bluuebunny/crossref_metadata_2025 huggingface dataset:
Bcl‐xL blocks mitochondrial multiple conductance channel activation and inhibits 6‐OHDA‐induced death in SH‐SY5Y cells
Authors: Jordán Joaquín , Galindo María F. , Tornero Daniel , González‐García Carmen , Ceña Valentín
Published: May 2006

Apoptosis is an active process that is regulated by different signalling pathways. One of the more important organelles involved in apoptosis regulation is the mitochondrion. Electron chain transport disruption increases free radical production leading to multiple conductance channel opening, release of cytochrome c and caspase activation. This death pathway can be blocked by anti‐apoptotic members of the Bcl‐2 protein family that might shift redox potential to a more reduced state, preventing free radical‐mediated damage. 6‐Hydroxydopamine (6‐OHDA) has been widely used to generate Parkinson's disease‐like models. It is able to generate free radicals and to induce catecholaminergic cell death. In this paper we have used the human neuroblastoma cell line SH‐SY5Y overexpressing Bcl‐xL as a model to gain insights into the mechanisms through which Bcl‐xL blocks 6‐OHDA‐induced cell death and to identify the molecular targets for this action. Herein, we present evidence supporting that the Bcl‐xL–anti‐apoptotic signal pathway seems to prevent mitochondrial multiple conductance channel opening, cytochrome c release and caspase‐3 like activity following 6‐OHDA treatment in the human neuroblastoma cell line SH‐SY5Y.
Molecular evolution and genetics of the Saitohin gene and tau haplotype in Alzheimer's disease and argyrophilic grain disease
Authors: Conrad Chris , Vianna Cintia , Schultz Christian , Thal Dietmar R. , Ghebremedhin Estifanos , Lenz Jack , Braak Heiko , Davies Peter
Published: May 2006

A single nucleotide polymorphism that results in an amino acid change (Q7R) has been identified in the Saitohin (STH) gene and was initially found to be over‐represented in the homozygous state in subjects with late‐onset Alzheimer's disease (AD). More extensive studies provide limited support for the association with AD, but confirm an association of the Q allele with progressive supranuclear palsy and argyrophilic grain disease. A homologous sequence was found in the appropriate location of the rat and mouse tau genes, but there was no open reading frame allowing STH expression in these species, suggesting relatively recent evolution of this gene. In some non‐human primates, the STH gene was identified, and this was found to differ from the human gene at two of 128 amino acids. All primates in which the STH gene was identified were homozygous for the R allele of STH, suggesting this is the ancestral allele. This observation was surprising, in that the Q allele is more common in human populations, and raises the possibility that natural selection has operated to favor individuals carrying this allele. The STH polymorphism is part of the tau gene haplotype, of which two major variants exist in human populations, the Q being part of the H1 haplotype and the R part of the H2 haplotype. More detailed studies confirm the H2 haplotype to be the ancestral tau gene. This situation is reminiscent of the evolution of the apolipoprotein (ApoE) gene, another locus that is potentially important for the risk of development of AD.
Kinetic approach to microscopic-macroscopic coupling in space and laboratory plasmas
Authors: Lapenta Giovanni , Brackbill J. U. , Ricci Paolo
Published: May 2006

Kinetic plasma simulation typically requires to handle a multiplicity of space and time scales. The implicit moment particle in cell (PIC) method provides a possible route to address the presence of multiple scales effectively. Here, a new implementation of the implicit moment method is described. The present paper has two goals. First, the most modern implementation of the implicit moment method is described. While many of the algorithms involved have been developed in the past, the present paper reports for the first time how the implicit moment method is currently implemented and what specific algorithms have been found to work best. Second, we present the CELESTE3D code, a fully electromagnetic and fully kinetic PIC code, based on the implicit moment method. The code has been in use for a number of years but no previous complete description of its implementation has been provided. The present work fills this gap and introduces a number of new methods not previously presented: a new implementation of the Maxwell solver and a new particle mover based on a Newton-Krylov nonlinear solver for the discretized Newton’s equations. A number of benchmarks of CELESTE3D are presented to shown the typical application and to investigate the improvements introduced by the new solver and the new mover.
Measurements of the parallel and transverse Spitzer resistivities during collisional magnetic reconnection
Authors: Kuritsyn A. , Yamada M. , Gerhardt S. , Ji H. , Kulsrud R. , Ren Y.
Published: May 2006

Plasma resistivity has been studied experimentally in a reconnecting current sheet. Resistivities during collisional reconnection, when the electron mean free path is much shorter than the current sheet thickness, in the presence and absence of the guide field are found to be in a good agreement with the parallel and transverse Spitzer values, respectively.
Tests of the hydrodynamic equivalence of direct-drive implosions with different D2 and He3 mixtures
Authors: Rygg J. R. , Frenje J. A. , Li C. K. , Séguin F. H. , Petrasso R. D. , Delettrez J. A. , Glebov V. Yu , Goncharov V. N. , Meyerhofer D. D. , Regan S. P. , Sangster T. C. , Stoeckl C.
Published: May 2006

Direct drive implosions of targets filled with different mixtures of D2 and He3 gas on the OMEGA laser system [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)] have shown an unexpected scaling of experimental nuclear yields. At temperatures above a few electron volts, D2 and He3 gases are fully ionized, and hydrodynamically equivalent fuels with different ratios of D2 and He3 can be chosen to have the same mass density, total particle density, and equation of state. Implosions with a 50/50 mixture of D:He3 by atom consistently result in measured nuclear yields half of that anticipated by scaling from measured yields of implosions with pure D2 and nearly pure He3. This observation is seen over a wide range of experimental configurations, including targets with a variety of shell thicknesses and fill pressures, simultaneously for two different nuclear yields (DD and DHe3), and for shock and compression yields. A number of possible mechanisms to cause the scaling are considered, but no dominant mechanism has been identified.
Green’s function of compressible Petschek-type magnetic reconnection
Authors: Penz Thomas , Semenov V. S. , Ivanova V. V. , Heyn M. F. , Ivanov I. B. , Biernat H. K.
Published: May 2006

We present a method to analyze the wave and shock structures arising from Petschek-type magnetic reconnection. Based on a time-dependent analytical approach developed by Heyn and Semenov [Phys. Plasmas 3, 2725 (1996)] and Semenov et al. [Phys. Plasmas 11, 62 (2004)], we calculate the perturbations caused by a delta function-shaped reconnection electric field, which allows us to achieve a representation of the plasma variables in the form of Green’s functions. Different configurations for the initial conditions are considered. In the case of symmetric, antiparallel magnetic fields and symmetric plasma density, the well-known structure of an Alfvén discontinuity, a fast body wave, a slow shock, a slow wave, and a tube wave occurs. In the case of asymmetric, antiparallel magnetic fields, additionally surface waves are found. We also discuss the case of symmetric, antiparallel magnetic fields and asymmetric densities, which leads to a faster propagation in the lower half plane, causing side waves forming a Mach cone in the upper half plane. Complex effects like anisotropic propagation characteristics, intrinsic wave coupling, and the generation of different nonlinear and linear wave modes in a finite β plasma are retained. The temporal evolution of these wave and shock structures is shown.
Theoretical study of structure and photoelectron spectroscopy of InxPy− and InxPy (x+y⩽6) clusters
Authors: Zhang Congjie
Published: May 2006

The geometries and vibrational frequencies of InxPy− and InxPy are investigated by hybrid B3LYP functional for x+y⩽6 and CCSD(T) method for x+y⩽3. As for the small clusters having two to three atoms, the geometrical and electronic structures and vibrational frequencies at the B3LYP level are in good agreement with those at the CCSD(T) level. Among the most stable structures of InxPy− and InxPy (x+y⩽6) clusters the P-rich clusters are more stable than In-rich clusters. Moreover, we found that those P atoms in InxPy− and InxPy (x+y⩽6) clusters prefer to form a P–P bond, triangle, quadrangle, and pentagon for y=2, 3, 4, and 5, respectively. Also, the vertical detachment energies of InxPy− (x+y⩽6) and electron affinities of InxPy (x+y⩽6) clusters obtained by B3LYP are in good agreement with the experimental values available. Theoretically, we show that the electron affinity of In3P3 is very low because, as observed in the experiment, there is a formation of a new P–P bond after an electron is lost from In3P3−, and we find that the similar phenomena exhibit in In2P4− cluster as well.
Self-organization of plasma due to electron beam instability
Authors: Liu Z. J. , Zhu Shao-ping , Cao L. H. , Zheng C. Y. , Li Bin
Published: May 2006

The evolution of electron beams in dense plasmas has been investigated by using two-dimensional particle-in-cell simulations with mobile and immobile ions, respectively. It is shown that electron beams are split into many filaments at the beginning due to the Weibel instability, and then different filamentation beams attract each other and coalesce. It is observed that there exist two different current density distributions, the Bennett-like equilibrium and the delta-like equilibrium, which are mainly determined by the total beam current. When the initial beam current exceeds Alfvén current, the system approaches a delta-like state. Otherwise, the system approaches a Bennett-like state. The physical mechanism for this phenomenon is pointed out; also the temporal evolution of particle distribution function is discussed.
Development of a carbon nanotube based microfocus x-ray tube with single focusing electrode
Authors: Liu Zejian , Zhang Jian , Yang Guang , Cheng Yuan , Zhou Otto , Lu Jianping
Published: May 2006

We report a detailed study on the design of carbon nanotube based microfocus x-ray tube with one electrostatic focusing electrode. Based on the electron optics simulations, such parameters as geometrical distances and applied voltages among all the electrodes are considered, respectively, in relation to the size of x-ray focal spot. The stability of the x-ray focal spot size is also examined with respect to the variation of gate and anode voltages. Experimental results that agree well with the simulated data are also provided to corroborate the design method. We also discuss the operating stability and limitations when designing a carbon nanotube based microfocus x-ray tube with only one electrostatic focusing electrode. The designed x-ray tube with an isotropic focal spot sees wide applications in in vivo medical imaging studies.
Canonical Hamiltonian theory of the guiding-center motion in an axisymmetric torus, with the different time scales well separated
Authors: Wang Shaojie
Published: May 2006

A new set of exact canonical variables of guiding-center motion in an axisymmetric torus has been systematically identified and an action-angle variable formalism has been established. In this new canonical Hamiltonian theory, the time scale of poloidal motion and the time scale of toroidal drift (precession) of the guiding-centers are well separated.
Current-driven microwave oscillations in current perpendicular-to-plane spin-valve nanopillars
Authors: Mistral Q. , Kim Joo-Von , Devolder T. , Crozat P. , Chappert C. , Katine J. A. , Carey M. J. , Ito K.
Published: May 2006

We study the current and temperature dependences of the microwave voltage emission of spin-valve nanopillars subjected to an in-plane magnetic field and a perpendicular-to-plane current. Despite the complex multilayer geometry, clear microwave emission is observed for current densities in the interval of 9×107–13×107Acm−2. The emission frequency stays near 12GHz when I<Ired=11.2×107Acm−2, then redshifts with a slope gradually reaching −350MHz∕mA for 16×107Acm−2. The linewidth narrows exponentially to 3.8MHz at 150K for I<Ired, then broadens again as the emitted voltage redshifts. The temperature dependence of the linewidth exhibits a curvature change around the linewidth minimum.
Quantitative dynamic-mode scanning force microscopy in liquid
Authors: Hoogenboom B. W. , Hug H. J. , Pellmont Y. , Martin S. , Frederix P. L. T. M. , Fotiadis D. , Engel A.
Published: May 2006

We describe a method to perform dynamic-mode scanning force microscopy in liquid with true atomic resolution. A frequency-modulation technique is used to maintain constant amplitude, phase, and frequency shift of the cantilever oscillation. As a consequence, the tip-sample interaction force is well defined and quantitative. The force sensitivity is demonstrated by imaging and deliberate bending of a peptide loop connecting transmembrane helices of the membrane protein bacteriorhodopsin. The experimental setup allows further enhancement of the force sensitivity by the use of small cantilevers.
Effect of post deposition annealing on the optical properties of HfOxNy films
Authors: Liu M. , Fang Q. , He G. , Li L. , Zhu L. Q. , Li G. H. , Zhang L. D.
Published: May 2006

We report in this letter that Hafnium oxynitride (HfOxNy) gate dielectrics were prepared by radio frequency (RF) reactive magnetron sputtering and optical properties of the HfOxNy thin films were investigated by spectroscopic ellipsometry with photon energy of 0.75–6.5eV at room temperature. The investigations showed that the annealing temperatures have a strong effect on the optical properties of HfOxNy thin films. With increased annealing temperature, the refractive index n is observed to increase, while the extinction coefficient k decreases, respectively. The changes of the complex dielectric functions and the optical band gap Eg with the annealing temperature are also discussed.
Crack-free fully epitaxial nitride microcavity with AlGaN∕GaN distributed Bragg reflectors and InGaN∕GaN quantum wells
Authors: Zhang X. H. , Chua S. J. , Liu W. , Wang L. S. , Yong A. M. , Chow S. Y.
Published: May 2006

Using metal-organic chemical vapor deposition, we have fabricated fully epitaxial nitride microcavties with AlGaN∕GaN distributed Bragg reflectors and InGaN quantum wells as the light emitter. To solve the problem of cracking, a thin AlN anticracking layer was used. The samples were characterized using transmission electron microscope, reflectivity spectroscopy, and photoluminescence spectroscopy. A cavity quality factor of 200 was obtained and the spontaneous emission of cavity mode was measured from a 1λ GaN microcavity, with 40-pair Al0.24Ga0.76N∕GaN distributed Bragg reflectors as the bottom and top reflectors and three period In0.10Ga0.90N∕GaN quantum wells in the GaN cavity layer.
Exciton related stimulated emission in ZnO polycrystalline thin film deposited by filtered cathodic vacuum arc technique
Authors: Zhang X. H. , Chua S. J. , Yong A. M. , Li H. D. , Yu S. F. , Lau S. P.
Published: May 2006

Random lasing was observed from ZnO polycrystalline thin film deposited by filtered cathodic vacuum arc technique. It is found that the random lasing action results from exciton-exciton scattering process when the excitation intensity is low. However, with increasing excitation intensity, the well-resolved discrete lasing modes evolve into broad stimulated emission band due to electron-hole plasma formation when the photogenerated exciton density exceeds the Mott density. The short spontaneous emission decay time measured at low temperature suggests that the radiative recombination rate is enhanced by the nanosized ZnO grains in the polycrystalline film through exciton-light coupling.
Correlation between 577cm−1 Raman scattering and green emission in ZnO ordered nanostructures
Authors: Yang Yingling , Yan Hongwei , Fu Zhengping , Yang Beifang , Zuo Jian
Published: May 2006

We have investigated resonant Raman scattering (RRS) and photoluminescence of ZnO inverse opal prepared by electrodeposition. The intensities of both 577cm−1 Raman scattering and green emission get weaker after aging or UV laser irradiation. The RRS and green emission intensities are highly correlated for different samples, regardless of the means of sample treatment. According to the deposition-temperature and annealing-temperature dependences, we propose that the origins of the two peaks are related to surface hydroxide.
Effects of growth temperature on the structural and optical properties of 1.6μm GaInNAs∕GaAs multiple quantum wells
Authors: Liu H. Y. , Tey C. M. , Jin C. Y. , Liew S. L. , Navaretti P. , Hopkinson M. , Cullis A. G.
Published: May 2006

We have investigated the effects of growth temperature on the properties of 1.6μm GaInNAs∕GaAs multilayer quantum wells (MQWs). Strong room-temperature optical efficiency is obtained at 1.58μm for the sample grown at 375°C. However, the photoluminescence intensities with emission at similar wavelength are dramatically degraded for the samples grown at 350 and 400°C. Structural investigations show that compositional modulation and defects occurred in the sample grown at 400°C and possible point defects within the MQWs grown at 350°C. Based on these observations, the mechanism of effects of growth temperature on near-1.55-μm GaInNAs∕GaAs MQWs is discussed.
Spectral cross-talk in dual-band quantum well infrared detectors
Authors: Nedelcu Alexandru , Marcadet Xavier , Huet Odile , Bois Philippe
Published: May 2006

We propose a general definition of the spectral cross-talk in dual-band infrared (IR) photodetectors, based on the common information carried by the spectral channels. This definition includes detector characteristics as well as scene characteristics and can be applied to any real configuration. We use it to evaluate narrowband and wideband quantum well infrared photodetector structures and set up their interest for dual-band imaging. The spectral cross-talk is negligible for interband IR (3–5μm∕8–12μm) applications and can be minimized for intraband IR (8–12μm) applications by properly tailoring the responsivity peaks.
Surface-emitting photonic-crystal distributed-feedback laser for the midinfrared
Authors: Kim M. , Kim C. S. , Bewley W. W. , Lindle J. R. , Canedy C. L. , Vurgaftman I. , Meyer J. R.
Published: May 2006

We demonstrate a surface-emitting photonic-crystal distributed-feedback laser, emitting at λ≈3.7μm from an antimonide type-II “W” active region. While single-mode operation was not achieved, the spectral emission linewidth for cw optical pumping was only 1.3Å. For pulsed operation with a pump-spot diameter of 0.8mm, 60% of the nearly circular output beam was transmitted through an aperture with an angular diameter approximately five times that of a Gaussian emitted beam, assuming that the emission area and pump area are the same.
The Hsp90 Chaperone Complex Regulates GDI-dependent Rab Recycling
Authors: Chen Christine Y. , Balch William E.
Published: May 2006

Rab GTPase regulated hubs provide a framework for an integrated coding system, the membrome network, that controls the dynamics of the specialized exocytic and endocytic membrane architectures found in eukaryotic cells. Herein, we report that Rab recycling in the early exocytic pathways involves the heat-shock protein (Hsp)90 chaperone system. We find that Hsp90 forms a complex with guanine nucleotide dissociation inhibitor (GDI) to direct recycling of the client substrate Rab1 required for endoplasmic reticulum (ER)-to-Golgi transport. ER-to-Golgi traffic is inhibited by the Hsp90-specific inhibitors geldanamycin (GA), 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), and radicicol. Hsp90 activity is required to form a functional GDI complex to retrieve Rab1 from the membrane. Moreover, we find that Hsp90 is essential for Rab1-dependent Golgi assembly. The observation that the highly divergent Rab GTPases Rab1 involved in ER-to-Golgi transport and Rab3A involved in synaptic vesicle fusion require Hsp90 for retrieval from membranes lead us to now propose that the Hsp90 chaperone system may function as a general regulator for Rab GTPase recycling in exocytic and endocytic trafficking pathways involved in cell signaling and proliferation.
The Docking Protein Cas Links Tyrosine Phosphorylation Signaling to Elongation of Cerebellar Granule Cell Axons
Authors: Huang Jinhong , Sakai Ryuichi , Furuichi Teiichi
Published: May 2006

Crk-associated substrate (Cas) is a tyrosine-phosphorylated docking protein that is indispensable for the regulation of the actin cytoskeletal organization and cell migration in fibroblasts. The function of Cas in neurons, however, is poorly understood. Here we report that Cas is dominantly enriched in the brain, especially the cerebellum, of postnatal mice. During cerebellar development, Cas is highly tyrosine phosphorylated and is concentrated in the neurites and growth cones of granule cells. Cas coimmunoprecipitates with Src family protein tyrosine kinases, Crk, and cell adhesion molecules and colocalizes with these proteins in granule cells. The axon extension of granule cells is inhibited by either RNA interference knockdown of Cas or overexpression of the Cas mutant lacking the YDxP motifs, which are tyrosine phosphorylated and thereby interact with Crk. These findings demonstrate that Cas acts as a key scaffold that links the proteins associated with tyrosine phosphorylation signaling pathways to the granule cell axon elongation.
Adenovirus E4orf4 Hijacks Rho GTPase-dependent Actin Dynamics to Kill Cells: A Role for Endosome-associated Actin Assembly
Authors: Robert Amélie , Smadja-Lamère Nicolas , Landry Marie-Claude , Champagne Claudia , Petrie Ryan , Lamarche-Vane Nathalie , Hosoya Hiroshi , Lavoie Josée N.
Published: May 2006

The adenovirus early region 4 ORF4 protein (E4orf4) triggers a novel death program that bypasses classical apoptotic pathways in human cancer cells. Deregulation of the cell cytoskeleton is a hallmark of E4orf4 killing that relies on Src family kinases and E4orf4 phosphorylation. However, the cytoskeletal targets of E4orf4 and their role in the death process are unknown. Here, we show that E4orf4 translocates to cytoplasmic sites and triggers the assembly of a peculiar juxtanuclear actin–myosin network that drives polarized blebbing and nuclear shrinkage. We found that E4orf4 activates the myosin II motor and triggers de novo actin polymerization in the perinuclear region, promoting endosomes recruitment to the sites of actin assembly. E4orf4-induced actin dynamics requires interaction with Src family kinases and involves a spatial regulation of the Rho GTPases pathways Cdc42/N-Wasp, RhoA/Rho kinase, and Rac1, which make distinct contributions. Remarkably, activation of the Rho GTPases is required for induction of apoptotic-like cell death. Furthermore, inhibition of actin dynamics per se dramatically impairs E4orf4 killing. This work provides strong support for a causal role for endosome-associated actin dynamics in E4orf4 killing and in the regulation of cancer cell fate.
Rho Kinase, Myosin-II, and p42/44 MAPK Control Extracellular Matrix-mediated Apical Bile Canalicular Lumen Morphogenesis in HepG2 Cells
Authors: Herrema Hilde , Czajkowska Dominika , Théard Delphine , van der Wouden Johanna M. , Kalicharan Dharamdajal , Zolghadr Behnam , Hoekstra Dick , van IJzendoorn Sven C.D.
Published: May 2006

The molecular mechanisms that regulate multicellular architecture and the development of extended apical bile canalicular lumens in hepatocytes are poorly understood. Here, we show that hepatic HepG2 cells cultured on glass coverslips first develop intercellular apical lumens typically formed by a pair of cells. Prolonged cell culture results in extensive organizational changes, including cell clustering, multilayering, and apical lumen morphogenesis. The latter includes the development of large acinar structures and subsequent elongated canalicular lumens that span multiple cells. These morphological changes closely resemble the early organizational pattern during development, regeneration, and neoplasia of the liver and are rapidly induced when cells are cultured on predeposited extracellular matrix (ECM). Inhibition of Rho kinase or its target myosin-II ATPase in cells cultured on glass coverslips mimics the morphogenic response to ECM. Consistently, stimulation of Rho kinase and subsequent myosin-II ATPase activity by lipoxygenase-controlled eicosatetranoic acid metabolism inhibits ECM-mediated cell multilayering and apical lumen morphogenesis but not initial apical lumen formation. Furthermore, apical lumen remodeling but not cell multilayering requires basal p42/44 MAPK activity. Together, the data suggest a role for hepatocyte-derived ECM in the spatial organization of hepatocytes and apical lumen morphogenesis and identify Rho kinase, myosin-II, and MAPK as potentially important players in different aspects of bile canalicular lumen morphogenesis.
An epigenetic state associated with areas of gene duplication
Authors: Gimelbrant Alexander A. , Chess Andrew
Published: May 2006

Asynchronous DNA replication is an epigenetically determined feature found in all cases of monoallelic expression, including genomic imprinting, X-inactivation, and random monoallelic expression of autosomal genes such as immunoglobulins and olfactory receptor genes. Most genes of the latter class were identified in experiments focused on genes functioning in the chemosensory and immune systems. We performed an unbiased survey of asynchronous replication in the mouse genome, excluding known asynchronously replicated genes. Fully 10% (eight of 80) of the genes tested exhibited asynchronous replication. A common feature of the newly identified asynchronously replicated areas is their proximity to areas of tandem gene duplication. Testing of other clustered areas supported the idea that such regions are enriched with asynchronously replicated genes.
Thimerosal – Is it really irrelevant?
Authors: Slodownik Dan , Ingber Arieh
Published: May 2006

Recently, several investigators claimed that thimerosal is one of the most irrelevant allergens existing in screening for contact dermatitis. 508 patients who were suspected to have allergic contact dermatitis were patch tested at our clinic. They completed a questionnaire including medical, demographic and occupational details. We used the standard tray of chemotechnique diagnostics (Malmö, Sweden) and additional series, which were case relevant. The relevance of the allergic reaction to thimerosal was scored from 1 to 6. 19 patients (3.7%) had an allergic reaction to thimerosal. 6 (31.5%) had a definite relevance and 8 (42.1%) had a probable relevance. Only 3 patients (15.8%) had an irrelevant reaction. SPIN value (significance–prevalence index number) was 2281. We found a high proportion of mechanics (42.1%) among the patients who had positive reaction to thimerosal (P < 0.0001). Although previous reports found thimerosal highly irrelevant, our daily experience being supported by the above data indicates that positive reactions to thimerosal could be relevant for many patients.
Clindamycin skin testing has limited diagnostic potential
Authors: Notman Melissa J. , Phillips Elizabeth J. , Knowles Sandra R. , Weber Elizabeth A. , Shear Neil H.
Published: May 2006

We examined the role of clindamycin prick and intradermal skin testing in a tertiary care clinic population. Experience with diagnostic modalities such as prick and intradermal testing has been limited with clindamycin. A retrospective chart review was conducted for patients with immunologic reactions temporally associated with clindamycin who were referred to the Drug Safety Clinic (Toronto, Ontario). A total of 31 patients were identified who had undergone prick and intradermal skin testing. All 31 negative immediate prick and intradermal tests were followed by a 150 mg oral dose of clindamycin. 10/31 (32%) subjects had significant reactions to the oral clindamycin provocation. 2 patients reported delayed reactions at the clindamycin intradermal test sites. Our experience suggests that prick and intradermal skin testing is not adequate in identifying patients with previous allergic reactions associated with clindamycin. Oral provocation tests can be used in patients with histories of clindamycin adverse reactions; however, it should be offered on a risk‐benefit basis.
Emollients in a propanol‐based hand rub can significantly decrease irritant contact dermatitis
Authors: Kampf Günter , Wigger‐Alberti Walter , Schoder Volker , Wilhelm Klaus‐Peter
Published: May 2006

The objective of this study is to determine the effect of emollients in a propanol‐based hand rub on skin dryness and erythema. In this prospective, randomized, controlled, double‐blind trial, 35 subjects participated; of them approximately half were atopic (modified Erlanger atopy score ≥8). 2 propanol‐based formulations were tested in a repeated open application test, 1 contained a mixture of emollients (0.81%, w/w). 2 aliquots of 0.7 ml of each formulation were applied twice per day over 2 weeks to the cubital fossa of each subject after random assignment of the preparations. Treatment areas were assessed before each application and 3 days postfinal application by visual inspection for erythema and dryness according to a standard scale. The sum score over all assessment time‐points served as primary parameter. The mean sum score for erythema and dryness was significantly lower for the hand rub with emollients (0.8 ± 2.4) in comparison with that for the hand rub without emollients (1.5 ± 3.5; P = 0.022; Wilcoxon signed rank test). A comparison of the atopic and non‐atopic subjects revealed no significant difference for any of the products (P > 0.05; Mann–Whitney U‐test). It is concluded that the addition of emollients to a propanol‐based hand rub can significantly decrease irritant contact dermatitis under frequent‐use conditions.
B cells and osteoblast and osteoclast development
Authors: Horowitz Mark C. , Bothwell Alfred L. M. , Hesslein David G. T. , Pflugh David L. , Schatz David G.
Published: May 2006

Summary:  The molecules that regulate bone cell development, particularly at the early stages of development, are only partially known. Data are accumulating that indicate a complex relationship exists between B cells and bone cell differentiation. Although the exact nature of this relationship is still evolving, it takes at least two forms. First, factors that regulate B‐cell growth and development have striking effects on osteoclast and osteoblast lineage cells. Similarly, factors that regulate bone cell development influence B‐cell maturation. Second, a series of transcription factors required for B‐cell differentiation have been identified, and these factors function in a developmentally ordered circuit. These transcription factors have unpredicted, pronounced, and non‐overlapping effects on osteoblast and/or osteoclast development. These data indicate that at least a regulatory relationship exists between B lymphopoiesis, osteoclastogenesis, and osteoblastogenesis.
Role of nuclear factor‐κB in the immune system and bone
Authors: Jimi Eijiro , Ghosh Sankar
Published: May 2006

Summary: Bone metabolism is regulated by hormonal or local factors in the bone microenvironment, and recent studies have revealed that bone homeostasis is also influenced by immune system. The term ‘osteoimmunology’ has been proposed to explain the cross‐talk between bone and the immune system. A critical element in this cross‐talk is the inducible transcription factor nuclear factor‐κB (NF‐κB), which regulates gene expression during inflammatory and immune responses. However, NF‐κB‐signaling pathways are also important for bone homeostasis, in particular for osteoclast differentiation. By bridging inflammation and bone homeostasis, NF‐κB also contributes to the onset and progression of arthritis. Several natural compounds, synthetic drugs, and gene‐transfer technologies that lead to inhibition of the inhibitor of NF‐κB kinase (IKK)/NF‐κB activation pathway can prevent arthritis in animal models. In this review, we discuss the signaling pathway that leads to NF‐κB activation and the role of NF‐κB on osteoclast differentiation. Furthermore, we discuss the possibility that inhibition of NF‐κB might provide novel therapeutic approach for inhibiting bone destruction in rheumatoid arthritis.
αvβ3and macrophage colony‐stimulating factor: partners in osteoclast biology
Authors: Ross F. Patrick , Teitelbaum Steven L.
Published: May 2006

Summary: Osteoclasts, the sole bone‐resorbing cells, arise by fusion and differentiation of monocyte/macrophage precursors. Matrix degradation requires adhesion of the osteoclast to bone, an integrin αvβ3‐mediated event that also stimulates signals which polarize the cell and secrete resorptive molecules such as hydrochloric acid and acidic proteases. Two cytokines are necessary and sufficient for osteoclastogenesis, receptor activator of nuclear factor κB ligand (RANKL) and macrophage colony‐stimulating factor (M‐CSF), both produced by mesenchymal cells in the bone marrow environment. M‐CSF promotes survival and proliferation of osteoclast precursors. It also contributes to their differentiation and regulates the cytoskeletal changes that accompany bone resorption. Binding of M‐CSF to c‐Fms, its receptor, recruits adapter proteins and cytosolic kinases, thereby activating a variety of intracellular signals. We herein review how αvβ3and M‐CSF, alone and in concert, impact production, survival, and function of the osteoclast, thereby controlling skeletal mass. Signals from αvβ3and/or c‐Fms activate Syk and Vav3, originally defined by their function in lymphoid cells. Genetic depletion of either protein generates a strong bone phenotype, underscoring the promise of osteoimmunobiology.
Skeletal development, bone remodeling, and hematopoiesis
Authors: Aguila Hector Leonardo , Rowe David W.
Published: May 2006

Summary:  In adult mammals, the bone marrow microenvironment is defined by close interactions between cells derived from mesenchymal progenitors and cells derived from hematopoietic progenitors. The influence that one population of cells has over the other has been a matter of intense study since it was established that hematopoietic stem cells (HSCs) require support of stromal elements to engraft, self‐renew, and progress towards lineage commitment. Within the stromal components, cells of the osteoblastic lineage have the ability to interact with HSCs, and it has been proposed that they could be one of the main cell types responsible for the generation and maintenance of hematopoietic niches. Possible molecular mechanisms involved in the interaction between osteoblastic and hematopoietic cells have been described. However, understanding the relative importance of each one of them, their production by defined cells, and their kinetics of appearance have been limited by the lack of in vivo models allowing the physical and/or temporal dissection of the components of the osteoblastic lineage. Here, we provide a summary of the evidence that have established the importance of osteoblasts in hematopoiesis, and we propose new experimental strategies that could help to define the nature of these interactions.
Drugs for sleep disorders: mechanisms and therapeutic prospects
Authors: Szabadi Elemer
Published: May 2006

The past decade has witnessed an explosion of knowledge about the neural mechanisms that control sleep and arousal, triggered by two discoveries relating to the sleep disorder narcolepsy. Narcolepsy is caused by the loss of orexin‐containing neurons in the hypothalamus, and a novel nonstimulant wakefulness‐promoting drug, modafinil, alleviates excessive day‐time sleepiness associated with the disorder. The level of arousal is controlled by an intricate interplay between distinct wakefulness‐ and sleep‐promoting nuclei situated in the hypothalamus and brainstem and the interconnections between the nuclei and the neurotransmitters involved have been mapped. Wakefulness‐promoting nuclei include the orexinergic lateral hypothalamic/perifornical area, the histaminergic tuberomammillary nucleus, the cholinergic pedunculopontine tegmental nucleus, the noradrenergic locus coeruleus, the 5‐hydroxytryptaminergic raphe nuclei and possibly the dopaminergic ventral tegmental area. The major sleep‐promoting nucleus is the GABAergic ventrolateral preoptic nucleus of the hypothalamus. Currently available and future drugs exert their therapeutic effects in the three major classes of sleep disorder (insomnia, hypersomnia, parasomnia) by modifying neurotransmission at distinct sites within the arousal‐controlling neuronal network. This enables classification of therapeutic drugs for sleep disorders on the basis of their modes of action: drugs that interact with the GABAergic sleep‐promoting system, drugs that interact with different wakefulness‐promoting systems and drugs that modulate the level of arousal by mechanisms that do not initially involve the basic network (e.g. melatonin, adenosine). The development of novel therapeutic drugs for sleep disorders is based on the synthesis of molecular/cellular mechanisms and the sites of action within the arousal‐controlling neuronal network.
The association of CTLA-4 and HLA class II autoimmune risk genotype with regulatory T cell marker expression in 5-year-old children
Authors: Jonson C-O , Hedman M , Karlsson Faresjö M , Casas R , Ilonen J , Ludvigsson J , Vaarala O
Published: May 2006

Regulatory T cells (Treg) are involved in the maintenance of peripheral tolerance by suppression of autoreactive lymphocytes that have avoided thymic depletion. The defective function of Treg cells has recently attracted attention in autoimmune diseases such as type 1 diabetes (T1D), rheumatoid arthritis and multiple sclerosis. Susceptibility to these diseases is associated with specific human leucocyte antigen (HLA) class II and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene polymorphisms. This study aimed to investigate the relationship between HLA class II and CTLA +49 A/G polymorphisms associated with susceptibility to T1D and the number and characteristics of Treg cells in children. Samples from 47 5-year-old children who participated in the All Babies in South-east Sweden (ABIS) follow-up study were grouped according to the presence of the T1D risk-associated HLA genotype (DQA1*0501–DQB1*0201, DQA1*0301–DQB1*0302) or neutral HLA genotypes. Lower percentages of CD4+ T cells (P = 0·03) and CD4+ CD25high cells (P = 0·06) expressing intracellular CTLA-4 were detected in samples from children with CTLA-4 +49GG compared to children with the +49AA genotype. Similarly, lower percentages of CD4+ (P = 0·002) and CD4+ CD25high (P = 0·002) cells expressing CTLA-4 were observed in children positive for HLA DQA1*0501–DQB1*0201 and DQA1*0301–DQB1*0302 (P = 0·04 for CD4+ and P = 0·02 for CD4+ CD25high) risk haplotypes when compared to children without these alleles. The percentage of CD25high cells among CD4+ cells was correlated inversely with CTLA-4 mRNA expression in PBMC (r = –0·56, P = 0·03). Decreased levels of CTLA-4 in CD4+ and CD4+ CD25high cells in individuals with CTLA-4 and HLA class II alleles associated with T1D may contribute to the initiation and/or progression of autoimmune response.
Role of BAFF and APRIL in human B‐cell chronic lymphocytic leukaemia
Authors: Haiat Stéphanie , Billard Christian , Quiney Claire , Ajchenbaum‐Cymbalista Florence , Kolb Jean‐Pierre
Published: May 2006

B‐cell chronic lymphocytic leukaemia (B‐CLL) is the most prevalent leukaemia in Western countries and is characterized by the gradual accumulation in patients of small mature B cells. Since the vast majority of tumoral cells are quiescent, the accumulation mostly results from deficient apoptosis rather than from acute proliferation. Although the phenomenon is relevant in vivo, B‐CLL cells die rapidly in vitro as a consequence of apoptosis, suggesting a lack of essential growth factors in the culture medium. Indeed, the rate of B‐CLL cell death in vitro is modulated by different cytokines, some favouring the apoptotic process, others counteracting it. Two related members of the tumour necrosis factor family, BAFF (B‐cell activating factor of the TNF family) and APRIL (a proliferation‐inducing ligand), already known for their crucial role in normal B‐cell survival, differentiation and apoptosis, were recently shown to be expressed by B‐CLL cells. These molecules are able to protect the leukaemic cells against spontaneous and drug‐induced apoptosis via autocrine and/or paracrine pathways. This review will focus on the role of BAFF and APRIL in the survival of tumoral cells. It will discuss the expression of these molecules by B‐CLL cells, their regulation, transduction pathways and their effects on leukaemic cells. The design of reagents able to counteract the effects of these molecules seems to be a new promising therapeutic approach for B‐CLL and is already currently developed in the treatment of autoimmune diseases.
Interleukin‐5 regulates genes involved in B‐cell terminal maturation
Authors: Horikawa Keisuke , Takatsu Kiyoshi
Published: May 2006

Interleukin (IL)‐5 induces CD38‐activated splenic B cells to differentiate into immunoglobulin M‐secreting cells and undergo µ to γ1 class switch recombination (CSR) at the DNA level, resulting in immunoglobulin G1 (IgG1) production. Interestingly, IL‐4, a well‐known IgG1‐inducing factor does not induce immunoglobulin production or µ to γ1 CSR in CD38‐activated B cells. In the present study, we implemented complementary DNA microarrays to investigate the contribution of IL‐5‐induced gene expression in CD38‐stimulated B cells to immunoglobulin‐secreting cell differentiation and µ to γ1 CSR. IL‐5 and IL‐4 stimulation of CD38‐activated B cells induced the expression of 418 and 289 genes, respectively, that consisted of several clusters. Surprisingly, IL‐5‐inducible 78 genes were redundantly regulated by IL‐4. IL‐5 and IL‐4 also suppressed the gene expression of 319 and 325 genes, respectively, 97 of which were overlapped. Genes critically regulated by IL‐5 include immunoglobulin‐related genes such as J chain and immunoglobulinκ, and genes involved in B‐cell maturation such as BCL6, activation‐induced cytidine deaminase (Aid) and B lymphocyte‐induced maturation protein‐1 (Blimp‐1) and tend to be induced slowly after IL‐5 stimulation. Intriguingly, among genes, the retroviral induction of Blimp‐1 and Aid in CD38‐activated B cells could induce IL‐4‐dependent maturation to Syndecan‐1+ antibody‐secreting cells and µ to γ1 CSR, respectively, in CD38‐activated B cells. Taken together, preferential Aid and Blimp‐1 expression plays a critical role in IL‐5‐induced immunoglobulin‐secreting cell differentiation and µ to γ1 CSR in CD38‐activated B cells.
Ticks have R2 retrotransposons but not the consensus transposon target site of other arthropods
Authors: Bunikis J. , Barbour A. G.
Published: May 2006

Some copies of the large subunit rRNA genes (LSU rDNA) of most arthropods studied to date are inactivated by R‐element retrotransposons at a specific target region that is highly conserved in sequence across all kingdoms of organisms. Here we report finding R2 elements in low copy numbers in the LSU rDNA of hard and soft ticks. Although the elements were inserted at the same LSU rDNA location as in insects, there were substitutions in the consensus R2 endonuclease cleavage site in the ticks and some other parasitiform mites. The substituted region comprises a critical contact point with small subunit rRNA, but in vitro structure probing analysis revealed novel, presumably stabilizing base‐pairing.
Effect of chronic dietary ethanol in the promotion of N‐nitrosomethylbenzylamine‐induced esophageal carcinogenesis in rats
Authors: TSUTSUMI MIKIHIRO , GEORGE JOSEPH , ISHIZAWA KIYOHIRO , FUKUMURA ATUSHI , TAKASE SHUJIRO
Published: May 2006

Background:  The pathogenetic correlation between chronic alcohol consumption and development of esophageal cancer is not clear. The role of alcohol abuse in the carcinogenic action of N‐nitrosomethylbenzylamine, which induces tumors in the esophagus, has been evaluated.

Methods:  Twenty male rats were fed liquid diets containing ethanol or carbohydrates for 30 weeks. N‐nitrosomethylbenzylamine (0.1 mg/kg, twice a week) was injected i.p. from the 9th to 19th week. The pair feeding was stopped at 9.00 am and N‐nitrosomethylbenzylamine was administered at 10.00 am. Ethanol was not detected in the blood at the time of injection. Liquid diets were provided again at 3 pm until 9 am next day. The animals were killed at the end of the 30th week. The esophagi were collected and examined for visible tumors. The tissue sections were stained for histology and CYP2E1expression.

Results:  While 5–8 esophageal squamous polyps developed in all rats in the ethanol group, only one polyp each was formed in five out of the 10 rats in the control group. The size of the polyps was significantly larger in the ethanol group, when compared to the control group. Invasive squamous cell carcinoma was also observed in 50% of the animals in the ethanol group. Cytochrome P4502E1 (CYP2E1) staining demonstrated marked expression in the esophageal mucosa in the ethanol group, but not in the control group.

Conclusions:  The increased expression of CYP2E1 induced by chronic ethanol consumption promotes the development of N‐nitrosomethylbenzylamine‐induced esophageal tumorigenesis. However, the molecular mechanism of the increased production of esophageal tumors during alternative administration of N‐nitrosomethylbenzylamine and ethanol is not clear.
An overview of methods used to assess vegetation condition at the scale of the site
Authors: Gibbons Philip , Freudenberger David
Published: May 2006

Summary  Rapid, on‐ground assessments of vegetation condition are frequently used as a basis for landholder education, development applications, distributing incentive funds, prescribing restoration treatments and monitoring change. We provide an overview of methods used to rapidly assess vegetation condition for these purposes. We encourage those developing new approaches to work through the steps we have presented here, namely define management objectives and operational constraints; develop an appropriate conceptual framework for the ecosystems under consideration; select an appropriate suite of indicators; and consider the options available for combining these into an index. We argue that information must be gained from broader scales to make decisions about the condition of individual sites. Remote sensing and spatial modelling might be more appropriate methods than on‐ground assessments for obtaining this information. However, we believe that spatial prediction of vegetation condition will only add value to on‐ground assessments rather than replace them. This is because the current techniques for spatially predicting vegetation condition cannot capture all of the information in a site assessment or at the required level of accuracy, and maps cannot replace the exchange of information between assessors and land managers that is an important component of on‐ground assessment. There is scope for more sophistication in the way on‐ground assessments of vegetation condition are undertaken, but the challenge will be to maintain the simplicity that makes rapid on‐ground assessment a popular vehicle for informing natural resource management. We encourage greater peer review and publishing in this field to facilitate greater exchange of ideas and experiences.