bluuebunny/crossref_metadata_2025 huggingface dataset:
Foreword: Towards markers for anthelmintic resistance in helminths of importance in animal and human health
Authors: PRICHARD R. K. , von SAMSON-HIMMELSTJERNA G. , BLACKHALL W. J. , GEARY T. G.
Published: July 2007

Anthelmintic resistance is a serious problem in veterinary medicine and appears to be developing in some helminths of importance to human health. Anthelmintic drugs remain the principal means of control of helminth infections in animals and humans and the continued dependence on these pharmaceuticals will continue to impose selection pressure for resistance development. Our ability to detect anthelmintic resistance before control breaks down and to monitor the spread of anthelmintic resistance is quite limited. We are currently dependent on biological methods which are not sufficiently sensitive to detect low levels of drug resistance and are particularly difficult to perform on helminth parasites of humans. There is a serious need for new molecular markers for detecting and monitoring for anthelmintic resistance. The problem of anthelmintic resistance is already very serious in nematode parasites of livestock. In addition, there should be great concern about possible anthelmintic resistance development and the lack of tools and efforts for monitoring it as part of the major worldwide programmes to control helminth parasites in people. An international Consortium has been formed to develop Anthelmintic Resistance Single nucleotide polymorphism markers (CARS). Discussions within the Consortium have addressed the need for such markers, the current state of knowledge about them, possible mechanisms of anthelmintic resistance and approaches and constraints to the development of markers. Summaries of the state of the art in these areas are presented in a series of papers in this Special Issue of Parasitology.
Labelling the salt content in foods: a useful tool in reducing sodium intake in Finland
Authors: Pietinen Pirjo , Valsta Liisa M , Hirvonen Tero , Sinkko Harri
Published: July 2007

Objective

To estimate the impact of choosing food products labelled either as low or high in salt on salt intake in the Finnish adult population.

Setting and subjects

The National FINDIET 2002 survey with 48-hour recalls from 2007 subjects aged 25–64 years. Sodium intake was calculated based on the Fineli® food composition database including the sodium content of natural and processed foods as well as the salt content of recipes. The distribution of salt intake was calculated in different ways: the present situation; assuming that all breads, cheeses, processed meat and fish, breakfast cereals and fat spreads consumed would be either ‘lightly salted’ or ‘heavily salted’ based on the current labelling practice; and, in addition, assuming that all foods would be prepared with 50% less or more salt.

Results

Excluding underreporters, the mean salt intake would be reduced by 1.8 g in men and by 1.0 g in women if the entire population were to choose lightly salted products and further by 2.5 and 1.8 g, respectively, if also salt used in cooking were halved. Choosing heavily salted products would increase salt intake by 2.1 g in men and by 1.4 g in women. In the worst scenarios, salt intake would be further increased by 2.3 g in men and by 1.6 g in women.

Conclusions

These calculations show that the potential impact of labelling and giving consumers the possibility to choose products with less salt is of public health importance. In addition, strategies to reduce the salt content of all food groups are needed.
Validating a nutrient profile model
Authors: Arambepola Carukshi , Scarborough Peter , Rayner Mike
Published: July 2007

Objective

To assess the validity of nutrient profiling Model WXYfm – developed for the purpose of regulating the promotion of ‘less healthy’ foods to children. The model ranks foods according to their healthiness and categorises foods into ‘healthier’ and ‘less healthy’ foods.

Design

Convergent and discriminant validity was tested by comparing the way Model WXYfm categorises foods with the way the UK’s national food guide – the Balance of Good Health (BGH) – categorises foods. Construct validity was assessed by testing a hypothesis relating the constructs of ‘healthiness’ of foods (as measured by Model WXYfm) and the ‘healthiness’ of diets (measured using the Diet Quality Index) and assessing whether this hypothesis was confirmed or refuted by using data on the dietary patterns of subjects (n= 1117) of the National Diet and Nutrition Survey of adults carried out in Great Britain in 2000–01.

Results

Model WXYfm showed good convergent and discriminant validity: the level of agreement between the way the model categorises foods and the way the BGH categorises foods was good (κ= 0.69). Model WXYfm also showed good construct validity: the energy intake from ‘less healthy’ foods amongst subjects with the least healthy diets was nearly twice the energy intake from ‘less healthy’ foods amongst the subjects with the healthiest diets.

Conclusions

Model WXYfm demonstrated good validity in categorising foods in a way that is related to the healthiness of diets both recommended and achieved. The methods for assessing the validity of a nutrient profile model used in this paper have not, to our knowledge, been used before.
Patterns of resistance to Candida albicans in inbred mouse strains
Authors: ASHMAN R. B. , BOLITHO ERIN M. , PAPADIMITRIOU J. M.
Published: July 2007

Candida albicans infections were established in eight inbred strains of mice. Using established histological criteria, only two strains (AKR and CBA/CaH) were found to exhibit severe lesions. The remainder showed only mild tissue damage. Deaths occurred in three strains: CBA/CaH, A/J and DBA/2. The last two strains lack the important complement component C5. Colony counts in the brain varied widely between strains and showed no correlation with the extent or severity of tissue destruction. However, strains lacking C5 had a significantly greater fungal burden in the brain than C5‐sufficient mice. The data are discussed in relation to concepts of susceptibility and resistance to C. albicans in experimental infections in mice.
Activated CD19+ B cell lamina propria lymphocytes in ulcerative colitis
Authors: YACYSHYN B. R.
Published: July 2007

Although isotype differences in lamina propria lymphocyte (LPL) immunoglobulin production has been recognized between normal, ulcerative colitis (UC) and Crohn's patients, differences in B cell activation between these conditions has not been described. Using flow cytometry, we studied B cell LPL activation using the CD71 (transferrin receptor), CD25 (interleukin‐2 receptor) and 4F2 (early B and T cell activation marker) monoclonal antibodies. CD19+ B cells from patients with UC had relatively increased expression of CD71, CD25 and 4F2 compared with patients with Crohn's disease or normal mucosa. This finding corresponds to an increased proportion of transitional (activated) B cells as defined by the co‐expression of CD45RA and CD45RO found in UC LPL compared with normal or Crohn's patient LPL. Such data may identify an important link between the cellular state of activation of UC LPL B cells and the differences in immunoglobulin production between the inflammatory bowel diseases and normal intestine. Such findings may have further diagnostic or pathophysiologic importance in the study of these diseases. This work also provides further support for the CD45 transition of CD19 B cells from the high to low molecular weight isoform.
Vaccination against tuberculosis: Is BCG more sinned against than sinner?
Authors: GRIFFIN J. FRANK T. , BUCHAN GLENN S.
Published: July 2007

While extensive experimental studies of tuberculosis (Tb) have provided the foundation data for the discovery of cell‐mediated immunity, there remains much to be disclosed about the critical pathways of immunity involved in this infectious process and the factors necessary to produce protective immunity. Studies on the actiology and pathology of this disease have failed to elucidate the mechanisms of protective immunity. Although Tb research has been neglected for the past 30 years, the re‐emergence of Tb worldwide as a significant zoonotic disease has re‐focused research in this area. Scientific solutions for the control of Tb in man or domestic animals have not been found using empirical methods. Composite studies involving animal models of experimental infection will be necessary to critically evaluate vaccine efficacy and elucidate the basic immunological mechanisms involved in both disease and immunity. Available data which suggest that disease‐related hypersensitivity and immunity are dissociable highlight the prospect that immunity to infection may be induced without compromising the continued need for ongoing systems of immunodiagnosis to exclude disease. In populations with a high prevalence of disease it is likely that a combination of immunodiagnosis, chemotherapy and immunoprophylaxis will be required to eradicate the disease.
Recombinant vaccines against ovine footrot
Authors: O'MEARA T. J. , EGERTON J. R. , RAADSMA H. W.
Published: July 2007

For the past 20 years footrot vaccines have evolved from simple bacterins to highly specific recombinant DNA (rDNA) fimbrial vaccines. The development of these vaccines has left a trail of discoveries, challenges and solutions; these processes continue as we move closer to understanding the requirements of a footrot vaccine. The initial whole cell vaccines were unsuccessful due to the short duration of immunity and incorporation of limited serotypes. A multistrain vaccine eliminated the problem of serotype inclusion, although the duration of immunity in many cases is still inadequate. The proteases of Dichelobacter nodosus appear to be cross protective; however, little is known of their ability to protect sheep against footrot. The major protective immunogen is the bacterial fimbriae, which also forms the basis for the K‐agglutination serotyping system. K‐agglutinin titre correlates directly with resistance to challenge. The protective fimbrial epitope is conformationally dependent, suggesting little advantage in the development of synthetic peptide vaccines. To enhance the efficiency of vaccine production D. nodosus fimbrial genes were eventually cloned and successfully expressed in Ps. aeruginosa. Monovalent vaccines based on recombinant fimbriae are omnipotent, inducing high levels of agglutinins and long lasting immunity. In multivalent vaccines, on the other hand, incorporation of each additional serogroup into the vaccine results in reduced efficacy both in terms of reduced K‐agglutinin titres and reduced protection following challenge. The least effective are multivalent formulations representing all major serogroups. In addition, considerable genetic variation has been observed in the ability of sheep to respond optimally to each serogroup in a multivalent vaccine. Results show that the limitation of the sheep to mount an effective immune response, rather than the quality or quantity of the immunogen, limits the efficacy of current footrot vaccines. Studies are being undertaken to examine in detail the immune response of sheep to potentially highly effective footrot vaccines.
Functional and phenotypic assessment of neonatal human leucocytes expressing natural killer cell‐associated antigens
Authors: BRADSTOCK K. F. , LUXFORD C. , GRIMSLEY P. G.
Published: July 2007

A subpopulation of mononuclear leucocytes was prepared from umbilical cord venous blood by immunomagnetic depletion of lymphocytes and monocytes using monoclonal antibodies to CD2, CD3, CD14 and CD19 antigens, and examined for NK cell‐associated phenotypic and functional properties. The depleted population was enriched for the NK markers CD16 (mean 53.6% positive) and CD56 (mean 42.7% positive). While there was considerable overlap of these two markers, approximately one‐third of CD16+ cells were CD56−; in contrast, few CD56+ CD16− cells were found. CD16+/CD56+ cells also co‐expressed CD7 and CD45RA antigens, while a minority weakly expressed CD8. Another marker of adult NK cells, CD57, was virtually absent from CD16+/GD56+ cells, as was MHG Class 2. Freshly depleted cord cells had virtually absent natural cytotoxicity to K562 targets in a chromium release assay, but NK activity could he induced after 18 h exposure to recombinant human IL‐2, without significant change in phenotype. These findings confirm the phenotypic differences and functional defects of NK cells in cord blood as compared to adult blood, and identify a subset of cells with unique phenotype (GD2− CD3− CD7+ CD16+ CD56− GD57−). The precise relationship of this subset of cells to NK lineage remains to be defined.
A comprehensive analysis of peripheral blood lymphocytes in healthy aged humans by flow cytometry
Authors: XU XIAONING , BECKMAN IAN , AHERN MICHAEL , BRADLEY JOHN
Published: July 2007

This study used a panel of mAb and multiparameter flow cytometry to assess the composition of PBL from healthy aged individuals. The results showed that while total lymphocyte numbers altered only marginally in the aged (≥ 70 years) there were significant changes in the distribution of various sub‐populations; for example, there were lower numbers of CD3+ and CD8+ cells, and higher numbers of CD16+ (NK) cells. As a direct result of these changes the numbers of CD2+ cells remained unchanged in the aged compared with young adult controls (18–25 years). The number of CD4+ T cells expressing CD45RO isoform (memory cells) exceeded the number of CD4+ CD45RA+ (naive) cells in aged donors, whereas the converse was true for young donors. In addition, associated with this increase in CD45RO+ cells, the aged showed an expanded population of CD45RO+ T cells displaying low surface levels of CD45RO. These data suggest that shifts in the distribution of regulatory T cell subsets may play a role in age‐related changes in immune response.
Electroporation and DNA‐dependent cell death in murine macrophages
Authors: STACEY KATRYN J. , ROSS IAN L. , HUME DAVID A.
Published: July 2007

The difficulty of transfecting primary macrophages and macrophage ceil lines has meant that relatively few studies on regulation of gene expression have been performed in these cells. This study has optimized an electroporation procedure for the macrophage cell line RAW 264, but shows that introduction of DNA into the cytoplasm of primary macrophages by electroporation is toxic to the cells. It is proposed that this cell death may have a physiological role in defence against certain viral infections which result in accumulation of cytoplasmic DNA. RAW 264 cells were efficiently transfected by electroporation, but electroporated bone marrow derived macrophages (BMM) showed large scale cell death over a period of 12 h. Electroporation without DNA was not toxic and DNase treatment of samples before transfection prevented cell death. The toxicity of DNA was concentration‐dependent and sequence independent. Synthetic, genomic and plasmid DNA all caused cell death. This sensitivity to DNA seems to be distinct from the antiviral state induced by double‐stranded RNA and may be part of an uncharacterized viral defence system.
Persistence of γ/δ T cell oligoclonality in the peripheral blood of rheumatoid arthritis patients
Authors: OLIVE COLLEEN , GATENBY PAUL A. , SERJEANTSON SUSAN W.
Published: July 2007

The peripheral blood of patients with rheumatoid arthritis (RA) contains oligocional γ/δ T cell populations which may contribute to the pathogenesis of the disease. To investigate whether there is persistent γ/δ T cell oligoclonality in RA peripheral blood, we screened polymerase chain reaction‐amplified T cell receptor (TCR) cDNA, derived from peripheral blood mononuclear cells (PBMC) of four RA patients, with sequence specific oligonucleotides (SSO). The SSO used were specific for TCR variable (V)δ1, Vδ2 and Vγ9 transcripts comprising V‐joining (J) junctions found over‐represented in PBMC of the same RA patients, when bled up to 3 years previously. The dominant transcripts were expressed in the new PBMC samples, although in most cases at a lower frequency than was originally detected. In one patient there was almost 100% oligoclonality of Vγ9‐(N)‐Jγ2 junctional region sequences among the Vγ9 cDNA clones. progressing from 55% oligoclonality in 15 months. These results indicate the persistence of clonally expanded γ/δ T cells in the peripheral blood of RA patients. Whether this reflects continual endogenous or exogenous antigenic stimulation remains to be investigated. The findings presented in this report may have important therapeutic implications in view of the potential for immuno‐intervention for the treatment of human autoimmune disorders, like RA.
Isolation and characterization of a neutrophil chemotactic factor from Tritrichomonas foetus organisms
Authors: OWHASHI M. , TOMIYOSHI F. , HAYASHI H.
Published: July 2007

A neutrophil chemotactic factor (TfNCF) was isolated from the crude extract of Tritrichomonas foetus organisms by a combination of anion‐exchange chromatography on DE52 and gel filtration on Sephacryl S200. TfNCF showed homogenicity by both PAGE and SDS‐PAGE. The molecular weight of TfNCF was estimated to be 22 and 24 kDa, by Sephacryl S200 gel chromatography and by SDS‐PAGE under reducing conditions. Immunization of TfNCF caused almost complete protection against T. foetus infection in mice. Western blot analysis probed with anti‐TfNCF antibody showed that the epitopes on TfNCF were not commonly shared on the other components of T. foetus organisms nor other helminthous parasite‐derived components. Furthermore, pre‐incubation of neutrophils with antigens of other helminthous parasites or N‐formylmethionyl‐leucyl‐phenylalanine did not affect the neutrophil chemotactic activity for TfNCF. These results suggest that TfNCF is a novel NCF consisting of unique epitopes for both antigenicity and neutrophil chemotactic activity. The role of NCF in the initiation of the immune response is discussed.
The L‐selectin (Leu8) molecule is associated with the TcR/CD3 receptor; fluorescence energy transfer measurements on live cells
Authors: SZABO GABOR , PINE P. SCOTT , WEAVER JAMES L. , RAO PATRICIA E. , ASZALOS ADORJAN
Published: July 2007

Several accessory molecules were shown to play important roles in T cell functions and be in dose proximity to the T cell receptor (TcRyCD3). The L‐selectin molecule (Leu8, LAM 1‐1, LECAM1) also plays an important role in lymphocyte homing and proliferation. We were interested in determining the proximity of this molecule to the TcR/CD3 complex on live peripheral human T cells. Using a fluorescence energy transfer method, designed to study individual cells, we could show that L‐selectin is within 170 Å of the TcR/CD3 complex. Monoclonal antibody directed against the LAMl‐l (Leu8) epitope of the L‐selectin molecule suppressed the mitogenic activity of antibodies specific for various CD3 epitopes in vitro. Intracellular Ca2+ mobilization obtained with wt31 followed by cross‐linking antibody or with anti‐CD3 was not influenced by anti‐Leu8 antibody. Also antibody directed against the LAMl‐1 epitope did not influence the binding of the mitogenic antibodies, as shown by fluorescence‐based flow cytometry. Therefore, we suggest that binding of TcR/CD3 bound mitogenic antibodies to accessory cell Fc receptors may be hindered by antibodies bound to the close proximity L‐selectin molecules.
Internalization of the anticoagulant thrombomodulin is constitutive and does not require a signal in the cytoplasmic domain
Authors: TEASDALE M. S. , BIRD C. H. , BIRD P.
Published: July 2007

Endocytosis of the protein C activation cofactor thrombomodulin (TM) is thought to be induced by interaction of TM with its ligand, thrombin, or by the action of inflammatory cytokines on endothelial cells. To examine the internalization of TM in the absence of thrombin or cytokines we used two assays. The first was a two‐colour indirect immunofluorescence technique to simultaneously monitor cell surface and internal pools of TM. The second involved labelling a cell surface pool of TM and following its cellular redistribution over time. Using these techniques we demonstrated that in both TM‐transfected COS cells and in endothelial cells, TM internalizes constitutively. Removal of the cytoplasmic domain, which in most receptors contains the internalization signal, did not abolish TM internalization. These results suggest that endocytosis of TM does not occur via coated pits, and that internalization probably is not a significant cause of the endothelial TM loss associated with several pathological states.
Infection of human and murine macrophages with Leishmania major is associated with early parasite heat shock protein synthesis but fails to induce a host cell stress response
Authors: KANTENGWA SALOMÉ , MÜLLER INGRID , LOUIS JACQUES , POLLA BARBARA S.
Published: July 2007

Heat shock/stress proteins (HSP) represent the most conserved proteins expressed in prokaryotes and eukaryotes. These constitutive and inducible proteins function as molecular chaperones and are part of virulence factors. They participate in self/non‐self discrimination and may protect phagocytes from the toxic effects of the reactive oxygen species generated by these cells during bacterial phagocytosis and infection. In this study, we investigated the early stress response of host cells [either human alveolar macrophages (AM) or murine peritoneal macrophages (PM)] during infection by an obligate intracellular parasite (Leishmania major), which lives within phagolysosomes. Immunoblotting with specific antibodies demonstrated that L. major had no effect on host stress protein synthesis, but synthesized high levels of its own stress proteins within AM and PM. The lack of induction of a host cell stress response may relate to the failure of L. major to activate the respiratory burst in these cells, whereas the upshift of L. major HSP within macrophages is part of an adaptive response of the parasite to the host.
T cell receptor Vα bias can be determined by TCR‐contact residues within an MHC‐bound peptide
Authors: STERRY SANDRA J. , KELLY JANICE M. , TURNER STEPHEN J. , CARBONE FRANCIS R.
Published: July 2007

Many antigen‐specific T cell responses show profound V‐region biases in one or both chains of the TCR αβ heterodimer. We have examined how changes in residues within an MHC‐bound peptide can influence V‐region selection. Single‐chain TCR transgenic mice were derived using a β‐chain specific for the Kb‐restricted peptide from ovalbumin, OVA257‐264 Transgenic T cells were stimulated in vitro using OVA257‐264 or a single residue variant having a lysine to aspartic acid substitution at determinant position 7 (7D). Recent crystallographic analyses have shown that this variant residue is involved in direct contact with the TCR. Sequence analysis of the T cell populations showed that the majority OVA257‐264 specific T cells used Vα10‐positive TCR while the majority of the 7D‐specific TCR expressed the Vα4 element. In both peptide responses we found that some cell lines appeared to be made up of more than one clone expressing the same Vα sequence but having limited variation at the V‐J junction. These results show that the TCR contact residues within the target peptide can influence V‐region bias and suggest that the first and second hypervariable regions of the TCR are directly or indirectly involved in determining peptide specificity.
Production of monoclonal antibodies specific to the carboxyl terminal region of the 85 kDa subunit of phosphatidylinositol 3‐kinase: Use of the antibodies in recognition of mutant p85
Authors: DADUANG SAKDA , NAGATA SATOSHI , MATSUDA MICHIYUKI , YAMORI TAKAO , ONODERA KAZUKIYO , FUKUI YASUHISA
Published: July 2007

We have established two hybridomas producing mAb to the carboxyl terminal region of phosphatidylinositol‐3 kinase 85 kDa subunit type α (p85α). Analysis using deletion mutants of p85 revealed that epitopes for the two mAb were located on the border of the src homology 2 (SH2) sequence located at the carboxyl end of p85. They immunoprecipitated free p85 efficiently, but reactivity to p85 bound to pi 10 was very weak. Together with the mAb which we have reported previously, a panel of mAb that covered the various parts of p85α was obtained. Using this panel, we characterized two mutants of p85 (70 and 50 kDa) expressed in the human colon carcinoma cell line, HCC2998. No wild‐type p85 was detected in these cells. A mAb specific to the carboxyl terminal region detected p70 but not p50, suggesting that this region is missing in p50. The panel of mAb is a useful tool to use to analyse mutant forms of p85.
The one signal theory of B cell activation revisited: A role for surface immunoglobulin in regulating T‐independent antibody responses?
Authors: MAMCHAK ALUSHA A , HODGKIN PHILIP D
Published: July 2007

Early theories of antibody production by B cells achieved considerable success in predicting B cell behaviour with simple deductive models. One such model, the one signal theory, postulated that the antigen receptor on B cells played only a passive non‐signalling role in focusing non‐specific activating signals to the B cell surface. This prediction is at least partially consistent with recent discoveries concerning the helper signals delivered to B cells by T cells. Here, we re‐examine the foundation of this theoretical prediction with the benefit of recent information. The experimental basis for the theory was a study of B cell activation by LPS and, in particular, the interpretation of a bell‐shaped dose‐response curve. The logic applied is appropriate to explain some, but not all, forms of B cell behaviour because, as is now clear, the role played by the antigen signal varies depending upon the method of activation. This re‐examination suggests an alternative interpretation of the LPS‐induced bell‐shaped curves that incorporates a role for an antigen signal. If correct, the mechanism would ensure that T‐independent responses are drawn from low affinity precursors.
Immunohistological staining of lymphoid tissue in four Australian marsupial species using species cross‐reactive antibodies
Authors: HEMSLEY SW , CANFIELD PJ , HUSBAND AJ
Published: July 2007

Antibodies raised against evolutionarily conserved intracytoplasmic peptide sequences of human T and B lymphocyte antigens and an antibody raised specifically against koala serum IgG were assessed for their capacity for immunoperoxidase staining of formalin fixed lymphoid tissues of koalas (Phascolarctos cinereus), common brushtail possums (Trichosurus vulpecula), common ringtail possums (Pseudocheirus peregrinus) and tammar wallabies (Macropus eugenii). Utilizing microwave pretreatment and a streptavidin biotin‐horseradish peroxidase method for histochemical staining, polyclonal anti‐human CD3 (for T cells), monoclonal anti‐human CD5 (for T cells), monoclonal anti‐human CD79b cy (for B cells) and polyclonal anti‐koala IgG (for plasma cells) consistently stained lymphoid elements in a wide range of tissues from all four marsupial species. Monoclonal anti‐human CD79a cy (for B cells) stained lymphoid elements in only brushtail possums.

This is the first report of Immunohistological staining of lymphocytes m Australian marsupials, thereby vastly increasing the scope for immunological studies in these species.
Cytokine mRNA expressed in tuberculin skin test biopsies from BCG‐vaccinated and Mycobacterium bovis inoculated cattle
Authors: NG KEE H , WATSON JAMES D , PRESTIDGE ROSS , BUDDLE BRYCE M
Published: July 2007

To obtain a better understanding of the delayed‐type hypersensitivity reaction to Mycobacterium bovis, we measured the expression of cytokine mRNA from tuberculin skin test biopsies of cattle. Non‐vaccinated and BCG‐vaccinated cattle were inoculated intratracheally with a low dose of virulent M. bovis or sham‐inoculated and 20 weeks later were skin tested with tuberculin. At necropsy 1–2 weeks later, tuberculous lesions were found in six of the nine non‐vaccinated and three of the nine BCG‐vaccinated animals. All of the lesioned and the majority of the non‐lesioned M. bovis inoculated cattle showed a distinct skin swelling response to tuberculin, irrespective of vaccination. However, cattle with tuberculous lesions displayed larger skin swelling responses than non‐lesioned cattle. Tuberculin‐induced expression of IFN‐γ, IL2, IL4, IL10 and TNF‐α mRNA occurred in the skin biopsies of all of the lesioned, M. bovis inoculated animals except for an absence of tuberculin‐induced TNF‐α mRNA expression in two animals. A lower proportion of the non‐lesioned M. bovis inoculated cattle displayed tuberculin‐induced expression of the five cytokine mRNA. There was no evidence of a unique pattern of cytokine expression which could be used to distinguish between diseased and protected animals. By 28 weeks after vaccination, the three BCG‐vaccinated, sham‐inoculated cattle displayed minimal skin swelling response to tuberculin, but tuberculin‐induced expression of IFN‐γ, IL2, IL4, TL10 and TNF‐α mRNA was observed in skin biopsies of all of these animals. The pattern of cytokine mRNA expressed in the tuberculin skin test reaction site of cattle appeared to be typical of a mixed T helper O‐like cell phenotype response and there was no clear‐cut relationship between the size of the tuberculin skin swelling response and cytokine mRNA expression.
Peritoneal cavity CD5 (Bla) B cells: Cytokine induced IgA secretion and homing to intestinal lamina propria in SCID mice
Authors: BEAGLEY KW , MURRAY AM , McGHEE JR , ELDRIDGE JH.
Published: July 2007

The mouse peritoneal cavity contains a unique population of B cells (Bla) with a high IgM/low IgD ratio, CD5+ (Lyl), MAC‐1 + phenotype. These cells arise early in ontogeny, utilize a limited repertoire of immunoglobulin V genes, produce polyreactive IgM antibodies and have been implicated as the source of many auto‐reactive immunoglobulins. Recent data from chimeric mice suggest that this B cell population also contains the precursors of many IgA plasma cells found in the lamina propria of the small intestine. In the present study we have investigated the potential of this cell population to secrete IgA (and IgG) in response to various cytokines. IL‐5 alone, or in combination with IL‐2, greatly enhanced secretion of both IgG and IgA. Cytokine‐induced IgA secretion resulted from expansion of a subset of CD5 B cells co‐expressing sIgA. Adoptive transfer of CD5 B cells to severe combined immunodeficient (SCID) mice resulted in repopulation of lamina propria with sIgA+ B cells while peripheral lymph nodes contained only IgM+ and some IgG+ B cells. Transfer of CD5+ B cells also reconstituted serum IgM. IgG and IgA levels in recipient SCID mice. These studies demonstrate that CD5′ B cells have the potential to secrete IgA and IgG, immunoglobulins characteristic of mucosal and anamnestic responses, when cultured in vitro with the appropriate cytokines. These cells also give rise to IgA plasma cells in the intestinal lamina propria following adoptive transfer to SCID mice, further supporting the hypothesis that cells of this lineage may be important in immune responses at mucosal surfaces.
Genetic approaches to the study of cytokine regulation of mucosal immunity
Authors: RAMSAY ALISTAIR J
Published: July 2007

Efforts to design effective mucosal vaccines have been hampered by an incomplete understanding of factors controlling the development of mucosal immunity. It is now clear, however, that T cell‐derived cytokines play a major role. Recent developments in ‘gene knockout’ technology have allowed the generation of strains of mice in which particular genes have been inactivated. The availability of mice rendered deficient for production of Th2 cytokines has facilitated studies of the induction and development of mucosal immune responses in the absence of these factors. We have used several genetic approaches, including cytokine‐deficient mice and recombinant vectors constructed to express genes for a range of different cytokines, to demonstrate the importance of these factors in the mucosa. Such genetic approaches appear to represent powerful tools for in vivo studies of the influence of cytokines in mucosal immunoregulation.
Altered calcium signal transduction in B‐1 malignant cells
Authors: DANG ANJU M , BALASUBRAMANYAM M , GARCIA ZENAIDA , RAVECHE ELIZABETH , GARDNER JEFFREY P
Published: July 2007

Lymphocyte proliferation is guided by receptor‐mediated signal transduction pathways that dictate the immunological response/clonality of that cell. We have previously reported that NZB‐derived malignant B‐1 cells, which serve as a murine model for human chronic lymphocytic leukaemia, demonstrate altered expression of surface IgM and CD45 signalling molecules, and a failure to proliferate following membrane IgM stimulation. To examine receptor‐mediated cytosolic calcium (Ca1) signalling in B cell leukaemia, we studied IgM‐induced Ca, responses in malignant B‐1 cells and B cells from non‐leukaemic mice. Basal Ca1 was slightly lower in malignant B‐l cells than in non‐leukaemic cells. Anti‐IgM stimulation induced a sustained increase in Ca1 to levels 1.3‐fold greater than basal Ca1 in conventional B cells. In contrast, leukaemic B‐1 cells demonstrated a sharp but transient rise in Ca1 followed by a gradual increase to levels 2.3‐fold greater than basal [Ca]1 Ca influx from extracellular sources contributed to the early and late Ca1 signal in both sets of cells. Pre‐incubation (2–30 min) with anti‐CD45 had no effect on basal Ca, or the anti‐IgM Ca1 signal in B cells, but reduced the Ca1 transient in malignant B‐1 cells. Additional experiments characterized the effects of phosphorylation/dephosphorylation events on the Ca1 profile following anti‐IgM stimulation. Protein tyrosine kinase inhibitors decreased the anti‐IgM‐induced Ca1 transient in malignant B‐1 cells by 80%, but only moderately affected 40% the Ca1 response in non‐leukaemic B cells. Protein tyrosine phosphatase inhibitors and protein kinase C (PKC) activators attenuated the Ca1 response to the same degree in normal and leukaemic B cells. These results show that Ca1 signalling differs widely between non‐malignant B cells and malignant B‐1 cells, and that tyrosine phosphorylation and CD45 modulation of IgM signalling are involved in the altered Ca1 responses in malignant B‐1 cells.
Dendritic cell presentation of PPD and 19 kDa protein of Mycobacterium tuberculosis and emergent T helper cell phenotype
Authors: BAIRD MARGARET A , HART DEREK NJ , ABERNETHY NEVIN , WATSON JAMES D
Published: July 2007

Protection against infection with Mycobacterium tuberculosis is preferentially associated with the development of the T helper 1 subset, IFN‐γ production and a cell‐mediated response, rather than with T helper 2 cells, 4 (IL‐4) and antibody production. The type of APC interacting with T cells responsive to mycobacterial peptides may influence which of these responses predominates. This investigation focuses on the role of dendritic cells (DC) because they are the most potent APC in both primary and recall immune responses. Our results show that splenic DC‐enriched suspensions prepared from C57BL/6 mice and pulsed with either purified protein derivative (PPD) or the immunodominant 19 kDa protein from M. tuberculosis, can activate antigen‐primed T cells in vitro, whereas spleen cell suspensions depleted of DC cannot. DC pulsed with PPD or 19 kDa antigen are able to prime naive T cells in vivo. Supernatants collected from cultures containing T cells from mice injected with PPD‐pulsed DC and then challenged in vitro with PPD‐pulsed DC were found to contain more IL‐2 and IFN‐γ than those from control mice which received either DC or PPD alone. No such antigen‐specific IFN‐γ response occurred if DC pulsed with 19 kDa were used in place of PPD‐pulsed DC. IL‐4 was not detected in any of the culture supernatants. We conclude that DC can induce production of cytokines associated with a protective immune response when presenting peptides derived from heterogeneous mycobacterial antigens but not when exposed to the single 19 kDa immunodominant protein.
Hierarchy of T cell antigen receptor assembly
Authors: MANOLIOS NICHOLAS
Published: July 2007

The formation of partial complexes in an African green monkey kidney cell line (COS cells) has been used to examine assembly of newly synthesized T cell antigen receptor (TCR) chains. The identification of assembly interactions between multiple subunits and the formation of higher order subcomplexes has led to the development of a model for the hierarchy of subunit assembly leading to a complete TCR. These assembly interactions suggest likely nearest neighbour relationships in the assembling structure and probably reflect the quarternary structure ofthe TCR complex. This may be important when examining the association of other molecules with TCR proteins or when trying to discern structural components involved with signal transduction.
The Biggest Computer Programme in the World…Ever!’: Time for a Change in Mindset?
Authors: Clegg Chris , Shepherd Craig
Published: July 2007

In this paper we offer a critique of The National Programme for Information Technology’ (NPfIT) currently being undertaken in the National Health Service (NHS) in the UK. We begin by offering a brief introduction to the project. Next, we review the lessons learned from a wide range of experience with IT and business change projects and comment on why changes in the NHS are likely to be harder than in most other organizations. We then elaborate the implications of these ideas and identify potential areas for change, with particular focus on the current guiding mindset that this project is about the provision of a technical infrastructure. We argue that this is, thus far, a technology project and question whether the current strategy is the most appropriate way forward to achieve service improvements. We suggest changes in the underlying mindset, along with the leadership, ownership, metrics and labelling of the project.
One-equation model for quasi-two-dimensional turbulent magnetohydrodynamic flows
Authors: Smolentsev S. , Moreau R.
Published: July 2007

In quasi-two-dimensional turbulent magnetohydrodynamic flows in a strong transverse magnetic field, three-dimensional effects and most of the Ohmic and viscous losses occur in the thin boundary layers at the flow-confining walls perpendicular to the magnetic field (Hartmann layers), while the bulk flow is essentially two-dimensional. A one-equation turbulence model capturing these specific flow features is introduced. The results are in fair agreement with the data obtained earlier in the MATUR experiment [K. Messadek and R. Moreau, J. Fluid Mech. 456, 137 (2002)].
Characterization of bubble core and cloudiness in Yb3+:Sr5(PO4)3F crystals using micro-Raman spectroscopy
Authors: Cui Yunlong , Roy Utpal N. , Bai Lihua , Burger Arnold , Qiu S. Roger , Schaffers Kathleen
Published: July 2007

Ytterbium doped strontium fluoroapatite Yb3+:Sr5(PO4)3F (Yb:S-FAP) crystals have been used in high average power laser systems as gain medium. Growth induced defects associated with the crystal often affect their performance. In order to improve the crystal quality and its optical applications, it is imperative to understand the nature of these defects. In this study, we utilize micro-Raman spectroscopy to characterize two common growth-induced defects: bubble core and cloudiness. We find the bubble core consist of voids and microcrystals of Yb:S-FAP. These microcrystals have very different orientation from that of the pure crystal outside the bubble core. In contrast to a previous report, neither Sr3(PO4)2 nor Yb2O3 are observed in the bubble core regions. On the other hand, the cloudy regions are made up of the host materials blended with a structural deformation along with impurities which include CaCO3, YbPO4, SrHPO4, and Sr2P2O7 . The impurities are randomly distributed in the cloudy regions. This analysis is necessary for understanding and eliminating these growth defects in Yb:S-FAP crystals.
Oscillatory exchange coupling in La0.67Sr0.33MnO3∕SrTiO3 superlattices
Authors: Zhu S. J. , Zhao B. R. , Zhu B. Y. , Xu B. , Cao L. X. , Qiu X. G.
Published: July 2007

The exchange bias effect has been observed in the superlattices consisting of ferromagnetic La0.67Sr0.33MnO3 and nonmagnetic insulating SrTiO3 layers. It is found that the exchange field shows an oscillatory decay with a period of ∼12 unit cells and approaches to a constant value of −100Oe when the SrTiO3 thickness is increased. The tunneling current also displays a nonmonotonic decrease with the SrTiO3 thickness. These observations can be discussed on the basis of the interlayer exchange coupling between La0.67Sr0.33MnO3 layers via the spin-polarized electrons tunneling across the SrTiO3 spacers.
Measurement of pressures in 10−10Pa range from the damping speed of field emission current
Authors: Cho B. , Itagaki T. , Ishikawa T. , Oshima C.
Published: July 2007

The damping behavior of field emission (FE) currents was monitored with W(111) tips under pressures down to 5×10−10Pa. Semilogarithmic damping curves of FE currents were linear for 0.3L hydrogen exposure in the thoroughly degassed extreme high vacuum (XHV) FE system. The slope of semilogarithmic damping curves was linearly proportional to the operation pressure, suggesting a method of measuring pressure in an XHV range. Electron stimulated desorption was not observed.
Growth and enhanced emission of silicon-germanium hemisphere shell arrays
Authors: Huang Zhipeng , Zhu Jing
Published: July 2007

Silicon-germanium (SiGe) alloy nanocrystals have been fabricated and assembled into hemisphere shell arrays by a method combining pulsed laser deposition and nanosphere lithography. Monolayer and double layer hemisphere shell arrays are fabricated. The hemisphere shell arrays remarkably enhance the photoluminescence intensity of SiGe, compared to that from unpatterned sample. The enhancement, as high as approximately 700 times, is obtained in double layer hemisphere shell arrays. Characterization of samples by scanning electron microscope and transmission electron microscope reveals that the enhancement and difference in photoluminescence spectra are mainly due to the unique optical structure of hemisphere shell arrays.
Temporal characteristics of surface-acoustic-wave-driven luminescence from a lateral p-n junction
Authors: Gell J. R. , Ward M. B. , Shields A. J. , Atkinson P. , Bremner S. P. , Anderson D. , Kataoka M. , Barnes C. H. W. , Jones G. A. C. , Ritchie D. A.
Published: July 2007

Short radio frequency pulses were used to study the surface-acoustic-wave-driven light emission from a molecular beam epitaxy regrown GaAs∕AlGaAs lateral p-n junction. The luminescence provides a fast probe of the signals arriving at the junction allowing the authors to temporally separate the effect of the surface-acoustic-wave from pickup of the free space electromagnetic wave. Oscillations in the light intensity are resolved at the resonant frequency of the transducer, suggesting that the surface-acoustic-wave is transporting electrons across the junction in packets.
High resolution structural characterization of giant magnetoresistance structures containing a nano-oxide layer
Authors: You C. Y. , Cerezo A. , Clifton P. H. , Folks L. , Carey M. J. , Petford-Long A. K.
Published: July 2007

The microstructure and chemistry of a current-perpendicular-to-plane giant magnetoresistance structure containing a nano-oxide layer (NOL) have been studied using a combination of high resolution transmission electron microscopy and three-dimensional atom probe analysis. It was found that the morphology of the NOL changes from a planar layer to discrete particles on annealing, indicating the dominance of surface energy on the morphology evolution. Direct evidence was obtained for significant Mn diffusion from the IrMn antiferromagnetic layer and partitioning to the oxide region during annealing.
Efficacy of permanent firebreaks and aerial prescribed burning in western Arnhem Land, Northern Territory, Australia
Authors: Price Owen F. , Edwards Andrew C. , Russell-Smith Jeremy
Published: July 2007

We investigated the efficacy of firebreaks in the prevention of wildfires in the Arnhem Land Plateau, a vast, rugged and sparsely populated region with high biodiversity value and frequent wildfires. A total of 623 events where a fire met a permanent firebreak (cliffs, stream order, tracks and roads) in different fire seasons were compiled. Cliffs were more effective than streams at stopping fires, which were more effective than roads. Larger streams were more effective than small ones. The largest streams stop 75% of early dry season fires, but there are no firebreak types with more than 50% likelihood of stopping a late dry season fire. Geographic Information System (GIS) surfaces of the relative density of the three firebreak features in the landscape were randomly sampled and compared with the total number of fires and late dry season fires using generalised linear modelling. Several of the density variables were weakly but significantly related to fire frequency, and it appears that late dry season fires are influenced by features at a larger scale (16-km radius) than total fires (4 km). The Aerial Prescribed Burning program for 2004 was studied to identify how effective it was at stopping subsequent wildfires by dividing ignition lines into 137 5-km sections. Only 20% of sections achieved a 100% burn and where gaps occurred, a subsequent fire was 88% likely to penetrate the line. Firebreaks are not certain instruments for fire management in this area.
Hurricanes benefit bleached corals
Authors: Manzello Derek P. , Brandt Marilyn , Smith Tyler B. , Lirman Diego , Hendee James C. , Nemeth Richard S.
Published: July 2007

Recent, global mass-mortalities of reef corals due to record warm sea temperatures have led researchers to consider global warming as one of the most significant threats to the persistence of coral reef ecosystems. The passage of a hurricane can alleviate thermal stress on coral reefs, highlighting the potential for hurricane-associated cooling to mitigate climate change impacts. We provide evidence that hurricane-induced cooling was responsible for the documented differences in the extent and recovery time of coral bleaching between the Florida Reef Tract and the U.S. Virgin Islands during the Caribbean-wide 2005 bleaching event. These results are the only known scenario where the effects of a hurricane can benefit a stressed marine community.
Corticothalamic synchronization leads to
c-fos
expression in the auditory thalamus
Authors: Guo Yi Ping , Sun Xia , Li Chuan , Wang Ning Qian , Chan Ying-Shing , He Jufang
Published: July 2007

In this study, we investigated the relationship between
c-fos
expression in the auditory thalamus and corticofugal activation. The contribution of neurotransmitters and related receptors, the involvement of thalamic reticular nucleus (TRN), and the role of neuronal firing patterns in this process were also examined. The principal nuclei of the medial geniculate body (MGB) showed
c-fos
expression when the auditory cortex (AC) was activated by direct injection of bicuculline methobromide. However, no expression was detectable with acoustic stimuli alone. This indicated that
c-fos
expression in the principal nuclei of the MGB was triggered by the corticofugal projection.
c-fos
expression could be elicited in the MGB by direct injection of glutamate. Direct administration of acetylcholine, alternatively, had no effect. Bicuculline methobromide injection in the AC also triggered synchronized oscillatory activities sequentially in the AC and MGB. Cortically induced
c-fos
expression in the MGB was not mediated by a pathway involving the TRN because it remained intact after a TRN lesion with kainic acid. The present results also conclude that
c-fos
expression is not simply associated with firing rate, but also with neuronal firing pattern. Burst firings that are synchronized with the cortical oscillations are proposed to lead to
c-fos
expression in the principal nuclei of the MGB.