bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of the nitric oxide pathway and the endocannabinoid system in neurogenic relaxation of corpus cavernosum from biliary cirrhotic rats
Authors: Ghasemi M , Sadeghipour H , Shafaroodi H , Nezami B G , Gholipour T , Hajrasouliha A R , Tavakoli S , Nobakht M , Moore K P , Mani A R , Dehpour A R
Published: May 2007

Background and purpose:

Relaxation of corpus cavernosum, which is mediated by nitric oxide (NO) released from non‐adrenergic non‐cholinergic (NANC) neurotransmission, is critical for inducing penile erection and can be affected by many pathophysiological conditions. However, the peripheral effect of liver cirrhosis on erectile function is as yet unknown. The aim of the present study was to investigate the effect of biliary cirrhosis on NANC‐mediated relaxation of rat corpus cavernosum and the possible roles of endocannabinoid and nitric oxide systems in this model.

Experimental approach:

Cirrhosis was induced by bile duct ligation. Controls underwent sham operation. Four weeks later, strips of corpus cavernosum were mounted in a standard organ bath and NANC‐mediated relaxations were obtained by applying electrical field stimulation.

Key results:

The NANC‐mediated relaxation was enhanced in corporal strips from cirrhotic animals. Anandamide potentiated the relaxations in both groups. Either AM251 (CB1 antagonist) or capsazepine (vanilloid VR1 antagonist), but not AM630 (CB2 antagonist), prevented the enhanced relaxations of cirrhotic strips. Either the non‐selective NOS inhibitor L‐NAME or the selective neuronal NOS inhibitor L‐NPA inhibited relaxations in both groups, but cirrhotic groups were more resistant to the inhibitory effects of these agents. Relaxations to sodium nitroprusside (NO donor) were similar in tissues from the two groups.

Conclusions and implications:

Cirrhosis potentiates the neurogenic relaxation of rat corpus cavernosum probably via the NO pathway and involving cannabinoid CB1 and vanilloid VR1 receptors.

British Journal of Pharmacology (2007) 151, 591–601; doi:10.1038/sj.bjp.0707279
Selective positive modulation of the SK3 and SK2 subtypes of small conductance Ca2+‐activated K+channels
Authors: Hougaard C , Eriksen B L , Jørgensen S , Johansen T H , Dyhring T , Madsen L S , Strøbæk D , Christophersen P
Published: May 2007

Background and purpose:

Positive modulators of small conductance Ca2+‐activated K+channels (SK1, SK2, and SK3) exert hyperpolarizing effects that influence the activity of excitable and non‐excitable cells. The prototype compound 1‐EBIO or the more potent compound NS309, do not distinguish between the SK subtypes and they also activate the related intermediate conductance Ca2+‐activated K+channel (IK). This paper demonstrates, for the first time, subtype‐selective positive modulation of SK channels.

Experimental approach:

Using patch clamp and fluorescence techniques we studied the effect of the compound cyclohexyl‐[2‐(3,5‐dimethyl‐pyrazol‐1‐yl)‐6‐methyl‐pyrimidin‐4‐yl]‐amine (CyPPA) on recombinant hSK1‐3 and hIK channels expressed in HEK293 cells. CyPPA was also tested on SK3 and IK channels endogenously expressed in TE671 and HeLa cells.

Key results:

CyPPA was found to be a positive modulator of hSK3 (EC50= 5.6 ± 1.6 μM, efficacy 90 ± 1.8 %) and hSK2 (EC50= 14 ± 4 μM, efficacy 71 ± 1.8 %) when measured in inside‐out patch clamp experiments. CyPPA was inactive on both hSK1 and hIK channels. At hSK3 channels, CyPPA induced a concentration‐dependent increase in the apparent Ca2+‐sensitivity of channel activation, changing the EC50(Ca2+) from 429 nM to 59 nM.

Conclusions and implications:

As a pharmacological tool, CyPPA may be used in parallel with the IK/SK openers 1‐EBIO and NS309 to distinguish SK3/SK2‐ from SK1/IK‐mediated pharmacological responses. This is important for the SK2 and SK1 subtypes, since they have overlapping expression patterns in the neocortical and hippocampal regions, and for SK3 and IK channels, since they co‐express in certain peripheral tissues.

British Journal of Pharmacology(2007)151, 655–665; doi:10.1038/sj.bjp.0707281
SK channels are on the move
Authors: Seutin V , Liégeois J‐F
Published: May 2007

Small‐conductance Ca2+‐activated K+ channels (SK channels) underlie the medium duration after hyperpolarization that follows single or trains of action potentials in many types of neurons. Three subtypes of SK subunits, SK1 (KCa2.1), SK2 (KCa2.2) and SK3 (KCa2.3), have been cloned and are expressed differentially within the central nervous system (CNS). A paper in this issue of BJP reports the discovery of the first example of a positive modulator displaying not only selectivity for SK channels over other channels, but also a subtype selectivity among SK and analogous channels (SK3>SK2⋙SK1=IK). Together with other recent progress in the field, this finding enriches the repertoire of tools available to test the hypothesis that SK channels may be targets for future CNS drugs.

British Journal of Pharmacology (2007) 151, 568–570; doi:10.1038/sj.bjp.0707282
Clean Energy
Authors: Dell R M , Rand D A J
Published: May 2007

Clean Energy presents a broad survey of the energy problems facing society over the coming decades and the prospects for their solution. The book emphasizes the importance of developing a strategy for the world's future energy supply. The strategy must take into account: the finite supplies of natural gas and petroleum; the increased consumption of fuel by developing economies; the concern over greenhouse gas emissions; the pollution caused by burning coal (especially coal with a high sulphur content); the difficulties and costs of extracting unconventional fossil fuels; and the technical, sociological and cost barriers that restrict the use of renewable forms of energy. Clean Energy sets the various renewable energies (wind, waves, solar etc) in the context of present and projected world production of energy and its use in the time-frame until 2020 and looks speculatively beyond that. It looks at the possibilities for reducing pollution from fossil fuels and tackles the serious problem of how to store energy, in order to smooth out fluctuations in supply and demand. Clean Energy is well illustrated with diagrams and photographs. It is accessible to anyone who has studied science to A-level and will appeal to anyone with a serious interest in environmental matters, and the interaction between energy usage and the environment.
Hybrid Lethality in Interspecific F1 Hybrid Nicotiana gossei×N. tabacum Involves a MAP‐Kinases Signalling Cascade
Authors: Mino M. , Kubota M. , Nogi T. , Zhang S. , Inoue M.
Published: May 2007

Abstract: A cultured cell line, GTH4 (Nicotiana gossei Domin ×N. tabacum L.), which exhibits hybrid lethality, died at 26 °C, but not at 37 °C. Pharmacological experiments using inhibitors of protein phosphatases and protein kinases indicated the involvement of a protein kinase signalling pathway in the cell death process. Immunoblot analysis revealed that salicylic acid‐induced protein kinase (SIPK) was phosphorylated soon after the shift in temperature from 37 °C to 26 °C. Cultured cells of the hybrid of N. gossei× transgenic N. tabacum harboring a steroid (dexamethasone; DEX)‐inducible NtMEK2DD or NtMEK2KR, constitutively active and inactive forms of NtMEK2, respectively, were established. Induction of NtMEK2DD by DEX in the hybrid cells induced the activation of SIPK, the generation of hydrogen peroxide (H2O2), and cell death at 37 °C. The activation of SIPK, generation of H2O2, and cell death at 26 °C were compromised by DEX treatment in hybrid cells harbouring NtMEK2KR. This study provides evidence for the involvement of MAPK signalling in the regulation of cell death in hybrids.
A Mutation in the AtPRP4 Splicing Factor Gene Suppresses Seed Development in Arabidopsis
Authors: Raab S. , Hoth S.
Published: May 2007

Abstract: The spliceosome catalyzes alternative splicing of many genes in eucaryotic cells. This leads to the expression of distinct proteins. Components of the spliceosome are conserved in mammals and plants. Because splicing can be affected by environmental stress, we analyzed the regulation of splicing‐related genes that encode small nuclear ribonucleoprotein particle (snRNP) proteins by the stress hormone abscisic acid (ABA). The transcript abundance of about 25 % of those genes was changed by at least 1.5‐fold after addition of ABA. The U4/U6‐specific snRNP gene AtPRP4 was strongly repressed by ABA. The homozygous knock‐out of AtPRP4 resulted in the suppression of seed development suggesting that the gene product of this stress hormone‐regulated gene is crucial for normal seed development.
Development of nanostructured, stress-free Co-rich CoPtP films for magnetic microelectromechanical system applications
Authors: Kulkarni Santosh , Roy Saibal
Published: May 2007

Co-rich CoPtP alloys have been electrodeposited using direct current (dc) and pulse-reverse (PR) plating techniques. The surface morphology, crystalline structure, grain size, and magnetic properties of the plated films have been compared. The x-ray analysis and magnetic measurements reveal the presence of Co hcp hard magnetic phase with c axis perpendicular to the substrate for dc and in plane for PR plated films. The dc plated films have a granular structure in the micron scale with large cracks, which are manifestation of stress in the film. Only by using a combination of optimized PR plating conditions and stress relieving additive, we are able to produce 1–6μm thick (for 1 hour of plating), stress-free, and nanostructured (∼20nm) Co-rich CoPtP single hcp phase at room temperature, with an intrinsic coercivity of 1500Oe.
Decoherence processes of a quantum two-level system coupled to a fermionic environment
Authors: Yamada Naoyoshi , Sakuma Akimasa , Tsuchiura Hiroki
Published: May 2007

We study decoherence processes of an S=1∕2 localized spin coupled to conduction band electrons in a metal or a semiconductor via an Ising-like interaction. We derive master equations for the density matrix of the localized spin by tracing out all degrees of freedom in the conduction electron system based on the linked-cluster-expansion technique. It is found that the decoherence occurs more rapidly for the metallic case than for semiconducting case.
Room-temperature magnetoresistance in magnetic tunnel junctions with Fe3O4 electrode
Authors: Kado T. , Saito H. , Ando K.
Published: May 2007

We report on the fabrication and spin-dependent transport properties of epitaxial Fe3O4∕MgO∕Co75Fe25 magnetic tunnel junctions (MTJs) grown on sapphire (00.1) substrates. The MTJs showed magnetoresistance (MR) ratios ranging from −14% to 10% at room temperature and a somewhat scattered resistance-area product (RA) ranging from 7×107to3×1010Ωμm2. The relationship between MR ratio and RA revealed a tendency for the MR ratio to go from positive to negative as RA increases. Because MTJs with fewer imperfections should show a higher RA, the negative MR ratio is considered to be intrinsic, and the electron transport via imperfections results in a reversal in the sign of the MR ratio.
Size triggered change in the magnetization mechanism of nearly zero magnetostrictive amorphous glass-coated microwires
Authors: Chiriac H. , Corodeanu S. , Ţibu M. , Óvári T. A.
Published: May 2007

Results on the change in the magnetization mechanism with microwire dimensions in nearly zero magnetostrictive Co-based amorphous glass-coated microwires are reported. Microwires with a metallic core diameter of 20μm or more display a change in the magnetization mechanism from domain wall displacement to magnetization rotation with the increase of an externally applied tensile stress, which is equivalent to an increase of the glass coating thickness. Microwires with the metallic core diameter below 20μm do not display this change in the magnetization mechanism. They are magnetized only through magnetization rotation. Experimental results are explained based on the competition between magnetostatic and magnetoelastic energy terms. Minimization of a preponderant magnetostatic term in the total free energy results in an axial easy axis of magnetization and a corresponding bistable magnetic behavior. Bistability vanishes if the magnetoelastic energy term becomes preponderant and the corresponding easy axis becomes transverse. A reasonable estimation of the magnetostatic energy density in Co-based microwires has been obtained based on hysteresis loop measurements with the applied tensile stress as a parameter.
Cryogenic hysteretic loss analysis for (Fe,Co,Ni)–Zr–B–Cu nanocrystalline soft magnetic alloys
Authors: Willard M. A. , Heil T. M.
Published: May 2007

The present study compares the hysteretic losses of a series of eight nanocrystalline soft magnetic alloys with compositions (Fe,Co,Ni)-Zr-B-Cu. The alloys were produced by a single wheel melt spinning technique followed by isothermal annealing to promote primary crystallization. As determined by x-ray diffraction experiments, these samples consist of fcc and/or bcc crystallites with average grain diameters of less than 15nm. Vibrating sample magnetometry was employed to measure hysteresis loops at 110 and 300K. The integrated hysteresis loops were larger for the (Fe0.22Ni0.78)89−xZr7B4Cux alloys and nearly unchanged for the other alloys with one exception [i.e., (Fe0.75Co0.125Ni0.125)85.5Zr8.5B5Cu1]. Additional hysteresis measurements with varying degrees of maximum flux density (between 0.03 and 1.1T) were performed at 110 and 300K for the alloy with composition (Fe0.75Co0.125Ni0.125)85.5Zr8.5B5Cu1, annealed at 823K for 1h. A 50% reduction in hysteretic losses was observed for this sample when measured at 110K (compared to room temperature).
Magnetic domain observations in a FeCo-based nanocrystalline alloy by Lorentz microscopy
Authors: Long Jianguo , Qin Yueling , Nuhfer Tom , De Graef M. , Laughlin D. E. , McHenry M. E.
Published: May 2007

Lorentz microscopy was used to investigate the domain structure in an (Fe0.5Co0.5)80Nb4B13Ge2Cu1 alloy annealed at 500, 550, and 610°C, respectively, for 1h. The average grain size d, observed by conventional transmission electron microscopy, is 10nm for the alloy annealed at 500°C, 18nm for 550°C, and 90nm for 610°C. The domain structure of sample annealed at 500°C exhibits few pinning sites and large domains, which correlate with the low coercivity and good soft magnetic properties. More pinning sites and smaller domains are observed in the sample annealed at 550°C. In the sample annealed at 610°C, the domain walls are observed to be localized at the grain boundaries and the domains include several grains. It therefore appears that the grain boundaries act as effective pinning sites in this sample. As expected, domain walls in the 610°C sample are less mobile in small applied fields than in the 500 and 550°C samples. This result is consistent with coercivity measurement and the random anisotropy model commonly used to rationalize the coercivity dependence on average grain size in these alloys.
Properties of microstructure on amorphous film of rare earth–transition metal alloy for ultrahigh density recording
Authors: Murakami Motoyoshi
Published: May 2007

Controlling the microstructure of amorphous rare earth–transition metal films via the sputtering process was found to be an effective way of controlling their magnetic properties for applications as magneto-optical storage media. This paper describes how the relationship between a TbFeCo film’s magnetic properties and its microcolumnar structure depends on the sputtering conditions. An enhancement of electric resistance value was observed for the devices with a constriction columnar width in the 5–20nm range. The measured electrical resistance was over 1.0×10−5Ωm in this case. It is believed that the change of electrical resistance on the thin film is due to fluctuations in the density on the arranged microstructure or constriction of current induced by scattering because the film structure contains impurities. These same impurities are believed to be associated with the restriction of the trapped domain wall’s mobility. Furthermore, we observed a significant resistance change subsequent to the application of lower Xe pressure sputtering. This paper also serves as a feasibility study for high-density magneto-optical recording on these media materials.
Improvement of soft magnetic properties by simultaneous addition of P and Cu for nanocrystalline FeNbB alloys
Authors: Makino Akihiro , Bingo Masaki , Bitoh Teruo , Yubuta Kunio , Inoue Akihisa
Published: May 2007

The additional effect of P and/or Cu on the structure and the magnetic properties of Fe–Nb–B nanocrystalline soft magnetic alloy tapes with a wide width of 5mm produced in air was investigated. Although Cu or P addition changes the magnetic softness a little, only the simultaneous addition of 1at.% P and 0.1at.% Cu significantly improves the soft magnetic properties of the crystallized alloys. The best magnetic properties (higher permeability than 45×103, lower coercivity than 5A∕m, and saturation magnetic flux density of 1.50–1.54T) were obtained in the compositional ranges of 6.6–6.8at.% Nb and 8.4–8.8at.% B with 1% P and 0.1% Cu, and these values are superior to the typical nanocrystallized Fe84Nb7B9 alloy prepared in a vacuum. The improvement probably originates from the decrease in the distribution of the α-Fe grain size in the crystallized structure by the simultaneous addition.
Multiferroic properties of HoMnO3 films and capacitor trilayers
Authors: Kim J.-W. , Dörr K. , Nenkov K. , Schultz L.
Published: May 2007

Low-temperature magnetization with epitaxial hexagonal HoMnO3 films and single crystal has been investigated. The magnetization data of films show three distinctive transitions which are compared with those of a single crystal. In order to test the ferroelectric behavior of HoMnO3 thin films, epitaxial capacitor trilayers with Pt electrodes have been grown. For the well-prepared trilayer, a ferroelectric switching at room temperature has been demonstrated in spite of a certain degree of leakage with a film resistivity of about 107Ωcm.
Magnetic properties of Co–Fe–B–Si–Nb bulk glassy alloy with zero magnetostriction
Authors: Amiya Kenji , Urata Akiri , Nishiyama Nobuyuki , Inoue Akihisa
Published: May 2007

The glass forming ability and magnetic properties of a Co–B–Si–Nb glassy alloy have been investigated. The maximum rod diameters for the formation of a glassy phase were 1.5mm for Co70B20Si8Nb2 and 3mm for Co70B22Si6Nb4. Zero-magnetostriction bulk metallic glass samples of (Co0.952Fe0.058)70B20Si8Nb2 were prepared in cylindrical form with a diameter of 1.5mm and in ring form with a thickness of 0.5mm. The (Co0.952Fe0.058)70B20Si8Nb2 glassy alloy samples exhibited a high glass forming ability and good soft magnetic properties, i.e., a saturation magnetization of 0.6T, a low coercivity within 0.1–0.2A∕m, and a high permeability of 104 000 at a frequency of 1kHz and zero magnetostriction. The success of the synthesis of the zero-magnetostriction Co–Fe–B–Si–Nb glassy alloy with good soft magnetic properties and a high glass forming ability is promising for the future development of sensitive magnetic sensors.
27.12 MHz plasma generation in supercritical carbon dioxide
Authors: Kawashima Ayato , Toyota Hiromichi , Nomura Shinfuku , Takemori Toshihiko , Mukasa Shinobu , Maehara Tsunehiro , Yamashita Hiroshi
Published: May 2007

An experiment was conducted for generating high-frequency plasma in supercritical carbon dioxide; it is expected to have the potential for applications in various types of practical processes. It was successfully generated at 6−20 MPa using electrodes mounted in a supercritical cell with a gap of 1 mm. Emission spectra were then measured to investigate the physical properties of supercritical carbon dioxide plasma. The results indicated that while the emission spectra for carbon dioxide and carbon monoxide could be mainly obtained at a low pressure, the emission spectra for atomic oxygen could be obtained in the supercritical state, which increased with the pressure. The temperature of the plasma in supercritical state was estimated to be approximately 6000−7000 K on the assumption of local thermodynamic equilibrium and the calculation results of thermal equilibrium composition in this state showed the increase of atomic oxygen by the decomposition of CO2.
Giant and zero electron g factors of dilute nitride semiconductor nanowires
Authors: Zhang X. W. , Fan W. J. , Li S. S. , Xia J. B.
Published: May 2007

The electronic structures and electron g factors of InSb1−sNs and GaAs1−sNs nanowires and bulk material under the magnetic and electric fields are investigated by using the ten-band k∙p model. The nitrogen doping has direct and indirect effects on the g factors. A giant g factor with absolute value larger than 900 is found in InSb1−sNs bulk material. A transverse electric field can increase the g factors, which has obviously asymmetric effects on the g factors in different directions. An electric field tunable zero g factor is found in GaAs1−sNs nanowires.
Vibronic and spin-orbit coupling of a d9 transition-metal ion encapsulated in an icosahedral cage: The (Γ8+Γ9)×(g+2h) Jahn-Teller problem
Authors: Sato Tohru , Ceulemans Arnout
Published: May 2007

Interplay between the vibronic and spin-orbit coupling in the (Γ8+Γ9)×(g+2h) Jahn-Teller problem, where Γ8 and Γ9 are the quartet and sextet spin representation, and g and h denote the fourfold and fivefold degenerate vibrational modes in icosahedral symmetry, respectively, is studied. A 4d9 or 5d9 transition-metal ion in an icosahedral field may provide a realization of this system.
Variable-temperature independently driven four-tip scanning tunneling microscope
Authors: Hobara Rei , Nagamura Naoka , Hasegawa Shuji , Matsuda Iwao , Yamamoto Yuko , Miyatake Yutaka , Nagamura Toshihiko
Published: May 2007

The authors have developed an ultrahigh vacuum (UHV) variable-temperature four-tip scanning tunneling microscope (STM), operating from room temperature down to 7K, combined with a scanning electron microscope (SEM). Four STM tips are mechanically and electrically independent and capable of positioning in arbitrary configurations in nanometer precision. An integrated controller system for both of the multitip STM and SEM with a single computer has also been developed, which enables the four tips to operate either for STM imaging independently and for four-point probe (4PP) conductivity measurements cooperatively. Atomic-resolution STM images of graphite were obtained simultaneously by the four tips. Conductivity measurements by 4PP method were also performed at various temperatures with the four tips in square arrangement with direct contact to the sample surface.
Recording and interpretation/analysis of tilt signals with five ASKANIA borehole tiltmeters at the KTB
Authors: Gebauer André , Jahr Thomas , Jentzsch Gerhard
Published: May 2007

In June 2003, a large scale injection experiment started at the Continental Deep Drilling site (KTB) in Germany. A tiltmeter array was installed which consisted of five high resolution borehole tiltmeters of the ASKANIA type, also equipped with three dimensional seismometers. For the next 11months, 86000m3 were injected into the KTB pilot borehole 4000m deep. The average injection rate was approximately 200l∕min. The research objective was to observe and to analyze deformation caused by the injection into the upper crust at the kilometer range. A new data acquisition system was developed by Geo-Research Center Potsdam (GFZ) to master the expected huge amount of seismic and tilt data. Furthermore, it was necessary to develop a new preprocessing software called PREANALYSE for long-period time series. This software includes different useful functions, such as step and spike correction, interpolation, filtering, and spectral analysis. This worldwide unique installation offers the excellent opportunity of the separation of signals due to injection and due to environment by correlation of the data of the five stations with the ground water table and meteorological data.
Effects of optical coupling in III-V multilayer systems
Authors: Baur Carsten , Hermle Martin , Dimroth Frank , Bett Andreas W.
Published: May 2007

A method to visualize and investigate radiative recombination processes in compound semiconductor materials by utilizing the effect of optical coupling in III-V multilayer systems is presented. For this purpose, a semiconductor material of interest is grown on an activated germanium (Ge) substrate which then serves as a photodiode. By means of spectral response measurements of the Ge photodiode, a response signal from the upper layers can be detected. It is proven both by experiment and by modeling that the signals from these layers can only be explained by optical transport mechanisms, i.e., radiative recombination.
Nonlocal effects in effective-medium response of nanolayered metamaterials
Authors: Elser Justin , Podolskiy Viktor A. , Salakhutdinov Ildar , Avrutsky Ivan
Published: May 2007

The authors analyze electromagnetic modes in multilayered nanocomposites and demonstrate that the response of a majority of realistic layered structures is strongly affected by the nonlocal effects originating from strong field oscillations across the system, and is not described by conventional effective-medium theories. They develop the analytical description of the relevant phenomena and confirm their results with numerical solutions of Maxwell equations. Finally, the authors use the developed formalism to demonstrate that multilayered plasmonic nanostructures support high-index volume modes, confined to deep subwavelength areas, opening a wide class of applications in nanoscale light management.
Habitat specialization, body size, and family identity explain lepidopteran density–area relationships in a cross-continental comparison
Authors: Hambäck Peter A. , Summerville Keith S. , Steffan-Dewenter Ingolf , Krauss Jochen , Englund Göran , Crist Thomas O.
Published: May 2007

Habitat fragmentation may strongly affect species density, species interactions, and the rate of ecosystem processes. It is therefore important to understand the observed variability among species responses to fragmentation and the underlying mechanisms. In this study, we compare density–area relationships (DARs) for 344 lepidopteran species belonging to 22 families (butterflies and moths). This analysis suggested that the DARslopeis generally positive for moths and negative for butterflies. The differences are suggested to occur because moths are largely olfactory searchers, whereas most butterflies are visual searchers. The analysis also suggests that DARs vary as a function of habitat specialization and body size. In butterflies, generalist species had a more negative DARslopethan specialist species because of a lower patch size threshold. In moths, the differences in DARslopebetween forest and open habitat species were large for small species but absent for large species. This difference is argued to occur because the DARslopein large species mainly reflects their search mode, which does not necessarily vary between moth groups, whereas the slope in small species reflects population growth rates.
Allosteric regulation of an essential trypanosome polyamine biosynthetic enzyme by a catalytically dead homolog
Authors: Willert Erin K. , Fitzpatrick Richard , Phillips Margaret A.
Published: May 2007

African sleeping sickness is a fatal disease that is caused by the protozoan parasite
Trypanosoma brucei
. Polyamine biosynthesis is an essential pathway in the parasite and is a validated drug target for treatment of the disease.
S
-adenosylmethionine decarboxylase (AdoMetDC) catalyzes a key step in polyamine biosynthesis. Here, we show that trypanosomatids uniquely contain both a functional AdoMetDC and a paralog designated prozyme that has lost catalytic activity. The
T. brucei
prozyme forms a high-affinity heterodimer with AdoMetDC that stimulates its activity by 1,200-fold. Both genes are expressed in
T. brucei
, and analysis of AdoMetDC activity in
T. brucei
extracts supports the finding that the heterodimer is the functional enzyme
in vivo
. Thus, prozyme has evolved to be a catalytically dead but allosterically active subunit of AdoMetDC, providing an example of how regulators of multimeric enzymes can evolve through gene duplication and mutational drift. These data identify a distinct mechanism for regulating AdoMetDC in the parasite that suggests new strategies for the development of parasite-specific inhibitors of the polyamine biosynthetic pathway.
The neural basis of the interaction between theory of mind and moral judgment
Authors: Young Liane , Cushman Fiery , Hauser Marc , Saxe Rebecca
Published: May 2007

Is the basis of criminality an act that causes harm, or an act undertaken with the belief that one will cause harm? The present study takes a cognitive neuroscience approach to investigating how information about an agent's beliefs and an action's consequences contribute to moral judgment. We build on prior developmental evidence showing that these factors contribute differentially to the young child's moral judgments coupled with neurobiological evidence suggesting a role for the right temporoparietal junction (RTPJ) in belief attribution. Participants read vignettes in a 2 × 2 design: protagonists produced either a negative or neutral outcome based on the belief that they were causing the negative outcome (“negative” belief) or the neutral outcome (“neutral” belief). The RTPJ showed significant activation above baseline for all four conditions but was modulated by an interaction between belief and outcome. Specifically, the RTPJ response was highest for cases of attempted harm, where protagonists were condemned for actions that they believed would cause harm to others, even though the harm did not occur. The results not only suggest a general role for belief attribution during moral judgment, but also add detail to our understanding of the interaction between these processes at both the neural and behavioral levels.
Immunization with hepatitis C virus-like particles results in control of hepatitis C virus infection in chimpanzees
Authors: Elmowalid Gamal A. , Qiao Ming , Jeong Sook-Hyang , Borg Brian B. , Baumert Thomas F. , Sapp Ronda K. , Hu Zongyi , Murthy Krishna , Liang T. Jake
Published: May 2007

Recombinant hepatitis C virus (HCV)-like particles (HCV-LPs) containing HCV structural proteins (core, E1, and E2) produced in insect cells resemble the putative HCV virions and are capable of inducing strong and broad humoral and cellular immune responses in mice and baboons. Here, we present evidence on the immunogenicity and induction of protective immunity by HCV-LPs in chimpanzees. Chimpanzees (two in each group), were immunized with HCV-LPs or HCV-LPs plus AS01B adjuvant. After immunizations, all animals developed an HCV-specific immune response including IFN-γ+, IL-2+, CD4+, and CD8+T cell and proliferative lymphocyte responses against core, E1, and E2. Upon challenge with an infectious HCV inoculum, one chimpanzee developed transient viremia with low HCV RNA titers (103to 104copies per ml) in the third and fourth weeks after the challenge. The three other chimpanzees became infected with higher levels of viremia (104to 105copies per ml), but their viral levels became unquantifiable (<103copies per ml) 10 weeks after the challenge. After the HCV challenge, all four chimpanzees demonstrated a significant increase in peripheral and intrahepatic T cell and proliferative responses against the HCV structural proteins. These T cell responses coincided with the fall in HCV RNA levels. Four naïve chimpanzees were infected with the same HCV inoculum, and three developed persistent infection with higher viremia in the range of 105to 106copies per ml. Our study suggests that HCV-LP immunization induces HCV-specific cellular immune responses that can control HCV challenge in the chimpanzee model.
Lymphomas can develop from B cells chronically helped by idiotype-specific T cells
Authors: Zangani Michael M. , Frøyland Marianne , Qiu Gao Yue , Meza-Zepeda Leonardo A. , Kutok Jeffery L. , Thompson Keith M. , Munthe Ludvig A. , Bogen Bjarne
Published: May 2007

B cell lymphomas have been associated with chronic infections and autoimmunity. However, most lymphomas develop in the absence of any known chronic antigenic stimulation. B cells process their highly diversified endogenous immunoglobulin and present clonally unique variable-region idiotypic (Id) peptides on their major histocompatibility complex (MHC) class II molecules to Id-specific T cells. We show that B cells chronically helped by Id-specific Th2 cells developed into large B cell lymphomas with cytogenetic DNA aberrations. The lymphomas expressed high amounts of Id, MHC class II, CD80/86, and CD40 and bidirectionally collaborated with Th2 cells. Thus, MHC class II–presented Id peptides may represent a chronic self-antigenic stimulus for T cell–dependent lymphomagenesis. Eventually, B lymphomas grew independent of T cells. Thus, T cells do not only eliminate cancers as currently believed. In fact, Id-specific Th2 cells can induce B lymphomas.
CCR7 ligands control basal T cell motility within lymph node slices in a phosphoinositide 3–kinase– independent manner
Authors: Asperti-Boursin François , Real Eliana , Bismuth Georges , Trautmann Alain , Donnadieu Emmanuel
Published: May 2007

The molecular mechanisms responsible for the sustained basal motility of T cells within lymph nodes (LNs) remain elusive. To study T cell motility in a LN environment, we have developed a new experimental system based on slices of LNs that allows the assessment of T cell trafficking after adoptive transfer or direct addition of T cells to the slice. Using this experimental system, we show that T cell motility is highly sensitive to pertussis toxin and strongly depends on CCR7 and its ligands. Our results also demonstrate that, despite its established role in myeloid cell locomotion, phosphoinositide 3–kinase (PI3K) activity does not contribute to the exploratory behavior of the T lymphocytes within LN slices. Likewise, although PI3K activation is detectable in chemokine-treated T cells, PI3K plays only a minor role in T cell polarization and migration in vitro. Collectively, our results suggest that the common amplification system that, in other cells, facilitates large phosphatidylinositol 3,4,5-trisphosphate increases at the plasma membrane is absent in T cells. We conclude that T cell motility within LNs is not an intrinsic property of T lymphocytes but is driven in a PI3K-independent manner by the lymphoid chemokine-rich environment.
The length of lipids bound to human CD1d molecules modulates the affinity of NKT cell TCR and the threshold of NKT cell activation
Authors: McCarthy Corinna , Shepherd Dawn , Fleire Sebastian , Stronge Victoria S. , Koch Michael , Illarionov Petr A. , Bossi Giovanna , Salio Mariolina , Denkberg Galit , Reddington Faye , Tarlton Andrea , Reddy B. Gopal , Schmidt Richard R. , Reiter Yoram , Griffiths Gillian M. , van der Merwe P. Anton , Besra Gurdyal S. , Jones E. Yvonne , Batista Facundo D. , Cerundolo Vincenzo
Published: May 2007

CD1d-restricted lymphocytes recognize a broad lipid range. However, how CD1d-restricted lymphocytes translate T cell receptor (TCR) recognition of lipids with similar group heads into distinct biological responses remains unclear. Using a soluble invariant NKT (iNKT) TCR and a newly engineered antibody specific for α-galactosylceramide (α-GalCer)–human CD1d (hCD1d) complexes, we measured the affinity of binding of iNKT TCR to hCD1d molecules loaded with a panel of α-GalCer analogues and assessed the rate of dissociation of α-GalCer and α-GalCer analogues from hCD1d molecules. We extended this analysis by studying iNKT cell synapse formation and iNKT cell activation by the same panel of α-GalCer analogues. Our results indicate the unique role of the lipid chain occupying the hCD1d F′ channel in modulating TCR binding affinity to hCD1d–lipid complexes, the formation of stable immunological synapse, and cell activation. These data are consistent with previously described conformational changes between empty and loaded hCD1d molecules (Koch, M., V.S. Stronge, D. Shepherd, S.D. Gadola, B. Mathew, G. Ritter, A.R. Fersht, G.S. Besra, R.R. Schmidt, E.Y. Jones, and V. Cerundolo. 2005. Nat. Immunol 6:819–826), suggesting that incomplete occupation of the hCD1d F′ channel results in conformational differences at the TCR recognition surface. This indirect effect provides a general mechanism by which lipid-specific lymphocytes are capable of recognizing both the group head and the length of lipid antigens, ensuring greater specificity of antigen recognition.
A primary immunodeficiency characterized by defective immunoglobulin class switch recombination and impaired DNA repair
Authors: Péron Sophie , Pan-Hammarström Qiang , Imai Kohsuke , Du Likun , Taubenheim Nadine , Sanal Ozden , Marodi Laszlo , Bergelin-Besançon Anne , Benkerrou Malika , de Villartay Jean-Pierre , Fischer Alain , Revy Patrick , Durandy Anne
Published: May 2007

Immunoglobulin class switch recombination (CSR) deficiencies are rare primary immunodeficiencies, characterized by a lack of switched isotype (IgG, IgA, or IgE) production, variably associated with abnormal somatic hypermutation (SHM). Deficiencies in CD40 ligand, CD40, activation-induced cytidine deaminase, and uracil-N-glycosylase may account for this syndrome. We previously described another Ig CSR deficiency condition, characterized by a defect in CSR downstream of the generation of double-stranded DNA breaks in switch (S) μ regions. Further analysis performed with the cells of five affected patients showed that the Ig CSR deficiency was associated with an abnormal formation of the S junctions characterized by microhomology and with increased cell radiosensitivity. In addition, SHM was skewed toward transitions at G/C residues. Overall, these findings suggest that a unique Ig CSR deficiency phenotype could be related to an as-yet-uncharacterized defect in a DNA repair pathway involved in both CSR and SHM events.
Lysosomal integral membrane protein 2 is a novel component of the cardiac intercalated disc and vital for load-induced cardiac myocyte hypertrophy
Authors: Schroen Blanche , Leenders Joost J. , van Erk Arie , Bertrand Anne T. , van Loon Mirjam , van Leeuwen Rick E. , Kubben Nard , Duisters Rudy F. , Schellings Mark W. , Janssen Ben J. , Debets Jacques J. , Schwake Michael , Høydal Morten A. , Heymans Stephane , Saftig Paul , Pinto Yigal M.
Published: May 2007

The intercalated disc (ID) of cardiac myocytes is emerging as a crucial structure in the heart. Loss of ID proteins like N-cadherin causes lethal cardiac abnormalities, and mutations in ID proteins cause human cardiomyopathy. A comprehensive screen for novel mechanisms in failing hearts demonstrated that expression of the lysosomal integral membrane protein 2 (LIMP-2) is increased in cardiac hypertrophy and heart failure in both rat and human myocardium. Complete loss of LIMP-2 in genetically engineered mice did not affect cardiac development; however, these LIMP-2 null mice failed to mount a hypertrophic response to increased blood pressure but developed cardiomyopathy. Disturbed cadherin localization in these hearts suggested that LIMP-2 has important functions outside lysosomes. Indeed, we also find LIMP-2 in the ID, where it associates with cadherin. RNAi-mediated knockdown of LIMP-2 decreases the binding of phosphorylated β-catenin to cadherin, whereas overexpression of LIMP-2 has the opposite effect.

Collectively, our data show that LIMP-2 is crucial to mount the adaptive hypertrophic response to cardiac loading. We demonstrate a novel role for LIMP-2 as an important mediator of the ID.
PQuad—a visual analysis platform for proteomic data exploration of microbial organisms
Authors: Webb-Robertson Bobbie-Jo M. , Peterson Elena S. , Singhal Mudita , Klicker Kyle R. , Oehmen Christopher S. , Adkins Joshua N. , Havre Susan L.
Published: May 2007

Summary: The visual Platform for Proteomics Peptide and Protein data exploration (PQuad) is a multi-resolution environment that visually integrates genomic and proteomic data for prokaryotic systems, overlays categorical annotation and compares differential expression experiments. PQuad requires Java 1.5 and has been tested to run across different operating systems.

Availability: http://ncrr.pnl.gov/software

Contact: bobbie-jo.webb-robertson@pnl.gov
Sparse non-negative matrix factorizations via alternating non-negativity-constrained least squares for microarray data analysis
Authors: Kim Hyunsoo , Park Haesun
Published: May 2007

Motivation: Many practical pattern recognition problems require non-negativity constraints. For example, pixels in digital images and chemical concentrations in bioinformatics are non-negative. Sparse non-negative matrix factorizations (NMFs) are useful when the degree of sparseness in the non-negative basis matrix or the non-negative coefficient matrix in an NMF needs to be controlled in approximating high-dimensional data in a lower dimensional space.

Results: In this article, we introduce a novel formulation of sparse NMF and show how the new formulation leads to a convergent sparse NMF algorithm via alternating non-negativity-constrained least squares. We apply our sparse NMF algorithm to cancer-class discovery and gene expression data analysis and offer biological analysis of the results obtained. Our experimental results illustrate that the proposed sparse NMF algorithm often achieves better clustering performance with shorter computing time compared to other existing NMF algorithms.

Availability: The software is available as supplementary material.

Contact:  hskim@cc.gatech.edu, hpark@acc.gatech.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
CALIB: a Bioconductor package for estimating absolute expression levels from two-color microarray data
Authors: Zhao Hui , Engelen Kristof , De Moor Bart , Marchal Kathleen
Published: May 2007

In this article we describe a new Bioconductor package ‘CALIB’ for normalization of two-color microarray data. This approach is based on the measurements of external controls and estimates an absolute target level for each gene and condition pair, as opposed to working with log-ratios as a relative measure of expression. Moreover, this method makes no assumptions regarding the distribution of gene expression divergence.

Availability: http://bioconductor.org/packages/2.0/bioc Open Source

Contact: Kathleen.marchal@biw.kuleuven.be
Phenotypic clustering of yeast mutants based on kinetochore microtubule dynamics
Authors: Jaqaman K. , Dorn J. F. , Marco E. , Sorger P. K. , Danuser G.
Published: May 2007

Motivation: Kinetochores are multiprotein complexes which mediate chromosome attachment to microtubules (MTs) of the mitotic spindle. They regulate MT dynamics during chromosome segregation. Our goal is to identify groups of kinetochore proteins with similar effects on MT dynamics, revealing pathways through which kinetochore proteins transform chemical and mechanical input signals into cues of MT regulation.

Results: We have developed a hierarchical, agglomerative clustering algorithm that groups Saccharomyces cerevisiae strains based on MT-mediated chromosome dynamics measured by high-resolution live cell microscopy. Clustering is based on parameters of autoregressive moving average (ARMA) models of the probed dynamics. We have found that the regulation of wildtype MT dynamics varies with cell cycle and temperature, but not with the chromosome an MT is attached to. By clustering the dynamics of mutants, we discovered that the three genes IPL1, DAM1 and KIP3 co-regulate MT dynamics. Our study establishes the clustering of chromosome and MT dynamics by ARMA descriptors as a sensitive framework for the systematic identification of kinetochore protein subcomplexes and pathways for the regulation of MT dynamics.

Availability: The clustering code, written in Matlab, can be downloaded from http://lccb.scripps.edu. (‘download’ hyperlink at bottom of website).

Contact: kjaqaman@scripps.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
Assessment of survival prediction models based on microarray data
Authors: Schumacher Martin , Binder Harald , Gerds Thomas
Published: May 2007

Motivation: In the process of developing risk prediction models, various steps of model building and model selection are involved. If this process is not adequately controlled, overfitting may result in serious overoptimism leading to potentially erroneous conclusions.

Methods: For right censored time-to-event data, we estimate the prediction error for assessing the performance of a risk prediction model (Gerds and Schumacher, 2006; Graf et al., 1999). Furthermore, resampling methods are used to detect overfitting and resulting overoptimism and to adjust the estimates of prediction error (Gerds and Schumacher, 2007).

Results: We show how and to what extent the methodology can be used in situations characterized by a large number of potential predictor variables where overfitting may be expected to be overwhelming. This is illustrated by estimating the prediction error of some recently proposed techniques for fitting a multivariate Cox regression model applied to the data of a prognostic study in patients with diffuse large-B-cell lymphoma (DLBCL).

Availability: Resampling-based estimation of prediction error curves is implemented in an R package called pec available from the authors.

Contact:  sec@imbi.uni-freiburg.de
Automated Improvement of Domain ANnotations using context analysis of domain arrangements (AIDAN)
Authors: Beaussart Francois , Weiner January , Bornberg-Bauer Erich
Published: May 2007

Motivation: Since protein domains are the units of evolution, databases of domain signatures such as ProDom or Pfam enable both a sensitive and selective sequence analysis. However, manually curated databases have a low coverage and automatically generated ones often miss relationships which have not yet been discovered between domains or cannot display similarities between domains which have drifted apart.

Methods: We present a tool which makes use of the fact that overall domain arrangements are often conserved. AIDAN (Automated Improvement of Domain ANnotations) identifies potential annotation artifacts and domains which have drifted apart. The underlying database supplements ProDom and is interfaced by a graphical tool allowing the localization of single domain deletions or annotations which have been falsely made by the automated procedure.

Availability:  http://www.uni-muenster.de/Evolution/ebb/Services/AIDAN

Contact:  ebb@uni-muenster.de

Supplementary information: Supplementary data are available at Bioinformatics online.