bluuebunny/crossref_metadata_2025 huggingface dataset:
Protease‐modified erythrocytes: CD55 and CD59 deficient PNH‐like cells
Authors: YUAN FANG F. , BRYANT JENNIFER A. , FLETCHER ANNE
Published: July 2007

The increased susceptibility to homologous complement in paroxysmal nocturnal haemoglobinuria (PNH) is known to be associated with the deficiency of the membrane complement inhibitors CD59 and CD55. Proteases have been used in this study to modify normal human RBC to complement sensitive PNH‐like cells. To investigate the protective role of CD59 and CD55, the relationship between the content of CD59 and CD55 and the complement susceptibility of the PNH‐like cells has been determined. The differential resistance of the enzyme‐treated RBC to complement‐mediated injury was measured by acidified serum lysis. Pronase‐treated erythrocytes lacked both CD59 and CD55 and were very susceptible to complement‐mediated lysis. Papain treatment of RBC reduced the CD55 content but did not affect CD59 and induced slight susceptibility to complement‐mediated lysis. Trypsin treatment of RBC destroyed 80% of CD59, had little effect on CD55 (unless incubation was extended) and slightly increased susceptibility to lysis. Thus, partial CD55 and CD59 activity was sufficient to protect cells from complement‐mediated lysis. In the reactive lysis assay, anti‐CD55 and anti‐CD59 induced haemolysis, anti‐CD59 having the more pronounced effect. Lysis was enhanced when RBC were treated by both antibodies simultaneously.
Apoptosis in B lymphocytes: The WEHI‐231 perspective
Authors: GOTTSCHALK ALEXANDER R. , QUINTANS JOSE
Published: July 2007

In this review we summarize recent work on the molecular basis of apoptosis in the murine B cell lymphoma WEHI‐231. WEHI‐231 cells undergo apoptosis in response to antigen receptor cross‐linking with anti‐Ig reagents. Death is specifically triggered via surface IgM (sIgM); cross‐linking sIgD, Ia or FcR has no effect. Apoptosis is preceded by growth arrest in the Go/G1 phase of the cell cycle and may not occur in all currently available WEHI‐231 sublines. The continuous passage of WEHI‐231 cells in different laboratories has yielded variants that differ greatly in their response to anti‐Ig treatment because apoptotic cells tend to be negatively selected in culture. Resistant and susceptible variants undergo growth arrest in response to anti‐Ig but only susceptible cells go on to die by apoptosis. Cells resistant to anti‐Ig have intact apoptotic machinery as indicated by their susceptibility to dexamethasone, irradiation and other treatments. However, anti‐Ig‐resistant cells are also resistant to apoptosis induced by the immunosuppressants cyclosporin A, FK‐506 and rapamycin. We discuss the experimental evidence indicating that the apoptotic machinery in WEHI‐231 cells is pre‐activated but under constant negative regulation by short‐lived protein inhibitors. Inhibition is removed by a mediator released in response to anti‐Ig treatment in susceptible sublines. The mediator of death is the sphingosine derivative, ceramide, presumably produced by membrane sphingomyelinases activated by anti‐Ig. A hypothetical model on how ceramide kills WEHI‐231 is presented.
Productive in vitro infection of human umbilical vein endothelial cells and three colon carcinoma cell lines with HIV‐1
Authors: CORBEIL JACQUES , EVANS LOUISE A. , MCQUEEN PAUL W. , VASAK EVA , EDWARD PAUL D. , RICHMAN DOUGLAS D. , PENNY RONALD , COOPER DAVID A.
Published: July 2007

The objective of this study was to assess the ability of HIV‐1 to establish an in vitro infection of primary human umbilical vein endothelial cells (HUVEC). The HUVEC and colon carcinoma cell lines were inoculated with different isolates of HIV‐1 (HIV‐1SF2, HIV‐1McK and HIV‐1LAI) and productive viral infection was assessed by both the detection of p24 core antigen in the culture supernatants and the presence of specific spliced HIV mRNA. The infection which was detected in the inoculated HUVEC and all the colon carcinoma cell lines could not be blocked using an antibody targeted against the CD4 receptor. Furthermore, the HIV‐inoculated HUVEC secreted elevated levels of IL‐6 and this increase was found to be proportional to the size of the viral inoculum. No changes in the production of IL‐lβ, TNF‐α, IFN‐α and IFN‐γ were detected following HIV infection. The colon carcinoma cells, however, did not secrete increased levels of these cytokines following HIV‐1 inoculation. These results confirm that non‐CD4 expressing cells, such as endothelial cells and certain colon epithelial cells, serve as targets and reservoirs for HIV. Moreover, the production of IL‐6 by HIV‐infected endothelial cells may be a contributing factor to the aberrant immunoregulation associated with HIV infection in vivo.
An analysis, using monoclonal antibodies, of the role of interferon‐γ in ovine immune responses
Authors: EMERY D. L. , DAVEY R. J.
Published: July 2007

A mAb (IFN‐9) which neutralizes biologically active ovine and bovine IFN‐γ was used to deplete levels of the cytokine in vivo in sheep and examine the consequences for immune responses to adjuvanted antigen and skin reactivity to Bacillus‐Calmette‐Guerin (BCG). Groups of sheep were immunized with ovalbumin in the adjuvants, Quil A or dextran sulphate (MW 500 000: DXS), both of which elicit production of IFN‐γ. MAb anti‐IFTM‐γ or an isotype control mAb (anti‐carbonic anhydrase positive particles) were inoculated i.v. during primary and/or secondary responses. Reactions monitored in efferent prefemoral lymph indicated that anti‐IFN‐γ effectively depleted levels of IFN‐γ in lymph but had no effects on the magnitude and kinetics of lymphocyte and lymphoblast traffic, or total or isotypic titres of specific Ig. When incubated in vitro with ovalbumin, antigen‐reactive cells from anti‐IFN‐γ treated sheep did not produce IFN‐γ, suggesting an on‐going modification to cytokine production. In contrast, skin reactions to purified‐protein derivative in sheep immunized with BCG were reduced by < 40% by anti‐IFN‐γ. The results indicate that IFN‐γ production may not be obligatory for delayed‐type hypersensitivity reactions or for the adjuvant action of Quil A or DXS, and that specific mAb can alter the profile of cytokines produced by antigen‐reactive cells in sheep.
The effect of IL‐4 on antigen expression: A comparison of fluorescence intensity and antigen density
Authors: MACARDLE PETER J. , WILLIAMS KERYN A. , BRADLEY JOHN , ZOLA HEDDY
Published: July 2007

We have compared the membrane expression of MHC class II antigen and Ig on murine splenic B lymphocytes by two flow cytometric methods. The first method, commonly used, determined the mean immunofluorescence intensity; the second measured antigen density as a ratio of mean fluorescence intensity to cell volume. The data generated by the two methods allow for different interpretations of antigen density in comparison lo antigen expression. By mean fluorescence intensity, activated B lymphocytes expressed more MHC class II antigen and membrane Ig than did resting B cells. However, resting B cells had the same density of MHC class II antigen and membrane Ig as activated B cells. Next we examined the effect of IL‐4 on antigen expression by the two methods. We found that although lL‐4 increased the mean fluorescence intensity and density of MHC class II and membrane Ig on each B cell population, the density of expression of membrane Ig tended to be greater on the resting B cells than on the activated, while the density of MHC class II antigen was essentially the same on each of the IL‐4 treated B cell populations.
SV40‐adenovirus immortalized cell lines derived from mouse lymphoid dendritic cell preparations
Authors: OHNISHI KAZUO , DAIGO MICHIKO , TOKUNAGA TOHRU
Published: July 2007

Dendritic cells (DC) are antigen‐presenting cells characteristic in their rarity and potent ability to stimulate resting T cells. We established several cell lines from purified mouse spleen DC and Langerhans' cells (LC) by infecting them with recombinant SV40ori− adenovirus. Using this method, cells from these fractions are efficiently transformed at a frequency as high as 5 × 10−6. Some established lines have dendritic morphology, express surface markers specific for DC (defined by mAb 33D1 and NLDC145) and weak substrate adherence. Interestingly, these lines simultaneously express B cell markers (B220 and Ly‐1) and/or macrophage markers (Mac‐l and F4/80). Among the lines, OT6.2 and OT8.3.1 have retained stimulating activity in mixed lymphocyte reactions (MLR) which is attributable to the primary T cell stimulating activity of native DC However, these lines also present soluble antigens to T cell clones, a secondary T cell stimulating activity, characteristic of B cells and macrophages. Although transformation has perturbed the functional discreteness of the DC cell lineage. DC‐specific properties are partially preserved in the cell lines. These cell lines may provide useful experimental systems for the elucidation of molecular mechanisms involved in the MLR and the differentiation of DC.
Absorption and presentation of antigens by epithelial cells of the small intestine: Hypotheses and predictions relating to the pathogenesis of coeliac disease
Authors: MAYRHOFER GRAHAM
Published: July 2007

Effects of the route of antigen absorption and presentation in the small intestine are discussed in relation to outcomes from antigen exposure. It is proposed that antigens presented by epithelial cells to intrinsic T cell populations in the mucosa induce anti‐inflammatory immune responses, while antigens presented to conventional T cells by lamina propria APC predisposes to inflammation. The pathogenesis of coeliac disease is attributed to three factors: a defect in antigen processing by epithelial cells; the intrinsic properties of the gliadins; and the HLA‐D haplotype of the individual. It is suggested that MHC class II molecules play a role in antigen uptake by enterocytes, in addition to their function in antigen presentation to T cells.
Expression of rabbit C‐reactive protein in transgenic mice
Authors: LIN CAROL S , XIA DONGYUAN , YUN JEUNG S , WAGNER THOMAS , MAGNUSON TERRY , MOLD CAROLYN , SAMOLS DAVID
Published: July 2007

C‐reactive protein (CRP) is a prototypic acute phase reactant in humans and rabbits whose serum concentration can increase up to 1000‐fold following an acute inflammatory stimulus. CRP binds to many phosphate ester‐containing compounds including phosphorylcholine, nucleotides, chromatin and snRNP. To examine the in vivo function of this protein, we produced transgenic mice capable of significant CRP synthesis. In contrast to most other vertebrates, mice synthesize CRP in only trace amounts. The transgenic animals express rabbit CRP from either the phosphoeno lpyruvate carboxykinase promoter (PEPCK‐CRP) or the mouse metallothionein I promoter (MT‐CRP). Manipulating the diet in one of the PEPCK‐CRP lines led to a rise in serum CRP levels from < 5 μg/mL to 100–200 μg/mL over a period of 2 days. The two MT‐CRP lines examined expressed CRP constitutively which could be further elevated 2–4‐fold following an inflammatory stimulus. Transgenic CRP bound phosphonlcholine was pentameric, had a circulating half‐life of 30–60 min and was capable of activating mouse complement when bound to a ligand. We conclude that these transgenic lines express CRP with many of the properties of authentic rabbit CRP, and that the expression of CRP can be controlled to be dependent or independent of the acute phase response.
Autoimmune diabetes: Caught in the causality trap?
Authors: GAZDA LAWRENCE S , GILCHRIST KIRSTY A , LAFFERTY KEVIN J
Published: July 2007

The lack of concordance between genotype and clinical diabetes has prompted a search for the infectious agent that precipitates this autoimmune disease. However, this approach may be misleading. It assumes that the disease‐prone individuals that do not develop diabetes do not have autoimmunity. In the non‐obese diabetic (NOD) mouse, the genotype is a primary determinant of autoimmunity. Not all animals of the disease‐prone genotype develop clinical disease; however, all have autoimmunity. This is expressed as a destructive or non‐destructive process. Multiple pathways are open to the immune system and whether or not the immune response is destructive and leads to the development of clinical disease, appears to be a random process. If this is the case, the most important questions relating to autoimmune disease are not those concerning the ‘causative’ agents. Instead we should be asking what are the differences between pathways open to the immune system and what factors affect the probability that one or another pathway is finally selected?
Depletion of IFN‐γ, CD8+ or Tcrγδ+ cells in vivo during primary infection with an enteric parasite (Trichostrongylus colubriformis) enhances protective immunity
Authors: McCLURE SJ , DAVEY RJ , LLOYD JB , EMERY DL
Published: July 2007

In order to examine the role of CD8+ and WCI+ T cells and of IFN‐γ in the development of protective immunity against infection with the enteric nematode parasite Trichostrongylus colubriformis in sheep, mAb were administered during induction of the immune response to deplete or neutralize these components. Protection against the primary and challenge infections were assessed by faecal egg count and total worm count. Prolonged administration of mAb recognizing IFN‐γ and CD8+ resulted in significantly increased protection during the 6‐week primary infection. CD8+ cells were depleted from blood but not intestinal mucosa. After injection of mAb (CC15) recognizing the surface antigen WCI, WCI+ and T cell receptor (Tcr) γδ+ cells were depleted from blood but not from enteric mucosa, and protection against challenge, although variable, was increased by up to 88%. It appears that CD8+ and WCI+/γδ+ cells and IFN‐γ all retard the potential development of naturally‐acquired immunity against the parasite.
The immunomodulatory Pseudomonas aeruginosa signalling molecule N‐(3‐oxododecanoyl)‐l‐homoserine lactone enters mammalian cells in an unregulated fashion
Authors: Ritchie Adam J , Whittall Christine , Lazenby James J , Chhabra Siri Ram , Pritchard David I , Cooley Margaret A
Published: July 2007

The Pseudomonas aeruginosa quorum‐sensing signal molecule N‐3‐oxododecanoyl)‐l‐homoserine lactone (OdDHL) has been reported to affect the function of a wide range of mammalian cell types, including cells of the immune system. In T cells, it has been reported to inhibit the production of most cytokines, and it has been reported to inhibit the function of antigen‐presenting cells. The intracellular target of OdDHL in these cells remains to be identified, although the lipophilic nature of the molecule suggested that the target could be membrane associated. We explored the association of radiolabelled OdDHL with the membrane and cytoplasm of Jurkat T‐cell lines and of primary murine T cells and dendritic cells. We found that not only did 3H‐OdDHL enter the cytoplasm of Jurkat cells without disproportionate association with the cell membrane, it also reached maximum levels in the cytoplasm very quickly, and that the intracellular concentration was proportional to the extracellular concentration. Similar results were obtained when 3H‐OdDHL was incubated with primary murine T cells or cultured dendritic cells. In addition, we show that the cellular distribution of OdDHL does not significantly alter after stimulation of Jurkat cells or primary murine CD4 T cells with immobilized anti‐CD3, with little activity being associated with nuclear fractions. Together, these data strongly suggest that OdDHL enters mammalian cells by passive mechanisms, and that it does not preferentially associate with the membrane or nucleus upon T‐cell receptor ligation.
Irreversibility implies the occurrence of nonmonotonic power spectra
Authors: Chen Yong , Qian Ming-Ping , Xie Jian-Sheng
Published: July 2007

Both continuous-time and discrete-time systems driven by L2-exponential ergodic stationary Markov processes are investigated. We prove that in both cases irreversibility implies the occurrence of nonmonotonic power spectra of some observables. This result combined with the work of Jiang and Zhang [J. Math. Phys. 44, 4681–4689 (2003)] tells us that in the continuous-time case, reversibility can be characterized by monotonicity in all power spectra, while this is not true in the discrete-time case.
Spin lifetime in silicon in the presence of parasitic electronic effects
Authors: Huang Biqin , Monsma Douwe J. , Appelbaum Ian
Published: July 2007

A hybrid ferromagnet/semiconductor device is used to determine a lower bound on the spin lifetime for conduction electrons in silicon. We use spin precession to self-consistently measure the drift velocity versus drift field of spin-polarized electrons, and use this electronic control to change the transit time between electron injection and detection. A measurement of normalized magnetocurrent as a function of drift velocity is used with a simple exponential-decay model to argue that the value obtained (≈2 ns) is artificially lowered by electronic effects and could potentially be orders of magnitude higher.
Perpendicular magnetic anisotropy in TbFeCo films studied by magnetic Compton scattering
Authors: Sakurai H. , Ota M. , Liu X. , Morisako A. , Sakurai Y. , Itou M. , Nagao T. , Koizumi A.
Published: July 2007

Magnetic Compton profiles (MCPs) of TbFeCo amorphous films have been measured from a viewpoint of perpendicular magnetic anisotropy (PMA). Analysis of anisotropies of the MCPs has shown that anisotropies of wave functions are small in both a PMA film and an isotropic magnetization (IM) film. Element selective analysis of the MCPs has shown that a Tb magnetic moment and a magnetic moment of 3d transition metal (TM) are coupled antiparallel in the PMA film. In the case the IM film, the magnetic moment of 3d TM tends to align toward the magnetic field but the Tb magnetic moment distributed to random orientations. The PMA natures reflect the magnetic structures of the Tb magnetic moment and the 3d TM magnetic moment in the TbFeCo films.
DNA hybridization detection by porous silicon-based DNA microarray in conjugation with infrared microspectroscopy
Authors: Yamaguchi Ryo-taro , Miyamoto Ko-ichiro , Ishibashi Ken-ichi , Hirano Ayumi , Said Suhana Mohd , Kimura Yasuo , Niwano Michio
Published: July 2007

A method is described for the label-free detection of DNA hybridization on porous silicon (por-Si), based upon the pairing of oligonucleotide chemistry and standard silicon nanotechnology. Por-Si with a pore diameter of approximately 30 nm was used to immobilize probe DNA. Infrared microspectroscopy was employed to monitor the hybridization of probe-DNA immobilized on pore surfaces with its complementary DNA (target-DNA). The immobilization of probe DNA on por-Si facilitates hybridization detection for a small sensing area (approximately 50×50 μm2) with a high detection efficiency. In this study, we fabricated a porous silicon-based DNA microarray (por-Si-microarray) using photolithographic and Si anodizing techniques. We demonstrate that DNA hybridization can be detected on a por-Si-microarray through the analysis of infrared absorption spectral profiles in the region where the vibration modes of the bases appear. This present approach demonstrates that por-Si-microarray in conjugation with infrared microspectroscopy has potential application in DNA sensing chips.
On overannealing of GaIn(N)As/Ga(N)As multiple quantum wells grown by molecular beam epitaxy
Authors: Liu H. F. , Chua S. J. , Xiang N.
Published: July 2007

Evolution of photoluminescence (PL) and strain is investigated in GaIn(N)As/Ga(N)As multiple quantum wells (MQWs) over a wide range of annealing temperatures from 700 to 900 °C. We observe two optimal annealing temperatures (Topt) that result in reduced PL linewidth and increased PL intensity irrespective of the thermal-induced strain relaxation. The decrease of PL intensity accompanied by peak splitting after the first Topt is mainly associated with the deterioration of the GaAs cap layer and the optical quenching after the second Topt is due to the overannealing-induced degradation of the bottom QWs. The strain relaxation in GaInAs/GaAs MQWs at elevated temperatures, which gives rise to extrinsic defects at the bottom of the MQWs stack, only plays a minor role in PL evolution, while no strain relaxation is observed in GaInNAs/GaNAs MQWs.
Volumetric negative-refractive-index medium exhibiting broadband negative permeability
Authors: Rudolph Scott M. , Grbic Anthony
Published: July 2007

In this article, a broadband, volumetric, negative-refractive-index metamaterial is presented and its operation is explained. The structure achieves a negative permeability bandwidth of 60% using a periodic cage of backward-wave transmission lines. The permeability is negative over a broad bandwidth due to contradirectional coupling between a backward wave guided by a transmission line and a forward, free-space wave. Negative permittivity is realized using an array of inductively loaded wires. Propagation within the infinite negative-refractive-index (NRI) medium as well as transmission through finite slabs of the NRI medium is presented. The results demonstrate that the proposed NRI medium exhibits a refractive index equal to −1 at 2.45 GHz and is well matched to free space throughout the NRI bandwidth.
Secondary growth of small ZnO tripodlike arms on the end of nanowires
Authors: Zhang Zengxing , Liu Yuzi , Liu Dongfang , Luo Shudong , Shen Jun , Liu Lifeng , Ma Wenjun , Ren Yan , Xiang Yanjuan , Zhou Weiya , Xie Sishen , Zheng Kaihong , Zhao Yuanchun , Sun Lianfeng , Zou Chenxia , Yu Dapeng
Published: July 2007

Small zinc oxide tripodlike arms were assembled at the end of nanowires through thermal evaporation of zinc powder in a horizontal tube furnace. These arms are hundreds of nanometers in length, and they are tens of nanometers in diameter, similar to that of the based nanowires. High-resolution transmission electron microscopy investigation exhibits that they are wurtzite structure and have clear twin planes at the junction of the arms and the based nanowires. The growth mechanism, Raman, and photoluminescence properties were discussed.
Magnetotransport properties of nanocrystalline Pr0.65(Ca1−ySry)0.35MnO3 (y∼0.4,0.3): Influence of phase coexistence
Authors: Biswas Anis , Das I.
Published: July 2007

The influence of the coexistence of charge ordered insulating and ferromagnetic metallic phases on magnetotransport properties of nanocrystalline Pr0.65(Ca1−ySry)0.35MnO3 (y∼0.4,0.3) has been studied. Large magnetoresistance at low magnetic field has been observed. The sharp increase of low field magnetoresistance with increase of temperature below the insulator to metal transition temperature is in complete contrast to the magnetoresistive properties of ferromagnetic manganite nanoparticles. The anomalous magnetoresistive behavior is attributed to the destabilization of the charge ordered insulating state by the magnetic field.
Electrical and structural properties of high-k Er-silicate gate dielectric formed by interfacial reaction between Er and SiO2 films
Authors: Choi Chel-Jong , Jang Moon-Gyu , Kim Yark-Yeon , Jun Myung-Sim , Kim Tae-Youb , Song Myeong-Ho
Published: July 2007

The authors investigate the electrical and structural properties of high-k Er-silicate film formed by the interfacial reaction between Er and SiO2 films. The increase in rapid thermal annealing temperature leads to the reduction of the interface trap density by one order of magnitude, indicating the improvement in the interface quality of Er-silicate gate dielectric. The increased capacitance value of Er-silicate gate dielectric with thermal treatment is attributed in part to the reduction of SiO2 thickness and to the increase in the relative dielectric constant of Er-silicate film caused by the chemical bonding change from Si-rich to Er-rich silicate.
Effect of intrinsic stress from a nanoscale high-dielectric constant gate oxide on strain in a transistor channel
Authors: Wang Hongtao , Ramanathan Shriram
Published: July 2007

The author propose using a nanoscale gate dielectric directly as stressor to alter the strain field in a transistor channel. Using experimentally determined intrinsic stress generated from a gate dielectric, they analyze the strain field in a channel by finite element methods simulation. Analysis shows that the gate dielectric induced strain can be as large as 0.2% corresponding to ∼25% hole mobility enhancement. The results predict that performance improvement in semiconductor devices can be achieved by choosing proper dielectric film deposition conditions and optimizing geometric dimensions. The approach is compatible with other methods presently utilized for generating local strains as well as high-mobility semiconductor channel layers.
Optical phonons assisted infrared absorption in VO2 based bolometer
Authors: Chen Changhong , Zhou Zhiping
Published: July 2007

Optical phonons assisted infrared absorption in VO2 based bolometer is demonstrated to be free, low, or over damping oscillation over different spectral ranges depending on the passivation thickness. In particular, it will become saturated due to the over damping oscillation in the spectral range corresponding to the absorption bands from strong phonon vibrations. The device reaches a peak absorbance of 99.9% at wavelength of 9.1μm and shows a broadband absorption, independent of metal-insulator transition and radiation incident angle up to 30° in the long wavelength (8–14μm) infrared region.
Multikilowatt chemical oxygen-iodine laser with chemical generation of molecular iodine
Authors: Zhang Yuelong , Sang Fengting , Zhang Peng , Jin Yuqi , Fang Benjie , Zhao Weili , Chen Fang , Li Qingwei , Xu Mingxiu
Published: July 2007

A multikilowatt chemical oxygen-iodine laser (COIL) using molecular iodine generated chemically as the iodine source was developed and tested. The COIL, with a gain length of 26.5cm, was energized by a square pipe-array jet singlet oxygen generator (JSOG), with a nozzle bank having a designed Mach number of 2.5. The JSOG, operating without a primary buffer gas, has a much better operation stability during basic hydrogen peroxide pumping circulations. Iodine injectors/nozzles made of polyimide were used. An output power of 7.8kW and a chemical efficiency of 24.5% were achieved with a chlorine flow rate of 353mmole∕s.
The chicken leukocyte receptor complex encodes a primordial, activating, high-affinity IgY Fc receptor
Authors: Viertlboeck Birgit C. , Schweinsberg Sonja , Hanczaruk Matthias A. , Schmitt Ramona , Du Pasquier Louis , Herberg Friedrich W. , Göbel Thomas W.
Published: July 2007

Fc receptors are key players of the immune system that link the fine specificity of immunoglobulins and innate effector responses. Here, we describe a nonmammalian Fcγ receptor, CHIR-AB1, a member of the leukocyte receptor complex, that binds IgY with high affinity with its single Ig domain. It is expressed on immature and mature B lymphocytes, monocytes, macrophages, and natural killer cells and harbors motifs of activating and inhibitory Fc receptors. In the absence of FcεRIγ, CHIR-AB1 can be expressed on B cells but cross-linking does not induce intracellular calcium release. In contrast, cells expressing CHIR-AB1 and FcεRIγ are triggered to release intracellular calcium upon stimulation with heat-aggregated IgY. CHIR-AB1 thus represents a primordial Fc receptor that combines features of different mammalian counterparts.
Analysis and functional evaluation of the hair-cell transcriptome
Authors: McDermott Brian M. , Baucom Jessica M. , Hudspeth A. J.
Published: July 2007

An understanding of the molecular bases of the morphogenesis, organization, and functioning of hair cells requires that the genes expressed in these cells be identified and their functions ascertained. After purifying zebrafish hair cells and detecting mRNAs with oligonucleotide microarrays, we developed a subtractive strategy that identified 1,037 hair cell-expressed genes whose cognate proteins subserve functions including membrane transport, synaptic transmission, transcriptional control, cellular adhesion and signal transduction, and cytoskeletal organization. To assess the validity of the subtracted hair-cell data set, we verified the presence of 11 transcripts in inner-ear tissue. Functional evaluation of two genes from the subtracted data set revealed their importance in hair bundles: zebrafish larvae bearing the
seahorse
and
ift 172
mutations display specific kinociliary defects. Moreover, a search for candidate genes that underlie heritable deafness identified a human ortholog of a zebrafish hair-cell gene whose map location is bracketed by the markers of a deafness locus.
Splicing remodels messenger ribonucleoprotein architecture via eIF4A3-dependent and -independent recruitment of exon junction complex components
Authors: Zhang Zuo , Krainer Adrian R.
Published: July 2007

Pre-mRNA splicing not only removes introns and joins exons to generate spliced mRNA but also results in remodeling of the spliced messenger ribonucleoprotein, influencing various downstream events. This remodeling includes the loading of an exon–exon junction complex (EJC). It is unclear how the spliceosome recruits the EJC onto the mRNA and whether EJC formation or EJC components are required for pre-mRNA splicing. Here we immunodepleted the EJC core component eIF4A3 from HeLa cell nuclear extract and found that eIF4A3 is dispensable for pre-mRNA splicing
in vitro
. However, eIF4A3 is required for the splicing-dependent loading of the Y14/Magoh heterodimer onto mRNA, and this activity of human eIF4A3 is also present in the
Drosophila
ortholog. Surprisingly, the loading of six other EJC components was not affected by eIF4A3 depletion, suggesting that their binding to mRNA involves different or redundant pathways. Finally, we found that the assembly of the EJC onto mRNA occurs at the late stages of the splicing reaction and requires the second-step splicing and mRNA-release factor HRH1/hPrp22. The EJC-dependent and -independent recruitment of RNA-binding proteins onto mRNA suggests a role for the EJC in messenger ribonucleoprotein remodeling involving interactions with other proteins already bound to the pre-mRNA, which has implications for nonsense-mediated mRNA decay and other mRNA transactions.
A ratiometric lectin microarray approach to analysis of the dynamic mammalian glycome
Authors: Pilobello Kanoelani T. , Slawek Deepika E. , Mahal Lara K.
Published: July 2007

Glycosylation creates an intricate and complex code for biological information that plays a role in cell–cell communication, infection, and immunity among many biological events. Dynamic changes in the glycosylation status of cells have been observed in tumor cell metastasis and cell differentiation but have been difficult to analyze because of a lack of high-throughput and facile technologies. Here, we present a method for the rapid evaluation of differences in the glycosylation of heterogeneous mammalian samples using a ratiometric two-color lectin microarray approach. This work represents a significant improvement in glycomics technology and sets the stage for the systematic evaluation of how glycans encode biological information in complex systems.
Structural basis for conserved complement factor-like function in the antimalarial protein TEP1
Authors: Baxter Richard H. G. , Chang Chung-I , Chelliah Yogarany , Blandin Stéphanie , Levashina Elena A. , Deisenhofer Johann
Published: July 2007

Thioester-containing proteins (TEPs) are a major component of the innate immune response of insects to invasion by bacteria and protozoa. TEPs form a distinct clade of a superfamily that includes the pan-protease inhibitors α
2
-macroglobulins and vertebrate complement factors. The essential feature of these proteins is a sequestered thioester bond that, after cleavage in a protease-sensitive region of the protein, is activated and covalently binds to its target. Recently, TEP1 from the malarial vector
Anopheles gambiae
was shown to mediate recognition and killing of ookinetes from the malarial parasite
Plasmodium berghei
, a model for the human malarial parasite
Plasmodium falciparum
. Here, we present the crystal structure of the TEP1 isoform TEP1r. Although the overall protein fold of TEP1r resembles that of complement factor C3, the TEP1r domains are repositioned to stabilize the inactive conformation of the molecule (containing an intact thioester) in the absence of the anaphylotoxin domain, a central component of complement factors. The structure of TEP1r provides a molecular basis for the differences between
TEP1
alleles
TEP1r
and
TEP1s
, which correlate with resistance of
A. gambiae
to infection by
P. berghei
.
Frequency-dependent physiological trade-offs between competing colour morphs
Authors: Pryke Sarah R , Astheimer Lee B , Buttemer William A , Griffith Simon C
Published: July 2007

Evolutionary theory suggests that alternative colour morphs (i.e. genetically controlled phenotypes) may derive similar fitness under frequency-dependent selection. Here we experimentally demonstrate opposing effects of frequency-dependent social environments on plasma hormone levels (testosterone and corticosterone) and immune function between red- and black-headed male morphs of the Gouldian finch (
Erythrura gouldiae
). Red-headed males are highly sensitive to changes in the social environment, especially towards the relative density of their own aggressive morph, exhibiting high stress responses and immunosuppression in socially competitive environments. In contrast, the non-aggressive black-headed males follow a more passive strategy that appears to buffer them against social stresses. The differential effect of hormones on aggressive behaviour and immune performance reinforces the contrasting behavioural strategies employed by these colour morphs, and highlights the importance of the social environment in determining the individual basis of behavioural and physiological responses.
Mechanics of a thin anisotropic elastic layer and a layer that is bonded to an anisotropic elastic body or bodies
Authors: Ting T.C.T
Published: July 2007

When a very thin elastic layer is bonded to an elastic body, it is desirable to have
effective boundary conditions
for the interface between the layer and the body that take into account the existence of the layer. In the literature, this has been done for special anisotropic elastic layers. We consider here the layer that is a general anisotropic elastic material. The mechanics of a thin layer is studied for elastostatics as well as steady state waves. It is shown that one-component surface waves cannot propagate in a semi-infinite thin layer. We then present Love waves in an anisotropic elastic half-space bonded to a thin anisotropic elastic layer. The dispersion equation so obtained is valid for long wavelength. Finally, effective boundary conditions are presented for two thin layers bonded to two surfaces of a plate and a thin layer bonded between two anisotropic elastic half-spaces.
A new probable stem lineage crustacean with three-dimensionally preserved soft parts from the Herefordshire (Silurian) Lagerstätte, UK
Authors: Siveter Derek J , Sutton Mark D , Briggs Derek E.G , Siveter David J
Published: July 2007

A new arthropod with three-dimensionally preserved soft parts,Tanazios dokeron, is described from the Wenlock Series (Silurian) of Herefordshire, England, UK. Serial grinding, digital photographic and computer rendering techniques yielded ‘virtual fossils’ in the round for study. The body tagmata ofT. dokeroncomprise a head shield and a long trunk. The head shield bears six pairs of horn-like spines and the head bears five pairs of appendages. The antennule, antenna and mandible are all uniramous, and the mandible includes a gnathobasic coxa. Appendages four and five are biramous and similar to those of the trunk: each comprises a limb base with an endite, an enditic membrane, and two epipodites, plus an endopod and exopod. The hypostome bears a large cone-like projection centrally, and there may be a short labrum. The trunk has some 64 segments and at least 60 appendage pairs. A very small telson has the anus sited ventrally in its posterior part and also bears a caudal furca. Comparative morphological and cladistic analyses ofT. dokeronindicate a crustacean affinity, with a probable position in the eucrustacean stem group. As such the epipodites inT. dokeronare the first recorded in a eucrustacean stem taxon. The new species is interpreted as a benthic or nektobenthic scavenger.
Dendritic cells and myeloid leukaemias: plasticity and commitment in cell differentiation
Authors: Rasaiyaah Jane , Yong Kwee , Katz David R. , Kellam Paul , Chain Benjamin M.
Published: July 2007

Dendritic cells (DCs) are key antigen‐presenting cells (APCs), which link innate and adaptive immunity, ultimately activating antigen‐specific T cells. This review examines the relationship between the acute and chronic myeloid leukaemias and cells with DC properties. DCs are non‐dividing terminally differentiated cells, and ex vivo leukaemic cells or cell lines show little similarity to DCs. However, many leukaemias differentiate further in response to defined stimuli, and retain a degree of lineage plasticity. Therefore, several studies have explored the response of leukaemic cells to the in vitro regimens used to differentiate ex vivo primary DCs. Recent data suggest that the most ‘dendritic‐like’ cells can be derived from more undifferentiated myeloid leukaemias, such as the myelomonocytic Mutz‐3 cell line. These findings have important implications for understanding the developmental origins of DCs, for harnessing the APC properties of this class of tumour to stimulate the therapeutic anti‐tumour immunity, and for developing useful models for the study of human DC physiology and pathology. There is a strong rationale for further exploration of this class of tumour and its relationship to the normal DC.
Distribution of t(14;18)‐positive, putative lymphoma precursor cells among B‐cell subsets in healthy individuals1
Authors: Hirt Carsten , Dölken Gottfried , Janz Siegfried , Rabkin Charles S.
Published: July 2007

The t(14;18)(q32;q21) is the characteristic chromosomal translocation of follicular lymphoma (FL). Highly sensitive polymerase chain reaction (PCR) techniques can also detect t(14;18)‐sequences in the blood and lymphoid tissues of healthy individuals (HI). The aim of this study was to determine the immunophenotypic markers of t(14;18)‐positive cells in HI and to relate these features to lymphocyte maturation. B cells from 10 subjects with t(14;18)‐positive and three subjects with t(14;18)‐negative peripheral blood mononuclear cells (PBMC) were fluorescence‐activated cell sorted for antigen‐naïve (CD27−), immunoglobulin M (IgM) memory (IgM+CD27+) and switched memory (IgM− CD27+) cells. t(14;18)‐recombinations were detected by quantitative PCR. Among PBMC‐positive subjects, t(14;18)‐frequency was significantly higher in IgM memory (median: 380/106) than in antigen‐naïve (median: 16/106) or switched memory (median: 5/106) B cells. All PBMC‐negative subjects nevertheless had detectable t(14;18) in sorted B cells; levels were lower than in PBMC‐positive subjects, but had the same relative predominance. These results suggest that t(14;18) is generated during early B‐cell development in the bone marrow and that affected cells may mature and expand in germinal centres. t(14;18)‐frequency was highest in IgM memory cells, a B‐cell subset that shares immunophenotypic similarities with FL. The significance of these cells as lymphoma precursors or indicators of lymphoma risk remains to be established.
Leucocytosis in polycythaemia vera predicts both inferior survival and leukaemic transformation
Authors: Gangat Naseema , Strand Jacob , Li Chin‐Yang , Wu Wenting , Pardanani Animesh , Tefferi Ayalew
Published: July 2007

Leucocytosis (leucocyte count >15 × 109/l) was recently associated with thrombosis in polycythaemia vera (PV). This study sought the prognostic relevance of leucocytosis for survival and leukaemic or fibrotic transformation. Amongst 459 patients with PV seen at our institution in recent years (median age, 60 years; 56% males), 146 deaths and 88 leukaemic (n = 34) or fibrotic (n = 54) transformations were documented. Arterial or venous thrombosis occurred in 14% and 9% of patients at diagnosis and in 25% and 15% during follow‐up, respectively. Multivariate analysis identified the advanced age (P < 0·0001), leucocytosis (leucocyte count ≥15 × 109/l; P = 0·0006) and arterial thrombosis at diagnosis (P = 0·01) as independent predictors of inferior survival. In the absence of the first two risk factors, median survival was projected at 272 months as opposed to 108 months in the presence of both risk factors (P < 0·0001). Leucocytosis was also identified as an independent predictor of both leukaemic transformation and venous thrombosis during follow‐up. Time‐to‐event analysis did not disclose a significant association between single or multiple cytotoxic drug exposure and either leukaemic or fibrotic transformation. The current study highlighted the prognostic relevance of leucocytosis on various aspects of the disease in PV.
Centrosome aberrations after nilotinib and imatinib treatment in vitro are associated with mitotic spindle defects and genetic instability
Authors: Fabarius Alice , Giehl Michelle , Frank Oliver , Spiess Birgit , Zheng Chun , Müller Martin C. , Weiss Christel , Duesberg Peter , Hehlmann Rüdiger , Hochhaus Andreas , Seifarth Wolfgang
Published: July 2007

Centrosomes play fundamental roles in mitotic spindle organisation, chromosome segregation and maintenance of genetic stability. Recently, we have demonstrated that the tyrosine kinase inhibitor imatinib induces centrosome and chromosome aberrations in vitro. Here, we comparatively investigated the effects of imatinib and the more potent successor drug nilotinib on centrosome, mitotic spindle and karyotype status in primary human fibroblasts. Therapeutic doses of imatinib and/or nilotinib administered separately, consecutively or in combination similarly induced centrosome, mitotic spindle, and karyotype aberrations. Our data suggest that distinct tyrosine kinases likewise targeted by both drugs are essential actuators in maintenance of centrosome and karyotype integrity.
Identification of novel allergens of Aspergillus fumigatus using immunoproteomics approach
Authors: Gautam P. , Sundaram C. S. , Madan T. , Gade W. N. , Shah A. , Sirdeshmukh R. , Sarma P. U.
Published: July 2007

Background
Approximately 20% of the world's asthmatics are suffering from Aspergillus fumigatus (Afu)‐induced allergies. The characterization of specific IgE‐inducing allergens in allergic aspergillosis patients is fundamental for clinical diagnosis and for immunotherapy.

Methods
Immunoproteomics combined with mass spectrometric analysis was used to identify proteins of third‐week culture filtrate (3wcf) potentially responsible for Afu‐specific IgE immunoreactivity, using pooled sera from Afu‐sensitized asthmatics. Their allergenic potential was also tested against patients with allergic bronchopulmonary aspergillosis (ABPA), by two‐dimensional (2‐D) gel electrophoresis immunoblotting of 3wcf proteins with individual sera from such patients. This helped us to establish a set of candidate allergens, which could be explored further for diagnostic application in allergic aspergillosis asthmatics including ABPA.

Results
Peptide mass fingerprint using matrix‐assisted laser desorption/ionization‐time of flight‐mass spectrometry (MALDI‐TOF‐MS) and/or de novo sequencing by MS/MS analysis of the protein spots from 2‐D gels led to the identification of a total of 16 allergens of Afu. Eleven of them are being reported as allergens for the first time and five had been reported earlier. Putative isoforms of the proteins Asp f 13 and chitosanase have been observed for the first time. When studied for reactivity of these proteins among patients with ABPA using their individual sera, these patients exhibited sensitization although the pattern was varying. Taken together, these proteins could thus be considered as potential allergens even among patients with ABPA. Three of these proteins viz. the hypothetical protein (# spot no. 5), extracellular arabinase (# spot no. 6) and chitosanase (# spot no. 11) could be major allergens with specific IgE immunoreactivity with six out of eight patients' sera.

Conclusions
The immunoproteomic approach applied to the analysis of culture filtrate proteins resulted in the identification of several candidate allergens, many of them novel, contributing to the catalogue of Afu allergenic proteins, which would facilitate improved serodiagnosis for allergic aspergillosis. In addition, the immunoreactivity of these proteins observed among the patients with ABPA may be potentially useful for its serodiagnosis and opens up further opportunities for the development of personalized immunotherapeutics for patients with ABPA.
Polymorphisms of histamine‐metabolizing enzymes and clinical manifestations of asthma and allergic rhinitis
Authors: García‐Martín E. , García‐Menaya J. , Sánchez B. , Martínez C. , Rosendo R. , Agúndez J. A. G.
Published: July 2007

Background
Polymorphisms of enzymes involved in histamine biodisposition may affect clinical symptoms in diseases related to histamine, such as asthma or allergic rhinitis (AR).

Objective
This study aims to analyse two common polymorphisms in genes coding for histamine‐metabolizing enzymes in patients with allergic diseases.

Methods
Five‐hundred and sixty‐five individuals participated in the study, including 270 unrelated patients with asthma and/or AR recruited from a single centre and 295 healthy volunteers. Participants were analysed for the presence of Thr105Ile and His645Asp amino acid substitutions at histamine N‐methyltransferase (HNMT) and diamine oxidase (amiloride binding protein 1) enzymes, respectively, by amplification‐restriction procedures.

Results
The variant HNMT allele frequencies were slightly higher among patients with asthma [16.0%, 95% confidence interval (CI) 12.0–20.0] and among patients with rhinitis (13.2, 95% CI 10.3–16.1) as compared with healthy subjects (11.5 95% CI 8.9–14.1). The variant ABP1 allele frequencies were similar among patients with asthma (30.8%, 95% CI 25.7–35.9), rhinitis (28.7, 95% CI 24.8–32.6) and healthy subjects (26.8 95% CI 23.2–30.3). Individuals carrying mutated ABP1 alleles presented allergy symptoms with significantly lower IgE levels as compared with individuals without mutated genes, with a significant gene‐dose effect (P<0.001). In addition, the percentage of individuals presenting symptoms without eosinophilia was significantly higher among homozygous carriers of ABP1 variant alleles (P<0.020) as compared with the rest of the atopic patients.

Conclusion
There is a lack of association between the allelic variants studied and the risk of developing allergic asthma and rhinitis. However, patients carrying the His645Asp polymorphism of ABP1 are more prone to developing symptoms with lower IgE levels.