bluuebunny/crossref_metadata_2025 huggingface dataset:
N- and C-Terminal Cooperation in Rotavirus Enterotoxin: Novel Mechanism of Modulation of the Properties of a Multifunctional Protein by a Structurally and Functionally Overlapping Conformational Domain
Authors: Jagannath M. R. , Kesavulu M. M. , Deepa R. , Sastri P. Narayan , Kumar S. Senthil , Suguna K. , Rao C. Durga
Published: December 2005

Rotavirus NSP4 is a multifunctional endoplasmic reticulum (ER)-resident nonstructural protein with the N terminus anchored in the ER and about 131 amino acids (aa) of the C-terminal tail (CT) oriented in the cytoplasm. Previous studies showed a peptide spanning aa 114 to 135 to induce diarrhea in newborn mouse pups with the 50% diarrheal dose approximately 100-fold higher than that for the full-length protein, suggesting a role for other regions in the protein in potentiating its diarrhea-inducing ability. In this report, employing a large number of methods and deletion and amino acid substitution mutants, we provide evidence for the cooperation between the extreme C terminus and a putative amphipathic α-helix located between aa 73 and 85 (AAH
73-85
) at the N terminus of ΔN72, a mutant that lacked the N-terminal 72 aa of nonstructural protein 4 (NSP4) from Hg18 and SA11. Cooperation between the two termini appears to generate a unique conformational state, specifically recognized by thioflavin T, that promoted efficient multimerization of the oligomer into high-molecular-mass soluble complexes and dramatically enhanced resistance against trypsin digestion, enterotoxin activity of the diarrhea-inducing region (DIR), and double-layered particle-binding activity of the protein. Mutations in either the C terminus, AAH
73-85
, or the DIR resulted in severely compromised biological functions, suggesting that the properties of NSP4 are subject to modulation by a single and/or overlapping highly sensitive conformational domain that appears to encompass the entire CT. Our results provide for the first time, in the absence of a three-dimensional structure, a unique conformation-dependent mechanism for understanding the NSP4-mediated pleiotropic properties including virus virulence and morphogenesis.
Mutations in the U5 Sequences Adjacent to the Primer Binding Site Do Not Affect tRNA Cleavage by Rous Sarcoma Virus RNase H but Do Cause Aberrant Integrations In Vivo
Authors: Oh Jangsuk , Chang Kevin W. , Hughes Stephen H.
Published: December 2005

In most retroviruses, the first nucleotide added to the tRNA primer becomes the right end of the U5 region in the right long terminal repeat (LTR); the removal of this tRNA primer by RNase H defines the right end of the linear double-stranded DNA. Most retroviruses have two nucleotides between the 5′ end of the primer binding site (PBS) and the CA dinucleotide that will become the end of the integrated provirus. However, human immunodeficiency virus type 1 (HIV-1) has only one nucleotide at this position, and HIV-2 has three nucleotides. We changed the two nucleotides (TT) between the PBS and the CA dinucleotide of the Rous sarcoma virus (RSV)-derived vector RSVP(A)Z to match the HIV-1 sequence (G) and the HIV-2 sequence (GGT), and we changed the CA dinucleotide to TC. In all three mutants, RNase H removes the entire tRNA primer. Sequence analysis of RSVP(HIV2) proviruses suggests that RSV integrase can remove three nucleotides from the U5 LTR terminus of the linear viral DNA during integration, although this mutation significantly reduced virus titer, suggesting that removing three nucleotides is inefficient. However, the results obtained with RSVP(HIV1) and RSVP(CATC) show that RSV integrase can process and integrate the normal U3 LTR terminus of a linear DNA independently of an aberrant U5 LTR terminus. The aberrant end can then be joined to the host DNA by unusual processes that do not involve the conserved CA dinucleotide. These unusual events generate either large duplications or, less frequently, deletions in the host genomic DNA instead of the normal 5- to 6-base duplications.
Entry of Vaccinia Virus and Cell-Cell Fusion Require a Highly Conserved Cysteine-Rich Membrane Protein Encoded by the A16L Gene
Authors: Ojeda Suany , Senkevich Tatiana G. , Moss Bernard
Published: December 2005

The vaccinia virus A16L open reading frame encodes a 378-amino-acid protein with a predicted C-terminal transmembrane domain and 20 invariant cysteine residues that is conserved in all sequenced members of the poxvirus family. The A16 protein was expressed late in infection and incorporated into intracellular virus particles with the N-terminal segment of the protein exposed on the surface. The cysteine residues were disulfide bonded via the poxvirus cytoplasmic redox system. Unsuccessful attempts to isolate a mutant virus with the A16L gene deleted suggested that the protein is essential for replication. To study the role of the A16 protein, we made a recombinant vaccinia virus that has the
Escherichia coli lac
operator system regulating transcription of the A16L gene. In the absence of inducer, A16 synthesis was repressed and plaque size and virus yield were greatly reduced. Nevertheless, virus morphogenesis occurred and normal-looking intracellular and extracellular virus particles formed. Purified virions made in the presence and absence of inducer were indistinguishable, though the latter had 60- to 100-fold-lower specific infectivity. A16-deficient virions bound to cells, but their cores did not penetrate into the cytoplasm. Furthermore, A16-deficient virions were unable to induce low-pH-triggered syncytium formation. The phenotype of the inducible A16L mutant was similar to those of mutants in which synthesis of the A21, A28, H2, or L5 membrane protein was repressed, indicating that at least five conserved viral proteins are required for entry of poxviruses into cells as well as for cell-cell fusion.
Simian Immunodeficiency Virus Vpx Is Imported into the Nucleus via Importin Alpha-Dependent and -Independent Pathways
Authors: Singhal Prabhat K. , Kumar P. Rajendra , Rao Malireddi R. K. Subba , Kyasani Mahesh , Mahalingam Sundarasamy
Published: December 2005

Vpx protein of human immunodeficiency virus type 2/simian immunodeficiency virus (SIV) has been implicated in the transport of the viral genome into the nuclei of nondividing cells. The mechanism by which Vpx enters the nucleus remains unknown. Here we have identified two distinct noncanonical nuclear localization signals (NLSs) in Vpx of SIV
smPbj1.9
and defined the pathways for its nuclear import. Although nuclear targeting signals identified here are distinct from known nuclear import signals, translocation of Vpx into the nucleus involves the interaction of its N-terminal NLS (amino acids 20 to 40) or C-terminal NLS (amino acids 65 to 75) with importin alpha and, in the latter case, also with importin beta. Collectively, these results suggest that importins interact with Vpx and ensure the effective import of Vpx into the nucleus to support virus replication in nondividing cells.
Expression of m157, a Murine Cytomegalovirus-Encoded Putative Major Histocompatibility Class I (MHC-I)-Like Protein, Is Independent of Viral Regulation of Host MHC-I
Authors: Tripathy Sandeep K. , Smith Hamish R. C. , Holroyd Erika A. , Pingel Jeanette T. , Yokoyama Wayne M.
Published: December 2005

A murine cytomegalovirus (MCMV)-encoded protein, m157, has a putative major histocompatibility complex class I (MHC-I) structure and is recognized by the Ly49H NK cell activation receptor. Using a monoclonal antibody against m157, in this study we directly demonstrated that m157 is a cell surface-expressed glycophosphatidylinositol-anchored protein with early viral gene kinetics. Beta-2 microglobulin and TAP1 (transporter associated with antigen processing 1) were not required for its expression. MCMV-encoded proteins that down-regulate MHC-I did not affect the expression of m157. Thus, m157 is expressed on infected cells in a manner independent of viral regulation of host MHC-I.
Anti-CD45RO Suppresses Human Immunodeficiency Virus Type 1 Replication in Microglia: Role of Hck Tyrosine Kinase and Implications for AIDS Dementia
Authors: Kim Mee-Ohk , Suh Hyeon-Sook , Si Qiusheng , Terman Bruce I. , Lee Sunhee C.
Published: December 2005

Macrophages and microglia are productively infected by HIV-1 and play a pivotal role in the pathogenesis of AIDS dementia. Although macrophages and microglia express CD45, a transmembrane protein tyrosine phosphatase, whether modulation of its activity affects human immunodeficiency virus type 1 (HIV-1) replication is unknown. Here, we report that of the five human CD45 isoforms, microglia express CD45RB and CD45RO (RB > RO) and treatment of microglia with a CD45 agonist antibody αCD45RO (UCHL-1) inhibits HIV-1 replication. αCD45RO prevented HIV-1 negative factor (Nef)-induced autophosphorylation of hematopoietic cell kinase (Hck), a myeloid lineage-specific Src kinase. Recombinant CD45 protein also inhibited HIV-1-induced Hck phosphorylation in microglia. Antennapedia-mediated delivery of Hck Src homology domain 3 (SH3), a domain that binds to the Nef PxxP motif with high affinity, reduced HIV-1-induced Hck phosphorylation and HIV-1 production in microglia. HIV-1-induced LTR transactivation was observed in U38 cells stably overexpressing wild-type Hck but not kinase-inactive Hck. In microglia, αCD45RO reduced activation of transcription factors (NF-κB and CCAAT enhancer binding protein) necessary for LTR transactivation in macrophages. These results establish that in myeloid lineage cells, Nef interacts with the Hck SH3 domain, resulting in autophosphorylation of Hck and an increase in HIV-1 transcription. αCD45RO-mediated inhibition of HIV-1 replication in microglia identifies the CD45 protein tyrosine phosphatase as a potential therapeutic target for HIV-1 infection/AIDS dementia.
The Equine Herpesvirus 1 UL20 Product Interacts with Glycoprotein K and Promotes Egress of Mature Particles
Authors: Guggemoos Simone , Just Frank T. , Neubauer Antonie
Published: December 2005

The aim of the present study was to identify and functionally characterize the equine herpesvirus 1 (EHV-1) UL20 protein (UL20p). Using a specific antiserum, UL20p was shown to be associated with membranes of infected cells, as well as with envelopes of purified virions. By Western blot analysis, UL20p was detected in two main forms exhibiting
M
r
s of 25,000 and 75,000. Both moieties did not enter the separating gel after heating of protein samples to 99°C. The slower-migrating form of UL20p contains N-linked carbohydrates, and its presence is dependent of that of other viral proteins. Infection of cells that either constitutively express UL20p or a gK-green fluorescent protein (GFP) fusion protein with various EHV-1 deletion mutants revealed a relatively stable hetero-oligomer containing gK and UL20p with an apparent
M
r
of 75,000. As demonstrated by confocal microscopy, UL20p distribution in Rk13 cells changed from a diffuse granular or netlike appearance to a pattern confined to the Golgi network when gK was coexpressed. Analysis of a UL20 deletion mutant of EHV-1 strain RacL11 indicated an involvement of UL20p in cell-to-cell spread, as well as in very late events in virus egress. Based on these and electron microscopic studies we suggest that the EHV-1 UL20 protein might be necessary to avoid fusion of mature virions with membranes of their transport vesicles.
Comparison of Spectral Responses between Front- and Back-Incidence Configurations in GaN Metal–Semiconductor–Metal Photodetector on Sapphire
Authors: Ohsawa Jun , Kozawa Takahiro , Miura Hideki , Fujishima Osamu , Itoh Hiroshi
Published: December 2005

Front and back illumination of a metal–semiconductor–metal structure on a 2-µm-thick GaN layer showed obvious differences in the spectral responsivity in the wavelength range of 300–500 nm. Pt/Au interdigitated electrodes on an unintentionally doped n-GaN were confirmed to be of extremely low leakage Schottky type, and simulations of the electrostatic potential distribution have revealed that the depletion regions do not prevail throughout the thick GaN layer even at a bias of 10 V. The difference observed in the wavelength region shorter than the fundamental absorption edge is due to incomplete depletion of the GaN layer off the Schottky contacts in conjunction with short optical penetration depths, while the back-incidence responsivity in the longer wavelength region reflects extrinsic optical absorptions characteristic to the epitaxial crystal.
Numerical Simulation of Conversion Efficiency and Beam Quality Factor in Second Harmonic Generation with Diffraction and Pump Depletion
Authors: Kasamatsu Tadashi , Kubomura Hiroyuki , Kan Hirofumi
Published: December 2005

We report numerical simulation of conversion efficiency and beam quality factor (M
2) in second harmonic generation taking into account diffraction and pump depletion. Compared with the results in Boyd and Kleinman's study [J. Appl. Phys. 39 (1968) 3597], which treated the no-depletion case, with the presence of pump depletion, conversion efficiency is maximized under substantially weaker focusing. Depletion also leads to the degradation of the beam quality factor of both the unconverted fundamental and the generated second harmonic radiation.
Femtosecond-Soliton Switching in a Three-Core Coupler
Authors: Kumar Ajit , Sarma Amarendra K.
Published: December 2005

Soliton switching in a three-core Kerr-coupler is studied numerically by taking into account intermodal dispersion (IMD), third-order dispersion and higher-order nonlinear effects, like the Raman and self-steepening effects. It is shown that the weak coupling regime is the most suitable for the purpose. Also, it is shown that IMD has negligible influence on switching, while, out of the higher-order nonlinear effects, Raman intrapulse scattering has the dominant effect.
Distributed-Parameter Based Treatment of Interaction Process between Elastic and Dielectric Energy in Piezoelectric Transducer
Authors: Ohki Michio
Published: December 2005

The interaction process between elastic and dielectric energy in a piezoelectric transducer, which has been treated on the basis of lumped parameters in the framework of electrical equivalent circuit, is treated on a distributed-parameter basis. The concept of coupling between elastic and dielectric energy modes is introduced, and the superposition of the energy mode after the coupling is considered, which allows us to determine the frequency characteristics of the transducer with an electromechanical coupling. Mathematically, the coupling effect is represented by the exponential of a matrix, and the superposition of the energy mode is calculated with the infinite geometric series of a matrix, Neumann series, which provides physically reasonable results.
Mechanical Stability of Pixel-Isolated Liquid Crystal Mode with Plastic Substrates
Authors: Jung Jong-Wook , Jin Min Young , Kim Hak-Rin , Lee You-Jin , Kim Jae-Hoon
Published: December 2005

We have fabricated a plastic liquid crystal display using the pixel-isolated liquid crystal (PILC) mode and characterized the mechanical stability of the sample against mechanical pressure and bending. Since the liquid crystal molecules are fully isolated in the pixels by the phase-separated polymer walls in the PILC mode, the electrooptic properties of the sample show good mechanical stability. In addition, a polymer layer formed on the upper substrate enhances the adhesion between two plastic substrates.
New Development of Ultrahigh-Vacuum Oriented-Molecular-Beam Machine and Its Application to Chemical Reactions on Silicon Surface
Authors: Okada Michio , Moritani Kousuke , Goto Seishiro , Kasai Toshio
Published: December 2005

The stereochemical control of surface reactions is one of the ultimate goals of surface scientists. An oriented-molecular-beam technique based on the Stark effect of a molecule in an inhomogeneous hexapole electrostatic field is a potential tool for achieving such a goal. This technique allows us to select a specific rotational quantum state and also an orientation of a reagent molecule. We have designed, built and tuned up a new UHV-compatible oriented-molecular-beam machine for the elucidation of the reaction dynamics on surfaces and for surface manufacturing application. In the dissociative adsorption of CH3Cl on a Si{100} surface, we found a dynamical steric effect on the initial sticking probability (S
0) using the new machine. S
0 in Cl-end collision is larger than that in CH3-end collision at an incident energy of 120 meV. To our knowledge, this is the first measurement of the steric effect in the chemisorption of a molecule on a Si surface.
Microstructure and Crystallographic Orientation Dependence of Electrical Properties in Lead Zirconate Thin Films Prepared by Sol–Gel Process
Authors: Alkoy Ebru Mensur , Alkoy Sedat , Shiosaki Tadashi
Published: December 2005

Lead zirconate (PbZrO3) thin films are grown on Pt(111)/Ti/SiO2/Si(100) substrates by sol–gel using precursor solutions with stoichiometric and 20 mol % excess Pb. Films with no preferred orientation and [111] pseudocubic texture (denoted as [111]pc) are obtained by changing the drying temperature at the pyrolysis stage. Randomly oriented films were found to have a two-phase microstructure consisting of large rosette-type perovskite regions with a nanocrystalline phase located in between. The ratio of the rosettes increase to cover the entire surface of the films with the increase of Pb content. The films with [111]pc orientation have a uniform microstructure with micron size grains. The electrical properties of the films were influenced markedly by the microstructure and orientation of the films. The [111]pc oriented films exhibit a square-like double hysteresis loop with maximum polarization (P
max) reaching 61×10-6 C/cm2 under 550 kV/cm, whereas stoichiometric films with no preferred orientation have a P
max of 36×10-6 C/cm2 with slimmer hysteresis curves.
Spectral Imaging for Electroluminescence Characterization of a Polymer-Blend Light-Emitting Diode
Authors: Takada Noriyuki , Kamata Toshihide
Published: December 2005

Spectral imaging for electroluminescence (EL) characterization of a light-emitting diode based on blends of poly[2,7-(9,9-di-n-octylfluorene)] (PFO) and poly[2,7-(9,9-di-n-octylfluorene)-alt-(1,4-phenylene-((4-sec-butylphenyl)amino)-1,4-phenylene)] (TFB) was performed using a two-dimensional microspectroscopy imaging system. We found that EL spectral images changed markedly with increasing applied voltage. Such a variation is presumed to have originated from the transfer of emission sites in the polymer blend layer.
Flow Structure in an Inner Rotating Annular Channel with Ribbed Wall Cylinder
Authors: Tzeng Sheng-Chung , Ma Wei-Ping , Huang K. David , Wu Tai-Sheng
Published: December 2005

In this investigation, we explore the flow field of an annular channel between two horizontal concentric rotating cylinders, i.e., between a rotating inner cylinder and a stationary outer cylinder. Resulting from interactions between centrifugal force, viscous force and different boundary conditions, flow fields in an annular channel probably develop groups of opposite Taylor vortices when the Taylor number is higher than a critical value. Geometrical parameters of rotating cylinder channels, such as the channel widths and circumferential ribs are also affected by the flow field. Four types of rotating inner cylinder are available in this experiment: smooth walled (Model A), and circumferential ribs of three different sizes (Models B–D). The aspect ratios for circumferential ribs are 5/3, 5/2, and 10/3, which generate periodically embedded cavities of 10, 15, and 20 mm. The radius ratios between the inner and outer cylinders were ηs=0.89, and ηrib=0.94, respectively. Taylor numbers ranged between (8.565–1312.943)×103, and centrifugal force arising from the rotation of Model A was F
s=0.22–3.3 N. The centrifugal forces arising from the inner cylinders with embedded circumferential ribs were F
rib=0.23–3.49 Nt. Because the wavelength of the Taylor vortices was subjected to the influence of different geometrical conditions, the flow field structure of Model A was different at both ends of the cylinder. Conversely, various forms of Taylor vortices occurred between annular channels with circumferential ribs in the case of Models B–D, and the vortex evolved from the edge of the circumferential ribs in a more stable manner than in Model A. The wavelengths of the Taylor vortices were λA=30 mm, λB and λD=20 mm, and λC=15 mm. Experimental results of flow visualization demonstrated it to be well suited for benchmarking engineering designs for heat transfer, cooling, and tribology of rotating machinery.
Enhanced K-edge Angiography Utilizing Tantalum Plasma X-ray Generator in Conjunction with Gadolinium-Based Contrast Media
Authors: Sato Eiichi , Hayasi Yasuomi , Kimura Koji , Tanaka Etsuro , Mori Hidezo , Kawai Toshiaki , Inoue Takashi , Ogawa Akira , Sato Shigehiro , Takayama Kazuyoshi , Onagawa Jun , Ido Hideaki
Published: December 2005

The tantalum plasma flash X-ray generator is useful for performing high-speed enhanced K-edge angiography using cone beams because K-series characteristic X-rays from the tantalum target are absorbed effectively by gadolinium-based contrast media. In the flash X-ray generator, a 150 nF condenser is charged up to 80 kV by a power supply, and flash X-rays are produced by the discharging. The X-ray tube is a demountable cold-cathode diode, and the turbomolecular pump evacuates air from the tube with a pressure of approximately 1 mPa. Since the electric circuit of the high-voltage pulse generator employs a cable transmission line, the high-voltage pulse generator produces twice the potential of the condenser charging voltage. At a charging voltage of 80 kV, the estimated maximum tube voltage and current were approximately 160 kV and 40 kA, respectively. When the charging voltage was increased, the K-series characteristic X-ray intensities of cerium increased. The K lines were clean and intense, and hardly any bremsstrahlung rays were detected. The X-ray pulse widths were approximately 100 ns, and the time-integrated X-ray intensity had a value of approximately 300 µGy at 1.0 m from the X-ray source with a charging voltage of 80 kV. Angiography was performed using a filmless computed radiography (CR) system and gadolinium-based contrast media. In the angiography of nonliving animals, we observed fine blood vessels of approximately 100 µm with high contrasts.
Mare versus Lago-mare: marine fishes and the Mediterranean environment at the end of the Messinian Salinity Crisis
Authors: Carnevale G. , Landini W. , Sarti G.
Published: December 2005

During the late Messinian,
c
. 5.5 Ma ago, after evaporitic sedimentation and before the Pliocene flooding, the Mediterranean recorded a major environmental change testified by deposition of non-marine sediments of the so-called ‘Lago-mare’ facies. Such deposits are widespread in the Mediterranean basin, usually characterized by molluscs and ostracodes of brackish affinity. Here we present marine fish remains from ‘Lago-mare’ deposits of central Italy. The fossils, represented by both articulated skeletons and otoliths, were collected from nine stratigraphic horizons of the upper portion of the ‘Lago-mare’ sequence of Cava Serredi, Tuscany. Marine euryhaline fishes strongly dominate the assemblages but fully marine stenohaline fishes belonging to the families Myctophidae and Bythitidae are also present. The fossil fish remains are associated with classic ‘Lago-mare’ ostracodes and molluscs. These fossil fishes clearly demonstrate that normal marine conditions were present at least during the upper interval of the ‘Lago-mare’ event, implying that the marine refilling of the Mediterranean was intra-Messinian rather early Pliocene. We argue in favour of the necessity of a new palaeoenvironmental interpretation for the post-evaporitic Messinian of the Mediterranean.
40
Ar/
39
Ar laserprobe dating of mylonitic fabrics in a polyorogenic terrane of NW Iberia
Authors: Gómez Barreiro Juan , Wijbrans Jan R. , Castiñeiras Pedro , Martínez Catalán José R. , Arenas Ricardo , Díaz García Florentino , Abati Jacobo
Published: December 2005

The tectonothermal evolution of a polyorogenic terrane in the Variscan belt of NW Spain has been constrained by
40
Ar/
39
Ar laserprobe incremental heating experiments on mylonitic fabrics developed in major structures. Transitional levels between HP–HT and IP upper units in the Órdenes Complex where metamorphic and structural records demonstrate two cycles of burial and exhumation were selected for dating. Two groups of ages have been defined: (1) Silurian–Early Devonian, obtained from mylonites of the Fornás extensional detachment, here considered as the minimum age for the start of tectonic exhumation of the HP–HT units and an upper age-limit for the HP–HT event itself; (2) Early to Mid-Devonian, from structures related to the Variscan convergence in the area, which include top-to-the-east thrusts and extensional detachments. A single, younger Carboniferous age obtained from the uppermost allochthonous sequences possibly reflects the final stages of emplacement of the allochthonous complexes. Our data indicate a polyorogenic character for a part of the Iberian allochthonous complexes, including Variscan (
sensu stricto
) and Early Variscan convergence, as well as an older, Early Palaeozoic cycle.
The mid-Norwegian margin: a discussion of crustal lineaments, mafic intrusions, and remnants of the Caledonian root by 3D density modelling and structural interpretation
Authors: Ebbing J. , Lundin E. , Olesen O. , Hansen E.K.
Published: December 2005

The high-density lower crustal body (LCB) on the mid-Norwegian margin is almost universally interpreted to represent magmatically underplated material, added to the crust during Early Tertiary opening of the NE Atlantic. The thickness of the LCB is uneven, and its distribution along the margin is sharply limited by margin-perpendicular lineaments. Three-dimensional density modelling constrained by petrophysical and seismic data was performed to investigate the expression of the various lineaments (Bivrost, Jan Mayen, Gleipne, etc.) in the crustal architecture, with and without the LCB. The Bivrost Lineament, separating the Vøring and Lofoten margin segments, is clearly expressed and so is arguably a lineament in the SW Vøring margin. Notably, most of the lineaments can be interpreted as offshore prolongations of major onshore detachments stemming from Late Caledonian orogenic collapse. An alternative interpretation of the LCB is thus that it represents high-grade metamorphic rocks, remnant from the Caledonian root. Determining the nature of the LCB has profound effects for the volume estimate of magmatic rocks in the North Atlantic Igneous Province, and consequently also for the degree of crustal thinning and heat flow.
Kinematics of active left-lateral faulting in SE Turkey from offset Pleistocene river gorges: improved constraint on the rate and history of relative motion between the Turkish and Arabian plates
Authors: Westaway Rob , Demir Tuncer , Seyrek Ali , Beck Anthony
Published: December 2005

In the Arabian Platform of SE Turkey abundant evidence exists of fluvial incision by
c
. 110 ± 10 m since the late Early Pleistocene, starting in or around marine oxygen isotope stage 22 at 870 ka. This incision, which has accompanied regional surface uplift as the isostatic response to regional erosion, has progressively ‘locked’ rivers into their gorges in landscape that formerly had much lower relief. We use this effect to estimate 4.44 ± 0.06 km of left-lateral slip on this time scale on the Gölbaşı–Türkoğlu Fault, a segment of the East Anatolian Fault Zone, from offset river gorges, giving a slip rate of 5.10 ± 0.07 mm a
−1
. Piercing points indicate that this fault has slipped a total of 19 km, making its age 3.73 ± 0.05 Ma. A total of 33 km of relative motion between the Turkish and Arabian plates is documented on this time scale in the vicinity of Gölbaşı, at an overall time-averaged rate of 8.85 ± 0.12 mm a
−1
, the estimated Euler vector for relative motion between these plates being 0.89 ± 0.01° Ma
−1
about 33.4°N, 42.3°E. This method can be readily applied to determine slip rates, time-averaged since the late Early Pleistocene, on other strike-slip fault zones worldwide.
Diet and exercise reduce low-grade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects
Authors: Bruun Jens M. , Helge Jørn W. , Richelsen Bjørn , Stallknecht Bente
Published: December 2005

Obesity is associated with low-grade inflammation, insulin resistance, type 2 diabetes, and cardiovascular disease. This study investigated the effect of a 15-wk lifestyle intervention (hypocaloric diet and daily exercise) on inflammatory markers in plasma, adipose tissue (AT), and skeletal muscle (SM) in 27 severely obese subjects (mean body mass index: 45.8 kg/m2). Plasma samples, subcutaneous abdominal AT biopsies, and vastus lateralis SM biopsies were obtained before and after the intervention and analyzed by ELISA and RT-PCR. The intervention reduced body weight ( P < 0.001) and increased insulin sensitivity (homeostasis model assessment; P < 0.05). Plasma adiponectin ( P < 0.001) increased, and C-reactive protein ( P < 0.05), IL-6 ( P < 0.01), IL-8 ( P < 0.05), and monocyte chemoattractant protein-1 ( P < 0.01) decreased. AT inflammation was reduced, determined from an increased mRNA expression of adiponectin ( P < 0.001) and a decreased expression of macrophage-specific markers (CD14, CD68), IL-6, IL-8, and tumor necrosis factor-α ( P < 0.01). After adjusting for macrophage infiltration in AT, only IL-6 mRNA was decreased ( P < 0.05). Only very low levels of inflammatory markers were found in SM. The intervention had no effect on adiponectin receptor 1 and 2 mRNA in AT or SM. Thus hypocaloric diet and increased physical activity improved insulin sensitivity and reduced low-grade inflammation. Markers of inflammation were particularly reduced in AT, whereas SM does not contribute to this attenuation of whole body inflammation.
Improvements in insulin resistance with weight loss, in contrast to rosiglitazone, are not associated with changes in plasma adiponectin or adiponectin multimeric complexes
Authors: Abbasi Fahim , Chang Sang-Ah , Chu James W. , Ciaraldi Theodore P. , Lamendola Cindy , McLaughlin Tracey , Reaven Gerald M. , Reaven Peter D.
Published: December 2005

It has been suggested that changes in adiponectin levels may contribute to improved insulin sensitivity in insulin-resistant individuals both after weight loss and after treatment with thiazolidinedione compounds. If this is correct, then changes in total circulating adiponectin and/or distribution of its multimeric complexes should coincide with improvements in insulin sensitivity after both interventions. To address this issue, fasting adiponectin concentrations and distribution of adiponectin complexes were measured in plasma samples in 24 insulin-resistant, nondiabetic subjects before and after 3–4 mo of treatment with either rosiglitazone or caloric restriction. The degree of insulin resistance in each group of 12 subjects was equal at baseline and improved to a similar extent (∼30%) after each therapy. Whereas total adiponectin levels increased by nearly threefold and the relative amount of several higher molecular weight adiponectin complexes increased significantly in the rosiglitazone treatment group, there were no discernible changes in adiponectin levels or in the distribution between high or low molecular weight complexes in the weight loss group. These data indicate that, although changes in total adiponectin and several specific adiponectin complexes paralleled improvements in insulin resistance in thiazolidinedione-treated subjects, neither circulating adiponectin concentrations nor multimeric complexes changed in association with enhanced insulin sensitivity after moderate weight loss in 12 insulin-resistant, obese individuals.
Automated Oscillometric Determination of the Ankle–Brachial Index Provides Accuracy Necessary for Office Practice
Authors: Beckman Joshua A. , Higgins Caitlin O. , Gerhard-Herman Marie
Published: December 2005

Peripheral arterial disease (PAD) remains underdiagnosed by primary care and cardiovascular physicians. The office-based assessment of PAD is limited by the need for specialized equipment and the time required for performance of the ankle–brachial index (ABI). We explored whether the accuracy of automated ABI measurement by oscillometry compared favorably with the gold-standard method using continuous-wave Doppler ultrasound. Consecutive patients referred to our university hospital noninvasive vascular laboratory for ABI measurement were invited for participation. Of 205 patients, 201 participated, including 55 with PAD. The ABI was measured by automated oscillometry and Doppler ultrasound. The test of trends revealed a correlation coefficient of 0.78 in the left leg and 0.78 in the right leg (
P
<0.01 for both). The mean ABI difference between methods was 0.04±0.01 and 0.06±0.01, respectively, in the left and right legs. The differences between the methods followed a normal distribution. Oscillometric determination of the ABI provides an accurate determination of the ABI in an outpatient population. Our findings show automated oscillometry to be a reliable and easier method of ABI measurement, lowering the barrier to incorporation of this diagnostic test into clinical practice.
Phagocytosis of Necrotic but Not Apoptotic Trophoblasts Induces Endothelial Cell Activation
Authors: Chen Qi , Stone Peter R. , McCowan Lesley M.E. , Chamley Larry W.
Published: December 2005

It is hypothesized that preeclampsia is caused by factors from the placenta that induce endothelial cell activation. Trophoblasts are cells that may be shed from the placenta, then deported in the maternal blood, and finally become trapped in the pulmonary capillaries. The ultimate fate of deported trophoblasts is unknown, but to prevent clogging of the pulmonary circulation they must be cleared from the capillary beds. We examined the hypothesis that endothelial cells phagocytose deported trophoblasts and also examined the consequent effects of the trophoblasts on endothelial cells. Fluorescently labeled trophoblast–derived choriocarcinoma cells were induced to become apoptotic or necrotic and exposed to endothelial cell monolayers. Confocal microscopy demonstrated uptake of both apoptotic and necrotic trophoblasts, and this phagocytosis could be inhibited by cytochalasin B. Phagocytosis of necrotic but not apoptotic trophoblasts induced increased endothelial intercellular adhesion molecule 1 (ICAM-1) expression, as well as increased adhesion of monocytes to endothelial cell monolayers. Inhibiting the phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase pathways blocked both expression of ICAM-1 and phagocytosis, whereas inhibition of the P42/44 mitogen-activated protein kinase pathway blocked only ICAM-1 expression. This work suggests that endothelial cells can phagocytose deported trophoblasts and that the mechanism of trophoblast death (apoptotic or necrotic) could have major effects on the maternal vascular response to shed trophoblasts.
Cost-Effectiveness of Ambulatory Blood Pressure
Authors: Krakoff Lawrence R.
Published: December 2005

Accurate diagnosis of hypertension and prognosis for future cardiovascular events can be enhanced through the use of 24-hour ambulatory blood pressure monitoring. It has been suggested that the use of ambulatory monitoring as a secondary screening for hypertension might be cost-effective. Many needed studies that are related to the calculation of cost-effectiveness for ambulatory monitoring have become available in recent years. More accurate estimates for cost of care, costs for testing, prevalence of white-coat hypertension, and incidence of the transition from normal pressures to hypertension have been reported. This study presents calculations of the cost savings likely to take place when ambulatory blood pressure monitoring is implemented for newly detected hypertensive subjects. These calculations are based on current estimates for cost of testing, cost of treatment, prevalence of white-coat hypertension at baseline, and varying the incidence of new hypertension after the initial screening. The results indicate a potential savings of 3% to 14% for cost of care for hypertension and 10% to 23% reduction in treatment days when ambulatory blood pressure monitoring is incorporated into the diagnostic process. At current reimbursement rates, the cost of ambulatory blood pressure monitoring for secondary screening on an annual basis would be <10% of treatment costs. Calculated savings for use of ambulatory blood pressure monitoring can take place when annual treatment costs are as little as $300. These estimates should be considered for the management of recently detected hypertension, especially when the risk of future cardiovascular is disease is low.
Blood Flow Remodels Growing Vasculature During Vascular Endothelial Growth Factor Gene Therapy and Determines Between Capillary Arterialization and Sprouting Angiogenesis
Authors: Rissanen Tuomas T. , Korpisalo Petra , Markkanen Johanna E. , Liimatainen Timo , Ordén Maija-Riitta , Kholová Ivana , de Goede Anna , Heikura Tommi , Gröhn Olli H. , Ylä-Herttuala Seppo
Published: December 2005

Background—

For clinically relevant proangiogenic therapy, it would be essential that the growth of the whole vascular tree is promoted. Vascular endothelial growth factor (VEGF) is well known to induce angiogenesis, but its capability to promote growth of larger vessels is controversial. We hypothesized that blood flow remodels vascular growth during VEGF gene therapy and may contribute to the growth of large vessels.

Methods and Results—

Adenoviral (Ad) VEGF or LacZ control gene transfer was performed in rabbit hindlimb semimembranous muscles with or without ligation of the profound femoral artery (PFA). Contrast-enhanced ultrasound and dynamic susceptibility contrast MRI demonstrated dramatic 23- to 27-fold increases in perfusion index and a strong decrease in peripheral resistance 6 days after AdVEGF gene transfer in normal muscles. Enlargement by 20-fold, increased pericyte coverage, and decreased alkaline phosphatase and dipeptidyl peptidase IV activities suggested the transformation of capillaries toward an arterial phenotype. Increase in muscle perfusion was attenuated, and blood vessel growth was more variable, showing more sprouting angiogenesis and formation of blood lacunae after AdVEGF gene transfer in muscles with ligated PFA than in normal muscles. Three-dimensional ultrasound reconstructions and histology showed that the whole vascular tree, including large arteries and veins, was enlarged manifold by AdVEGF. Blood flow was normalized and enlarged collaterals persisted in operated limbs 14 days after AdVEGF treatment.

Conclusions—

This study shows that (1) blood flow modulates vessel growth during VEGF gene therapy and (2) VEGF overexpression promotes growth of arteries and veins and induces capillary arterialization leading to supraphysiological blood flow in target muscles.
Peristent Remodeling and Neointimal Suppression 2 Years After Polymer-Based, Paclitaxel-Eluting Stent Implantation
Authors: Aoki Jiro , Colombo Antonio , Dudek Dariusz , Banning Adrian P. , Drzewiecki Janusz , Zmudka Krzysztof , Schiele Francois , Russell Mary E. , Koglin Joerg , Serruys Patrick W.
Published: December 2005

Background—

The purpose of this study was to evaluate long-term vascular responses as long as 2 years after implantation of polymer-based, paclitaxel-eluting stents in contrast to uncoated stents.

Methods and Results—

TAXUS II is a randomized, double-blind trial comparing slow-release (SR) and moderate-release (MR) TAXUS stents with bare-metal control stents (BMSs). One hundred sixty-one event-free patients (SR, 43; MR, 41; and BMS, 77) underwent serial intravascular ultrasound (IVUS) analysis after the procedure and at 6 months and 2 years. At 2 years, neointimal responses continued to be significantly suppressed in the SR and MR groups when compared with the BMS group (BMS, 1.49±1.12 mm
2
; SR, 0.94±0.76 mm
2
[
P
=0.004]; and MR, 1.06±0.90 mm
2
[
P
=0.02]). Between 6 months and 2 years, the BMS group showed compaction of the neointima (Δ, −0.22±1.05 mm
2
[
P
=0.08]). In contrast, both the SR and MR groups exhibited an increase (Δ SR, 0.30±0.76 mm
2
(
P
=0.01); MR, 0.41±0.94 mm
2
[
P
=0.009]). Between 6 months and 2 years, the initial increase in plaque outside the stent regressed in the BMS and SR groups to levels comparable to those after the procedure, whereas expansive remodeling partially regressed in the MR group (Δ between after the procedure and 2 years BMS, −0.34±1.28 mm
2
[
P
=0.05]; SR, −0.02±1.40 mm
2
[
P
=0.93]; MR, 0.32±1.56 mm
2
[
P
=0.27]).

Conclusions—

The 2-year follow-up demonstrates that neointimal suppression was dose independent and that this effect was still sustained at 2 years. However, the increase in area outside the stent seen at 6 months regressed to different extents in a dose-dependent manner at 2 years.
Pharmacological Preconditioning With Tumor Necrosis Factor-α Activates Signal Transducer and Activator of Transcription-3 at Reperfusion Without Involving Classic Prosurvival Kinases (Akt and Extracellular Signal–Regulated Kinase)
Authors: Lecour Sandrine , Suleman Naushaad , Deuchar Graeme A. , Somers Sarin , Lacerda Lydia , Huisamen Barbara , Opie Lionel H.
Published: December 2005

Background—

We previously reported that tumor necrosis-factor-α (TNF-α) can mimic classic ischemic preconditioning (IPC) in a dose- and time-dependent manner. Because TNF-α activates the signal transducer and activator of transcription-3 (STAT-3), we hypothesized that TNF-α–induced preconditioning requires phosphorylation of STAT-3 rather than involving the classic prosurvival kinases, Akt and extracellular signal–regulated kinase (Erk) 1/2, during early reperfusion.

Methods and Results—

Isolated, ischemic/reperfused rat hearts were preconditioned by either IPC or low-dose TNF-α (0.5 ng/mL). Western blot analysis confirmed that IPC phosphorylated Akt and Erk 1/2 after 5 minutes of reperfusion (Akt increased by 34±6% and Erk, by 105±28% versus control;
P
<0.01). Phosphatidylinositol 3-kinase/Akt inhibition (wortmannin) or mitogen-activated protein kinase–Erk 1/2 kinase inhibition (PD-98059) during early reperfusion abolished the infarct-sparing effect of IPC. In contrast, TNF-α preconditioning did not phosphorylate these kinases (Akt increased by 7±7% and Erk, by 17±14% versus control;
P
=NS). Neither wortmannin nor PD-98059 inhibited TNF-α–mediated cardioprotection. However, TNF-α and IPC both phosphorylated STAT-3 and the proapoptotic protein Bcl-2 antagonist of cell death (BAD) (STAT-3 increased by 58±17% with TNF-α or by 68±12% with IPC; BAD increased by 75±8% with TNF-α or by 205±20% with IPC;
P
<0.01 versus control), thereby activating the former and inactivating the latter. The STAT-3 inhibitor AG 490 abolished cardioprotection and BAD phosphorylation with both preconditioning stimuli.

Conclusions—

Activation of the classic prosurvival kinases (Akt and Erk 1/2) is not essential for TNF-α–induced preconditioning in the early reperfusion phase. We show the existence of an alternative protective pathway that involves STAT-3 activation specifically at reperfusion in response to both TNF-α and classic IPC. This novel prosurvival pathway may have potential therapeutic significance.
Expecting the Unexpected: Cultural Components of Arab Governance
Authors: Rosen Lawrence
Published: December 2005

The development of democracy in the Arab world does not always pay sufficient attention to the cultural foundations of Arab political and social life. Concepts of the person, time, memory, and relationship need to be considered as vital elements of the political cultures of these countries. Against that background, it may be possible to suggest elements of constitutional and legal organization that are more in keeping with Arab cultural orientations, rather than supposing that the imposition of Western constitutional forms will necessarily suit local needs in the Middle East.
Divided Nations: The Paradox of National Protection
Authors: Deng Francis M.
Published: December 2005

Internal displacement, which in many cases leads to refuge across international borders, has emerged as one of the major crises confronting the world today. The assumption, clearly erroneous, is that unlike refugees, who have lost the protection of their own governments by crossing international borders, the internally displaced remain under the protection of their national governments. In most cases, these same governments are actually the cause of their displacement, and worse—they neglect and even persecute them. This article aims to develop a new international response to the global crisis of internal displacement in acutely divided nations. It suggests the problem is more than a humanitarian and human rights issue; the underlying causes have much to do with gross inequities in the shaping and sharing of values and the gross discrimination and marginalization of certain groups. Citizenship becomes largely of paper value. The crisis is ultimately a challenge of nation building.
The Federal Constitutional Court: Guardian of German Democracy
Authors: Kommers Donald P.
Published: December 2005

Germany's Federal Constitutional Court rivals the Supreme Court of the United States in protecting political democracy. Its jurisprudence of democracy has shaped the course and character of German politics while upholding the rule of law and defending the constitutionally prescribed “free democratic basic order.” In furtherance of these objectives, the Constitutional Court has invalidated regulations limiting the rights of minor parties and constitutionalizing measures designed to stabilize Germany's system of parliamentary government. These purposes have been served by constitutional decisions on voting rights, public funding of election campaigns, dissolution of Parliament, and proportional representation, including the limiting 5 percent clause. These decisions, along with a discussion of the Hessian Election Review Case—a reminder of Bush v. Gore—are calculated to make political representation both responsive and responsible and to anchor the political system firmly in the democratic values at the heart of the Basic Law.
Late-Life Emergence of Early-Life Trauma
Authors: Davison Eve H. , Pless Anica P. , Gugliucci Marilyn R. , King Lynda A. , King Daniel W. , Salgado Dawn M. , Spiro Avron , Bachrach Peter
Published: December 2005

This study aimed to provide preliminary evidence for, and explore potential antecedents and correlates of, a phenomenon observed in aging combat veterans termed late-onset stress symptomatology (LOSS). LOSS is a hypothesized phenomenon among older veterans who (a) experienced highly stressful combat events in early adulthood; (b) functioned successfully throughout their lives, with no chronic stress-related disorders; but (c) begin to register increased combat-related thoughts, feelings, reminiscences, memories, or symptoms commensurate with the changes and challenges of aging, sometimes decades after their combat experiences. Using a qualitative focus group methodology with 47 World War II, Korean Conflict, and Vietnam War veterans, the authors obtained preliminary evidence for the presence of LOSS as defined, identified some of its features, revealed some normative late-life stressors that may precipitate LOSS, and uncovered potential intrapersonal risk and resilience factors for LOSS. The authors present illustrative quotations from the group discussions and discuss the implications and future directions of this research.