bluuebunny/crossref_metadata_2025 huggingface dataset:
Bias-dependent photocurrent of Hg1−xCdxTe photodiodes
Authors: Cao Guangming , Gong Haimei , Qiu Huiguo , Kong Lingcai , Hu S. H. , Dai N.
Published: September 2005

Experimental data are presented on the bias dependence of the photocurrent of short-wave infrared n+-on-p Hg1−xCdxTe (MCT) photodiodes responding to an attenuated Nd: yttrium lithium fluoride laser, and the results are interpreted using the sweep-out theory. At high photon injection level, it is observed that the photocurrent is linearly dependent at reverse bias before saturating, and a high reverse bias is required to recover the linear response of the photocurrent to the irradiance. The conventional photocurrent model fails to explain our observations. The bias dependence is attributed to recombination of the photogenerated carriers instead of their being swept out of the depletion region, as a result of the partial cancellation of the built-in field by the spatial distribution of the high density of photogenerated electrons and holes in this region. An interpretation based upon the photoconductivity of MCT photoconductors is proposed and found to be in good agreement with the experimental results.
A model for the pressure dependence of viscosity in liquids
Authors: Kapoor Kamal , Dass Narsingh
Published: September 2005

In the present paper, a model with two adjustable parameters is developed to study the viscosity of liquid as a function of pressure. The model so developed has been applied in 38 liquids. The computed results have been found to be in very good agreement with the experimental data in case of each liquid. The minimum and the maximum ranges of viscosity studied in the present paper are 0.054–0.515cp in CO2 and 16.9–57200.0cp in 2-ethylhexyl-benzoate, respectively. It is interesting to note that the relation is found valid even in the liquid in which the viscosity varies by a factor of 3400, i.e., 2-ethylhexyl-benzoate.
Impact of microstructure on grain-boundary diffusion in polycrystals
Authors: Bedu-Amissah K. , Rickman J. M. , Chan H. M. , Harmer M. P.
Published: September 2005

The impact of a complex microstructure on polycrystalline diffusion is investigated using both numerical and analytical methods. In particular, the diffusion equation is numerically integrated using the finite-difference method to obtain the concentration profile for a diffusant in a simplified microstructural representation. The methodology is first validated for an idealized model of diffusion in a prototypical, single grain-boundary system and then applied to a Voronoi model of a microstructure resulting from homogeneous nucleation and growth. The diffusive behavior is quantified by obtaining uptake curves as a function of time for different ratios of grain boundary to lattice diffusivities. Such curves can be used to estimate an unknown grain-boundary diffusivity, given certain microstructural assumptions. Finally, approximate analytical equations describing a diffusant uptake in polycrystalline microstructural models are developed and found to agree well with the numerical results.
A molecular-beam study of the collision dynamics of methane and ethane upon a graphitic monolayer on Pt(111)
Authors: Kondo Takahiro , Mori Daisuke , Okada Ryuta , Sasaki Masahiro , Yamamoto Shigehiko
Published: September 2005

Utilizing a supersonic molecular-beam scattering technique, the angular intensity distributions of alkane molecules (CH4 and C2H6) have been measured, which are scattered from a chemically inert and highly oriented monolayer graphite (MG) on Pt(111). A MG which covers the Pt(111) surface with a full monolayer is found to induce a large energy loss of alkanes during collision with the surface by phonon creation due to the large mass ratio of an alkane molecule with respect to MG. Based on the classical cube model, only applicable to the molecules without internal mode excitation, the effective masses of MG of 76 (six atoms of carbon) and Pt(111) of 585 (three atoms of platinum) are determined from rare-gas atom scattering data. Despite the difference in the degree of freedom between CH4 and rare-gas atoms, CH4 scattering is found to be well described by the simple hard-cube model as a result of the high symmetry of the CH4 structure. With the recently developed ellipsoid-washboard model, an extension of the hard-cube model to include some internal mode excitation of impinging molecules in addition to the surface corrugation, it is found that unlike CH4 the cartwheel rotation mode of C2H6 is significantly excited during collision, while the helicopter mode excitation is negligible on a flat MG surface.
On the role of optimal perturbations in the instability of monochromatic gravity waves
Authors: Achatz U.
Published: September 2005

Motivated by the useful new insights from optimal-perturbation theory into the onset of turbulence in other fields singular vectors (SVs) in stable and unstable gravity waves have been determined within the framework of the Boussinesq equations on an f plane. The difference between the dynamics of normal modes (NMs) and SV is characterized by a time invariance in the comparative role of the various possible exchange processes between NM and basic wave, while SV can have a highly time-dependent structure, allowing a more efficient energy exchange over a finite time. Both inertia-gravity waves (IGWs) and high-frequency gravity waves (HGWs) have been considered. At Reynolds numbers typical for the middle to upper mesosphere IGW admit rapid nonmodal growth even when no unstable NMs exist. SV energy growth within one Brunt-Vaisala period can cover two orders of magnitude, suggesting the possibility of turbulence onset under conditions where this would not be predicted by a NM analysis. HGWs show a dependence of short-term optimal growth on the direction of propagation of the perturbation with respect to the wave which is, at weak to moderate wave amplitudes, quite different from that of NM but reproduced in ensemble integrations from random initial perturbations. Their SVs are sharply peaked pulses with negligible group velocity which are repeatedly excited as the rapidly propagating wave passes over them. The transition of these to the leading NM, which is not moving with respect to the wave and which is typically broader in structure, is very slow, so that in many cases the turbulence onset via local perturbations of a gravity wave might be more appropriately described using optimal-perturbation theory. This might contribute to a better understanding of the often observed occurrence of thin turbulent layers in the middle atmosphere.
Electron acceleration and electron-positron pair production by laser in tunnel ionized inhomogeneous plasma
Authors: Gupta D. N. , Suk H. , Ryu C. M.
Published: September 2005

A high intensity laser short pulse causes rapid tunnel ionization of an inhomogeneous gas. The tunnel ionization of the gas causes a defocusing of the laser pulse. The electron experiences an unequal ponderomotive force due to the trailing and rising part of the laser pulse, hence, gains net energy. The net acquired electron energy is reduced due to the inhomogeneity in gas density. If the accelerated electrons are targeted to a low-Z material nucleus, the electron-positron pair will be created via a trident process.
Feedback stabilization of resistive wall modes in a reversed-field pinch
Authors: Brunsell P. R. , Yadikin D. , Gregoratto D. , Paccagnella R. , Liu Y. Q. , Cecconello M. , Drake J. R. , Manduchi G. , Marchiori G.
Published: September 2005

An array of saddle coils having Nc=16 equally spaced positions along the toroidal direction has been installed for feedback control of resistive wall modes (RWMs) on the EXTRAP T2R reversed-field pinch [P. R. Brunsell, H. Bergsaker, M. Cecconello et al., Plasma Phys. Controlled Fusion 43, 1457 (2001)]. Using feedback, multiple nonresonant RWMs are simultaneously suppressed for three to four wall times. Feedback stabilization of RWMs results in a significant prolongation of the discharge duration. This is linked to a better sustainment of the plasma and tearing mode toroidal rotation with feedback. Due to the limited number of coils in the toroidal direction, pairs of modes with toroidal mode numbers n,n′ that fulfill the condition ∣n−n′∣=Nc are coupled by the feedback action from the discrete coil array. With only one unstable mode in a pair of coupled modes, the suppression of the unstable mode is successful. If two modes are unstable in a coupled pair, two possibilities exist: partial suppression of both modes or, alternatively, complete stabilization of one target mode while the other is left unstable.
Self-alignment of glass spheres using the electromeniscus phenomenon
Authors: Matsuura Hiroshi , Miyazaki Manabu , Komatsu Mamoru , Ogawa Makoto
Published: September 2005

This letter reports on the self-alignment of glass spheres using a liquid interacting with an electric field for surface modification. The liquid is electrically attracted and trapped between the glass spheres as a result of the electromeniscus phenomenon. The liquid between the spheres removes the electric charge on the spheres, enhances the attractive forces between the spheres, and works as a lubricant for their smooth alignment. These roles of the liquid enable the electric field to smoothly self-assembly glass spheres three-dimensionally. The three-dimensional self-assembly of glass spheres will greatly contribute to the fabrication of micro-optics and biomedical devices using a laser.
Bead lightning formation
Authors: Ludwig G. O. , Saba M. M. F.
Published: September 2005

Formation of beaded structures in triggered lightning discharges is considered in the framework of both magnetohydrodynamic (MHD) and hydrodynamic instabilities. It is shown that the space periodicity of the structures can be explained in terms of the kink and sausage type instabilities in a cylindrical discharge with anomalous viscosity. In particular, the fast growth rate of the hydrodynamic Rayleigh-Taylor instability, which is driven by the backflow of air into the channel of the decaying return stroke, dominates the initial evolution of perturbations during the decay of the return current. This instability is responsible for a significant enhancement of the anomalous viscosity above the classical level. Eventually, the damping introduced at the current channel edge by the high level of anomalous viscous stresses defines the final length scale of bead lightning. Later, during the continuing current stage of the lightning flash, the MHD pinch instability persists, although with a much smaller growth rate that can be enhanced in a M-component event. The combined effect of these instabilities may explain various aspects of bead lightning.
Observation of nanoindentation rosettes on {0001}ZnO using scanning Kelvin probe microscopy
Authors: Klopfstein M. J. , Lucca D. A.
Published: September 2005

Nanoindentation rosettes have been observed by scanning Kelvin probe microscopy on chemomechanical polished and etched {0001}ZnO while under illumination by a broadband light source. The rosette pattern consisted of a central region with a lower surface potential extending beyond the indentation and six arms emanating from this region along the ⟨112¯0⟩ directions. The length of the longest rosette arm was found to be proportional to the square root of the maximum force of indentation minus the average load at which pop-in occurred.
Electrodeposition and room temperature ferromagnetic anisotropy of Co and Ni-doped ZnO nanowire arrays
Authors: Cui J. B. , Gibson U. J.
Published: September 2005

Cobalt and nickel doped ZnO nanowire arrays were synthesized by an electrochemical process at a temperature of 90°C. Energy dispersive x-ray spectroscopy and x-ray diffraction show that the dopants are incorporated into the wurtzite-structure ZnO. Anisotropic ferromagnetism with an easy direction of magnetization either perpendicular or parallel to the wire axis, depending on the wire geometry and density, was observed in 1.7% Co and 2.2% Ni-doped ZnO nanowires at room temperature. The anisotropic magnetism was explained in terms of a competition between self-demagnetization and magnetostatic coupling among the nanowires.
Metastasis-associated protein 1 (MTA1) is an essential downstream effector of the c-MYC oncoprotein
Authors: Zhang Xiao-yong , DeSalle Lauren M. , Patel Jagruti H. , Capobianco Anthony J. , Yu Duonan , Thomas-Tikhonenko Andrei , McMahon Steven B.
Published: September 2005

The c-
myc
oncogene is among the most commonly overexpressed genes in human cancer. c-
myc
encodes a basic helix–loop–helix/leucine zipper (bHLH/LZ) transcription factor (c-MYC) that activates a cascade of downstream targets that ultimately mediate cellular transformation. Although a large number of genes are regulated by c-MYC, only a few have been functionally linked to c-MYC-mediated transformation. By expression profiling, the metastasis-associated protein 1 (MTA1) gene was identified here as a target of the c-MYC oncoprotein in primary human cells, a result confirmed in human cancer cells. MTA1 itself has been previously implicated in cellular transformation, in part through its ability to regulate the epithelial-to-mesenchymal transition and metastasis. MTA1 is a component of the Mi-2/nucleosome remodeling and deacetylating (NURD) complex that contains both histone deacetylase and nucleosome remodeling activity. The data reported here demonstrate that endogenous c-MYC binds to the genomic MTA1 locus and recruits transcriptional coactivators. Most importantly, short hairpin RNA (shRNA)-mediated knockdown of MTA1 blocks the ability of c-MYC to transform mammalian cells. These data implicate MTA1 and the Mi-2/NURD complex as one of the first downstream targets of c-MYC function that are essential for the transformation potential of c-MYC.
A conserved trimerization motif controls the topology of short coiled coils
Authors: Kammerer Richard A. , Kostrewa Dirk , Progias Pavlos , Honnappa Srinivas , Avila David , Lustig Ariel , Winkler Fritz K. , Pieters Jean , Steinmetz Michel O.
Published: September 2005

In recent years, short coiled coils have been used for applications ranging from biomaterial to medical sciences. For many of these applications knowledge of the factors that control the topology of the engineered protein systems is essential. Here, we demonstrate that trimerization of short coiled coils is determined by a distinct structural motif that encompasses specific networks of surface salt bridges and optimal hydrophobic packing interactions. The motif is conserved among intracellular, extracellular, viral, and synthetic proteins and defines a universal molecular determinant for trimer formation of short coiled coils. In addition to being of particular interest for the biotechnological production of candidate therapeutic proteins, these findings may be of interest for viral drug development strategies.
EphA4 defines a class of excitatory locomotor-related interneurons
Authors: Butt Simon J. B. , Lundfald Line , Kiehn Ole
Published: September 2005

Relatively little is known about the interneurons that constitute the mammalian locomotor central pattern generator and how they interact to produce behavior. A potential avenue of research is to identify genetic markers specific to interneuron populations that will assist further exploration of the role of these cells in the network. One such marker is the EphA4 axon guidance receptor. EphA4-null mice display an abnormal rabbit-like hopping gait that is thought to be the result of synchronization of the normally alternating, bilateral locomotor network via aberrant crossed connections. In this study, we have performed whole-cell patch clamp on EphA4-positive interneurons in the flexor region (L2) of the locomotor network. We provide evidence that although EphA4 positive interneurons are not entirely a homogeneous population, most of them fire in a rhythmic manner. Moreover, a subset of these interneurons provide direct excitation to ipsilateral motor neurons as determined by spike-triggered averaging of the local ventral root DC trace. Our findings substantiate the role of EphA4-positive interneurons as significant components of the ipsilateral locomotor network and describe a group of putative excitatory central pattern generator neurons.
Mimicking natural evolution in metallo-β-lactamases through second-shell ligand mutations
Authors: Tomatis Pablo E. , Rasia Rodolfo M. , Segovia Lorenzo , Vila Alejandro J.
Published: September 2005

Metallo-β-lactamases (MBLs) represent the latest generation of β-lactamases. The structural diversity and broad substrate profile of MBLs allow them to confer resistance to most β-lactam antibiotics. To explore the evolutionary potential of these enzymes, we have subjected the
Bacillus cereus
MBL (BcII) to a directed evolution scheme, which resulted in an increased hydrolytic efficiency toward cephalexin. A systematic study of the hydrolytic profile, substrate binding, and active-site features of the evolved lactamase reveal that directed evolution has shaped the active site by means of remote mutations to better hydrolyze cephalosporins with small, uncharged C-3 substituents. One of these mutations is found in related enzymes from pathogenic bacteria and is responsible for the increase in that enzyme's hydrolytic profile. The mutations lowered the activation energy of the rate-limiting step rather than improved the affinity of the enzyme toward these substrates. The following conclusions can be made: (
i
) MBLs are able to expand their substrate spectrum without sacrificing their inherent hydrolytic capabilities; (
ii
) directed evolution is able to mimic mutations that occur in nature; (
iii
) the metal-ligand strength is tuned by second-shell mutations, thereby influencing the catalytic efficiency; and (
iv
) changes in the position of the second Zn(II) ion in MBLs affect the substrate positioning in the active site. Overall, these results show that the evolution of enzymatic catalysis can take place by remote mutations controlling reactivity.
Monomeric inducible nitric oxide synthase localizes to peroxisomes in hepatocytes
Authors: Loughran P. A. , Stolz D. B. , Vodovotz Y. , Watkins S. C. , Simmons R. L. , Billiar T. R.
Published: September 2005

Hepatocytes are capable of repeated inducible NO synthase (iNOS) expression, which occurs under inflammatory and stress conditions. This iNOS expression regulates a number of cellular functions as well as cell viability. To better understand the posttranslational mechanisms that regulate the fate of iNOS in these cells, we characterized the iNOS distributed within peroxisomes. The selective permeabilization of membranes (plasma vs. peroxisomal) confirmed that there are cytosolic and peroxisomal pools of iNOS in cytokine-stimulated hepatocytes and that the iNOS protein associates with peroxisome. Detergent solubilization of the membrane fraction released iNOS to the soluble fraction. iNOS localized to membrane fraction is predominantly monomeric, but dimerization is partially reconstituted rapidly upon incubation with tetrahydrobiopterin. The reconstituted iNOS exhibits a lower specific activity than iNOS isolated from the soluble pool. Depletion of intracellular tetrahydrobiopterin with an inhibitor ofde novopterin synthesis resulted in a predominance of monomeric iNOS without a greater relative distribution of iNOS to the peroxisomal pool. Thus, iNOS exists in a least two pools in hepatocytes: a soluble pool composed of both active dimer and monomer and a peroxisomal pool of monomeric iNOS. iNOS might localize to peroxisomes in long-lived cells such as hepatocytes as a protective mechanism to remove incompetent enzyme.
Electrochemical imaging of fusion pore openings by electrochemical detector arrays
Authors: Hafez Ismail , Kisler Kassandra , Berberian Khajak , Dernick Gregor , Valero Vicente , Yong Ming G. , Craighead Harold G. , Lindau Manfred
Published: September 2005

Opening of individual exocytotic fusion pores in chromaffin cells was imaged electrochemically with high time resolution. Electrochemical detector arrays that consist of four platinum microelectrodes were microfabricated on a glass coverslip. Exocytosis of single vesicles containing catecholamines from a cell positioned on top of the array is detected by the individual electrodes as a time-resolved oxidation current, reflecting the time course of arrival of catecholamine molecules at the electrode surfaces. The signals exhibit low noise and reveal foot signals indicating fusion pore formation and expansion. The position of individual release events is determined from the fraction of catecholamines recorded by the individual electrodes. Simultaneous fluorescence imaging of release of acridine orange from individual vesicles confirmed the electrochemical position assignments. This electrochemical camera provides very high time resolution, spatiotemporal localization of individual fusion pore openings and quantitative data on the flux of transmitter from individual vesicles. Analysis of the amperometric currents employing random walk simulations indicates that the time course of amperometric spikes measured near the cell surface is due to a low apparent diffusion coefficient of cat-echolamines near the cell surface and not due to slow dissociation from the granular matrix.
Dissociation of telomerase activity and telomere length maintenance in primitive human hematopoietic cells
Authors: Wang J. C. Y. , Warner J. K. , Erdmann N. , Lansdorp P. M. , Harrington L. , Dick J. E.
Published: September 2005

Primitive human hematopoietic cells have low endogenous telomerase activity, yet telomeres are not maintained. In contrast, ectopic telomerase expression in fibroblasts and other cells leads to telomere length maintenance or elongation. It is unclear whether this disparity can be attributed to telomerase level or stems from fundamentally different telomere biology. Here, we show that telomerase overexpression does not prevent proliferation-associated telomere shortening in human hematopoietic cells, pointing to the existence of cell type-specific differences in telomere dynamics. Furthermore, we observed eventual stabilization of telomere length without detectable changes in telomerase activity during establishment of two leukemic cell lines from normal cord blood cells, indicating that additional cooperating events are required for telomere maintenance in immortalized human hematopoietic cells.
Amplification of a chromatin remodeling gene, Rsf-1/HBXAP, in ovarian carcinoma
Authors: Shih Ie-Ming , Sheu Jim Jinn-Chyuan , Santillan Antonio , Nakayama Kentaro , Yen M. Jim , Bristow Robert E. , Vang Russell , Parmigiani Giovanni , Kurman Robert J. , Trope Claes G. , Davidson Ben , Wang Tian-Li
Published: September 2005

A genomewide technology, digital karyotyping, was used to identify subchromosomal alterations in ovarian cancer. Amplification at 11q13.5 was found in three of seven ovarian carcinomas, and amplicon mapping delineated a 1.8-Mb core of amplification that contained 13 genes. FISH analysis demonstrated amplification of this region in 13.2% of high-grade ovarian carcinomas but not in any of low-grade carcinomas or benign ovarian tumors. Combined genetic and transcriptome analyses showed that Rsf-1 (HBXAPalpha) was the only gene that demonstrated consistent overexpression in all of the tumors harboring the 11q13.5 amplification. Patients with Rsf-1 amplification or overexpression had a significantly shorter overall survival than those without. Overexpression of Rsf-1 gene stimulated cell proliferation and transform nonneoplastic cells by conferring serum-independent and anchorage-independent growth. Furthermore, Rsf-1 gene knockdown inhibited cell growth in OVCAR3 cells, which harbor Rsf-1 amplification. Taken together, these findings indicate an important role of Rsf-1 amplification in ovarian cancer.
NO-mediated cytoprotection: Instant adaptation to oxidative stress in bacteria
Authors: Gusarov Ivan , Nudler Evgeny
Published: September 2005

Numerous sophisticated systems have been described that protect bacteria from increased levels of reactive oxygen species. Although indispensable during prolonged oxidative stress, these response systems depend on newly synthesized proteins, and are hence both time and energy consuming. Here, we describe an “express” cytoprotective system in
Bacillus subtilis
which depends on nitric oxide (NO). We show that NO immediately protects bacterial cells from reactive oxygen species by two independent mechanisms. NO transiently suppresses the enzymatic reduction of free cysteine that fuels the damaging Fenton reaction. In addition, NO directly reactivates catalase, a major antioxidant enzyme that has been inhibited
in vivo
by endogenous cysteine. Our data also reveal a critical role for bacterial NO-synthase in adaptation to oxidative stress associated with fast metabolic changes, and suggest a possible role for NO in defending pathogens against immune oxidative attack.
Gene expression profiling reveals a signaling role of glutathione in redox regulation
Authors: Fratelli Maddalena , Goodwin Leslie O. , Ørom Ulf Andersson , Lombardi Sarah , Tonelli Rossella , Mengozzi Manuela , Ghezzi Pietro
Published: September 2005

Proteins can form reversible mixed disulfides with glutathione (GSH). It has been hypothesized that protein glutathionylation may represent a mechanism of redox regulation, in a fashion similar to that mediated by protein phosphorylation. We investigated whether GSH has a signaling role in the response of HL60 cells to hydrogen peroxide (H2O2), in addition to its obvious antioxidant role. We identified early changes in gene expression induced at different times by H2O2treatment, under conditions that increase protein glutathionylation and minimal toxicity. We then investigated the effect of prior GSH depletion by buthionine sulfoximine and diethylmaleate on this response. The analysis revealed 2,016 genes regulated by H2O2. Of these, 215 genes showed GSH-dependent expression changes, classifiable into four clusters displaying down- or up-regulation by H2O2, either potentiated or inhibited by GSH depletion. The modulation of 20 selected genes was validated by real-time RT-PCR. The biological process categories overrepresented in the largest cluster (genes whose up-regulation was inhibited by GSH depletion) were NF-κB activation, transcription, and DNA methylation. This cluster also included several cytokine and chemokine ligands and receptors, the redox regulator thioredoxin interacting protein, and the histone deacetylase sirtuin. The cluster of genes whose up-regulation was potentiated by GSH depletion included two HSPs (HSP40 and HSP70) and the AP-1 transcription factor components Fos and FosB. This work demonstrates that GSH, in addition to its antioxidant and protective function against oxidative stress, has a specific signaling role in redox regulation.
Pathogenic myelin oligodendrocyte glycoprotein antibodies recognize glycosylated epitopes and perturb oligodendrocyte physiology
Authors: Marta Cecilia B. , Oliver Alfred R. , Sweet Rebecca A. , Pfeiffer Steven E. , Ruddle Nancy H.
Published: September 2005

Antibodies to myelin components are routinely detected in multiple sclerosis patients. However, their presence in some control subjects has made it difficult to determine their contribution to disease pathogenesis. Immunization of C57BL/6 mice with either rat or human myelin oligodendrocyte glycoprotein (MOG) leads to experimental autoimmune encephalomyelitis (EAE) and comparable titers of anti-MOG antibodies as detected by ELISA. However, only immunization with human (but not rat) MOG results in a B cell-dependent EAE. In this study, we demonstrate that these pathogenic and nonpathogenic anti-MOG antibodies have a consistent array of differences in their recognition of antigenic determinants and biological effects. Specifically, substituting proline at position 42 with serine in human MOG (as in rat MOG) eliminates the B cell requirement for EAE. All MOG proteins analyzed induced high titers of anti-MOG (tested by ELISA), but only antisera from mice immunized with unmodified human MOG were encephalitogenic in primed B cell-deficient mice. Nonpathogenic IgGs bound recombinant mouse MOG and deglycosylated MOG in myelin (tested by Western blot), but only pathogenic IgGs bound glycosylated MOG. Only purified IgG to human MOG bound to live rodent oligodendrocytes in culture and, after cross-linking, induced repartitioning of MOG into lipid rafts, followed by dramatic changes in cell morphology. The data provide a strong link betweenin vivoandin vitroobservations regarding demyelinating disease, further indicate a biochemical mechanism for anti-MOG-induced demyelination, and suggestin vitrotools for determining autoimmune antibody pathogenicity in multiple sclerosis patients.
Identification of slow correlated motions in proteins using residual dipolar and hydrogen-bond scalar couplings
Authors: Bouvignies Guillaume , Bernadó Pau , Meier Sebastian , Cho Kyuil , Grzesiek Stephan , Brüschweiler Rafael , Blackledge Martin
Published: September 2005

Despite their importance for biological activity, slower molecular motions beyond the nanosecond range remain poorly understood. We have assembled an unprecedented set of experimental NMR data, comprising up to 27 residual dipolar couplings per amino acid, to define the nature and amplitude of backbone motion in protein G using the Gaussian axial fluctuation model in three dimensions. Slower motions occur in the loops, and in the β-sheet, and are absent in other regions of the molecule, including the α-helix. In the β-sheet an alternating pattern of dynamics along the peptide sequence is found to form a long-range network of slow motion in the form of a standing wave extending across the β-sheet, resulting in maximal conformational sampling at the interaction site. The alternating nodes along the sequence match the alternation of strongly hydrophobic side chains buried in the protein core. Confirmation of the motion is provided through extensive cross-validation and by independent hydrogen-bond scalar coupling analysis that shows this motion to be correlated. These observations strongly suggest that dynamical information can be transmitted across hydrogen bonds and have important implications for understanding collective motions and long-range information transfer in proteins.
Rapid inactivation of a moth pheromone
Authors: Ishida Yuko , Leal Walter S.
Published: September 2005

We have isolated, cloned, and expressed a male antennae-specific pheromone-degrading enzyme (PDE) [
Antheraea polyphemus
PDE (ApolPDE), formerly known as Sensillar Esterase] from the wild silkmoth,
A. polyphemus
, which seems essential for the rapid inactivation of pheromone during flight. The onset of enzymatic activity was detected at day 13 of the pupal stage with a peak at day 2 adult stage.
De novo
sequencing of ApolPDE, isolated from day 2 male antennae by multiple chromatographic steps, led to cDNA cloning. Purified recombinant ApolPDE, expressed by baculovirus, migrated with the same mobility as the native protein on both native polyacrylamide and isoelectric focusing gel electrophoresis. Concentration of ApolPDE (0.5 μM) in the sensillar lymph is ≈20,000 lower than that of a pheromone-binding protein. Native and recombinant ApolPDE showed comparable kinetic parameters, with turnover number similar to that of carboxypeptidase and substrate specificity slightly lower than that of acetylcholinesterase. The rapid inactivation of pheromone, even faster than previously estimated, is kinetically compatible with the temporal resolution required for sustained odorant-mediated flight in moths.
Replica exchange with solute tempering: A method for sampling biological systems in explicit water
Authors: Liu Pu , Kim Byungchan , Friesner Richard A. , Berne B. J.
Published: September 2005

An innovative replica exchange (parallel tempering) method called replica exchange with solute tempering (REST) for the efficient sampling of aqueous protein solutions is presented here. The method bypasses the poor scaling with system size of standard replica exchange and thus reduces the number of replicas (parallel processes) that must be used. This reduction is accomplished by deforming the Hamiltonian function for each replica in such a way that the acceptance probability for the exchange of replica configurations does not depend on the number of explicit water molecules in the system. For proof of concept, REST is compared with standard replica exchange for an alanine dipeptide molecule in water. The comparisons confirm that REST greatly reduces the number of CPUs required by regular replica exchange and increases the sampling efficiency. This method reduces the CPU time required for calculating thermodynamic averages and for the
ab initio
folding of proteins in explicit water.
Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway
Authors: Kang Yibin , He Wei , Tulley Shaun , Gupta Gaorav P. , Serganova Inna , Chen Chang-Rung , Manova-Todorova Katia , Blasberg Ronald , Gerald William L. , Massagué Joan
Published: September 2005

TGF-β can signal by means of Smad transcription factors, which are quintessential tumor suppressors that inhibit cell proliferation, and by means of Smad-independent mechanisms, which have been implicated in tumor progression. Although Smad mutations disable this tumor-suppressive pathway in certain cancers, breast cancer cells frequently evade the cytostatic action of TGF-β while retaining Smad function. Through immunohistochemical analysis of human breast cancer bone metastases and functional imaging of the Smad pathway in a mouse xenograft model, we provide evidence for active Smad signaling in human and mouse bone-metastatic lesions. Genetic depletion experiments further demonstrate that Smad4 contributes to the formation of osteolytic bone metastases and is essential for the induction of
IL-11
, a gene implicated in bone metastasis in this mouse model system. Activator protein-1 is a key participant in Smad-dependent transcriptional activation of
IL
-
11
and its overexpression in bone-metastatic cells. Our findings provide functional evidence for a switch of the Smad pathway, from tumor-suppressor to prometastatic, in the development of breast cancer bone metastasis.
Mammalian sprouty proteins assemble into large monodisperse particles having the properties of intracellular nanobatteries
Authors: Wu Xinle , Alexander Peter B. , He Ying , Kikkawa Masahide , Vogel Pia D. , McKnight Steven L.
Published: September 2005

Sprouty proteins act as intracellular inhibitors of receptor tyrosine kinase signaling. Here we show that the mammalian Sprouty2 protein contains an iron-sulfur complex that can exist in an oxidized, reduced, or nitrosylated state. Purified Sprouty2 assembles into large monodisperse spheres containing ≈24 polypeptides per particle. Biochemical experiments indicate that the charge state of the iron within Sprouty2 particles may be insulated from ambient intracellular redox. These features offer the possibility that Sprouty2 particles are capable of receiving, maintaining, and dissipating electrical charge in a manner formally equivalent to a battery.
Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice
Authors: Cummings Brian J. , Uchida Nobuko , Tamaki Stanley J. , Salazar Desirée L. , Hooshmand Mitra , Summers Robert , Gage Fred H. , Anderson Aileen J.
Published: September 2005

We report that prospectively isolated, human CNS stem cells grown as neurospheres (hCNS-SCns) survive, migrate, and express differentiation markers for neurons and oligodendrocytes after long-term engraftment in spinal cord-injured NOD-
scid
mice. hCNS-SCns engraftment was associated with locomotor recovery, an observation that was abolished by selective ablation of engrafted cells by diphtheria toxin. Remyelination by hCNS-SCns was found in both the spinal cord injury NOD-
scid
model and myelin-deficient
shiverer
mice. Moreover, electron microscopic evidence consistent with synapse formation between hCNS-SCns and mouse host neurons was observed. Glial fibrillary acidic protein-positive astrocytic differentiation was rare, and hCNS-SCns did not appear to contribute to the scar. These data suggest that hCNS-SCns may possess therapeutic potential for CNS injury and disease.
Rapid hydrolysis of ATP by mitochondrial F
1
-ATPase correlates with the filling of the second of three catalytic sites
Authors: Milgrom Yakov M. , Cross Richard L.
Published: September 2005

Strong positive catalytic cooperativity is a central feature of the binding change mechanism for F
1
-ATPases. However, a detail of the mechanism that remains controversial is whether the kinetic enhancement derived from using substrate-binding energy at one catalytic site to promote product release from another site occurs upon the filling of the second or third of three catalytic sites on F
1
. To address this question, we compare the ATP concentration dependence of the rate of ATP hydrolysis by F
1
from beef heart mitochondria to the ATP concentration dependence of the level of occupancy of catalytic sites during steady-state catalysis as measured by a centrifuge filtration assay. A single
K
m
(ATP) is observed at 77 ± 6 μM. Analysis of the nucleotide-binding data shows that half-maximal occupancy of a second catalytic site occurs at 78 ± 18 μM ATP. We conclude that ATP binding to a second catalytic site is sufficient to support rapid rates of catalysis.
Symbolic Boundaries and National Borders: The Construction of an Estonian Russian Identity
Authors: Fein Lisa C.
Published: September 2005

If the destruction of the Berlin Wall came to symbolize freedom in Central Europe, for the republics of the former Soviet Union it was the construction and recognition of new walls in the form of national borders that represented liberation. In the case of Estonia, the end of what was considered illegal Soviet occupation marked a return to the country's republic's rightful place as an independent, European nation. In demographic respects, however, Estonia could not easily escape the legacies of Soviet rule, due in part to the migration of hundreds of thousands of non-ethnic Estonians to the Estonian SSR. Far from completing a clean break with the past, Estonian independence has replaced legal distinctions between nationalities with social and symbolic boundaries between ethnic groups.
The effect of contextual factors on the judgement of informal reasoning fallacies
Authors: Neuman Yair , Weinstock Michael P. , Glasner Amnon
Published: September 2005

Informal reasoning fallacies are arguments that are psychologically persuasive but not valid. In order to judge the validity of these arguments one has to be sensitive to the context in which they appear. However, there is no empirical study that examines students’ sensitivity to contextual factors and whether contextual factors actually influence their ability to identify informal reasoning fallacies. We hypothesized that when explicitly presented with different argumentative contexts, students’ performance would reflect their sensitivity to the contextual nature of informal reasoning fallacies. The two experiments that we conducted support this hypothesis and emphasize the mediating role of perspective taking in students’ ability to identify fallacious arguments.
Ganglioside-induced differentiation associated protein 1 is a regulator of the mitochondrial network
Authors: Niemann Axel , Ruegg Marcel , La Padula Veronica , Schenone Angelo , Suter Ueli
Published: September 2005

Mutations in GDAP1 lead to severe forms of the peripheral motor and sensory neuropathy, Charcot-Marie-Tooth disease (CMT), which is characterized by heterogeneous phenotypes, including pronounced axonal damage and demyelination. We show that neurons and Schwann cells express ganglioside-induced differentiation associated protein 1 (GDAP1), which suggest that both cell types may contribute to the mixed features of the disease. GDAP1 is located in the mitochondrial outer membrane and regulates the mitochondrial network. Overexpression of GDAP1 induces fragmentation of mitochondria without inducing apoptosis, affecting overall mitochondrial activity, or interfering with mitochondrial fusion. The mitochondrial fusion proteins, mitofusin 1 and 2 and Drp1(K38A), can counterbalance the GDAP1-dependent fission. GDAP1-specific knockdown by RNA interference results in a tubular mitochondrial morphology. GDAP1 truncations that are found in patients who have CMT are not targeted to mitochondria and have lost mitochondrial fragmentation activity. The latter activity also is reduced strongly for disease-associated GDAP1 point mutations. Our data indicate that an exquisitely tight control of mitochondrial dynamics, regulated by GDAP1, is crucial for the proper function of myelinated peripheral nerves.
Modulations on turbulent characteristics by dispersed particles in gas–solid jets
Authors: Luo Kun , Fan Jianren , Cen Kefa
Published: September 2005

A direct numerical simulation technique combined with a two-way coupling method was developed to study a gas–solid turbulent jet with a moderately high Reynolds number. The flow was weakly compressible and spatially developing. A high-resolution solver was performed for the gas phase flow-field and the Lagrangian method was used to trace particles. The modulations on flow structures and other turbulent characteristics by particles at different Stokes numbers were investigated. It is found that the particles at Stokes numbers of 0.01 and 50 can advance the development of the large-scale vortex structures and make the turbulence intensity profiles wider and lower, but the particles at a Stokes number of 1 delay the evolution of the large-scale vortex structures and decrease the turbulence intensities. The jet velocity half-width and the decay of the streamwise mean velocity in the jet centreline are reduced by all particles, in which particles at a Stokes number of 0.01 result in a larger reduction of the velocity half-width and particles at a Stokes number of 1 lead to a larger reduction of the streamwise mean velocity decay. All particles decrease the vorticity thickness, but increase the fluid momentum thickness. In addition, the two-way coupled particle distribution is more uniform than that of the one-way coupled case.
Geometry of Călugăreanu's theorem
Authors: Dennis M.R , Hannay J.H
Published: September 2005

A central result in the space geometry of closed twisted ribbons is Călugăreanu's theorem (also known as White's formula, or the Călugăreanu–White–Fuller theorem). This enables the integer linking number of the two edges of the ribbon to be written as the sum of the ribbon twist (the rate of rotation of the ribbon about its axis) and its writhe. We show that twice the twist is the average, over all projection directions, of the number of places where the ribbon appears edge-on (signed appropriately)—the ‘local’ crossing number of the ribbon edges. This complements the common interpretation of writhe as the average number of signed self-crossings of the ribbon axis curve. Using the formalism we develop, we also construct a geometrically natural ribbon on any closed space curve—the ‘writhe framing’ ribbon. By definition, the twist of this ribbon compensates its writhe, so its linking number is always zero.
Genetic linkage between a sexually selected trait and X chromosome meiotic drive
Authors: Johns Philip M , Wolfenbarger L. LaReesa , Wilkinson Gerald S
Published: September 2005

Previous studies on the stalk-eyed fly,Cyrtodiopsis dalmanni, have shown that males with long eye-stalks win contests and are preferred by females, and artificial selection on male relative eye span alters brood sex-ratios. Subsequent theory proposes that X-linked meiotic drive can catalyse the evolution of mate preferences when drive is linked to ornament genes. Here we test this prediction by mapping meiotic drive and quantitative trait loci (QTL) for eye span. To map QTL we genotyped 24 microsatellite loci using 1228 F2 flies from two crosses between lines selected for long or short eye span. The crosses differed by presence or absence of a drive X chromosome, XD, in the parental male. Linkage analysis reveals that XDdramatically reduces recombination between X and XDchromosomes. In the XDcross, half of the F2 males carried the drive haplotype, produced partially elongated spermatids and female-biased broods, and had shorter eye span. The largest QTL mapped 1.3 cM from drive on the X chromosome and explained 36% of the variation in male eye span while another QTL mapped to an autosomal region that suppresses drive. These results indicate that selfish genetic elements that distort the sex-ratio can influence the evolution of exaggerated traits.
Evolution of body size in Galapagos marine iguanas
Authors: Wikelski Martin
Published: September 2005

Body size is one of the most important traits of organisms and allows predictions of an individual's morphology, physiology, behaviour and life history. However, explaining the evolution of complex traits such as body size is difficult because a plethora of other traits influence body size. Here I review what we know about the evolution of body size in a group of island reptiles and try to generalize about the mechanisms that shape body size. Galapagos marine iguanas occupy all 13 larger islands in this Pacific archipelago and have maximum island body weights between 900 and 12 000 g. The distribution of body sizes does not match mitochondrial clades, indicating that body size evolves independently of genetic relatedness. Marine iguanas lack intra- and inter-specific food competition and predators are not size-specific, discounting these factors as selective agents influencing body size. Instead I hypothesize that body size reflects the trade-offs between sexual and natural selection. We found that sexual selection continuously favours larger body sizes. Large males establish display territories and some gain over-proportional reproductive success in the iguanas' mating aggregations. Females select males based on size and activity and are thus responsible for the observed mating skew. However, large individuals are strongly selected against during El Niño-related famines when dietary algae disappear from the intertidal foraging areas. We showed that differences in algae sward (‘pasture’) heights and thermal constraints on large size are causally responsible for differences in maximum body size among populations. I hypothesize that body size in many animal species reflects a trade-off between foraging constraints and sexual selection and suggest that future research could focus on physiological and genetic mechanisms determining body size in wild animals. Furthermore, evolutionary stable body size distributions within populations should be analysed to better understand selection pressures on individual body size.
Rural Women, Displacement and the Three Gorges Project
Authors: Tan Yan , Hugo Graeme , Potter Lesley
Published: September 2005

Based on empirical research, this article examines the status, situations and development issues of rural women displaced by the monumental Three Gorges Project (TGP) in China. The study reveals that TGP resettlement is leaving women worse off as family members, as well as worse off than male members. Woman resettlers are more likely to become impoverished than men, partly because women make up the main labour force in agricultural sectors. Most women are unable to achieve occupational mobility in the process of resettlement. Fewer employment opportunities, a gender‐segregated labour market, low level of human capital and social prejudice are principal causes. Land provision for resettlers is inadequate with a lower quality of productivity. Marriage is a means for some women to remain in or move to the reservoir area to improve their socio‐economic status, but bias against granting of ‘resettler’ status to married women and their generally low levels of education and lack of occupational skills work against them. It is imperative that the authorities integrate a gender perspective into policy‐making and design of resettlement schemes.