bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydration force between model hydrophilic surfaces: Computer simulations
Authors: Lu L. , Berkowitz M. L.
Published: March 2006

We performed molecular dynamics simulations to study the interactions between model hydrophilic plates made of carbon atoms distributed on a hexagonal lattice. Although neutral, the plates carry equal amounts of positive and negative charges to represent physical dipoles. Using the thermodynamic perturbation theory we calculated the potential of mean force (PMF) acting between the plates as a function of the distance between these plates. We observed that, at distances when more than one water layer can be found between the plates, the contribution of water into the PMF can be either attractive or repulsive depending on the correlation between the charges situated on the plates.
Dielectric stripes on gold as surface plasmon waveguides
Authors: Steinberger B. , Hohenau A. , Ditlbacher H. , Stepanov A. L. , Drezet A. , Aussenegg F. R. , Leitner A. , Krenn J. R.
Published: February 2006

We report on surface plasmon polariton (SPP) waveguiding by SiO2 stripes on gold thin films. Compared to other SPP waveguide schemes, these systems provide relatively large effective refractive indices which can be described by the effective index method. By leakage radiation and near-field optical microscopy, we observe directly multimode and monomode behavior in straight SPP waveguides of different widths. Furthermore, we demonstrate waveguide bends and cross-talk free propagation across waveguide crossings.
Uniaxial in-plane magnetic anisotropy of a CoPt thin film induced by ion irradiation
Authors: Chang G. S. , Moewes A. , Kim S. H. , Lee J. , Jeong K. , Whang C. N. , Kim D. H. , Shin S.-C.
Published: February 2006

The mechanism for ion-induced uniaxial magnetic anisotropy of ferromagnetic CoPt thin films is investigated using x-ray diffraction and soft x-ray emission spectroscopy. When Co∕Pt multilayers 64nm thick are irradiated with 80keV Ar+ ions in an externally applied magnetic field, the magnetization of the ion-irradiated area shows a significant anisotropic angular dispersion in its hysteresis. Analysis of x-ray diffraction patterns and CoL3 emission spectra reveals that the formation of partially ordered (face-centered-tetragonal) CoPt phase and nonequivalent electronic hybridization between easy and hard axes causes the induction of a uniaxial magnetic anisotropy.
Tuning emission color of electroluminescence from two organic interfacial exciplexes by modulating the thickness of middle gadolinium complex layer
Authors: Li Mingtao , Li Wenlian , Chen Lili , Kong Zhiguo , Chu Bei , Li Bin , Hu Zhizhi , Zhang Zhiqiang
Published: February 2006

Electroluminescent colors of organic light-emitting diodes (OLEDs) can be tuned by modulating the thickness of gadolinium (Gd) complex layer sandwiched between an electron-transporting layer (ETL) and a hole-transporting layer (HTL). The emission colors, which originate from the two interfacial exciplexes simultaneously, can be tuned from green to orange by increasing the thickness of the Gd-complex layer. The atom force microscope images have proved that there are many gaps in the thinner Gd-complex layers. Therefore, besides the exciplex formation between Gd complex and HTL, the exciplex between ETL and HTL is also formed. The results demonstrate that a simple way of color tuning can be realized by inserting a thin layer of color tuning material between HTL with lower ionization potentials and ETL with higher electron affinities. Moreover, photovoltaic device and white OLED based on the two exciplexes are also discussed.
Effect of gettered iron on recombination in diffused regions of crystalline silicon wafers
Authors: Macdonald D. , Mäckel H. , Cuevas A.
Published: February 2006

Crystalline silicon wafers, intentionally precontaminated with iron, were diffused with phosphorus and boron, and the recombination properties of the bulk and diffused regions extracted from injection-dependent carrier lifetime measurements. While the phosphorus diffusions were found to getter more than 99% of the iron from the bulk, the boron diffusions only extracted 65% in the best case. The presence of this gettered iron caused significant additional recombination in the boron diffused layers, while it had no measurable impact on the phosphorus diffused regions. This may be a consequence of the small capture cross section for holes of interstitial iron.
Simultaneous formation of surface ripples and metallic nanodots induced by phase decomposition and focused ion beam patterning
Authors: Lian Jie , Zhou Wei , Wei Q. M. , Wang L. M. , Boatner L. A. , Ewing Rodney C.
Published: February 2006

We report the simultaneous formation of self-assembled surface ripples in Cd2Nb2O7 pyrochlore caused by focused ion beam (FIB) patterning and uniformly distributed metallic nanodots induced by phase decomposition under ion bombardment. The characteristic wavelength of the surface ripples is controllable from the nm to the sub-μm scale. High-density Cd metallic nanoparticles, ∼5nm, formed and the distribution of nanoparticles is consistent with the morphological characteristics of the ripple pattern. This approach provides a means of fabricating surface nanostructure with various patterns and a controllable particle size and distribution by combining ion beam-induced phase decomposition with high-precision FIB patterning.
Ab initio calculations for properties of MAX phases Ti2TlC, Zr2TlC, and Hf2TlC
Authors: Warner J. A. , Patil S. K. R. , Khare S. V. , Masiulaniec K. C.
Published: March 2006

Using ab initio calculations we have computed the lattice constants, bulk moduli, and local and total density of states of the MAX phases, Ti2TlC, Zr2TlC, and Hf2TlC in the hexagonal P63∕mmc space group. The results for lattice constants are within 2% of experimental results. The bulk moduli are predicted to be 125, 120, and 131GPa, respectively. These are the lowest values of bulk moduli among all MAX phases studied to date. The electronic density of states shows that all three materials are conducting. These low values of their bulk moduli are attributed to weak metal M (M=Ti,Zr,Hf) bonding with the A element thallium.
Negative feedback optical amplification effect based on cross-gain modulation in semiconductor optical amplifiers
Authors: Maeda Yoshinobu
Published: March 2006

A negative feedback optical amplification effect was confirmed using negative feedback based on cross-gain modulation in an InGaAsP∕InP semiconductor optical amplifier. The optical amplifier with negative feedback was capable of providing an output signal whose gain, wave form and baseline, were stabilized optically. The distortion of the wave form was extremely small in a wide frequency band of 0.1–10GHz. In addition, the gain can be adjusted by controlling the amount of negative feedback power using a variable optical attenuator. In physics, the optical amplifier is considered as the optical equivalent of a noninverting operational amplifier in electronics.
Passivation of an isoelectronic impurity by atomic hydrogen: The case of ZnTe:O
Authors: Felici Marco , Polimeni Antonio , Capizzi Mario , Nabetani Y. , Okuno T. , Aoki K. , Kato T. , Matsumoto T. , Hirai T.
Published: March 2006

We investigated the optical properties of ZnTe:O∕GaAs before and after atomic hydrogen irradiation. Oxygen incorporation gives rise to energy levels associated with single O atoms, O–O pairs, and O clusters, and to a blueshift of the energy gap of the material with respect to that of pure ZnTe∕GaAs. All of these effects disappear progressively after irradiation with H, which also leads to an increase in the tensile strain of the epilayer. These observations provide experimental evidence of H-induced passivation of an isoelectronic impurity in II–VI alloys.
Fabrication of n-type carbon nanotube field-effect transistors by Al doping
Authors: Oh Hwangyou , Kim Ju-Jin , Song Woon , Moon Sunkyung , Kim Nam , Kim Jinhee , Park Noejung
Published: March 2006

We report the effect of an Al layer, covering the central part of the nanotube channel, on the electrical transport properties of carbon nanotube field-effect transistors (CNFETs). The CNFETs, consisting of single-walled carbon nanotube or double-walled carbon nanotube between two Pd electrodes on top of SiO2 layer, which showed p-type or ambipolar transport behaviors, exhibit clear n-type characteristics after the Al deposition. We ascribe such conversions into n-type behaviors to the electron doping in the Al-covered nanotube region, which results in the bending of the nanotube bands nearby the edges of the Al layer. This technique, Al deposition under a high vacuum, may give rise to a practical fabrication method for the n-type CNFET, which may enable us to develop complementary logic nanotube electronic devices.
Tuning of magnetocaloric effect in a La0.69Ca0.31MnO3 single crystal by pressure
Authors: Sun Young , Kamarad J. , Arnold Z. , Kou Zhi-qi , Cheng Zhao-hua
Published: March 2006

We report a study of the effect of hydrostatic pressure on the magnetocaloric effect in a La0.69Ca0.31MnO3 single crystal. The single crystal exhibits a much larger magnetic entropy change (ΔSm) than the corresponding polycrystalline samples, reaching 5.2J∕kgK and 8.5J∕kgK for a magnetic field variation of 1T and 5T, respectively. Under hydrostatic pressure, the peak position of ΔSm significantly moves to higher temperatures due to the shift of the magnetic phase transition, from 213.5K under ambient pressure up to 236.5K under a pressure of 1.1GPa, while the maximum value of ΔSm remains nearly the same. These exceptional results demonstrate that the magnetocaloric effect in magnetic materials with strong spin-lattice coupling can be effectively tuned by pressure.
Seed predation by birds shortly after a wildfire in a Corsican pine forest
Authors: Thibault Jean-Claude , Prodon Roger
Published: March 2006

We examined the response of birds to a severe summer wildfire in a Corsican pine forest during the first months following the disturbance. Only seed-eating species visited the burnt areas in large numbers. While certain trunks or branches were still burning, numerous birds, among them the coal tit Parus ater and the Corsican nuthatch Sitta whiteheadi, were attracted by the large amount of pine seeds made available by the opening of the cones under the action of heat. The number of seed-harvesting birds declined afterwards. We discuss how seed hoarding by tits and nuthatches enabled these resident birds to survive during the first winter after the fire in a burnt environment where seeds remained the only potential food source.
Soil water dynamics after fire in a Portuguese shrubland
Authors: Silva Joaquim S. , Rego Francisco C. , Mazzoleni Stefano
Published: March 2006

This paper presents a study where soil water content (SW) was measured before and after an experimental fire in a shrubland dominated by Erica scoparia L. in Portugal. Two plots were established: one was kept as a control plot and the other was burned by an experimental fire in June 2001. Measurements were taken before fire (2000), and after fire (2001, 2002, and 2003) at six depths down to 170 cm, from June to December. Measurements before fire allowed comparison of the two plots in terms of the SW differential, using 2000 as a reference. Results for 2001 showed that SW decreased less during the drying season (June–September) and increased more during the wetting season (October–December) in the burned plot than in the control plot. The magnitude of these effects decreased consistently in 2002 and 2003, especially at surface layers. The maximum gain of SW for the total profile in the burned plot was estimated as 105.5 mm in 2001, 70.2 mm in 2002, and 35.6 mm in 2003. The present paper discusses the mechanisms responsible for the increase in SW taking into account the characteristics of the plant community, including the root distribution, and the results of other studies.
Prediction and measurement of thermally induced cambial tissue necrosis in tree stems
Authors: Jones Joshua L. , Webb Brent W. , Butler Bret W. , Dickinson Matthew B. , Jimenez Daniel , Reardon James , Bova Anthony S.
Published: March 2006

A model for fire-induced heating in tree stems is linked to a recently reported model for tissue necrosis. The combined model produces cambial tissue necrosis predictions in a tree stem as a function of heating rate, heating time, tree species, and stem diameter. Model accuracy is evaluated by comparison with experimental measurements in two hardwood and two softwood species: red maple (Acer rubrum), chestnut oak (Quercus prinus), ponderosa pine (Pinus ponderosa), and Douglas-fir (Pseudotsuga menziesii). Results are promising, and indicate that the model predicts stem mortality/survival correctly in ~75–80% of the test cases. A limited sensitivity analysis of model kill depth predictions suggests that the model is more sensitive to required input data for some species than for others, and that the certainty in predicting vascular cambium necrosis decreases as stem diameter decreases.
Post-fire epicormic branching in Sierra Nevada Abies concolor (white fir)
Authors: Hanson Chad T. , North Malcolm P.
Published: March 2006

In California’s mixed-conifer forest, which historically had a regime of frequent fires, two conifers, Sequoiadendron giganteum and Pseudotsuga menziesii, were previously known to produce epicormic sprouts from branches. We found epicormic branching in a third mixed-conifer species, Abies concolor, 3 and 4 years after a wildfire in the central Sierra Nevada Mountains of California. Sprouting occurred only from the boles. We investigated (1) whether the degree of crown loss and the extent of epicormic branching were independent; and (2) whether epicormic branching differed by tree size. The vertical extent of epicormic foliage increased with increasing severity of crown loss. There was a significantly greater proportion of large diameter-class (>50 cm diameter at breast height [dbh]) trees with epicormic branching than small/medium diameter-class (25–50 cm dbh) trees. These results suggest large diameter Abies concolor may survive high levels of crown loss, aided by crown replacement through epicormic branching, but that reiterative green foliage may not appear for up to 3 years after fire damage. If this response is widespread, it would suggest some ‘dying’ trees logged under current salvage guidelines could survive, and that higher-intensity fire may substantially reduce the density of small post-fire suppression white fir, while retaining many larger overstory trees.
Analysing initial attack on wildland fires using stochastic simulation
Authors: Fried Jeremy S. , Gilless J. Keith , Spero James
Published: March 2006

Stochastic simulation models of initial attack on wildland fire can be designed to reflect the complexity of the environmental, administrative, and institutional context in which wildland fire protection agencies operate, but such complexity may come at the cost of a considerable investment in data acquisition and management. This cost may be well justified when it allows for analysis of a wider spectrum of operational problems in wildland fire protection planning. The California Fire Economics Simulator version 2 (CFES2), is a sophisticated stochastic simulation model designed to facilitate quantitative analysis of the potential effects of changes in many key components of most wildland fire systems, e.g. availability and stationing of resources, dispatch rules, criteria for setting fire dispatch level, staff schedules, and deployment and line-building tactics. The CFES2 model can also be used to support strategic planning with respect to vegetation management programs, development at the wildland–urban interface, reallocation of responsibilities among fire protection agencies, and climatic change. The analytical capacity of stochastic simulations models to address such key issues is demonstrated using the CFES2 model in four case studies addressing the impact on initial attack effectiveness of: (1) multiple fire starts; (2) diversion of firefighting resources to structure protection; (3) alternate stationing of firefighting resources; and (4) multi-agency cooperation.
Predicting the ignition of crown fuels above a spreading surface fire. Part II: model evaluation
Authors: Cruz Miguel G. , Butler Bret W. , Alexander Martin E.
Published: March 2006

A crown fuel ignition model (CFIM) describing the temperature rise and subsequent ignition of the lower portion of tree crowns above a spreading surface fire was evaluated through a sensitivity analysis, comparison against other models, and testing against experimental fire data. Results indicate that the primary factors influencing crown fuel ignition are those determining the depth of the surface fire burning zone and the vertical distance between the ground/surface fuel strata and the lower boundary of the crown fuel layer. Intrinsic crown fuel properties such as fuel particle surface area-to-volume ratio and foliar moisture content were found to have a minor influence on the process of crown fuel ignition. Comparison of model predictions against data collected in high-intensity experimental fires and predictions from other models gave encouraging results relative to the validity of the model system.
Delayed testicular aging in pituitary adenylate cyclase-activating peptide (PACAP) null mice
Authors: Lacombe Arnaud , Lelievre Vincent , Roselli Charles E. , Salameh Wael , Lue Yan-he , Lawson Gregory , Muller Jean-Marc , Waschek James A. , Vilain Eric
Published: February 2006

Age-related decline in male sex hormones is a direct consequence of testicular aging. These changes in the hormonal complement cause physiological disturbances affecting the quality of life for millions of aging men. To assess the influence on testicular aging of pituitary adenylate cyclase-activating peptide (PACAP), a polypeptide that regulates testicular steroidogenesisin vitro, we compared the testicular structure and function between C57BL/6 wild-type and PACAP−/−male mice, at 4 and 15 months of age. We show that, in 4-month-old PACAP−/−mice, steroidogenesis (evaluated by levels of testosterone, steroidogenic acute regulatory protein, 3β-hydroxysteroid dehydrogenase, and P450c17) was impaired. However, the testicular structure of these animals was not affected. At 15 months of age, wild-type testis displayed typical signs of aging (patchy seminiferous tubules, germ cell depletion, and vacuolization), whereas testicular structure was remarkably well conserved in PACAP−/−animals. The depletion of germ cells found in wild-type animals was associated with a higher content of peroxynitrites, a marker of reactive oxygen species, and a higher number of apoptotic cells compared with PACAP−/−mice. Our results show that testicular aging is delayed in PACAP−/−animals. Because the expression levels of steroidogenic factors are low and constant over time in knockout animals, a proposed mechanism for the protection against testicular degeneration is that production of reactive oxygen species, a byproduct of steroidogenesis that induces apoptosis, is down-regulated in PACAP−/−animals.
Insights into excited-state and isomerization dynamics of bacteriorhodopsin from ultrafast transient UV absorption
Authors: Schenkl S. , van Mourik F. , Friedman N. , Sheves M. , Schlesinger R. , Haacke S. , Chergui M.
Published: March 2006

A visible-pump/UV-probe transient absorption is used to characterize the ultrafast dynamics of bacteriorhodopsin with 80-fs time resolution. We identify three spectral components in the 265- to 310-nm region, related to the
all-trans
retinal, tryptophan (Trp)-86 and the isomerized photoproduct, allowing us to map the dynamics from reactants to products, along with the response of Trp amino acids. The signal of the photoproduct appears with a time delay of ≈250 fs and is characterized by a steep rise (≈150 fs), followed by additional rise and decay components, with time scales characteristic of the J intermediate. The delayed onset and the steep rise point to an impulsive formation of a transition state on the way to isomerization. We argue that this impulsive formation results from a splitting of a wave packet of torsional modes on the potential surface at the branching between the
all-trans
and the cis forms. Parallel to these dynamics, the signal caused by Trp response rises in ≈200 fs, because of the translocation of charge along the conjugate chain, and possible mechanisms are presented, which trigger isomerization.
Fatty acid transduction of nitric oxide signaling: Nitrolinoleic acid potently activates endothelial heme oxygenase 1 expression
Authors: Wright Marcienne M. , Schopfer Francisco J. , Baker Paul R. S. , Vidyasagar Vijay , Powell Pam , Chumley Phil , Iles Karen E. , Freeman Bruce A. , Agarwal Anupam
Published: March 2006

Nitroalkenes are a class of cell signaling mediators generated by NO and fatty acid-dependent redox reactions. Nitrated fatty acids such as 10- and 12-nitro-9,12-octadecadienoic acid (nitrolinoleic acid, LNO
2
) exhibit pluripotent antiinflammatory cell signaling properties. Heme oxygenase 1 (HO-1) is up-regulated as an adaptive response to inflammatory mediators and oxidative stress. LNO
2
(1–10 μM) induced HO-1 mRNA and protein up to 70- and 15-fold, respectively, in human aortic endothelial cells. This induction of HO-1 occurred within clinical LNO
2
concentration ranges, far exceeded responses to equimolar amounts of linoleic acid and oxidized linoleic acid, and rivaled that induced by hemin.
Ex vivo
incubation of rat aortic segments with 25 μM LNO
2
resulted in a 40-fold induction of HO-1 protein that localized to endothelial and smooth muscle cells. Actinomycin D inhibited LNO
2
induction of HO-1 in human aortic endothelial cells, and LNO
2
activated a 4.5-kb human HO-1 promoter construct, indicating transcriptional regulation of the HO-1 gene. The peroxisome proliferator-activated receptor γ (PPARγ) receptor antagonist GW9662 did not inhibit LNO
2
-mediated HO-1 induction, and a methyl ester derivative of LNO
2
with diminished PPARγ binding capability also induced HO-1, affirming a PPARγ-independent mechanism. The NO scavengers 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide and oxymyoglobin partially reversed induction of HO-1 by LNO
2
, revealing that LNO
2
regulates HO-1 expression by predominantly NO-independent mechanisms. In summary, the metabolic and inflammatory signaling actions of nitroalkenes can be transduced by robust HO-1 induction.
Rules for biological regulation based on error minimization
Authors: Shinar Guy , Dekel Erez , Tlusty Tsvi , Alon Uri
Published: March 2006

The control of gene expression involves complex mechanisms that show large variation in design. For example, genes can be turned on either by the binding of an activator (positive control) or the unbinding of a repressor (negative control). What determines the choice of mode of control for each gene? This study proposes rules for gene regulation based on the assumption that free regulatory sites are exposed to nonspecific binding errors, whereas sites bound to their cognate regulators are protected from errors. Hence, the selected mechanisms keep the sites bound to their designated regulators for most of the time, thus minimizing fitness-reducing errors. This offers an explanation of the empirically demonstrated Savageau demand rule: Genes that are needed often in the natural environment tend to be regulated by activators, and rarely needed genes tend to be regulated by repressors; in both cases, sites are bound for most of the time, and errors are minimized. The fitness advantage of error minimization appears to be readily selectable. The present approach can also generate rules for multi-regulator systems. The error-minimization framework raises several experimentally testable hypotheses. It may also apply to other biological regulation systems, such as those involving protein–protein interactions.
Reprogramming metastatic melanoma cells to assume a neural crest cell-like phenotype in an embryonic microenvironment
Authors: Kulesa Paul M. , Kasemeier-Kulesa Jennifer C. , Teddy Jessica M. , Margaryan Naira V. , Seftor Elisabeth A. , Seftor Richard E. B. , Hendrix Mary J. C.
Published: February 2006

Human metastatic melanoma cells express a dedifferentiated, plastic phenotype, which may serve as a selective advantage, because melanoma cells invade various microenvironments. Over the last three decades, there has been an increased focus on the role of the tumor microenvironment in cancer progression, with the goal of reversing the metastatic phenotype. Here, using an embryonic chick model, we explore the possibility of reverting the metastatic melanoma phenotype to its cell type of origin, the neural-crest-derived melanocyte. GFP-labeled adult human metastatic melanoma cells were transplanted
in ovo
adjacent to host chick premigratory neural crest cells and analyzed 48 and 96 h after egg reincubation. Interestingly, the transplanted melanoma cells do not form tumors. Instead, we find that transplanted melanoma cells invade surrounding chick tissues in a programmed manner, distributing along host neural-crest-cell migratory pathways. The invading melanoma cells display neural-crest-cell-like morphologies and populate host peripheral structures, including the branchial arches, dorsal root and sympathetic ganglia. Analysis of a melanocyte-specific phenotype marker (MART-1) and a neuronal marker (Tuj1) revealed a subpopulation of melanoma cells that invade the chick periphery and express MART-1 and Tuj1. Our results demonstrate the ability of adult human metastatic melanoma cells to respond to chick embryonic environmental cues, a subset of which may undergo a reprogramming of their metastatic phenotype. This model has the potential to provide insights into the regulation of tumor cell plasticity by an embryonic milieu, which may hold significant therapeutic promise.
Evidence for the ancient origin of the NF-κB/IκB cascade: Its archaic role in pathogen infection and immunity
Authors: Wang Xiao Wei , Tan Nguan Soon , Ho Bow , Ding Jeak Ling
Published: March 2006

The evolutionary conservation of the NF-κB transcription factors, from
Drosophila
to humans, underscores its pivotal role in immune response. Unexpectedly, the canonical NF-κB signaling pathway is not functional in the immune system of
Caenorhabditis elegans
. Therefore, the ancient origin of the NF-κB signaling pathway is still unknown. Here, we report the discovery and characterization of a primitive and functional NF-κB/IκB pathway in the immune defense of a “living fossil,” the horseshoe crab,
Carcinoscorpius rotundicauda
. The ancient NF-κB/IκB homologues, CrNFκB, CrRelish, and CrIκB, share numerous signature motifs with their vertebrate orthologues. CrNFκB recognizes both horseshoe crab and mammalian κB response elements. CrIκB interacts with CrNFκB and inhibits its nuclear translocation and DNA-binding activity. The activation of the CrNFκB is autoregulated by a feedback mechanism mediated by CrIκB, the natural inhibitor of CrNFκB. We further show that Gram-negative bacteria infection causes rapid degradation of CrIκB and nuclear translocation of CrNFκB. Infection also leads to an increase in the κB-binding activity and up-regulation of immune-related gene expression, like inducible nitric oxide synthase and Factor C, an LPS-activated serine protease. Altogether, our study shows that, although absent in
C. elegans
, the NF-κB/IκB signaling cascade remains well conserved from horseshoe crab to humans, playing an archaic but fundamental role in regulating the expression of critical immune defense molecules.
Structural determinants of selective α-conotoxin binding to a nicotinic acetylcholine receptor homolog AChBP
Authors: Ulens Chris , Hogg Ronald C. , Celie Patrick H. , Bertrand Daniel , Tsetlin Victor , Smit August B. , Sixma Titia K.
Published: February 2006

The nicotinic acetylcholine receptor (nAChR) is the prototype member of the superfamily of pentameric ligand-gated ion channels. How the extracellular ligand-binding domain coordinates selective binding of ligand molecules to different subtypes of the receptor is unknown at the structural level. Here, we present the 2.2-Å crystal structure of a homolog of the ligand-binding domain of the nAChR,
Aplysia californica
AChBP (Ac-AChBP), in complex with α-conotoxin ImI. This conotoxin is unique in its selectivity toward the neuronal α
3
β
2
and α
7
nAChR, a feature that is reflected in its selective binding to Ac-AChBP compared with other AChBP homologs. We observe a network of interactions between the residues of the ligand-binding site and the toxin, in which ImI Arg-7 and Trp-10 play a key role. The toxin also forms interactions in the ligand-binding site that were not seen in the complex of Ac-AChBP with PnIA(A10L D14K), a conotoxin variant that lacks binding selectivity to AChBP homologs. In combination with electrophysiological recordings obtained by using the wild-type α
7
nAChR and L247T mutant, we show that conotoxin ImI inhibits ion conduction by stabilizing the receptor in a desensitized conformation. Comparison of the Ac-AChBP–ImI crystal structure with existing AChBP structures offers structural insight into the extent of flexibility of the interface loops and how their movement may couple ligand binding to channel gating in the context of a nAChR.
Human centromeric chromatin is a dynamic chromosomal domain that can spread over noncentromeric DNA
Authors: Lam Ai Leen , Boivin Christopher D. , Bonney Caitlin F. , Rudd M. Katharine , Sullivan Beth A.
Published: March 2006

Human centromeres are specialized chromatin domains containing the centromeric histone H3 variant CENP-A. CENP-A nucleosomes are interspersed with nucleosomes containing histone H3 dimethylated at lysine 4, distinguishing centromeric chromatin (CEN chromatin) from flanking heterochromatin that is defined by H3 lysine 9 methylation. To understand the relationship between chromatin organization and the genomic structure of human centromeres, we compared molecular profiles of three endogenous human centromeres, defined by uninterrupted higher-order α-satellite DNA, with human artificial chromosomes that contain discontinuous blocks of higher-order α-satellite DNA and noncentromeric DNA. The underlying sequence did not correlate with chromatin states, because both higher-order α-satellite DNA and noncentromeric DNA were enriched for modifications that define CEN chromatin, euchromatin, and heterochromatin. Human artificial chromosomes were also organized into distinct domains. CENP-A and heterochromatin were assembled over noncentromeric DNA, including the gene blasticidin, into nonoverlapping domains. Blasticidin transcripts were enriched at sites of CENP-A binding but not at H3 methylated at lysine 9, indicating that formation of CEN chromatin within a repetitive DNA environment does not preclude gene expression. Finally, we tested the role of centric heterochromatin as a centromeric boundary by increasing CENP-A dosage to expand the CEN domain. In response, H3 lysine 9 dimethylation, but not trimethylation, was markedly decreased at all centromeres examined. We propose that human centromere regions normally exist in a dynamic state in which a regional boundary, defined by H3 lysine 9 dimethylation, separates CEN chromatin from constitutive heterochromatin.
Presynaptic and postsynaptic Ca
2+
and CamKII contribute to long-term potentiation at synapses between individual CA3 neurons
Authors: Lu Fang-Min , Hawkins Robert D.
Published: March 2006

Long-term potentiation (LTP) in the Schaffer collateral pathway from the CA3 to the CA1 region of the hippocampus is thought to involve postsynaptic mechanisms including Ca
2+
- and CamKII-dependent α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor insertion. However, very little is known about possible presynaptic mechanisms. It is easier to address that question at synapses between individual neurons in the CA3 region, where both sides of the synapses are accessible to substances injected into the cell bodies. Previous studies using that method showed that CA3–CA3 LTP involves presynaptic protein kinases as well as postsynaptic receptor insertion. We have extended those findings by exploring the pre- and postsynaptic roles of Ca
2+
and CamKII, and we have also compared results with two induction protocols, 1-Hz-paired and θ-burst-paired, which may involve pre- and/or postsynaptic mechanisms in addition to receptor insertion in CA1. Similar to results in CA1, we find that CA3–CA3 LTP completely depends on postsynaptic Ca
2+
with the 1-Hz-paired protocol but depends only partially on postsynaptic Ca
2+
or CamKII with the θ-burst-paired protocol. Potentiation with that protocol also partially depends on presynaptic Ca
2+
or CamKII, suggesting that the additional mechanisms of potentiation, at least in part, are presynaptic. Furthermore, the pre- and postsynaptic mechanisms seem to act in series, suggesting coordinate regulation of the two sides of the synapses. CA3–CA3 LTP with the 1-Hz-paired protocol also partially depends on presynaptic Ca
2+
, suggesting that it may involve presynaptic mechanisms as well.
The partitioned
Rhizobium etli
genome: Genetic and metabolic redundancy in seven interacting replicons
Authors: González Víctor , Santamaría Rosa I. , Bustos Patricia , Hernández-González Ismael , Medrano-Soto Arturo , Moreno-Hagelsieb Gabriel , Janga Sarath Chandra , Ramírez Miguel A. , Jiménez-Jacinto Verónica , Collado-Vides Julio , Dávila Guillermo
Published: February 2006

We report the complete 6,530,228-bp genome sequence of the symbiotic nitrogen fixing bacterium
Rhizobium etli
. Six large plasmids comprise one-third of the total genome size. The chromosome encodes most functions necessary for cell growth, whereas few essential genes or complete metabolic pathways are located in plasmids. Chromosomal synteny is disrupted by genes related to insertion sequences, phages, plasmids, and cell-surface components. Plasmids do not show synteny, and their orthologs are mostly shared by accessory replicons of species with multipartite genomes. Some nodulation genes are predicted to be functionally related with chromosomal loci encoding for the external envelope of the bacterium. Several pieces of evidence suggest an exogenous origin for the symbiotic plasmid (p42d) and p42a. Additional putative horizontal gene transfer events might have contributed to expand the adaptive repertoire of
R. etli
, because they include genes involved in small molecule metabolism, transport, and transcriptional regulation. Twenty-three putative sigma factors, numerous isozymes, and paralogous families attest to the metabolic redundancy and the genomic plasticity necessary to sustain the lifestyle of
R. etli
in symbiosis and in the soil.
Interaction between the membrane protein of a pathogen and insect microfilament complex determines insect-vector specificity
Authors: Suzuki Shiho , Oshima Kenro , Kakizawa Shigeyuki , Arashida Ryo , Jung Hee-Young , Yamaji Yasuyuki , Nishigawa Hisashi , Ugaki Masashi , Namba Shigetou
Published: March 2006

Many insect-transmissible pathogens are transmitted by specific insect species and not by others, even if they are closely related. The molecular mechanisms underlying such strict pathogen–insect specificity are poorly understood.
Candidatus Phytoplasma asteris
, OY strain, line W (OY), is a phytopathogenic bacterium transmitted from plant to plant by sap-feeding insect vectors (leafhoppers). Our study focused on an abundant cell-surface membrane protein of the phytoplasma named antigenic membrane protein (Amp), which is not homologous with any reported functional protein. Immunofluorescence microscopy of the phytoplasma-infected insect showed that OY phytoplasma was localized to the microfilaments of the visceral smooth muscle surrounding the insect’s intestinal tract. The affinity column assay showed that Amp forms a complex with three insect proteins: actin, myosin heavy chain, and myosin light chain. Amp–microfilament complexes were detected in all OY-transmitting leafhopper species, but not in the non-OY-transmitting leafhoppers, suggesting that the formation of the Amp–microfilament complex is correlated with the phytoplasma-transmitting capability of leafhoppers. Although several studies have reported interactions between pathogens and mammalian microfilaments, this is an example of host-specific interactions between a bacterial surface protein and a host microfilament in insect cells. Our data also suggest that the utilization of a host microfilament may be a universal system for pathogenic bacteria infecting mammals or insects.
An elongated spine of buried core residues necessary for
in vivo
folding of the parallel β-helix of P22 tailspike adhesin
Authors: Simkovsky Ryan , King Jonathan
Published: February 2006

The parallel β-helix is an elongated β-sheet protein domain associated with microbial virulence factors, toxins, viral adhesins, and allergens. Long stacks of similar, buried residues are a prominent feature of this fold, as well as the polypeptide chain fold of an amyloid structure. The 13-rung, right-handed, parallel β-helix of the homotrimeric P22 tailspike adhesin exhibits predominantly hydrophobic stacks. The role of these stacked residues in the folding and stabilization of the protein is unclear. Through scanning alanine mutagenesis we have identified a folding spine of stacked residues in continuous contact along the length of P22 tailspike’s β-helix domain that is necessary for folding within cells. Nearly all chains carrying alanine substitutions of the 103 buried nonalanines were defective in folding
in vivo
at 37°C. However, the majority of these chains successfully reached a native state, stable to >80°C, when folded inside cells at low temperatures. Thus, nearly the entire buried core was critical for
in vivo
β-helix folding but negligible for stability. Folding at 18°C revealed the minimal folding spine of 29 nonglycine stack positions that were intolerant to alanine substitution. These results indicate that a processive folding mechanism, dependent on stacking contacts, controls β-helix formation. Such a stepwise folding pathway offers a new target for drug design against this class of microbial virulence factors.
An ancient evolutionary origin of the
Rag1
/
2
gene locus
Authors: Fugmann Sebastian D. , Messier Cynthia , Novack Laura A. , Cameron R. Andrew , Rast Jonathan P.
Published: February 2006

The diversity of antigen receptors in the adaptive immune system of jawed vertebrates is generated by a unique process of somatic gene rearrangement known as V(D)J recombination. The Rag1 and Rag2 proteins are the key mediators of this process. They are encoded by a compact gene cluster that has exclusively been identified in animal species displaying V(D)J-mediated immunity, and no homologous gene pair has been identified in other organisms. This distinctly restricted phylogenetic distribution has led to the hypothesis that one or both of the
Rag
genes were coopted after horizontal gene transfer and assembled into a
Rag1/2
gene cluster in a common jawed vertebrate ancestor. Here, we identify and characterize a closely linked pair of genes,
SpRag1L
and
SpRag2L
, from an invertebrate, the purple sea urchin (
Strongylocentrotus purpuratus
) with similarity in both sequence and genomic organization to the vertebrate
Rag1
and
Rag2
genes. They are coexpressed during development and in adult tissues, and recombinant versions of the proteins form a stable complex with each other as well as with Rag1 and Rag2 proteins from several vertebrate species. We thus conclude that
SpRag1L
and
SpRag2L
represent homologs of vertebrate
Rag1
and
Rag2
. In combination with the apparent absence of V(D)J recombination in echinoderms, this finding strongly suggests that linked
Rag1
- and
Rag2
-like genes were already present and functioning in a different capacity in the common ancestor of living deuterostomes, and that their specific role in the adaptive immune system was acquired much later in an early jawed vertebrate.
STIM1 has a plasma membrane role in the activation of store-operated Ca
2+
channels
Authors: Spassova Maria A. , Soboloff Jonathan , He Li-Ping , Xu Wen , Dziadek Marie A. , Gill Donald L.
Published: March 2006

Receptor-induced Ca
2+
signals are key to the function of all cells and involve release of Ca
2+
from endoplasmic reticulum (ER) stores, triggering Ca
2+
entry through plasma membrane (PM) “store-operated channels” (SOCs). The identity of SOCs and their coupling to store depletion remain molecular and mechanistic mysteries. The single transmembrane-spanning Ca
2+
-binding protein, STIM1, is necessary in this coupling process and is proposed to function as an ER Ca
2+
sensor to provide the trigger for SOC activation. Here we reveal that, in addition to being an ER Ca
2+
sensor, STIM1 functions within the PM to control operation of the Ca
2+
entry channel itself. Increased expression levels of STIM1 correlate with a gain in function of Ca
2+
release-activated Ca
2+
(CRAC) channel activity. Point mutation of the N-terminal EF hand transforms the CRAC channel current (
I
CRAC
) into a constitutively active, Ca
2+
store-independent mode. Mutants in the EF hand and cytoplasmic C terminus of STIM1 alter operational parameters of CRAC channels, including pharmacological profile and inactivation properties. Last, Ab externally applied to the STIM1 N-terminal EF hand blocks both
I
CRAC
in hematopoietic cells and SOC-mediated Ca
2+
entry in HEK293 cells, revealing that STIM1 has an important functional presence within the PM. The results reveal that, in addition to being an ER Ca
2+
sensor, STIM1 functions within the PM to exert control over the operation of SOCs. As a cell surface signaling protein, STIM1 represents a key pharmacological target to control fundamental Ca
2+
-regulated processes including secretion, contraction, metabolism, cell division, and apoptosis.
Dissecting toxin immunity in virus-infected killer yeast uncovers an intrinsic strategy of self-protection
Authors: Breinig Frank , Sendzik Tanja , Eisfeld Katrin , Schmitt Manfred J.
Published: February 2006

Toxin-secreting “killer” yeasts were initially identified >40 years ago in
Saccharomyces cerevisiae
strains infected with a double-stranded RNA “killer” virus. Despite extensive research conducted on yeast killer toxins, the mechanism of protecting immunity by which toxin-producing cells evade the lethal activities of these proteins has remained elusive. Here, we identify the mechanism leading to protecting immunity in a killer yeast secreting a viral α/β protein toxin (K28) that enters susceptible cells by receptor-mediated endocytosis and, after retrograde transport into the cytosol, blocks DNA synthesis, resulting in both cell-cycle arrest and caspase-mediated apoptosis. We demonstrate that toxin immunity is effected within the cytosol of a toxin-secreting yeast and occurs via the formation of complexes between reinternalized toxin and unprocessed precursor moieties that are subsequently ubiquitinated and proteasomally degraded, eliminating the active form of the toxin. Interference with cellular ubiquitin homeostasis, either through overexpression of mutated ubiquitin (Ub-RR
48/63
) or by blocking deubiquitination, prevents ubiquitination of toxin and results in an impaired immunity and the expression of a suicidal phenotype. The results presented here reveal the uniquely elegant and efficient strategy that killer cells have developed to circumvent the lethal effects of the toxin they produce.
Three RNA cells for ribosomal lineages and three DNA viruses to replicate their genomes: A hypothesis for the origin of cellular domain
Authors: Forterre Patrick
Published: February 2006

The division of the living world into three cellular domains, Archaea, Bacteria, and Eukarya, is now generally accepted. However, there is no consensus about the evolutionary relationships among these domains, because all of the proposed models have a number of more or less severe pitfalls. Another drawback of current models for the universal tree of life is the exclusion of viruses, otherwise a major component of the biosphere. Recently, it was suggested that the transition from RNA to DNA genomes occurred in the viral world, and that cellular DNA and its replication machineries originated via transfers from DNA viruses to RNA cells. Here, I explore the possibility that three such independent transfers were at the origin of Archaea, Bacteria, and Eukarya, respectively. The reduction of evolutionary rates following the transition from RNA to DNA genomes would have stabilized the three canonical versions of proteins involved in translation, whereas the existence of three different founder DNA viruses explains why each domain has its specific DNA replication apparatus. In that model, plasmids can be viewed as transitional forms between DNA viruses and cellular chromosomes, and the formation of different levels of cellular organization (prokaryote or eukaryote) could be traced back to the nature of the founder DNA viruses and RNA cells.
Discrete and continuous min-energy schedules for variable voltage processors
Authors: Li Minming , Yao Andrew C. , Yao Frances F.
Published: March 2006

Current dynamic voltage scaling techniques allow the speed of processors to be set dynamically to save energy consumption, which is a major concern in microprocessor design. A theoretical model for min-energy job scheduling was first proposed a decade ago, and it was shown that for any convex energy function, the min-energy schedule for a set of
n
jobs has a unique characterization and is computable in
O
(
n
3
) time. This algorithm has remained as the most efficient known despite many investigations of this model. In this work, we give an algorithm with running time
O
(
n
2
log
n
) for finding the min-energy schedule. In contrast to the previous algorithm, which outputs optimal speed levels from high to low iteratively, our algorithm is based on finding successive approximations to the optimal schedule. At the core of the approximation is an efficient partitioning of the job set into high and low speed subsets by any speed threshold, without computing the exact speed function.
Mechanism of arylating quinone toxicity involving Michael adduct formation and induction of endoplasmic reticulum stress
Authors: Wang Xinhe , Thomas Beena , Sachdeva Rakesh , Arterburn Linnea , Frye Lucy , Hatcher Patrick G. , Cornwell David G. , Ma Jiyan
Published: February 2006

Quinones permeate our biotic environment, contributing to both homeostasis and cytotoxicity. All quinones generate reactive oxygen species through redox cycling, while partially substituted quinones also undergo arylation (Michael adduct formation) yielding covalent bonds with nucleophiles such as cysteinyl thiols. In contrast to reactive oxygen species, the role of arylation in quinone cytotoxicity is not well understood. We found that the arylating quinones, including unsubstituted 1,4-benzoquinone (1,4-BzQ) and partially substituted vitamin E congener γ-tocopherol quinone (γ-TQ), were cytotoxic, with γ-TQ > 1,4-BzQ, whereas the fully substituted nonarylating vitamin E congener α-tocopherol quinone was not.
In vitro
, both arylating quinones formed Michael adducts with the thiol nucleophile
N-
acetylcysteine (NAC) at rates where 1,4-BzQ > γ-TQ. In cultured cells, concurrent addition of NAC eliminated 1,4-BzQ caused toxicity, but preincubation was required for the same NAC detoxification effect on γ-TQ. These data clearly established the role of arylation in quinone toxicity and revealed that arylating quinone structure affects cytotoxicity by governing detoxification through the rate of adduct formation. Furthermore, arylating quinones induced endoplasmic reticulum (ER) stress by activating the pancreatic ER kinase (PERK) signaling pathway including elF2α, ATF4, and C/EBP homologous protein (CHOP). Detoxification by NAC greatly attenuates CHOP induction in arylating quinone-treated cells, suggesting that ER stress is a cellular mechanism for arylating quinone cytotoxicity.