bluuebunny/crossref_metadata_2025 huggingface dataset:
Protection against non‐typable Haemophilus influenzae following sensitization of gut associated lymphoid tissue: Role of specific antibody and phagocytes
Authors: WALLACE FIONA J , WITT CAMPBELL S , CLANCY ROBERT L , CRIPPS ALLAN W
Published: July 2007

Rats intestinally immunized with whole killed non‐typable Haemophilus influenzae clear this organism from the lungs faster than non‐immunized rats. This study investigated the role of antibody and phagocytes in the clearance mechanism. First, dose‐response experiments demonstrated that while lowering the dose of non‐typable H. influenzae reduced the level of detectable specific antibody in bronchial washings, the ability to accelerate bacterial clearance persisted to much lower doses. Second, specificity experiments showed that intestinal immunization with non‐typable H. influenzae cross‐protected against Pseudomonas aeruginosa. even though antibodies were not absorbed out of serum by incubation with P. aeruginosa. Third, serum antibody was shown to be bactericidal for non‐typable H. irtfltienzae in the presence of complement (P < 0.05), while bronchial washings antibody was not. The bactericidal effect of the serum was abrogated by the addition of bronchial washings. Fourth, an ELISA quenching assay demonstrated that neutrophils from intestinally immunized rats were able to phagocytose more bacteria in a given time period (P < 0.05) than unimmunized rats and rats immunized by other routes. In the fifth experiment, the chemotactic response of neutrophils to casein was shown to be significantly depressed by the addition of bronchial washings obtained from immunized rats (P < 0.01). It is proposed that specific antibody in bronchial washings does not have a direct role in opsonizing bacteria for killing or phagocytosis, but instead has an anti‐inflammatory effect. Non‐specific effectors such as neutrophils driven by specific immune cells are a likely means of clearance of bacteria following intestinal immunization and acute challenge.
MHC proteins and heparan sulphate proteoglycans regulate murine cytomegalovirus infection
Authors: PRICE PATRICIA , ALLCOCK RICHARD JN , COOMBE DEIRDRE R , SHELLAM GEOEFREY R , McCLUSKEY JAMES
Published: July 2007

Factors influencing MCMV infection mediated by MHC class I molecules were analysed further as previous studies showed that the effects of the MHC genotype on sensitivity to this virus are important in vivo. Here we show that H‐2d, H‐2b, H‐2r and H‐2v macrophages are highly sensitive to MCMV.

Moreover, transfection of H‐2k L‐cells with Kb or Dd conferred sensitivity to MCMV. This was not affected by amino acid substitutions in Kbα1 or α2, although previous studies demonstrated that exchange of the αl domain of Dd with Ldα1 compromised sensitivity. Here replacement of Kbα3 with Ldα3 reduced susceptibility to low doses of MCMV. In addition, extracellular β2‐microglobulin (β2m) promoted infection of β2m‐negative R1E/TL8X.1 cells transfected with Db with or without a β2m gene. Hence MCMV infection can involve p2m and the al and β3 domains of MHC heavy chains.

MCMV infection of L‐cells expressing Dd or Kb was also inhibited by heparin, but infection of the parental L‐cell line was not reproducibly affected. A role for heparan sulphate proteoglycan in MHC‐mediated MCMV infection was confirmed using cells pre‐treated with heparinase I or III, or propagated in chlorate to inhibit the sulphation of the glycosaminoglycan chains.
Establishment of a natural suppressor cell line producing soluble suppressor factor other than transforming growth factor‐β
Authors: YANAGIE HIRONOBU , SUGIYAMA HIROTAKA , SEKIGUCHI MORIMASA
Published: July 2007

Natural suppressor (NS) cell line (Clone 59) was established from the bone marrow of adult C3H/Hej mice in the presence of WEHI‐3 conditioned media. Clone 59 cells suppressed the generation of cytotoxic T lymphocytes from normal mouse spleen. This suppression was seen at a responder‐to‐suppressor cell ratio of 1000:1 and lacked antigen specificity or MHC restriction. Clone 59 cells expressed the ‘null’ surface phenotype (Thyl.2−, CD3−, Lyt‐2−, L3T4 −, surface Ig−, MAC–l−) by immunofluorescent staining. Clone 59 cells exhibited no cytolytic activity against NK cell‐sensitive YAC‐1 and natural cytotoxic L929 target cell lines. Non‐specific suppression, with a cell‐free supernatant from the Clone 59‐NS cells, also was observed. The supernatant did not inhibit [3H]‐thymidine uptake by CTLL‐2 cells which were proliferating in response to IL‐2. Anti‐transforming growth factor‐β (TGF‐β) monoclonal antibody had no effect on suppression, suggesting that the non‐specific suppression is mediated by some soluble factors other than TGF‐β. Clone 59 cells may be useful in identifying non‐specific suppressor cells in adult bone marrow and studying their functional role in the regulation of tolerance and self‐reactivity.
Co‐operative effect between insulin‐like growth factor‐1 and interleukin‐2 on DNA synthesis and interleukin‐2 receptor‐α chain expression in human lymphocytes
Authors: SCHILLACI ROXANA , BROCARDO MARIANA G , ROLDAN ALICIA
Published: July 2007

Recently we demonstrated that IGF‐1 has the same effect on DNA synthesis and G1‐phase length during human lymphocyte proliferation as IL‐2. In order to determine the link between IGF‐1 and IL‐2 on lymphocyte proliferation, we tested the ability of these cytokines, alone or in combination, to induce DNA synthesis and increase the number of cells expressing IL‐2‐α chain receptors. Our results showed that the increase in DNA synthesis produced by the addition of IGF‐1 to cells cultured with saturable concentrations of IL‐2, correlated well with an increase in the number of cells expressing IL‐2‐α chain receptor. The effect on both DNA synthesis and IL‐2‐α chain receptor expression was greater at lower concentrations of PHA. This study suggests that the proliferative effect of IGF‐1 might be due to separate stimulation of different cell populations and/or by activation of a tyrosine‐kinase signal transduction pathway complementary to the IL‐2 activation signal.
Modifiers of the human mucosal immune system
Authors: GLEESON MAREE , CRIPPS ALLAN W , CLANCY ROBERT L
Published: July 2007

This review focuses on saliva as a measure of mucosal immunity in man. The review will cover studies of parameters that modify the early ontogeny patterns of mucosal immunity and the impact of infections and physiological variables on the human mucosal immune response. The most significant modifiers of human mucosal immunity are events that occur in the neonatal maturation period and, later in life, the interplay between the immune system and the neuroendocrine systems. IgA antibodies are the predominant isotype involved in the human mucosal immune response and are important for protection at mucosal surfaces. The level of IgA in mucosal secretions is modified by antigenic stimulation as well as by many physiological variables. Studies have also revealed that IgM plays a significant immunoregulatory role at mucosal surfaces, particularly during episodes of infection or stress. The detection patterns of IgD in saliva of neonates suggests a role for IgD in the initial maturation process of mucosal immunity. The role of IgG at mucosal surfaces is unclear and although IgG may play a compensatory role in IgA deficiency, the detection of high levels of IgG in saliva appears to be associated with periods of increased membrane permeability.
Prolactin and insulin regulate the release of IL‐1‐α and IFN‐γ from murine splenocytes activated with porins or LPS of Salmonella typhimurium
Authors: VITIELLO MARIATERESA , SCARFOGLIERO PASQUALE , GALDIERO MARILENA , GORGA FERNANDA , SOMMESE LINDA
Published: July 2007

Murine splenocytes treated with prolactin (PRL) or insulin were stimulated in vitro with porins or lipopolysaccharide (LPS) of Salmonella typhimurium. It was seen that PRL inhibits the release of IFN‐γ from splenocytes treated with porins by about 20% while having no effect on the release of IL‐1‐α. Splenocytes stimulated with LPS, in the presence of PRL, had a reduced release of IFN‐γ (35%) and IL‐1‐α (70%). The porin‐stimulated splenocytes exhibited a remarkable increase in IL‐1‐α release (100%) and a diminished release of IFN‐γ (about 50%) in the presence of insulin. The splenocytes stimulated with LPS had a reduced release of IL‐1‐α (75%) and IFN‐γ (about 50%) when insulin was added.

The data suggest that the classical endocrine system participates in a bioregulatory feedback loop that may prevent unwanted toxicity from cytokine excess. However, some bacterial products sometimes enormously unbalance this regulatory network.
Cycloheximide‐induced apoptosis in Burkitt lymphoma (BJA‐B) cells with and without Epstein‐Barr virus infection
Authors: ISHII HIDEAKI H , ETHERIDGE MARIA R , GOBÉ GLENDA C
Published: July 2007

Epstein‐Barr virus (EBV) has been shown, in many instances, to protect B cells from apoptosis via expression of select EBV proteins and up‐regulation of bcl‐2 or its homologues. However, at present little is known about the influence of EBV infection against cancer therapy‐induced apoptosis in EBV‐associated cancers. Many anti‐cancer treatments act via inhibition of protein synthesis and so could influence the reported protein‐dependent mechanisms involved in EBV inhibition of apoptosis. In the present study. Burkitt lymphoma (BJA‐B) cells were treated with a potent protein synthesis inhibitor, cycloheximide (CHX). Two variants of BJA‐B cells were used, one with EBV infection (EBV(+)), and one free of infection (EBV(‐)). Cells were collected 0, 3, 6, 12, 24 and 48 h after addition of either 1 or 50 μg/mL of CHX. Control cultures were untreated. Apoptosis was quantified using established morphological and biochemical characteristics, and protein concentrations assessed. CHX treatment of EBV(‐) BJA‐B cells induced massive levels of apoptosis. Apoptosis was inhibited, but remained significantly higher than that found in control cultures, in similarly treated EBV(+) cells. The study demonstrates that induction of apoptosis in EBV(‐) and EBV(+) cells is not dependent on new protein synthesis, and may be caused by removal of a ‘cell survival’ protein. In addition, the reduction in CHX‐induced apoptosis in the EBV(+) cells, when compared with similarly treated EBV(‐) cells, is not dependent on new protein synthesis and so may be indicative of a bcl‐2 independent mechanism in this instance. The results have important implications for devising and assessing treatment of EBV‐associated malignancies.
Extrathymic and thymic origin of murine IEL: Are most IEL in euthymic mice derived from the thymus?
Authors: LIN TESU , MATSUZAKI GORO , KENAI HIROYUKI , NOMOTO KIKUO
Published: July 2007

Although an abundance of literature supports the hypothesis that murine intestinal intraepithelial lymphocytes (IEL) can develop extrathymically, whether most IEL in euthymic mice are extrathymically derived is unknown. Recent evidence, however, suggests that the development of most IEL in euthymic mice is influenced either directly or indirectly by the thymus. While some evidence suggests that the thymus can influence the extrathymic development of IEL through thymus‐derived factors, clearly a substantial portion (if not most) of the IEL in euthymic mice are derived directly from the thymus. The ability of the thymus to generate IEL depends on the age of the thymus, as fetal/neonatal thymus up to approximately 2 weeks of age generates a totally different subset of IEL than the adult thymus. These results suggest that the IEL generated from the fetal early neonatal thymus recognize a different antigen than the IEL generated from the adult thymus. The former probably recognizes self‐antigen and the later recognizes bacterial antigen.
The T cell antigen receptor beta chain interacts with the extracellular domain of CD3‐γ
Authors: MANOLIOS NICHOLAS , LI ZHAN GUO
Published: July 2007

Selective pairwise interactions between a number of CD3 chains and the clonotypic T cell antigen receptor (TCR‐α, ‐β) chains have recently been reported.1 What still remains unanswered is the site of interaction between TCR‐β and CD3‐γ chains. To examine the region of interaction between TCR‐β and CD3‐γ chains, a variety of genetically altered TGR‐β and CD3‐γ chains were constructed using recombinant cDNA techniques. Non‐T cells (COS‐7) were transfected with cDNA constructs, metabolically labelled, and immunoprecipitates were analysed for assembly using non‐equilibrium pH gel electrophoresis (NEPHGE)/ SDS‐PAGE. The results demonstrated that assembly between TCR‐β and CD3‐γ chains was localized to their extracellular domain. These findings, when coupled with the information on pairwise interactions and formation of higher order subcomplexes, extend our model of the structure of the TCR complex.
Human melanoma integrins contribute to arrest and stabilization potential while flowing over extracellular matrix
Authors: MENTER DAVID G , FITZGERALD LARRY , PATTON JOHN T , MCINTIRE LARRY V , NICOLSON GARTH L
Published: July 2007

To form distant metastases, tumour cells must stabilize adhesive interactions that prevent detachment at secondary sites. Primary receptor‐ligand interactions alone may not maintain prolonged adhesive contacts without secondary events that lead to adhesion stabilization. Computerized imaging methods enable us to examine various substrates for: (i) the wall shear adhesion threshold (WSAT). a measure of the dynamic adhesive potential of tumour cells; (ii) the number of tumour cells that adhered; and (iii) the adhesion stabilization lag time (ASLT) or length of time required for tumour cells to stabilize adhesive contacts capable of withstanding high wall shear force (up to 100 dynes/cm‐). The relative WSAT ratios found were: wheat germ agglutinin (WGA) > laminin > fibronectin > vitronectin > collagen I > collagen IV > von Willebrand factor (vWF) (the greater the shear rate the higher the adhesive potential). The relative stabilization ratios found were as follows: laminin < fibronectin < vitronectin < collagen IV < collagen I < vWF < WGA (shorter times correlate with greater stabilization potential). Stabilization data using fibronectin as a substrate correlated the best with metastatic potential. Using three melanoma lines of ditterent metastatic potential semi‐quantitative reverse transcriptase‐polymerase chain reaction (PCR) showed a two‐ to four‐fold increase in α1, α3, α4, α5, α6, and ICAM‐1 in the highly metastatic 70W cells compared to the Me Wo and non‐metastatic 3SS melanoma cells. There were no differences in α, β1 and β3 levels among the three melanoma lines, and PCR products for αIIb, α2, CD36, or ICAM‐2 were not detected. The 70W cells also had higher levels of αx and β2 (CD11/CD18 and pl50 leukocyte antigen) than either the MeWo or 3S5 cells. The data indicate that melanoma cells exhibit differences in the adhesion properties under fluid shear and differences in the expression of adhesion components that correlate with their metastatic potential.
Natural Diet of an Australian Freshwater Pipefish
Authors: Jones Andrew , Rudstam Lars , Rayner Thomas
Published: July 2007

Globally, the family Syngnathidae (seahorses and pipefish) is recognized as being both under threat from anthropogenic pressures and poorly studied. Of the 47 species that are listed on the IUCN Red List, 33 are currently listed as ‘data deficient’, with inadequate information available to make an assessment of their risk of extinction. Within Australia, this has prompted environmental assessments of specific fisheries, as well as a number of recent ecological studies of marine syngnathids. However, no work has been published on the continent’s four freshwater species. To begin to remedy this, a thorough analysis of the feeding habits of one such species was conducted. Twenty-two specimens of Hippichthys heptagonus Bleeker, 1849 were collected from the Mulgrave River in north Queensland. Dissection and subsequent analysis revealed that microcrustaceans comprised the vast majority of the species diet, with calanoid and cyclopoid copepods being by far the most prevalent prey items (66%). Dipteran, as well as ephemeropteran, larvae were moderately abundant (5% and 10%), and made a notable contribution to the volume of the average diet (16% and 12%). A percent principal component analysis of the volume data reinforced these findings. The first factor accounted for 69.7% of the observed variation, with largest factor loading (0.88) belonging to copepods. there were no significant differences in prey consumption Between genders, but, the percent volume of copepod prey significantly higher in adults was than in juveniles (Mann-Whitney’s U: P < 0.01). These findings indicate that H. heptagonus is primarily a predaceous planktivore, with a specialized diet that is comparable to coastal marine syngnathids. Also, the prevalence of a single prey type suggests that the H. heptagonus occupies a narrow ecological niche, and that its distribution within the watershed may be limited by prey availability.
Identification of switching fields in magnetic nanostructures by partial first order reversal curves
Authors: Clime L. , Veres T. , Yelon A.
Published: July 2007

A nonparametric approach to the identification of magnetic anisotropies in ferromagnetic nanostructures is described in this article. By an adequate choice of convenient measurement points on the first order reversal curves (FORC), essential information about either switching fields or symmetry of FORC diagrams are obtained from sets of five-point reversal curves only. Numerical simulations performed on assemblies of particles with known switching field distributions indicate that this method presents a high degree of accuracy and can successfully be used in order to characterize individual entities in magnetic nanostructures.
Development of dielectric barrier discharge plasma processing apparatus for mass spectrometry and thin film deposition
Authors: Majumdar Abhijit , Hippler Rainer
Published: July 2007

Cost effective and a very simple dielectric barrier discharge plasma processing apparatus for thin film deposition and mass spectroscopic analysis of organic gas mixture has been described. The interesting features of the apparatus are the construction of the dielectric electrodes made of aluminum oxide or alumina (Al2O3) and glass and the generation of high ignition voltage from the spark plug transformer taken from car. Metal capacitor is introduced in between ground and oscilloscope to measure the executing power during the discharge and the average electron density in the plasma region. The organic polymer films have been deposited on Si (100) substrate using several organic gas compositions. The experimental setup provides a unique drainage system from the reaction chamber controlled by a membrane pump to suck out and remove the poisonous gases or residuals (cyanogens, H–CN, CHxNH2, etc.) which have been produced during the discharge of CH4∕N2 mixture.
Single crystalline ZnMgO pleated nanosheets and quasinanotubes
Authors: Wang J. R. , Ye Z. Z. , He H. P. , Zhu L. P. , Jiang J. , Zeng Y. J.
Published: July 2007

ZnMgO pleated nanosheets and quasinanotubes were synthesized in the same region on Si substrate using [Mg(H2O)6](NO3)2 and zinc diethyl as the reactant source. The nanosheets are periodically pleated with the angles of 120° and 60° between two adjacent pleats. Some of the nanosheets fold into quasinanotubes. Homoepitaxial interconnections are observed at the boundaries of the pleats, and the whole pleated nanosheet is a single wurtzite crystal. The growth mechanism is discussed, which is proposed to be a combination of vapor-solid process of two-dimensional growth of the (1¯21¯0) planes and their random along the ⟨101¯0⟩ directions.
Optical second-order nonlinearity of the infrared transmitting 82GeS2∙18CdGa2S4 nanocrystallized chalcogenide glass
Authors: Tao Haizheng , Lin Changgui , Gu Shaoxuan , Jing Chengbin , Zhao Xiujian
Published: July 2007

The infrared (IR) transmitting nanocrystallized chalcogenide glass only containing α-CdGa2S4 IR nonlinear optical crystallites, which were confirmed by x-ray diffraction and Raman scattering measurements, was fabricated through the controllable nucleation and crystallization of the glass with the composition 82GeS2∙18CdGa2S4 at a temperature of 325°C far below the glass transition temperature (Tg:415°C) for a long duration. A clear second harmonic generation (green light, 532nm) could be observed in the transparent 82GeS2∙18CdGa2S4 nanocrystallized chalcogenide glass, demonstrating the IR frequency-doubling function of the prepared nanocrystallized composite material.
Diversity and plasticity of C4 photosynthesis in Eleocharis (Cyperaceae)
Authors: Murphy Lesley R. , Barroca João , Franceschi Vincent R. , Lee Raymond , Roalson Eric H. , Edwards Gerald E. , Ku Maurice S. B.
Published: July 2007

Eleocharis contains many amphibious species, and displays diversity of photosynthetic mechanism (C3, C4 or C3-C4 intermediates). A unique feature of Eleocharis is the plasticity in the photosynthetic mechanism of some species in response to the environment. In this study, we have examined the culm anatomy and photosynthetic property of several Eleocharis species grown terrestrially and the changes in the newly produced culms over a short period time frame after switching from terrestrial to submerged condition. Eleocharis baldwinii (Torrey) Chapman is C4-like in terrestrial habitat, exhibiting O2 inhibition of photosynthesis with Rubisco expressed in both mesophyll and bundle sheath cells and PEPC strictly in the mesophyll cells, but switches to C3-C4 intermediacy when submerged. In addition to Eleocharis vivipara Link type 1 (which switches from C4-like to C3), two other photosynthetic types examined in this study were shown to have different responses to growth in either terrestrial or submerged conditions. E. vivipara type 2 is a typical C4 plant in the terrestrial habitat, but becomes a C3-C4 intermediate under submerged conditions. Further, terrestrially, E. vivipara type 3 is a C3-C4 intermediate, but when submerged the δ13C value increases to –6.7‰, indicating its use of bicarbonate as a major carbon source. The submerged form of this plant exhibited about three times higher photosynthetic O2 evolution rate, compared to the C3 species Eleocharis erythropoda Steudel. These Eleocharis species possess different molecular switches for regulating C4 gene expression in response to environmental stimuli both between different species, and in E. vivipara among different populations. The apparent expression of a bicarbonate transport system by E. vivipara type 3 while submerged represents a unique adaptation to low CO2 availability.
Lentiviral Vpr usurps Cul4–DDB1[VprBP] E3 ubiquitin ligase to modulate cell cycle
Authors: Hrecka Kasia , Gierszewska Magdalena , Srivastava Smita , Kozaczkiewicz Lukasz , Swanson Selene K. , Florens Laurence , Washburn Michael P. , Skowronski Jacek
Published: July 2007

The replication of viruses depends on the cell cycle status of the infected cells. Viruses have evolved functions that alleviate restrictions imposed on their replication by the host. Vpr, an accessory factor of primate lentiviruses, arrests cells at the DNA damage checkpoint in G
2
phase of the cell cycle, but the mechanism underlying this effect has remained elusive. Here we report that Vpr proteins of both the human (HIV-1) and the distantly related simian (SIVmac) immunodeficiency viruses specifically associate with a protein complex comprising subunits of E3 ubiquitin ligase assembled on Cullin-4 scaffold (Cul4–DDB1[VprBP]). We show that Vpr binding to Cul4–DDB1[VprBP] leads to increased neddylation and elevated intrinsic ubiquitin ligase activity of this E3. This effect is mediated through the VprBP subunit of the complex, which recently has been suggested to function as a substrate receptor for Cul4. We also demonstrate that VprBP regulates G
1
phase and is essential for the completion of DNA replication in S phase. Furthermore, the ability of Vpr to arrest cells in G
2
phase correlates with its ability to interact with Cul4–DDB1[VprBP] E3 complex. Our studies identify the Cul4–DDB1[VprBP] E3 ubiquitin ligase complex as the downstream effector of lentiviral Vpr for the induction of cell cycle arrest in G
2
phase and suggest that Vpr may use this complex to perturb other aspects of the cell cycle and DNA metabolism in infected cells.
Identification of a fourth family of lycopene cyclases in photosynthetic bacteria
Authors: Maresca Julia A. , Graham Joel E. , Wu Martin , Eisen Jonathan A. , Bryant Donald A.
Published: July 2007

A fourth and large family of lycopene cyclases was identified in photosynthetic prokaryotes. The first member of this family, encoded by the
cruA
gene of the green sulfur bacterium
Chlorobium tepidum
, was identified in a complementation assay with a lycopene-producing strain of
Escherichia coli
. Orthologs of
cruA
are found in all available green sulfur bacterial genomes and in all cyanobacterial genomes that lack genes encoding CrtL- or CrtY-type lycopene cyclases. The cyanobacterium
Synechococcus
sp. PCC 7002 has two homologs of CruA, denoted CruA and CruP, and both were shown to have lycopene cyclase activity. Although all characterized lycopene cyclases in plants are CrtL-type proteins, genes orthologous to
cruP
also occur in plant genomes. The CruA- and CruP-type carotenoid cyclases are members of the FixC dehydrogenase superfamily and are distantly related to CrtL- and CrtY-type lycopene cyclases. Identification of these cyclases fills a major gap in the carotenoid biosynthetic pathways of green sulfur bacteria and cyanobacteria.
Reduced gap junctional coupling leads to uncorrelated motor neuron firing and precocious neuromuscular synapse elimination
Authors: Personius Kirkwood E. , Chang Qiang , Mentis George Z. , O'Donovan Michael J. , Balice-Gordon Rita J.
Published: July 2007

During late embryonic and early postnatal life, neuromuscular junctions undergo synapse elimination that is modulated by patterns of motor neuron activity. Here, we test the hypothesis that reduced spinal neuron gap junctional coupling decreases temporally correlated motor neuron activity that, in turn, modulates neuromuscular synapse elimination, by using mutant mice lacking connexin 40 (Cx40), a developmentally regulated gap junction protein expressed in motor and other spinal neurons. In Cx40−/−mice, electrical coupling among lumbar motor neurons, measured by whole-cell recordings, was reduced, and single motor unit recordings in awake, behaving neonates showed that temporally correlated motor neuron activity was also reduced. Immunostaining and intracellular recording showed that the neuromuscular synapse elimination was accelerated in muscles from Cx40−/−mice compared with WT littermates. Our work shows that gap junctional coupling modulates neuronal activity patterns that, in turn, mediate synaptic competition, a process that shapes synaptic circuitry in the developing brain.
Otopetrin 1 activation by purinergic nucleotides regulates intracellular calcium
Authors: Hughes Inna , Saito Mitsuyoshi , Schlesinger Paul H. , Ornitz David M.
Published: July 2007

Otopetrin1 (Otop1) is a multitransmembrane domain protein required for the formation of otoconia in the vertebrate inner ear. Otoconia are complex calcium carbonate (CaCO3) biominerals that are required for the sensation of gravity. Examination of the phenotypes of animals with mutations or deficiencies inOtop1suggests a direct role for Otop1 in the initiation of extracellular biomineralization, possibly through the regulation of intracellular Ca2+. Here, we demonstrate that Otop1 overexpression can modulate purinergic-mediated Ca2+homeostasis in transfected cell lines. These experiments define a unique set of biochemical activities of Otop1, including depletion of endoplasmic reticulum Ca2+stores, specific inhibition of the purinergic receptor P2Y, and regulation of the influx of extracellular Ca2+in response to ATP, ADP, and UDP. These activities can be inhibited by the polyanion suramin in a rapidly reversible manner. This first characterization of the consequences of Otop1 overexpression indicates a profound effect on cellular Ca2+regulation. In a physiologic setting, these activities could direct the formation and growth of otoconia and regulate other biomineralization processes.
Prevalence and patterns of alcohol use in the Australian workforce: findings from the 2001 National Drug Strategy Household Survey
Authors: Berry Jesia G. , Pidd Ken , Roche Ann M. , Harrison James E.
Published: July 2007

Aims To describe Australian workers' prevalence and patterns of alcohol use.

Design A secondary analysis of the 2001 National Drug Strategy Household Survey.

Participants A total of 13 582 workers ≥ 14 years old.

Measurements Alcohol consumption levels associated with National Health and Medical Research Council (NHMRC) guidelines for short‐ and long‐term harm were stratified by occupation and industry.

Findings Approximately 8% of the workforce drank at least weekly at short‐term risky or high risk levels, 17% drank at least monthly, 18% drank at least yearly and 11% drank at long‐term risky or high risk levels. The prevalence of risky or high risk drinking was higher for younger than for older workers. Controlling for socio‐demographic factors, the risk of workers frequently drinking at levels associated with short‐term harm was lowest in the education industry and significantly higher in the hospitality, agriculture, manufacturing and construction industries. Drinking patterns associated with long‐term harm were more prevalent in the agriculture, retail and manufacturing industries, compared to the education industry. Drinking patterns associated with both short‐ and long‐term harm were more prevalent for blue‐collar workers than professionals.

Conclusions Risky and high risk drinking occurred at least occasionally in 44% of Australian workers. Workers in the hospitality, agriculture, manufacturing, construction and retail industries, workers in blue‐collar occupations and young workers were identified as at‐risk subgroups. These data provide evidence that patterns of consumption differ between occupational and industry groups, and highlight the pressing need to develop policies, prevention and intervention strategies to reduce harmful alcohol use in Australia, particularly among young adults.
Phase Ib clinical trial of starch‐conjugated deferoxamine (40SD02): a novel long‐acting iron chelator
Authors: Harmatz Paul , Grady Robert W. , Dragsten Paul , Vichinsky Elliott , Giardina Patricia , Madden Jacqueline , Jeng Michael , Miller Becky , Hanson Gregory , Hedlund Bo
Published: July 2007

The most widely used drug for iron chelation is deferoxamine (DFO) mesylate. While effective in promoting iron excretion, it requires prolonged daily infusions, often resulting in poor compliance. A clinical trial was conducted using starch‐conjugated DFO (S‐DFO; 40SD02), a high‐molecular‐weight iron chelator possessing prolonged vascular retention. Single doses of S‐DFO were infused intravenously into groups of four transfusion‐dependent patients with β‐thalassaemia at doses of 150, 300, 600 and 900 mg/kg. Urinary iron excretion and various pharmacologic parameters were evaluated for 1 week and safety for 3 weeks. No drug‐related effects were observed on clinical chemistries, haematological and coagulation parameters, urinalyses, vital signs or electrocardiograms. Drug‐related adverse events were limited to four urticarial reactions, none requiring termination of the infusion. The drug stimulated clinically significant urinary iron excretion, with the highest dose (900 mg/kg) inducing excretion of 1·31 mg of iron/kg (range 0·79–1·90 mg/kg) over 1 week, with residual iron‐binding capacity present in the plasma for over 6 d. In summary, treatment with S‐DFO, administered weekly, has the potential to achieve iron balance in the poorly compliant patient.
Expression of the γ‐globin gene is sustained by the cAMP‐dependent pathway in β‐thalassaemia
Authors: Bailey Lakiea , Kuroyanagi Yuichi , Franco‐Penteado Carla F. , Conran Nicola , Costa Fernando F. , Ausenda Sabrina , Cappellini Maria D. , Ikuta Tohru
Published: July 2007

The present study found that the cyclic adenosine monophosphate (cAMP)‐dependent pathway efficiently induced γ‐globin expression in adult erythroblasts, and this pathway plays a role in γ‐globin gene (HBG) expression in β‐thalassaemia. Expression ofHBGmRNA increased to about 46% of non‐HBA mRNA in adult erythroblasts treated with forskolin, while a cyclic guanosine monophosphate (cGMP) analogue inducedHBGmRNA to levels <20% of non‐HBA mRNA. In patients with β‐thalassaemia intermedia, cAMP levels were elevated in both red blood cells and nucleated erythroblasts but no consistent elevation was found with cGMP levels. The transcription factor cAMP response element binding protein (CREB) was phosphorylated in nucleated erythroblasts and its phosphorylation levels correlated withHBGmRNA levels of the patients. Other signalling molecules, such as mitogen‐activated protein kinases and signal transducers and activators of transcription proteins, were phosphorylated at variable levels and showed no correlations with theHBGmRNA levels. Plasma levels of cytokines, such as erythropoietin, stem cell factor and transforming growth factor‐β were increased in patients, and these cytokines induced bothHBGmRNA expression and CREB phosphorylation. These results demonstrate that the cAMP‐dependent pathway, the activity of which is augmented by multiple cytokines, plays a role in regulatingHBGexpression in β‐thalassaemia.
Young people's and carers' perspectives on the mental health needs of looked‐after adolescents
Authors: Stanley Nicky
Published: July 2007

While the mental health needs of looked‐after young people have been described in a number of clinical studies, the views of looked‐after adolescents themselves concerning their mental health needs have only rarely been reported. This study used focus groups to elicit the ideas and experiences of looked‐after young people in two local authorities in England. Front‐line carers in the region were also surveyed. Young people and carers were agreed in highlighting the damaging effects of the discontinuity and change experienced in the looked‐after system. Young people emphasized the importance of exercising choice and control when seeking and receiving support and identified the value of positive role models provided by ‘survivors’ of the care system. Carers reported high levels of risk behaviour, particularly self‐harm, among young people in children's homes. These differing perspectives need to be openly acknowledged and negotiated within care settings in order that relevant and accessible therapeutic and support services can be offered to looked‐after adolescents.
Do immune responses to inhaled skin flakes modulate the expression of allergic disease?
Authors: Tovey E. R. , Kemp A. S. , Almqvist C. , Sharland A. , Marks G. B.
Published: July 2007

We examine the nature of the immune responses to inhaled skin particles and query whether early exposure could play a role in providing protection against the development of allergic disease. Currently, the main hypothesis used to explain environmental modulation of allergic diseases, the ‘hygiene hypothesis’, is linked exclusively to microbial exposures acting upon the innate immune system. However, many of the exposures sustaining this hypothesis also involve co‐exposure to skin flakes from humans or animals. Such skin flakes contain a complex mixture of antigens, glycolipids and small peptides that may induce immune responses. Should these responses prove relevant to the modulation of allergic diseases, it provides new opportunities to better understand the epidemic of allergic disease and to develop new interventions for its prevention.
Preliminary evidence for interaction of PTPN12 polymorphism with TSHR genotype and association with Graves’ ophthalmopathy
Authors: Syed A. A. , Simmonds M. J. , Brand O. J. , Franklyn J. A. , Gough S. C. L. , Heward J. M.
Published: July 2007

Objective  Protein tyrosine phosphatases (PTPs), such as PTPN22, are important regulators of signal transduction from the T cell receptor and have been associated with autoimmunity. PTPN12 interacts with the same T cell activation accessory molecules, Grb2 and Csk kinase, as the Graves’ disease (GD) associated PTPN22 encoded lymphoid tyrosine phosphatase (LYP) molecule and also plays a key role in T cell receptor signalling, leading to the hypothesis that it too may be involved in GD susceptibility.

Design  PTPN12 was tested for association in a large well‐characterized UK Caucasian case control cohort using seven tagging single nucleotide polymorphisms (SNPs).

Patients  A total of 1058 GD patients and 864 controls.

Measurements  Tests for association with the disease.

Results  Despite adequate statistical power to detect an effect if present, none of the seven tag SNPs were associated with GD (P = 0·925–0·089). Three SNPs (rs1468682, rs4729535 and rs17467232), however, demonstrated association with the presence of ophthalmopathy NOSPECS classes 2–4 (P = 0·039–0·004). Four SNPs (rs1468682, rs4729535, rs17155601 and rs17467232) revealed evidence of interaction with the previously associated thyrotropin hormone receptor (TSHR) rs2268458 SNP (P = 0·035–0·002).

Conclusions  No association was detected between individual PTPN12 tag SNPs and GD but preliminary evidence suggests PTPN12 confers an increased risk of mild/moderate ophthalmopathy (NOSPECS classes 2–4) and that PTPN12 interacts with the TSHR. Replication of these preliminary results is now required in larger independent datasets to validate these findings.
Over‐expression of the bovine FcRn in the mammary gland results in increased IgG levels in both milk and serum of transgenic mice
Authors: Lu Wei , Zhao Zhihui , Zhao Yaofeng , Yu Shuyang , Zhao Yiqiang , Fan Baoliang , Kacskovics Imre , Hammarström Lennart , Li Ning
Published: July 2007

The neonatal Fc receptor (FcRn) protects immunoglobulin G (IgG) from catabolism and is also responsible for IgG absorption in the neonatal small intestine. However, whether it mediates the transfer of IgG from plasma to milk still remains speculative. In the present study, we have generated transgenic mice that over‐express the bovine FcRn (bFcRn) in their lactating mammary glands. Significantly increased IgG levels were observed in the sera and milk from transgenic animals, suggesting that the over‐expressed bFcRn could bind and protect endogenous mouse IgG and thus extend its lifespan. We also found that injected human IgG showed a significantly longer half‐life (7–8 days) in the transgenic mice than in controls (2·9 days). Altogether, the data suggested that bFcRn could bind both mouse and human IgG, showing a cross‐species FcRn–IgG binding activity. However, we found no selective accumulation of endogenous mouse IgG or injected bovine IgG in the milk of the transgenic females, supporting a previous hypothesis that IgG was transported from serum to milk in an inverse correlation to its binding affinity to FcRn.
Molecular evidence for long‐distance dispersal in the New Zealand pteridophyte flora
Authors: Perrie Leon , Brownsey Patrick
Published: July 2007

Aim  To examine the relative importance of long‐distance dispersal in shaping the New Zealand pteridophyte (ferns and lycophytes) flora and its relationships with other floras, with the null hypothesis that the extant New Zealand pteridophyte flora has been isolated since New Zealand’s separation from Gondwana.

Location  New Zealand.

Methods  rbcL DNA sequences were assembled for 31 New Zealand pteridophyte genera, with each genus represented by one New Zealand species and the most closely related non‐New Zealand species for which data were available. Maximum‐likelihood, maximum‐parsimony, and Bayesian analysis phylograms were constructed and used as input for r8s molecular dating, along with 23 fossil calibrations. Divergence estimates less than conservatively recent ages for New Zealand’s geological isolation, namely Ho > 30 Ma for pairs involving New Caledonian and Norfolk Island species and Ho > 55 Ma for all others, were taken as rejection of the null hypothesis.

Results  The null hypothesis was rejected for all pairs except, under some parameter conditions, for those involving the New Zealand species Cardiomanes reniforme, Lindsaea trichomanoides, Loxsoma cunninghamii, Lygodium articulatum, Marattia salicina, and Pteris comans. However, the Lindsaea and Pteris results probably reflect the absence in the analyses of closely related non‐New Zealand samples, while the Marattia divergence was highly contingent on which fossil calibrations were used.

Main conclusions  Rejection of the null hypothesis for the majority of pairs implies that the extant New Zealand lineage has undergone long‐distance dispersal either into or out of New Zealand. The notion of a long isolation since geological separation can, therefore, be dismissed for much of New Zealand’s pteridophyte flora. The analyses do not identify the direction of the long‐distance dispersal, and these New Zealand lineages could have had vicariant origins with subsequent long‐distance emigration. However, the alternative that many extant New Zealand pteridophyte lineages only arrived by long‐distance immigration after geological isolation seems likely.
Bacteria between protists and phages: from antipredation strategies to the evolution of pathogenicity
Authors: Brüssow Harald
Published: July 2007

Bacteriophages and protists are major causes of bacterial mortality. Genomics suggests that phages evolved well before eukaryotic protists. Bacteria were thus initially only confronted with phage predators. When protists evolved, bacteria were caught between two types of predators. One successful antigrazing strategy of bacteria was the elaboration of toxins that would kill the grazer. The released cell content would feed bystander bacteria. I suggest here that, to fight grazing protists, bacteria teamed up with those phage predators that concluded at least a temporary truce with them in the form of lysogeny. Lysogeny was perhaps initially a resource management strategy of phages that could not maintain infection chains. Subsequently, lysogeny might have evolved into a bacterium–prophage coalition attacking protists, which became a food source for them. When protists evolved into multicellular animals, the lysogenic bacteria tracked their evolving food source. This hypothesis could explain why a frequent scheme of bacterial pathogenicity is the survival in phagocytes, why a significant fraction of bacterial pathogens have prophage‐encoded virulence genes, and why some virulence factors of animal pathogens are active against unicellular eukaryotes. Bacterial pathogenicity might thus be one playing option of the stone–scissor–paper game played between phages–bacteria–protists, with humans getting into the crossfire.
A case of idiopathic granulomatous cheilitis and vulvitis
Authors: Sbano Paolo , Rubegni Pietro , Risulo Massimiliano , De Nisi Maria Caterina , Fimiani Michele
Published: July 2007

A 36‐year‐old woman presented with chronic recurring dermatitis of the vulva, perineum, and lips. The genital lesions had a 3‐year history and were associated with slight pruritus and occasional pain. The lesions of the upper lip had a history of 6 months. The patient had been treated with cycles of antimycotics and topical steroids which only partially controlled the symptoms during treatment. Dermatologic examination showed erythematous, infiltrative dermatitis with edema of the labia majora and persistent edema of the upper lip (Fig. 1a,b). Routine blood chemistry, urine analysis, and chest X‐ray were normal. Microscopic examination and cultures of vaginal swabs did not reveal any pathogenic bacteria or fungi. Histologic examination of a biopsy of vulval lesional skin showed lichenoid lymphocytic infiltration of the papillary dermis and small, nonnecrotic epithelioid granulomas in the deep dermis (Fig. 1c,d). No microorganisms, including acid‐fast bacilli or fungi, were identified. Culture was negative for fungi. Polymerase chain reaction was negative for the mycobacterial genome. Histologic examination of a biopsy from the upper lip showed similar results. The pathology reports of both regions were compatible with a diagnosis of granulomatous cheilitis and vulvitis. To investigate concomitant asymptomatic inflammatory bowel disease, the patient underwent colonoscopy with retrograde ileoscopy and gastroscopy, which were both negative. The patient refused radiographic examination of the small intestine with a barium meal. The patient was treated with systemic metronidazole (500 mg/day). After 6 months of therapy, the upper lip showed significant improvement and erythema and desquamation in the genital area showed slight improvement, but genital edema was unaffected.

Granulomatous vulvitis and cheilitis: (a) erythematous infiltrative dermatitis with edema of the vulva; (b) edema of the upper lip; (c) lichenoid lymphocytic infiltration of the papillary dermis and small, nonnecrotic epithelioid granulomas in the deep dermis (hematoxylin and eosin, ×2.5); (d) detail of granulomatous infiltrate (hematoxylin and eosin, ×40)

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Meeting information needs to facilitate decision making: report cards for people with disabilities1
Authors: Palsbo Susan E. , Kroll Thilo
Published: July 2007

Background  Several states within the United States offer low‐income adults with disabilities a choice of health plans. No states issue comparative ‘report cards’ specifically for adults with disabilities.

Objective  To explore conceptualizations of quality, information needs, and report card preferences from the perspective of people with disabilities.

Research design Eight focus group interviews were conducted in 2003. Existing report cards for California, Maryland, Michigan and Texas were shared for feedback.

Subjects 34 women and 15 men with various behavioural, physical or sensory disabilities in Oregon, California, Virginia, Maryland and the District of Columbia.

Results Quality was mostly defined in terms of choice and disability sensitivity of service providers. Respondents identified various obstacles to receiving appropriate health plan and service information. All beneficiaries were keenly interested in the comparative health plan report cards, but did not think the report cards provided enough pertinent information, especially with regard to provider ratings, accessibility, disability competence and reasons for participating in the Medicaid program.

Conclusions Existing comparative report cards omit several major content domains important to people with disabilities. Organizations providing decision support to people with disabilities should cultivate novel avenues for distribution, such as food banks, libraries and places of worship.
Non‐target organism risk assessment of MIR604 maize expressing mCry3A for control of corn rootworm
Authors: Raybould A. , Stacey D. , Vlachos D. , Graser G. , Li X. , Joseph R.
Published: July 2007

Abstract:  Event MIR604 maize expresses a modified Cry3A protein (mCry3A), for control of corn rootworm. As part of the environmental safety assessment of MIR604 maize, risks to non‐target organisms of mCry3A were assessed. The potential exposure of non‐target organisms to mCry3A following cultivation of MIR604 maize was determined, and the hypothesis that such exposure is not harmful was tested. The hypothesis was tested rigorously by making worst‐case or highly conservative assumptions about exposure, along with laboratory testing for hazards using species taxonomically related to the target pest and species expected to have high exposure to mCry3A, or both. Further rigour was introduced by study designs incorporating long exposures and measurements of sensitive endpoints. No adverse effects were observed in any study, and in most cases exposure to mCry3A in the study was higher than the worst‐case expected exposure. In all cases, exposure in the study was higher than realistic, but still conservative, estimates of exposure. These results indicate minimal risk of MIR604 maize to non‐target organisms.