bluuebunny/crossref_metadata_2025 huggingface dataset:
Whispering gallery modes in highly hexagonal symmetric structures of SBA-1 mesoporous silica
Authors: Chen C. W. , Chen Y. F.
Published: February 2007

An interesting optical resonant mode, called whispering gallery mode (WGM), has been discovered inside the highly hexagonal three dimensional symmetry of SBA-1 mesoporous silica. The hexagonal structure provides a suitable environment for the light wave to circulate around due to multiple total internal reflections at the resonator’s boundary and generates the resonant states. Based on the hexagonal total internal reflecting model, the observed eigenmodes can be explained quite well. The authors also discovered that under the condition of WGMs, the absorption of CO2 and H2O molecules can be greatly enhanced.
Room temperature green light emission from nonpolar cubic InGaN∕GaN multi-quantum-wells
Authors: Li Shunfeng , Schörmann Jörg , As Donat J. , Lischka Klaus
Published: February 2007

Cubic InGaN∕GaN multi-quantum-wells (MQWs) with high structural and optical quality are achieved by utilizing freestanding 3C-SiC (001) substrates and optimizing InGaN quantum well growth. Superlattice peaks up to fifth order are clearly resolved in x-ray diffraction. Bright green room temperature photoluminescence (PL) from c-InxGa1−xN∕GaN MQWs (x=0.16) is observed. The full width at half maximum of the PL emission is about 240meV at 300K. The PL intensity increases with well thickness, prooving that polarization fields which can limit the performance of the wurtzite III-nitride based devices are absent. The diffusion length of excess carriers is about 17nm.
Period multiplication and chaotic phenomena in atmospheric dielectric-barrier glow discharges
Authors: Wang Y. H. , Zhang Y. T. , Wang D. Z. , Kong M. G.
Published: February 2007

In this letter, evidence of temporal plasma nonlinearity in which atmospheric dielectric-barrier discharges undergo period multiplication and chaos using a one-dimensional fluid model is reported. Under the conditions conducive for chaotic states, several frequency windows are identified in which period multiplication and secondary bifurcations are observed. Such time-domain nonlinearity is important for controlling instabilities in atmospheric glow discharges.
Leakage mechanisms in BiFeO3 thin films
Authors: Pabst Gary W. , Martin Lane W. , Chu Ying-Hao , Ramesh R.
Published: February 2007

The authors report results of transport studies on high quality, fully epitaxial BiFeO3 thin films grown via pulsed laser deposition on SrRuO3∕DyScO3 (110) substrates. Ferroelectric tests were conducted using symmetric and asymmetric device structures with either SrRuO3 or Pt top electrodes and SrRuO3 bottom electrodes. Comparison between these structures demonstrates the influence of electrode selection on the dominant transport mechanism. Analysis of film electrical response suggests Poole-Frenkel emission as the limiting leakage current mechanism in the symmetric structure. Temperature dependent measurements yield trap ionization energies of ∼0.65–0.8eV. No clear dominant leakage mechanism was observed for the asymmetric structure.
Anomalous Hall effect in anatase Ti1−xCoxO2−δ at low temperature regime
Authors: Ueno K. , Fukumura T. , Toyosaki H. , Nakano M. , Kawasaki M.
Published: February 2007

Anomalous Hall effect (AHE) of a ferromagnetic semiconductor anatase Ti1−xCoxO2−δ thin film is studied from 10to300K. Magnetic field dependence of anomalous Hall resistance is coincident with that of magnetization, while the anomalous Hall resistance decreases at low temperature in spite of nearly temperature-independent magnetization. Anomalous Hall conductivity σAHE is found to be proportional to the square of Hall mobility, suggesting that charge scattering strongly affects the AHE in this system. The anatase Ti1−xCoxO2−δ also follows a scaling relationship to conductivity σxx as σAHE∝σxx1.6, which was observed for another polymorph rutile Ti1−xCoxO2−δ, suggesting an identical mechanism of their AHE.
Wash-free immunomagnetic detection for serum through magnetic susceptibility reduction
Authors: Hong Chin-Yih , Chen W. S. , Jian Z. F. , Yang S. Y. , Horng H. E. , Yang L. C. , Yang H. C.
Published: February 2007

In this study, a platform for wash-free immunomagnetic detections is discussed. The reagent is a magnetic fluid composed of biofunctionalized magnetic particles dispersed in water. The assay instrument is a mixed-frequency magnetosusceptometer. The mixed-frequency ac magnetic susceptibility χac of the magnetic reagent is reduced, as a result of the formation of magnetic clusters via the association among magnetic nanoparticles and a specific biotarget. The immunoassay detection of proteins in water, such as aqueous c-reactive protein, is characterized and is compared to that in serum. These observations demonstrate the advantages of high convenience, high sensitivity, and high specificity for χac-reduction immunomagnetic detection.
Intrinsic electron doping in nominal “nondoped” superconducting (La,Y)2CuO4 thin films grown by magnetron sputtering
Authors: Zhao L. , Wu G. , Liu R. H. , Chen X. H.
Published: February 2007

The superconducting nominal “nondoped” La1.85Y0.15CuO4 (LYCO) thin films are prepared by magnetron sputtering. The best TC0 of more than 13K is achieved in the optimal films with highly pure c-axis oriented T′-type structure. The quasiquadratic temperature dependence of resistivity and the negative Hall coefficient in the normal state, effect of oxygen content are all quite similar to the known Ce-doped n-type cuprate superconductors, suggesting the electron-doping nature in T′-LYCO. The charge carriers are considered to arise from oxygen deficiency.
Piezoelectric, nonliner optical, electro-optical, and pyroelectric properties of cesium hydrogen malate hydrate crystal
Authors: Isakov D. V. , Ferreira F. P. , Barbosa J. , Ribeiro J. L. , de Matos Gomes E. , Belsley M. S.
Published: February 2007

Cesium hydrogen L-malate monohydrate crystals are shown to be a promising material for several potential applications. The crystals display an exceptionally large piezoelectric coefficient, d22=23.7pm∕V. They are also an efficient generator of the optical second harmonic of near infrared light, being close to an order of magnitude more efficient than potassium diphosphate crystals. A relatively strong electro-optic response (the figure of merit 12∣n1r12−n3r32∣ was found to be 4.83pm∕V) and a reasonable pyroelectric coefficient (p2=2.5×10−4μC∕cm2K at 245K) are also observed.
Effect of oxygen vacancies on spin-dependent tunneling in Fe∕MgO∕Fe magnetic tunnel junctions
Authors: Velev J. P. , Belashchenko K. D. , Jaswal S. S. , Tsymbal E. Y.
Published: February 2007

First-principles calculations based on density functional theory are used to elucidate the effect of O vacancies, forming F centers, on spin-dependent tunneling in Fe∕MgO∕Fe(001) magnetic tunnel junctions. O vacancies produce occupied localized s states and unoccupied resonant p states, which is consistent with available experimental data. The authors find that O vacancies affect the conductance by nonresonant scattering of tunneling electrons causing a substantial reduction of tunneling magnetoresistance (TMR). Improving the quality of the MgO barrier to reduce O vacancy concentration would improve TMR in these and similar junctions.
120
Hz
pulse tube cryocooler for fast cooldown to 50K
Authors: Vanapalli Srinivas , Lewis Michael , Gan Zhihua , Radebaugh Ray
Published: February 2007

A pulse tube cryocooler operating at 120Hz with 3.5MPa average pressure achieved a no-load temperature of about 49.9K and a cooldown time to 80K of 5.5min. The net refrigeration power at 80K was 3.35W with an efficiency of 19.7% of Carnot when referred to input pressure-volume (PV or acoustic) power. Such low temperatures have not been previously achieved for operating frequencies above 100Hz. The high frequency operation leads to reduced cryocooler volume for a given refrigeration power, which is important to many applications and can enable development of microcryocoolers for microelectromechanical system applications.
Infrared reflection absorption spectroscopy investigation of carbon nanotube growth on cobalt catalyst surfaces
Authors: Kimura Yasuo , Numasawa Takeru , Nihei Mizuhisa , Niwano Michio
Published: February 2007

To clarify the effect the oxygen has on the carbon nanotube (CNT) growth mechanisms, the authors use infrared absorption spectroscopy for the monitoring of CNT growth on cobalt catalyst surfaces. CNT grew when methanol was used as a reaction gas, while they did not grow when methane was used. The authors observed spectral changes due to the formation of cobalt oxides and methoxides on the cobalt catalyst surfaces only during the growth of CNT. The results indicate that partial oxidation of the cobalt catalyst surface increases the adsorption probability of the reaction gas and ultimately induces growth of CNT.
Peptide translocators with engineered dehydration-prone hydrogen bonds
Authors: Maddipati Sridhar , Fernández Ariel
Published: February 2007

The unfavorable crossing of cell membranes by water-soluble peptides poses a challenge to peptide-based drug delivery. Thus the authors engineered a conformational switch that modulates cellular translocation. The peptide design hinges on dehydration propensities of hydrogen bonds that form to mitigate polar-group internalization penalties and is experimentally corroborated through cell-internalization assays.
Kinetic Studies on the Synthesis of Hydroxyapatite Nanowires by Solvothermal Methods
Authors: Zhang Shiying , Lai Chen , Wei Kun , Wang Yingjun
Published: February 2007

Hydroxyapatite nanowires with a high axial ratio have been synthesized in reverse micelle solutions that consist of cetyltrimethylammonium bromide (CTAB), n-pentanol, cyclohexane, and the reactant solution by solvothermal methods. This paper focusses on the kinetic studies of the solvothermal reaction and the linear growth of hydroxyapatite nanowires. When the reaction was carried out at low temperatures (65°C), the experimental results showed that the reaction rate was of zero order since the whole reaction was diffusion controlled with constant diffusion coefficients. In the middle to high temperature range (130–200°C), the kinetics were characterized by second order reaction kinetics. Since the controlling factor was activation energy and the apparent activation energy was large, the reaction rate was more sensitive to the temperature. Therefore, the exponent of the reaction rate constant increased by two when the temperature was increased from 130 to 200°C. By calculating the yields of products and the specific surface areas at different times, the linear and overall growth rate equations of the hydroxyapatite nanowires could be obtained. The experimental effective growth order of the crystals was 11. The larger growth order indicated that the crystal could grow more effectively in one direction because of the induction of the surfactant in the experiment system.
Low-Temperature Synthesis of Titanate Nanotubes in Aqueous KOH
Authors: Bavykin Dmitry V. , Cressey Barbara A. , Walsh Frank C.
Published: February 2007

Although hydrothermal alkaline treatment of TiO2 in a concentrated, aqueous solution of KOH usually results in the formation of solid fibrous titanates, analysis of the temperature dependence of Ti(iv) concentration in KOH solution and comparison of these data with that for NaOH solution suggests that, at low temperatures, the treatment of TiO2 with KOH may result in formation of titanate nanotubes. This result was confirmed by 12 days treatment of TiO2 in 10 mol dm–3 KOH at 56°C, resulting in the formation of nanotubular titanates with similar morphology to those produced in a shorter time at higher temperatures using NaOH. The mechanism of nanotube formation and the necessary conditions of nanotube phase formation are considered.
N,N-Dialkyl-N′-Chlorosulfonyl Chloroformamidines in Heterocyclic Synthesis. III. Pyrido- and Pyridazo-Fused [1,2,4,6]Thiatriazine Dioxides
Authors: Cablewski Teresa , Carter Erin J. , Francis Craig L. , Liepa Andris J. , Perkins Michael V.
Published: February 2007

N,N-Dialkyl-N′-chlorosulfonylchloroformamidines 1 reacted with 2-aminopyridines 2 to give novel pyrido[1,2-b][1,2,4,6]thiatriazine dioxides 3 and pyrido[2,1-c][1,2,4,6]thiatriazine dioxides 4. Reaction of 1 with 3-aminopyridazines 5 afforded pyridazo[3,2-c][1,2,4,6]thiatriazine dioxides 6 and a pyridazo[2,3-b][1,2,4,6]thiatriazine dioxide 7. The compounds 6 and 7 are derivatives of new ring systems.
Monobromoborane - Dimethyl Sulfide—a Highly Promising Reagent for the Regio- and Chemoselective Brominative Cleavage of Terminal Epoxides into Vicinal Bromohydrins
Authors: Roy Chandra D. , Brown Herbert C.
Published: February 2007

Monobromoborane–dimethyl sulfide (BH2Br–SMe2) is a highly regio- and chemoselective reagent useful for the brominative cleavage of the epoxy moiety into bromohydrins in the presence of alkenes, alkynes, ethers, acetals, ketals, and acetonides at 0°C, besides being an excellent hydroborating reagent. Several reactive functional groups, such as chloride, ketones, esters, nitriles, nitros, and thioethers, have been accommodated during such transformations. Although the reduction of acetophenone was completely suppressed at –25°C, 4-chlorobenzaldehyde still underwent 12–13% reduction of an aldehydic group.
A Serendipitous Synthesis of the Novel Spiroacetal Core of Cynandione B
Authors: Tewierik Leonie M. , Donner Christopher D. , White Jonathan M. , Gill Melvyn
Published: February 2007

The novel spiroacetal core of cynandione B 2 is prepared from the isochromenone (S)-mellein 4 by treatment with methylmagnesium bromide. The expected lactol product undergoes spontaneous dimerization to form the spiroacetal system 8 as a single diastereoisomer, the stereochemistry of which is established from a single crystal X-ray structure analysis of a methanol solvate.
A synthetic time-delay circuit in mammalian cells and mice
Authors: Weber Wilfried , Stelling Jörg , Rimann Markus , Keller Bettina , Daoud-El Baba Marie , Weber Cornelia C. , Aubel Dominique , Fussenegger Martin
Published: February 2007

Time-delay circuitries in which a transcription factor processes independent input parameters can modulate NF-κB activation, manage quorum-sensing cross-talk, and control the circadian clock. We have constructed a synthetic mammalian gene network that processes four different input signals to control either immediate or time-delayed transcription of specific target genes. BirA-mediated ligation of biotin to a biotinylation signal-containing VP16 transactivation domain triggers heterodimerization of chimeric VP16 to a streptavidin-linked tetracycline repressor (TetR). At increasing biotin concentrations up to 20 nM, TetR-specific promoters are gradually activated (off to on, input signal 1), are maximally induced at concentrations between 20 nM and 10 μM, and are adjustably shut off at biotin levels exceeding 10 μM (on to off, input signal 2). These specific expression characteristics with a discrete biotin concentration window emulate a biotin-triggered bandpass filter. Removal of biotin from the culture environment (input signal 3) results in time-delayed transgene expression until the intracellular biotinylated VP16 pool is degraded. Because the TetR component of the chimeric transactivator retains its tetracycline responsiveness, addition of this antibiotic (input signal 4) overrides biotin control and immediately shuts off target gene expression. Biotin-responsive immediate, bandpass filter, and time-delay transcription characteristics were predicted by a computational model and have been validated in standard cultivation settings or biopharmaceutical manufacturing scenarios using trangenic CHO-K1 cell derivatives and have been confirmed in mice. Synthetic gene circuitries provide insight into structure–function correlations of native signaling networks and foster advances in gene therapy and biopharmaceutical manufacturing.
Interaction between chromatin proteins MECP2 and ATRX is disrupted by mutations that cause inherited mental retardation
Authors: Nan Xinsheng , Hou Jianghui , Maclean Alan , Nasir Jamal , Lafuente Maria Jose , Shu Xinhua , Kriaucionis Skirmantas , Bird Adrian
Published: February 2007

Mutations in the human methyl-CpG-binding protein gene
MECP2
cause the neurological disorder Rett syndrome and some cases of X-linked mental retardation (XLMR). We report that MeCP2 interacts with ATRX, a SWI2/SNF2 DNA helicase/ATPase that is mutated in ATRX syndrome (α-thalassemia/mental retardation, X-linked). MeCP2 can recruit the helicase domain of ATRX to heterochromatic foci in living mouse cells in a DNA methylation-dependent manner. Also, ATRX localization is disrupted in neurons of
Mecp2
-null mice. Point mutations within the methylated DNA-binding domain of MeCP2 that cause Rett syndrome or X-linked mental retardation inhibit its interaction with ATRX
in vitro
and its localization
in vivo
without affecting methyl-CpG binding. We propose that disruption of the MeCP2–ATRX interaction leads to pathological changes that contribute to mental retardation.
Dynamic pressure-induced dendritic and shock crystal growth of ice VI
Authors: Lee Geun Woo , Evans William J. , Yoo Choong-Shik
Published: February 2007

Crystal growth mechanisms are crucial to understanding the complexity of crystal morphologies in nature and advanced technological materials, such as the faceting and dendrites found in snowflakes and the microstructure and associated strength properties of structural and icy planetary materials. In this article, we present observations of pressure-induced ice VI crystal growth, which have been predicted theoretically, but had never been observed experimentally to our knowledge. Under modulated pressure conditions in a dynamic-diamond anvil cell, rough single ice VI crystal initially grows into well defined octahedral crystal facets. However, as the compression rate increases, the crystal surface dramatically changes from rough to facet, and from convex to concave because of a surface instability, and thereby the growth rate suddenly increases by an order of magnitude. Depending on the compression rate, this discontinuous jump in crystal growth rate or “shock crystal growth” eventually produces 2D carpet-type fractal morphology, and moreover dendrites form under sinusoidal compression, whose crystal morphologies are remarkably similar to those predicted in theoretical simulations under a temperature gradient field. The observed strong dependence of the growth mechanism on compression rate, therefore, suggests a different approach to developing a comprehensive understanding of crystal growth dynamics.
A single-molecule barcoding system using nanoslits for DNA analysis
Authors: Jo Kyubong , Dhingra Dalia M. , Odijk Theo , de Pablo Juan J. , Graham Michael D. , Runnheim Rod , Forrest Dan , Schwartz David C.
Published: February 2007

Molecular confinement offers new routes for arraying large DNA molecules, enabling single-molecule schemes aimed at the acquisition of sequence information. Such schemes can rapidly advance to become platforms capable of genome analysis if elements of a nascent system can be integrated at an early stage of development. Integrated strategies are needed for surmounting the stringent experimental requirements of nanoscale devices regarding fabrication, sample loading, biochemical labeling, and detection. We demonstrate that disposable devices featuring both micro- and nanoscale features can greatly elongate DNA molecules when buffer conditions are controlled to alter DNA stiffness. Furthermore, we present analytical calculations that describe this elongation. We also developed a complementary enzymatic labeling scheme that tags specific sequences on elongated molecules within described nanoslit devices that are imaged via fluorescence resonance energy transfer. Collectively, these developments enable scaleable molecular confinement approaches for genome analysis.
Delta-like ligand 4 (Dll4) is induced by VEGF as a negative regulator of angiogenic sprouting
Authors: Lobov I. B. , Renard R. A. , Papadopoulos N. , Gale N. W. , Thurston G. , Yancopoulos G. D. , Wiegand S. J.
Published: February 2007

Genetic deletion studies have shown that haploinsufficiency of Delta-like ligand (Dll) 4, a transmembrane ligand for the Notch family of receptors, results in major vascular defects and embryonic lethality. To better define the role of Dll4 during vascular growth and differentiation, we selected the postnatal retina as a model because its vasculature develops shortly after birth in a highly stereotypic manner, during which time it is accessible to experimental manipulation. We report that Dll4 expression is dynamically regulated by VEGF in the retinal vasculature, where it is most prominently expressed at the leading front of actively growing vessels. Deletion of a single Dll4 allele or pharmacologic inhibition of Dll4/Notch signaling by intraocular administration of either soluble Dll4-Fc or a blocking antibody against Dll4 all produced the same set of characteristic abnormalities in the developing retinal vasculature, most notably enhanced angiogenic sprouting and increased endothelial cell proliferation, resulting in the formation of a denser and more highly interconnected superficial capillary plexus. In a model of ischemic retinopathy, Dll4 blockade also enhanced angiogenic sprouting and regrowth of lost retinal vessels while suppressing ectopic pathological neovascularization. Our data demonstrate that Dll4 is induced by VEGF as a negative feedback regulator and acts to prevent overexuberant angiogenic sprouting, promoting the timely formation of a well differentiated vascular network.
Alkynyl sugar analogs for the labeling and visualization of glycoconjugates in cells
Authors: Hsu Tsui-Ling , Hanson Sarah R. , Kishikawa Kuniyuki , Wang Sheng-Kai , Sawa Masaaki , Wong Chi-Huey
Published: February 2007

Developing tools for investigating the cellular activity of glycans will help to delineate the molecular basis for aberrant glycosylation in pathological processes such as cancer. Metabolic oligosaccharide engineering, which inserts sugar-reporting groups into cellular glycoconjugates, represents a powerful method for imaging the localization, trafficking, and dynamics of glycans and isolating them for glyco-proteomic analysis. Herein, we show that the alkyne-reporting group can be incorporated into cellular glycans. The alkyne group is a small, inert, bio-orthogonal handle that can be chemoselectively labeled by using the Cu(I) catalyzed [3 + 2] azide-alkyne cycloaddition, or click chemistry. Alkynyl sugar monomers, based on fucose (Fuc) and
N
-acetylmannosamine (ManNAc), were incorporated into fucosylated and sialylated glycans in several cancer cell lines, allowing for cell surface and intracellular visualization of glycoconjugates, as well as, observation of alkyne-bearing glycoproteins. Similarly to our previous results with an azido Fuc/alkynyl probe system, we demonstrated that click-activated fluorogenic probes are practical tools for efficiently and selectively labeling alkynyl-modified glycans. Because Fuc and sialic acid are terminal glycan residues with a notably increased presence in many tumors, we hope that our method will provide useful information about their roles in cancer and ultimately can be used for diagnostic and therapeutic purposes.
Reciprocal asymmetry of SYS-1/β-catenin and POP-1/TCF controls asymmetric divisions in
Caenorhabditis elegans
Authors: Phillips Bryan T. , Kidd Ambrose R. , King Ryan , Hardin Jeff , Kimble Judith
Published: February 2007

β-Catenins are conserved regulators of metazoan development that function with TCF DNA-binding proteins to activate transcription. In
Caenorhabditis elegans
, SYS-1/β-catenin and POP-1/TCF regulate several asymmetric divisions, including that of the somatic gonadal precursor cell (SGP). In the distal but not the proximal SGP daughter, SYS-1/β-catenin and POP-1/TCF transcriptionally activate
ceh-22
to specify the distal fate. Here, we investigate the distribution of SYS-1/β-catenin and its regulation. Using a rescuing transgene, VNS::SYS-1, which fuses VENUS fluorescent protein to SYS-1, we find more VNS::SYS-1 in distal than proximal SGP daughters, a phenomenon we call “SYS-1 asymmetry.” In addition, SYS-1 asymmetry is seen in many other tissues, consistent with the idea that SYS-1 regulates asymmetric divisions broadly during
C. elegans
development. In particular, SYS-1 is more abundant in E than MS, and SYS-1 is critical for the endodermal fate. In all cases, SYS-1 is reciprocal to POP-1 asymmetry: cells with higher SYS-1 have lower POP-1, and vice versa. SYS-1 asymmetry is controlled posttranslationally and relies on frizzled and dishevelled homologs, which also control POP-1 asymmetry. Therefore, upstream regulators modulate the SYS-1 to POP-1 ratio by increasing SYS-1 and decreasing POP-1 within the same cell. By contrast, SYS-1 asymmetry does not rely on WRM-1, which appears specialized for POP-1 asymmetry. We suggest a two-pronged pathway for control of SYS-1:POP-1, which can robustly accomplish differential gene expression in daughters of an asymmetric cell division.
Nitric oxide
S
-nitrosylates serine racemase, mediating feedback inhibition of
d
-serine formation
Authors: Mustafa Asif K. , Kumar Manish , Selvakumar Balakrishnan , Ho Gary P. H. , Ehmsen Jeffrey T. , Barrow Roxanne K. , Amzel L. Mario , Snyder Solomon H.
Published: February 2007

Serine racemase (SR) generates
d
-serine, a coagonist with glutamate at NMDA receptors. We show that SR is physiologically
S
-nitrosylated leading to marked inhibition of enzyme activity. Inhibition involves interactions with the cofactor ATP reflecting juxtaposition of the ATP-binding site and cysteine-113 (C113), the site for physiological
S
-nitrosylation. NMDA receptor physiologically enhances SR
S
-nitrosylation by activating neuronal nitric-oxide synthase (nNOS). These findings support a model whereby postsynaptic stimulation of nitric-oxide (NO) formation feeds back to presynaptic cells to
S
-nitrosylate SR and decrease
d
-serine availability to postsynaptic NMDA receptors.
Dendritic cell expression of the transcription factor T-bet regulates mast cell progenitor homing to mucosal tissue
Authors: Alcaide Pilar , Jones Tatiana G. , Lord Graham M. , Glimcher Laurie H. , Hallgren Jenny , Arinobu Yojiro , Akashi Koichi , Paterson Alison M. , Gurish Michael A. , Luscinskas Francis W.
Published: February 2007

The transcription factor T-bet was identified in CD4+ T cells, and it controls interferon γ production and T helper type 1 cell differentiation. T-bet is expressed in certain other leukocytes, and we recently showed (Lord, G.M., R.M. Rao, H. Choe, B.M. Sullivan, A.H. Lichtman, F.W. Luscinskas, and L.H. Glimcher. 2005. Blood. 106:3432–3439) that it regulates T cell trafficking. We examined whether T-bet influences homing of mast cell progenitors (MCp) to peripheral tissues. Surprisingly, we found that MCp homing to the lung or small intestine in T-bet−/− mice is reduced. This is reproduced in adhesion studies using bone marrow–derived MCs (BMMCs) from T-bet−/− mice, which showed diminished adhesion to mucosal addresin cellular adhesion molecule–1 (MAdCAM-1) and vascular cell adhesion molecule–1 (VCAM-1), endothelial ligands required for MCp intestinal homing. MCp, their precursors, and BMMCs do not express T-bet, suggesting that T-bet plays an indirect role in homing. However, adoptive transfer experiments revealed that T-bet expression by BM cells is required for MCp homing to the intestine. Furthermore, transfer of WT BM-derived dendritic cells (DCs) to T-bet−/− mice restores normal MCp intestinal homing in vivo and MCp adhesion to MAdCAM-1 and VCAM-1 in vitro. Nonetheless, T-bet−/− mice respond vigorously to intestinal infection with Trichinella spiralis, eliminating a role for T-bet in MC recruitment to sites of infection and their activation and function. Therefore, remarkably, T-bet expression by DCs indirectly controls MCp homing to mucosal tissues.
WASP regulates suppressor activity of human and murine CD4+CD25+FOXP3+ natural regulatory T cells
Authors: Marangoni Francesco , Trifari Sara , Scaramuzza Samantha , Panaroni Cristina , Martino Silvana , Notarangelo Luigi D. , Baz Zeina , Metin Ayse , Cattaneo Federica , Villa Anna , Aiuti Alessandro , Battaglia Manuela , Roncarolo Maria-Grazia , Dupré Loïc
Published: February 2007

A large proportion of Wiskott-Aldrich syndrome (WAS) patients develop autoimmunity and allergy. CD4+CD25+FOXP3+ natural regulatory T (nTreg) cells play a key role in peripheral tolerance to prevent immune responses to self-antigens and allergens. Therefore, we investigated the effect of WAS protein (WASP) deficiency on the distribution and suppressor function of nTreg cells. In WAS−/− mice, the steady-state distribution and phenotype of nTreg cells in the thymus and spleen were normal. However, WAS−/− nTreg cells engrafted poorly in immunized mice, indicating perturbed homeostasis. Moreover, WAS−/− nTreg cells failed to proliferate and to produce transforming growth factor β upon T cell receptor (TCR)/CD28 triggering. WASP-dependent F-actin polarization to the site of TCR triggering might not be involved in WAS−/− nTreg cell defects because this process was also inefficient in wild-type (WT) nTreg cells. Compared with WT nTreg cells, WAS−/− nTreg cells showed reduced in vitro suppressor activity on both WT and WAS−/− effector T cells. Similarly, peripheral nTreg cells were present at normal levels in WAS patients but failed to suppress proliferation of autologous and allogeneic CD4+ effector T cells in vitro. Thus, WASP appears to play an important role in the activation and suppressor function of nTreg cells, and a dysfunction or incorrect localization of nTreg cells may contribute to the development of autoimmunity in WAS patients.
The Wiskott-Aldrich syndrome protein is required for the function of CD4+CD25+Foxp3+ regulatory T cells
Authors: Maillard Michel H. , Cotta-de-Almeida Vinicius , Takeshima Fuminao , Nguyen Deanna D. , Michetti Pierre , Nagler Cathryn , Bhan Atul K. , Snapper Scott B.
Published: February 2007

The Wiskott-Aldrich syndrome, a primary human immunodeficiency, results from defective expression of the hematopoietic-specific cytoskeletal regulator Wiskott-Aldrich syndrome protein (WASP). Because CD4+CD25+Foxp3+ naturally occurring regulatory T (nTreg) cells control autoimmunity, we asked whether colitis in WASP knockout (WKO) mice is associated with aberrant development/function of nTreg cells. We show that WKO mice have decreased numbers of CD4+CD25+Foxp3+ nTreg cells in both the thymus and peripheral lymphoid organs. Moreover, we demonstrate that WKO nTreg cells are markedly defective in both their ability to ameliorate the colitis induced by the transfer of CD45RBhi T cells and in functional suppression assays in vitro. Compared with wild-type (WT) nTreg cells, WKO nTreg cells show significantly impaired homing to both mucosal (mesenteric) and peripheral sites upon adoptive transfer into WT recipient mice. Suppression defects may be independent of antigen receptor–mediated actin rearrangement because both WT and WKO nTreg cells remodeled their actin cytoskeleton inefficiently upon T cell receptor stimulation. Preincubation of WKO nTreg cells with exogenous interleukin (IL)-2, combined with antigen receptor–mediated activation, substantially rescues the suppression defects. WKO nTreg cells are also defective in the secretion of the immunomodulatory cytokine IL-10. Overall, our data reveal a critical role for WASP in nTreg cell function and implicate nTreg cell dysfunction in the autoimmunity associated with WASP deficiency.
Leukocyte-specific protein 1 interacts with DC-SIGN and mediates transport of HIV to the proteasome in dendritic cells
Authors: Smith Alvin L. , Ganesh Lakshmanan , Leung Kwanyee , Jongstra-Bilen Jenny , Jongstra Jan , Nabel Gary J.
Published: February 2007

Dendritic cells (DCs) capture and internalize human immunodeficiency virus (HIV)-1 through C-type lectins, including DC-SIGN. These cells mediate efficient infection of T cells by concentrating the delivery of virus through the infectious synapse, a process dependent on the cytoplasmic domain of DC-SIGN. Here, we identify a cellular protein that binds specifically to the cytoplasmic region of DC-SIGN and directs internalized virus to the proteasome. This cellular protein, leukocyte-specific protein 1 (LSP1), was defined biochemically by immunoprecipitation and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. LSP1 is an F-actin binding protein involved in leukocyte motility and found on the cytoplasmic surface of the plasma membrane. LSP1 interacted specifically with DC-SIGN and other C-type lectins, but not the inactive mutant DC-SIGNΔ35, which lacks a cytoplasmic domain and shows altered virus transport in DCs. LSP1 diverts HIV-1 to the proteasome. Down-regulation of LSP1 with specific small interfering RNAs in human DCs enhanced HIV-1 transfer to T cells, and bone marrow DCs from lsp1−/− mice also showed an increase in transfer of HIV-1BaL to a human T cell line. Proteasome inhibitors increased retention of viral proteins in lsp1+/+ DCs, and substantial colocalization of virus to the proteasome was observed in wild-type compared with LSP1-deficient cells. Collectively, these data suggest that LSP1 protein facilitates virus transport into the proteasome after its interaction with DC-SIGN through its interaction with cytoskeletal proteins.
Dyslipidemia inhibits Toll-like receptor–induced activation of CD8α-negative dendritic cells and protective Th1 type immunity
Authors: Shamshiev Abdijapar T. , Ampenberger Franziska , Ernst Bettina , Rohrer Lucia , Marsland Benjamin J. , Kopf Manfred
Published: February 2007

Environmental factors, including diet, play a central role in influencing the balance of normal immune homeostasis; however, many of the cellular mechanisms maintaining this balance remain to be elucidated. Using mouse models of genetic and high-fat/cholesterol diet–induced dyslipidemia, we examined the influence of dyslipidemia on T cell and dendritic cell (DC) responses in vivo and in vitro. We show that dyslipidemia inhibited Toll-like receptor (TLR)–induced production of proinflammatory cytokines, including interleukin (IL)-12, IL-6, and tumor necrosis factor-α, as well as up-regulation of costimulatory molecules by CD8α− DCs, but not by CD8α+ DCs, in vivo. Decreased DC activation profoundly influenced T helper (Th) cell responses, leading to impaired Th1 and enhanced Th2 responses. As a consequence of this immune modulation, host resistance to Leishmania major was compromised. We found that oxidized low-density lipoprotein (oxLDL) was the key active component responsible for this effect, as it could directly uncouple TLR-mediated signaling on CD8α− myeloid DCs and inhibit NF-κB nuclear translocation. These results show that a dyslipidemic microenvironment can directly interfere with DC responses to pathogen-derived signals and skew the development of T cell–mediated immunity.
Interleukin-10 production by effector T cells: Th1 cells show self control
Authors: Trinchieri Giorgio
Published: February 2007

Interleukin (IL)-10 is a cytokine that modulates both innate and adaptive immunity, primarily by exerting antiinflammatory effects. IL-10 was originally thought to be produced only by T helper (Th)2 cells, but is now known to be made by a variety of cell types. During many infections, CD4+ T cells produce both interferon (IFN)-γ, the signature Th1 cytokine, and IL-10. New data now show that the IL-10 produced by effector Th1 cells helps limit the collateral damage caused by exaggerated inflammation. But this control may also limit the effectiveness of the immune response, resulting in a failure to fully eliminate pathogens.
The returning tide
Authors: Wells William A.
Published: February 2007

When China turned its back on the Cultural Revolution, it aimed to build a thriving capitalist sector. It got one. Now, it wants a world-class research enterprise. How far has it progressed in the biosciences, how did it get there, and how far does it have to go?
A Role for the S0 Transmembrane Segment in Voltage-dependent Gating of BK Channels
Authors: Koval Olga M. , Fan Yun , Rothberg Brad S.
Published: February 2007

BK (Maxi-K) channel activity is allosterically regulated by a Ca2+ sensor, formed primarily by the channel's large cytoplasmic carboxyl tail segment, and a voltage sensor, formed by its transmembrane helices. As with other voltage-gated K channels, voltage sensing in the BK channel is accomplished through interactions of the S1–S4 transmembrane segments with the electric field. However, the BK channel is unique in that it contains an additional amino-terminal transmembrane segment, S0, which is important in the functional interaction between BK channel α and β subunits. In this study, we used perturbation mutagenesis to analyze the role of S0 in channel gating. Single residues in the S0 region of the BK channel were substituted with tryptophan to give a large change in side chain volume; native tryptophans in S0 were substituted with alanine. The effects of the mutations on voltage- and Ca2+-dependent gating were quantified using patch-clamp electrophysiology. Three of the S0 mutants (F25W, L26W, and S29W) showed especially large shifts in their conductance–voltage (G-V) relations along the voltage axis compared to wild type. The G-V shifts for these mutants persisted at nominally 0 Ca2+, suggesting that these effects cannot arise simply from altered Ca2+ sensitivity. The basal open probabilities for these mutants at hyperpolarized voltages (where voltage sensor activation is minimal) were similar to wild type, suggesting that these mutations may primarily perturb voltage sensor function. Further analysis using the dual allosteric model for BK channel gating showed that the major effects of the F25W, L26W, and S29W mutations could be accounted for primarily by decreasing the equilibrium constant for voltage sensor movement. We conclude that S0 may make functional contact with other transmembrane regions of the BK channel to modulate the equilibrium between resting and active states of the channel's voltage sensor.
Shock break-out: how a GRB revealed the beginnings of a supernova
Authors: Blustin Alexander J
Published: February 2007

In February 2006, Swift caught a gamma-ray burst (GRB) in the act of turning into a supernova, and made the first ever direct observations of the break-out and early expansion of a supernova shock wave. GRB 060218 began with an exceptionally long burst of non-thermal gamma-rays, lasting over 2000 s, as a jet erupted through the surface of the star. While this was in progress, an optically-thick thermal component from the shock wave of the supernova explosion grew to prominence, and we were able to track the mildly relativistic expansion of this shell as the blackbody peak moved from the X-rays into the UV and optical bands. The initial radius of the shock implied that it was a blue supergiant that had exploded, but the lack of hydrogen emission lines in the supernova spectrum indicated a more compact star. The most likely scenario is that the shock ploughed into the massive stellar wind of a Wolf–Rayet progenitor, with the shock breaking-out and becoming visible to us once it reached the radius where the wind became optically-thin. I present the Swift observations of this landmark event, and discuss the new questions and answers it leaves us with.
Very high-energy gamma rays from gamma-ray bursts
Authors: Chadwick Paula M
Published: February 2007

Very high-energy (VHE) gamma-ray astronomy has undergone a transformation in the last few years, with telescopes of unprecedented sensitivity having greatly expanded the source catalogue. Such progress makes the detection of a gamma-ray burst at the highest energies much more likely than previously. This paper describes the facilities currently operating and their chances for detecting gamma-ray bursts, and reviews predictions for VHE gamma-ray emission from gamma-ray bursts. Results to date are summarized.
Swift observations of gamma-ray bursts
Authors: Gehrels Neil
Published: February 2007

Since its launch on 20 November 2004, the Swift mission has been detecting approximately 100 gamma-ray bursts (GRBs) each year, and immediately (within approx. 90 s) starting simultaneous X-ray and UV/optical observations of the afterglow. It has already collected an impressive database, including prompt emission to higher sensitivities than BATSE, uniform monitoring of afterglows and a rapid follow-up by other observatories notified through the GCN. Advances in our understanding of short GRBs have been spectacular. The detection of X-ray afterglows has led to accurate localizations and the conclusion that short GRBs can occur in non-star-forming galaxies or regions, whereas long GRBs are strongly concentrated within the star-forming regions. This is consistent with the NS merger model. Swift has greatly increased the redshift range of GRB detection. The highest redshift GRBs, at
z
∼5–6, are approaching the era of reionization. Ground-based deep optical spectroscopy of high redshift bursts is giving metallicity measurements and other information on the source environment to a much greater distance than other techniques. The localization of GRB 060218 to a nearby galaxy, and the association with SN 2006aj, added a valuable member to the class of GRBs with detected supernova.
Gamma-ray bursts spectral correlations and their cosmological use
Authors: Ghirlanda Giancarlo
Published: February 2007

The correlations involving the long-gamma-ray bursts (GRBs) prompt emission energy represent a new key to understand the GRB physics. These correlations have been proved to be the tool that makes long-GRBs a new class of standard candles. Gamma Ray Bursts, being very powerful cosmological sources detected in the hard X-ray band, represent a new tool to investigate the Universe in a redshift range, which is complementary to that covered by other cosmological probes (SNIa and CMB). A review of the

,

,

and

correlations is presented. Open issues related to these correlations (e.g. presence of outliers and selection effects) and to their use for cosmographic purposes (e.g. dependence on model assumptions) are discussed. Finally, the relevance of thermal components in GRB spectra is discussed in the light of some of the models recently proposed for the interpretation of the spectral-energy correlations.
Gamma-ray burst models
Authors: King Andrew
Published: February 2007

I consider various possibilities for making gamma-ray bursts, particularly from close binaries. In addition to the much-studied neutron star+neutron star and black hole+neutron star cases usually considered good candidates for short-duration bursts, there are also other possibilities. In particular, neutron star+massive white dwarf has several desirable features. These systems are likely to produce long-duration gamma-ray bursts (GRBs), in some cases definitely without an accompanying supernova, as observed recently. This class of burst would have a strong correlation with star formation and occur close to the host galaxy. However, rare members of the class need not be near star-forming regions and could have any type of host galaxy. Thus, a long-duration burst far from any star-forming region would also be a signature of this class. Estimates based on the existence of a known progenitor suggest that this type of GRB may be quite common, in agreement with the fact that the absence of a supernova can only be established in nearby bursts.
Gamma-ray burst jet dynamics and their interaction with the progenitor star
Authors: Lazzati Davide , Morsony Brian J , Begelman Mitchell C
Published: February 2007

The association of at least some long gamma-ray bursts with type Ic supernova explosions has been established beyond reasonable doubt. Theoretically, the challenge is to explain the presence of a light hyper-relativistic flow propagating through a massive stellar core without losing those properties. We discuss the role of the jet–star interaction in shaping the properties of the outflow emerging on the surface of the star. We show that the nature of the inner engine is hidden from the observer for most of the evolution, well beyond the time of the jet breakout on the stellar surface. The discussion is based on analytical considerations as well as high resolution numerical simulations. Finally, the observational consequences of the scenario are addressed in light of the present capabilities.
Short gamma-ray bursts near and far
Authors: Levan Andrew J
Published: February 2007

Progress in understanding the nature of short gamma-ray bursts (GRBs) has been rapid since the discovery of the first afterglows in mid-2005. The emerging picture appears to be of short GRBs, which originate at moderate redshift (a few tenths) and appear in galaxies of all ages. This discovery has been used to argue for their origin in compact binary mergers. However, this population does not describe all short bursts. Here, I will present results of observations of several short GRBs, which challenge the conclusions drawn from the early observations. The observations show that some short GRBs originate in the very low redshift Universe (below 100 Mpc), while some may also lie at redshifts comparable with the long GRBs (i.e.
z
>2). I will discuss the properties of these bursts and the implications they have for the progenitors of short GRBs.
Optical/UV afterglows: Swift UVOT overview
Authors: Mason Keith O , Boyd Patricia , Page Mathew , Pandey Shashi , Roming Pete , Schady Patricia
Published: February 2007

The ultraviolet and optical telescope (UVOT) on Swift provides coverage of gamma-ray bursts and their afterglows in the 170–650 nm band, yielding multiwavelength data of considerable diagnostic power in conjunction with the Swift X-ray Telescope. The results from the first eighteen months of operation show a broad range of afterglow behaviour, with considerably more complexity in many bursts than would be expected from the simple fireball model for the explosion. We briefly illustrate the capabilities of UVOT for measuring the evolution of nearby supernovae by reference to the observations of GRB 060218, and discuss the peculiar case of GRB 060614, which apparently resides in a nearby galaxy but which did not show the expected supernova feature in its light curve due to radioactive nickel decay. We discuss how the combination of X-ray and UV/optical spectral data can be used to investigate the environment of GRB host galaxies.
Electron acceleration in relativistic GRB shocks
Authors: Medvedev Mikhail V
Published: February 2007

The shock model of gamma-ray bursts (GRBs) has two free parameters:
ϵ

B

and
ϵ

e

. It has been shown that
ϵ

B

should range between few×10
−3
and few×10
−4
. However, how to calculate the value of
ϵ

e

has remained an outstanding theoretical problem for over a decade. Here, we demonstrate that the Weibel theory inevitably predicts that

. The GRB afterglow data fully agree with this theoretical prediction. Our result explains why the electrons are close to equipartition in GRBs. This
ϵ

e

–
ϵ

B

relation can potentially be used to reduce the number of free parameters in afterglow models.