yokoyama Tomoya , Silljé Herman , Hanisch Anja , Uldschmid Andreas , Takai Yasushi , Oguri Takashi , Nigg Erich A. , Inagaki Masaki
Published: November 2005

Several kinases phosphorylate vimentin, the most common intermediate filament protein, in mitosis. Aurora-B and Rho-kinase regulate vimentin filament separation through the cleavage furrow-specific vimentin phosphorylation. Cdk1 also phosphorylates vimentin from prometaphase to metaphase, but its significance has remained unknown. Here we demonstrated a direct interaction between Plk1 and vimentin-Ser55 phosphorylated by Cdk1, an event that led to Plk1 activation and further vimentin phosphorylation. Plk1 phosphorylated vimentin at ∼1 mol phosphate/mol substrate, which partly inhibited its filament forming ability, in vitro. Plk1 induced the phosphorylation of vimentin-Ser82, which was elevated from metaphase and maintained until the end of mitosis. This elevation followed the Cdk1-induced vimentin-Ser55 phosphorylation, and was impaired by Plk1 depletion. Mutational analyses revealed that Plk1-induced vimentin-Ser82 phosphorylation plays an important role in vimentin filaments segregation, coordinately with Rho-kinase and Aurora-B. Taken together, these results indicated a novel mechanism that Cdk1 regulated mitotic vimentin phosphorylation via not only a direct enzyme reaction but also Plk1 recruitment to vimentin.
Drosophila melanogaster Cad99C, the orthologue of human Usher cadherin PCDH15, regulates the length of microvilli
Authors: D'Alterio Cecilia , Tran Dao D.D. , Yeung Maggie W.Y. Au , Hwang Michael S.H. , Li Michelle A. , Arana Claudia J. , Mulligan Vikram K. , Kubesh Mary , Sharma Praveer , Chase Maretta , Tepass Ulrich , Godt Dorothea
Published: November 2005

Actin-based protrusions can form prominent structures on the apical surface of epithelial cells, such as microvilli. Several cytoplasmic factors have been identified that control the dynamics of actin filaments in microvilli. However, it remains unclear whether the plasma membrane participates actively in microvillus formation. In this paper, we analyze the function of Drosophila melanogaster cadherin Cad99C in the microvilli of ovarian follicle cells. Cad99C contributes to eggshell formation and female fertility and is expressed in follicle cells, which produce the eggshells. Cad99C specifically localizes to apical microvilli. Loss of Cad99C function results in shortened and disorganized microvilli, whereas overexpression of Cad99C leads to a dramatic increase of microvillus length. Cad99C that lacks most of the cytoplasmic domain, including potential PDZ domain–binding sites, still promotes excessive microvillus outgrowth, suggesting that the amount of the extracellular domain determines microvillus length. This study reveals Cad99C as a critical regulator of microvillus length, the first example of a transmembrane protein that is involved in this process.
How does the TOM complex mediate insertion of precursor proteins into the mitochondrial outer membrane?
Authors: Rapaport Doron
Published: November 2005

A multisubunit translocase of the outer mitochondrial membrane (TOM complex) mediates both the import of mitochondrial precursor proteins into the internal compartments of the organelle and the insertion of proteins residing in the mitochondrial outer membrane. The proposed β-barrel structure of Tom40, the pore-forming component of the translocase, raises the question of how the apparent uninterrupted β-barrel topology can be compatible with a role of Tom40 in releasing membrane proteins into the lipid core of the bilayer. In this review, I discuss insertion mechanisms of proteins into the outer membrane and present alternative models based on the opening of a multisubunit β-barrel TOM structure or on the interaction of outer membrane precursors with the outer face of the Tom40 β-barrel structure.