bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of detrital mineral populations: insights from mixing of U–Pb zircon ages in Himalayan rivers
Authors: Amidon William H. , Burbank Douglas W. , Gehrels George E.
Published: November 2005

Fission‐track, U–Pb and Pb–Pb analyses of detrital heavy mineral populations in depositional basins and modern river sediments are widely used to infer the exhumational history of mountain belts. However, relatively few studies address the underlying assumption that detrital mineral populations provide an accurate representation of their entire source region. Implicit in this assumption is the idea that all units have equal potential to contribute heavy minerals in proportion to their exposure area in the source region. In reality, the detrital mineral population may be biased by variable concentrations of minerals in bedrock and differential erosion rates within the source region. This study evaluates the relative importance of these two variables by using mixing of U–Pb zircon ages to trace zircon populations from source units, through the fluvial system, and into the foreland.

The first part of the study focuses on the Marsyandi drainage in central Nepal, using tributaries that drain single formations to define the U–Pb age distributions of individual units and using trunk river samples to evaluate the relative contributions from each lithology. Observed mixing proportions are compared with proportions predicted by a simple model incorporating lithologic exposure area and zircon concentration. The relative erosion rates that account for the discrepancy between the observed and predicted mixing proportions are then modelled and compared with independent erosional proxies. The study also compares U–Pb age distributions from four adjacent drainages spanning ∼250 km along the Himalayan front using the Kolmogorov–Smirnov statistic and statistical estimates of the proportion of zircon derived from each upstream lithology. Results show that, along this broad swath of rugged mountains, the U–Pb age distributions are remarkably similar, thereby allowing data from more localized sources to be extrapolated along strike.
Seal capacity estimation from subsurface pore pressures
Authors: Nordgård Bolås Hege M. , Hermanrud Christian , Teige Gunn M. G.
Published: November 2005

A cap rock's capacity to seal hydrocarbons depends on its wettability and the sizes of the pore throats within the interconnected pore system that the leaking hydrocarbons must penetrate. These critical pore throat sizes are often poorly constrained in hydrocarbon exploration, partly because measurements of pore throat sizes have not been performed, and partly because pore throat measurements on a few individual samples in the cap rock may not be representative for the seal capacity of the top seal as a whole.

To the contrary, the presence of formation overpressure can normally be estimated in drilled exploration targets. The presence of overpressure in reservoirs testifies to small pore throats in the cap rocks, as large pore throats will result in sufficiently high cap rock permeability to bleed off the overpressure.

We suggest a stepwise procedure that enables quantification of top seal capacities of overpressured traps, based on subsurface pressure information. This procedure starts with the estimation of cap rock permeabilities, which are consistent with observed overpressure gradients across the top seals. Knowledge of burial histories is essential for these estimations. Relationships between pore throat size and permeability from laboratory experiments are then applied to estimate critical pore throat diameters in cap rocks. These critical pore throat diameters, combined with information of the physical properties of the pore fluids, are then used to calculate membrane seal capacity of cap rocks.

Estimates of top seal capacity based on this procedure are rather sensitive to the vertical fluid velocity, but they are also to some extent sensitive to inaccuracies of the pore throat/permeability relationship, overpressure gradient, interfacial tensions between pore fluids, hydrocarbon density and water viscosity values. Despite these uncertainties, applications of the above‐mentioned procedure demonstrated that the mere presence of reservoir overpressures testifies to sufficient membrane seal capacity of cap rocks for most geological histories. Exempt from this statement are basins with rapid and substantial sediment compaction in the recent past.
P210 Bcr‐abl tyrosine kinase interaction with histone deacetylase 1 modifies histone H4 acetylation and chromatin structure of chronic myeloid leukaemia haematopoietic progenitors
Authors: Brusa Gianluca , Zuffa Elisa , Mancini Manuela , Benvenuti Michela , Calonghi Natalia , Barbieri Enza , Santucci Maria Alessandra
Published: November 2005

The BCR‐ABL fusion gene, originating from the balanced (9;22) translocation, is the molecular hallmark and the causative event of chronic myeloid leukaemia (CML). The interactions of its p210 protein constitutively activated and improperly confined to the cytoplasm with multiple regulatory signals of cell cycle progression, apoptosis and self‐renewal, induce the illegitimate enlargement of clonal haematopoiesis and genetic instability that drives its progression towards the fully transformed phenotype of blast crisis. However, its effects on the basic transcription machinery and chromatin remodelling are unknown. Our study underscored histone H4 hyperacetylation associated with p210 tyrosine kinase in vitro and in vivo and its role in BCR‐ABL transcription. Histone H4 hyperacetylation proceeds, at least partly, from the ‘loss of function’ of histone deacetylase 1 protein, a critical component of Rb‐mediated transcriptional repression, in consequence of its cytoplasmatic compartmentalisation.
Tissue factor pathway inhibitor anticoagulant activity: risk for venous thrombosis and effect of hormonal state
Authors: Dahm Anders , R. Rosendaal Frits , Andersen Trine O. , Sandset Per M.
Published: November 2005

Full‐length tissue factor pathway inhibitor (TFPI) is assumed to be biologically more important than truncated TFPI because of its stronger anticoagulant effect in the diluted prothrombin time (dPT) assay. We have developed a dPT‐based assay for TFPI anticoagulant activity. Here, we report the effect of hormonal state on TFPI anticoagulant activity and whether TFPI anticoagulant activity assesses the risk for deep‐vein thrombosis (DVT) better than conventional TFPI assays. We undertook a case‐control study of 474 patients with DVT and 474 controls and compared the odds ratio (OR) for DVT for those with low TFPI anticoagulant activity with the ORs obtained for TFPI free and total antigen, and TFPI chromogenic substrate activity. Hormonal state affected clot time in dPT, but this effect was ameliorated by anti‐TFPI antibodies. Low TFPI anticoagulant activity gave an OR of 1·5 (0·97–2·1) for DVT, similar to the ORs obtained with conventional TFPI assays, ranging from 1·2 to 1·4. Individuals low in both the activity assays obtained an OR of 5·9 (1·7–20). We concluded that the effect of hormonal state on dPT was mediated through TFPI, and a dPT‐based assay of TFPI anticoagulant activity did not assess the risk for DVT better than conventional TFPI assays.
Retracted: Transactivation of CCL20 gene by Epstein–Barr virus latent membrane protein 1
Authors: Okudaira Taeko , Yamamoto Kazuo , Kawakami Hirochika , Uchihara Jun‐Nosuke , Tomita Mariko , Masuda Masato , Matsuda Takehiro , Sairenji Takeshi , Iha Hidekatsu , Jeang Kuan‐Teh , Matsuyama Toshifumi , Takasu Nobuyuki , Mori Naoki
Published: November 2005

CCL20 is expected to play a crucial role in the initiation of immune responses and tumour growth. However, expression of CCL20 in Epstein–Barr virus (EBV)‐associated diseases has not been studied. We examined the contribution of EBV infection and EBV‐encoded latent membrane protein (LMP)‐1 to CCL20 expression. EBV infection and LMP‐1 induced CCL20 mRNA expression in the EBV‐negative Burkitt lymphoma (BL) cell lines and the embryonic kidney cell line. Histone deacetylase inhibitor‐stimulated endogenous LMP‐1 also induced CCL20 expression in an EBV‐positive BL cell line. Analysis of the CCL20 promoter showed that it was activated by LMP‐1 C‐terminal activation region (CTAR)‐1 and CTAR‐2. Co‐expression of IκBα, IκBβ, IκB kinase (IKK)α, IKKβ, IKKγ, nuclear factor (NF)‐κB‐inducing kinase and tumour necrosis factor receptor‐associated factor 2 dominant‐negative constructs with LMP‐1 inhibited the activation of the CCL20 promoter by LMP‐1, suggesting that LMP‐1 induces CCL20 via NF‐κB signalling. The requirement for the NF‐κB‐binding site in the CCL20 promoter in LMP‐1 responsiveness was established. Our results indicate that activation of the NF‐κB pathway by LMP‐1 is required for the activation of CCL20 expression.
Inhibition of the phosphatidylinositol‐3 kinase/Akt promotes G1 cell cycle arrest and apoptosis in Hodgkin lymphoma
Authors: Georgakis Georgios V. , Li Yang , Rassidakis Georgios Z. , Medeiros L. Jeffrey , Mills Gordon B. , Younes Anas
Published: November 2005

Activation of the phosphatidylinositol 3‐kinase (PI3K) pathway has been linked with tumour cell growth, survival and resistance to therapy in several cancer types. The active, phosphorylated form of Akt (pAkt) was found to be aberrantly expressed in Hodgkin lymphoma (HL)‐derived cell lines and in Hodgkin–Reed–Sternberg (HRS) cells in 27 of 42 (64·3%) of primary lymph node sections of HL, indicative of PI3K activity. Akt phosphorylation was not associated with loss of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) expression, but with its phosphorylation in HL‐cell lines, suggesting that its biological function is impaired. Akt phosphorylation was further induced by CD30 ligand (CD30L), CD40L and receptor activator of nuclear factor kappa B (RANK) ligand. The PI3K inhibitor LY294002 demonstrated antiproliferative effects in a dose‐ and time‐dependent manner, which was associated with Akt dephosphorylation on Thr308 and Ser473 sites and dephosphorylation of the downstream ribosomal protein S6. LY209002 induced cell cycle arrest in the G0/G1 phase and apoptosis, which were associated with upregulation of MDM2, downregulation of cyclin D1, activation of caspase 9 and poly‐ADP‐ribose polymerase cleavage. The Akt inhibitor QLT394 also demonstrated antiproliferative effects in a dose‐ and time‐dependent manner, dephosphorylated ribosomal S6 and cleaved caspase 9. Collectively, these data suggest that the aberrant activation of the PI3K/Akt survival pathway in HRS cells is not because of loss of PTEN expression. Our data suggest that PTEN phosphorylation and activation of CD30, CD40 and RANK may play a role in activating Akt in HRS cells.
Bi‐directional soil/atmosphere N2O exchange over two mown grassland systems with contrasting management practices
Authors: FLECHARD CHRISTOPHE R. , NEFTEL ALBRECHT , JOCHER MARKUS , AMMANN CHRISTOF , FUHRER JÜRG
Published: November 2005

Nitrous oxide (N2O) fluxes from soil under mown grassland were monitored using static chambers over three growing seasons in intensively and extensively managed systems in Central Switzerland. Emissions were largest following the application of mineral (NH4NO3) fertilizer, but there were also substantial emissions following cattle slurry application, after grass cuts and during the thawing of frozen soil. Continuous flux sampling, using automatic chambers, showed marked diurnal patterns in N2O fluxes during emission peaks, with highest values in the afternoon. Net uptake fluxes of N2O and subambient N2O concentrations in soil open pore space were frequently measured on both fields. Flux integration over 2.5 years yields a cumulated emission of +4.7 kgN2O‐N ha−1 for the intensively managed field, equivalent to an average emission factor of 1.1%, and a small net sink activity of −0.4 kg N2O‐N ha−1 for the unfertilized system. The data suggest the existence of a consumption mechanism for N2O in dry, areated soil conditions, which cannot be explained by conventional anaerobic denitrification. The effect of fertilization on greenhouse gas budgets of grassland at the ecosystem level is discussed.
Interleukin‐16 inhibits interleukin‐13 production by allergen‐stimulated blood mononuclear cells
Authors: El Bassam Souad , Pinsonneault Stéphane , Kornfeld Hardy , Ren Fucheng , Menezes José , Laberge Sophie
Published: November 2005

Expression of interleukin (IL)‐16 is increased in bronchial mucosal biopsies of atopic asthmatics compared to normal controls. The functional significance of increased expression of IL‐16 at sites of allergic inflammation is not yet clear. We have previously shown that IL‐16 inhibits IL‐5 secretion by allergen‐stimulated peripheral blood mononuclear cells (PBMC). We investigated whether IL‐16 inhibits the production of other T helper 2 cytokines, namely IL‐13 and IL‐4, by allergen‐specific T cells. PBMC from ragweed‐sensitive atopic subjects were stimulated with allergen extract for cytokine production in the presence or absence of rhIL‐16. Production of cytokines was assessed by enzyme‐linked immunosorbent assay and reverse transcription–polymerase chain reaction. To evaluate whether the modulatory effect of IL‐16 on cytokine synthesis was mediated by interferon‐γ (IFN‐γ), IL‐10, IL‐12 or IL‐18, allergen‐stimulated PBMC were cultured in presence of IL‐16 and neutralizing concentrations of relevant antibodies. Allergen‐stimulated PBMC produced significantly elevated levels of IL‐13 (90–740 pg/ml) as compared to unstimulated PBMC (0–375 pg/ml, P < 0·01). Addition of rhIL‐16 resulted in down‐regulation of IL‐13 mRNA expression as well as significantly reduced amounts of IL‐13 released by allergen‐stimulated PBMC (0–457 pg/ml, P < 0·001), as observed for IL‐5. No effect of IL‐16 was observed on IL‐4 mRNA expression. Treatment with IL‐16 resulted in increased levels of IL‐10 and IL‐18 in allergen‐stimulated cell culture. Neutralization of IFN‐γ, IL‐12, IL‐10 or IL‐18 did not alter the inhibitory effects of IL‐16 on IL‐13 and IL‐5 secretion by allergen‐stimulated PBMC. IL‐16 did not modify IL‐13 synthesis by anti‐CD3‐stimulated CD4+ T cells, but it significantly reduced the production of IL‐5. These data suggest that IL‐16 may play an important immunoregulatory role in allergic states in response to allergen.
The delivery of an antigen from the endocytic compartment into the cytosol for cross‐presentation is restricted to early immature dendritic cells
Authors: Hotta Chie , Fujimaki Haruka , Yoshinari Masahiro , Nakazawa Masatoshi , Minami Mutsuhiko
Published: November 2005

Dendritic cells (DCs) are the only antigen‐presenting cell population having a cross‐presentation capacity. For cross‐presentation, however, the intracellular antigen‐processing pathway and its regulatory mechanism have not been defined. Here we report the differences in cross‐presentation ability among murine bone marrow‐derived immature DC, early immature day8‐DC and late immature day10‐DC, and fully mature day10 + lipopolysaccharide DC. Day8‐DCs and day10‐DCs show an immature phenotypic profile but are different in morphology. Day8‐DCs can internalize an abundant volume of exogenous soluble ovalbumin (OVA) and result in cross‐presentation. In contrast, day10‐DCs are not able to cross‐present, although they maintain efficient macropinocytosis. Exogenously internalized OVA antigens are stored in the endocytic compartments. The endocytic compartments are temporarily maintained at mildly acidic pH in day8‐DCs and are rapidly acidified in day10‐DCs after uptake of antigens. We show that OVA antigens accumulated in the endocytic compartments move into the cytosol in day8‐DCs but do not in day10‐DCs. NH4Cl‐treatment, which neutralizes the acidic endocytic compartments and/or delays endosomal maturation, restores day10‐DCs for transport the stored OVA antigens from the endocytic compartments into the cytosol. Diphenyleneiodonium chloride‐treatment, which acidifies the endocytic compartments, decreases an amount of transported OVA antigen into the cytosol in day8‐DCs. These data indicate that only the early immature stage of DC interferes with endosomal maturation, even after uptake of exogenous antigens, and then transports the antigens into the cytosol.
OX40 interactions in gastrointestinal nematode infection
Authors: Ierna Michelle X. , Scales Hannah E. , Schwarz Herbert , Bunce Campbell , McIlgorm Anne , Garside Paul , Lawrence Catherine E.
Published: November 2005

The immune expulsion of gastrointestinal nematode parasites is usually associated with T helper type 2 (Th2) responses, but the effector mechanisms directly responsible for parasite loss have not been elucidated. The intestinal inflammatory response accompanying infection with gastrointestinal helminths is thought to be a contributory factor leading to the expulsion of the parasite. However, we have shown that the intestinal inflammation, which is controlled by interleukin (IL)‐4, is not required for parasite expulsion. OX40–OX40 ligand (L) signals have been shown to be important for the development of Th2 immune responses but are also involved in a number of inflammatory diseases including those of the intestine. Here, we have investigated the effect of OX40 and OX40L fusion protein treatment on the induction of protective Th2 responses and enteropathy following infection with the gastrointestinal nematode Trichinella spiralis. Treatment with an OX40–immunoglobulin (Ig) blocking fusion protein resulted in enhanced expulsion of the parasite and an increase in the accompanying mastocytosis, despite unaltered levels of Th2 cytokines. Furthermore, there was a delay in the villus atrophy and crypt hyperplasia usually associated with this infection. In contrast, levels of Th2 cytokines were greatly up‐regulated in mice treated with an OX40L–Ig activating fusion protein, yet the expulsion of the parasite and the enteropathy were unaffected. Therefore, OX40 ligation potentiates the Th2 response without enhancing host protective immune responses, whereas blocking the OX40–OX40L interaction enhances host protection without promoting Th2 cytokine responses during Trichinella spiralis infection.
Rapid and preferential distribution of blood‐borne αCD3εAb to the liver is followed by local stimulation of T cells and natural killer T cells
Authors: Wingender Gerhard , Schumak Beatrix , Schurich Anna , Gessner J. Engelbert , Endl Elmar , Limmer Andreas , Knolle Percy A.
Published: November 2005

Dissemination of soluble molecules or antigens via the blood stream is considered to lead to a uniform distribution in the various organs of the body, but organ‐specific microarchitecture and vascularization may influence this. Following intravenous injection of αCD3ε antibody (αCD3εAb) we observed clear differences in antibody binding to Fcγ receptor (FcγR)+ antigen‐presenting cells (APCs) or T lymphocytes in different organs. Significant binding of blood‐borne αCD3εAb was only detected in the spleen and liver and not in the thymus or lymph node. In the spleen, only 10% of dendritic cells/macrophages and 40% of T‐cell receptor (TCR)‐β+ cells were positive for αCD3εAb, and, dependent on FcγR‐mediated cross‐linking of αCD3εAb, a similar percentage of splenic TCR‐β+ cells were stimulated and became CD69+. Stimulation of TCR‐β+ cells in the liver was at least as efficient as in the spleen, but almost all T cells and all scavenger liver sinusoidal endothelial cells bound αCD3εAb. In contrast to CD69 up‐regulation, only CD4+ natural killer T (NKT) cells and CD11ahigh CD8+ T cells were activated by αCD3εAb and expressed interferon (IFN)‐γ. Again, IFN‐γ release from NKT/T cells was at least as efficient in the liver as in the spleen. Taken together, our results support the notion that the combination of extensive hepatic vascularization and very high scavenger activity allows the liver to fulfill its metabolic tasks and to promote stimulation of the large but widely distributed hepatic population of NKT/T cells.
Reasons why DBA/2 mice are resistant to malarial infection: expansion of CD3int B220+ γδ T cells with double‐negative CD4– CD8– phenotype in the liver
Authors: Bakir Hanaa Y. , Tomiyama‐Miyaji Chikako , Watanabe Hisami , Nagura Toru , Kawamura Toshihiko , Sekikawa Hiroho , Abo Toru
Published: November 2005

DBA/2 (H‐2d) mice are known to be more resistant than C57BL/6 (B6, H‐2b) mice to the non‐lethal 17XNL strain of Plasmodium yoelii. This is a very strange phenomenon because the functions of conventional T cells, especially CD8+ T cells, are known to be somewhat lower in DBA/2 mice than in other strains of mice. We examined herein how immune responses differed between DBA/2 mice and B6 mice during malarial infection. DBA/2 mice and (DBA/2 × B6)F1 (BDF1, H‐2b/d) mice were found to have milder parasitaemia and to recover more quickly from malarial infection than B6 mice. These DBA/2 and BDF1 mice were also found to experience a marked expansion of interleukin (IL)‐2Rβ+ CD3int cells and γδ T cells in the liver, especially in the recovery phase. The expansion of unconventional T cells (i.e. B220+ T cells) was also marked in DBA/2 and BDF1 mice. The majority of B220+ T cells were γδ T cells and these T cells were double‐negative CD4− CD8−. More importantly, the production of immunoglobulin M (IgM)‐type anti‐DNA autoantibody was also higher in DBA/2 and BDF1 mice than in B6 mice. In conjunction with data on cytokine production, these results indicate that primitive T and B cells, namely autoreactive extrathymic T cells and autoantibody‐producing B cells, may be much more activated in DBA/2 mice and therefore resistant to the non‐lethal 17XNL strain of P. yoelii.
Differential regulation of neutrophil chemotaxis to IL‐8 and fMLP by GM‐CSF: lack of direct effect of oestradiol
Authors: Shen Li , Smith Jennifer M. , Shen Zheng , Hussey Stephen B. , Wira Charles R. , Fanger Michael W.
Published: November 2005

Neutrophils are a normal constituent of the female reproductive tract and their numbers increase in the late secretory phase of the menstrual cycle prior to menses. Several cytokines are produced in female reproductive tract tissue. In particular granulocyte–macrophage colony‐stimulating factor (GM‐CSF), a potent activator of neutrophils, is secreted in high concentrations by female reproductive tract epithelia. We previously observed that GM‐CSF synergizes strongly with interleukin‐8 (IL‐8) in enhancing chemotaxis of neutrophils. Thus we investigated whether pretreatment of neutrophils with GM‐CSF would prime subsequent chemotaxis to IL‐8 in the absence of GM‐CSF. Surprisingly, a 3‐hr pulse of GM‐CSF severely diminished chemotaxis to IL‐8, whereas N‐formyl‐methyl‐leucyl‐phenylalanine (fMLP)‐mediated chemotaxis was retained. Conversely, when cells were incubated without GM‐CSF they retained IL‐8‐mediated migration but lost fMLP chemotaxis. These changes in chemotaxis did not correlate with expression of CXCR1, CXCR2 or formyl peptide receptor. However, IL‐8‐mediated phosphorylation of p44/42 mitogen‐activated protein kinase was greatly reduced in neutrophils that no longer migrated to IL‐8, and was diminished in cells that no longer migrated to fMLP. Oestradiol, which is reported by some to exert an anti‐inflammatory effect on neutrophils, did not change the effects of GM‐CSF. These data suggest that neutrophil function may be altered by cytokines such as GM‐CSF through modulation of signalling and independently of surface receptor expression.
High‐risk human papilloma virus infection decreases the frequency of dendritic Langerhans' cells in the human female genital tract
Authors: Jimenez‐Flores Rafael , Mendez‐Cruz Rene , Ojeda‐Ortiz Jorge , Muñoz‐Molina Rebeca , Balderas‐Carrillo Oscar , De La Luz Diaz‐Soberanes Maria , Lebecque Serge , Saeland Sem , Daneri‐Navarro Adrian , Garcia‐Carranca Alejandro , Ullrich Stephen E. , Flores‐Romo Leopoldo
Published: November 2005

Dendritic cells (DC) are often arranged in planar layers in tissues with high antigenic exposure, such as skin and mucosae. Providing an en face view, this arrangement optimizes in situ analysis regarding morphology (even of individual dendrites), topographic distribution (regular/clustered) and quantification. The few reports on human genital DC usually utilize single markers and conventional sections, restricting immunolabelling only to cell parts sectioned by the cut. To better assess DC in situ, we labelled epithelial sheets, prepared from fresh cervix biopsies, with antibodies to major histocompatibility complex (MHC)‐CII, CD1a and Langerin, revealing (with each of these markers) a dense DC network in a planar‐like, regular distribution. Using the hybrid capture system to detect the high‐risk mucotropic human papilloma virus (HPV) group, 16 positive and five negative women were studied and the results were compared between these groups. DC frequency per area was substantially reduced (to ≈ 50% for the three markers) in samples from all HPV‐infected patients compared with samples from controls. Unlike HPV– samples, Langerin+ DC in HPV+ cervix exhibited a highly accentuated dendritic appearance. We believe this to be the first study using these three DC‐restricted markers (Langerin, CD1a and MHC‐CII) in cervical epithelial sheets from high‐risk HPV+ donors and also the first study to demonstrate the morphological and quantitative changes triggered by high‐risk HPV infection. Cervical DC reduction in early, premalignant high‐risk HPV infection might represent viral subversion strategies interfering with efficient antigen handling by the immune system's peripheral sentinels, the DC, perhaps hampering appropriate recruitment and subsequent development of effector (cytotoxic) T cells.
Avifaunal gradients in two arid zones of central Iran in relation to vegetation, climate, and topography
Authors: Kaboli Mohammad , Guillaumet Alban , Prodon Roger
Published: November 2005

Aim  To identify the ecological factors (related to vegetation, altitude, climate, or geomorphology) that could explain the main gradients of avifaunal richness and composition in arid environments of Central Iran.

Location  The study was carried out in two nearby semi‐arid protected areas of the Ispahan province: the Kolah‐Ghazi National Park (c. 50,000 ha; 1540–2535 m a.s.l.) and the Mouteh Wildlife Refuge (c. 220,000 ha; 1493–2900 m a.s.l.). Annual average precipitation and temperature range from 155–205 mm and 15–19.5 °C, respectively. Vegetation cover is sparse.

Methods  The two study areas were sampled with a 1 × 1 km grid design. A subset of 405 squares was randomly chosen and each was visited once during spring or summer by a team of five observers walking from one side of a square to the other and back, recording the birds encountered. Raptors and species considered to be accidental or migrating were not taken into account. We first looked for avifaunal, vegetation, and geomorphological gradients using Correspondence Analysis. As we found spatial autocorrelation within our response variables (avifaunal richness, abundance and/or composition), we first calculated an autocorrelation term, then added this autocorrelation term in anova, ancova (separate slope design) and stepwise regression to assess the relative role of spatial autocorrelation and environmental explanatory variables (vegetation, altitude, climate, or topography). We also partitioned the variance of the avifaunal matrix between several sets of co‐variables, after controlling for spatial effects, using a series of partial Canonical Correspondence Analyses.

Results  A main gradient, common to the two areas, distinguishes bird species characteristic of flat sedimentary areas and species dwelling in mountainous and/or rocky areas. Despite the generally low values of the correlations measured, we found that richness, abundance and composition of the avifauna were better correlated with topography, especially the altitudinal amplitude within each square, than any other variable, including vegetation. Altitudinal amplitude is related to substrate complexity.

Main conclusions  In arid zones of central Iran, topographic features seem to be the main factors structuring avifaunal composition and abundance. Avifaunal composition and richness are mainly correlated with the complexity of the substrate, but both avifaunal richness and abundance increase with altitude, probably in response to decreasing aridity. We did not observe any bird altitudinal zonation in a strict sense. These results contrast with those generally observed in mid‐latitude regions of the Palaearctic.
Verbal intrusions precede memory decline in adults with Down syndrome
Authors: Kittler P. , Krinsky‐McHale S. J. , Devenny D. A.
Published: November 2005

Background  Verbal intrusion errors are irrelevant responses made in the course of verbal memory retrieval or language production that have been associated with disruption of executive functions and the prefrontal cortex. They have been observed to occur more frequently both with normal aging and with neurodegenerative diseases such as Alzheimer's disease (AD). The purpose of this study was to longitudinally examine the production of verbal intrusions among middle‐aged adults with Down syndrome (DS) and unspecified intellectual disability (ID) to determine whether producing verbal intrusions at one point in time was related to subsequent verbal memory performance. Because of the combination of a relative deficit in verbal working memory (WM), premature aging, and higher risk of AD among adults with DS, it was predicted that they would make more verbal intrusions than adults with unspecified ID.

Methods  Word List recall (WLR), the Selective Reminding Test (SRT), and the Cued Recall Test (CRT), were administered three times at 18‐month intervals during a 3‐year period. In Analysis 1, aetiology differences in making intrusion errors were examined. Twenty‐three adults with unspecified ID in the moderate to mild range [time 1(T1) mean age = 47.2 years] and 42 adults with DS (T1 mean age = 44.3) participated. WLR is a serial WM task beginning at two word sequences and progressively increasing by one word every three trials. WLR intrusions were analysed because they were least likely to include ‘educated guesses’ because this test is not based on semantic categories. In Analysis 2, we only examined participants with DS. They were divided into two groups, 16 individuals who made at least one intrusion error at T1 (T1 mean age = 45.8) and 26 who did not (T1 mean age = 43.3). Longitudinal performance for these groups was analysed to determine whether the group that intruded at T1 did more poorly on subsequent memory tests.

Results  A higher proportion of responses comprised intrusions for the group with DS and a higher percentage of the participants with DS made at least one intrusion error when compared with participants with unspecified ID (74% and 44% respectively). Those participants with DS who made at least one intrusion error at T1 showed a subsequent decline in performance on both WLR and the SRT.

Conclusions  The production of intrusion errors during a verbal WM task is a characteristic of middle‐aged adults with DS. This suggests compromised executive function and control of inhibition within the verbal modality for this group. Further, verbal intrusions are a qualitative aspect of verbal processing that merit attention in considering the issue of deficiencies of language and verbal WM abilities among people with DS. Last, and perhaps most importantly, although not definitive diagnostically, an increase in verbal intrusions is a potentially noteworthy signal when evaluating the cognitive health of adults with DS.
A long‐term population‐based clinical and morbidity review of Prader–Willi syndrome in Western Australia
Authors: Thomson A. K. , Glasson E. J. , Bittles A. H.
Published: November 2005

Background  An investigation of the clinical morbidity and genetic profiles of individuals with Prader–Willi syndrome (PWS) in Western Australia (WA) was undertaken as part of a wider study into the effects of intellectual disability (ID) on the life course of individuals.

Methods  All persons with a diagnosis of PWS were identified from the records of the Disability Services Commission of WA (DSC). The DSC client files formed the main data source, and were supplemented by information from other state health data sets. The analysis was retrospective and quantitative in nature.

Results  A total of 56 individuals were identified, 10 of whom exhibited normal methylation patterns and so were analysed separately (PWS‐like). The ages of the PWS group ranged from 0.9 to 48.3 years, with six persons deceased. Most people with PWS (76%) had mild or moderate ID, and 70% lived in their family home. The birth prevalence of the disorder was 1 in 29 500 births. Respiratory disorders, dentistry and gastrointestinal disorders were common reasons for hospital admission, with epilepsy or convulsions also reported at moderate frequency. The PWS‐like group shared many clinical features in common with PWS patients, the principal exceptions being hypotonia and feeding difficulties in infancy.

Conclusions  The estimated birth prevalence of PWS was lower than expected; however, the case ascertainment method may have excluded some individuals. Older people with PWS were generally living in sheltered accommodation. As the cohort ages, demand for places in similar accommodation will increase, adding to the existing burden on service providers. Substantial future increases in the use of medical services and hospital‐based care also are predicted with the onset of age‐associated disorders.
Effects of pioglitazone in familial combined hyperlipidaemia
Authors: ABBINK E. J. , DE GRAAF J. , DE HAAN J. H. , HEERSCHAP A. , STALENHOEF A. F. , TACK C. J.
Published: November 2005

Objectives.  Familial combined hyperlipidaemia (FCH) is associated with insulin resistance. We hypothesized that pioglitazone treatment of FCH patients might increase insulin sensitivity, but may also improve serum lipid levels, body fat distribution, intramyocellular lipids (IMCL) and endothelial function.

Design.  Double blind, randomized, cross‐over study.

Subjects.  Seventeen FCH patients.

Interventions.  Sixteen weeks of pioglitazone treatment (30 mg) compared with 16 weeks of placebo.

Main outcome measurements.  Insulin sensitivity was measured using the hyperinsulinaemic euglycaemic clamp procedure, body fat distribution and IMCL using magnetic resonance techniques and endothelial function using flow‐mediated vasodilatation.

Results.  Pioglitazone improved insulin sensitivity (M value 37.7 ± 3.6 μmol min−1 kg−1 vs. 33.0 ± 3.3 μmol min−1 kg−1 during placebo, P < 0.05) and LDL composition by increasing the K value (−0.11 ± 0.06 vs. −0.20 ± 0.06 during placebo, P < 0.05). However, pioglitazone did not affect other serum lipid levels. Endothelial function, body fat distribution and IMCL were also not affected. In addition, pioglitazone was associated with a decrease in liver enzymes (alkaline phosphatase).

Conclusion.  Pioglitazone treatment of FCH patients without type 2 diabetes mellitus increases insulin sensitivity, decreases liver enzymes and improves LDL composition but has a neutral effect on total serum lipid levels. The change in insulin sensitivity might be too small to induce changes in endothelial function, body fat distribution and IMCL.
Modelling and imaging cardiac repolarization abnormalities
Authors: RUDY Y.
Published: November 2005

Repolarization abnormalities, including those induced by the congenital or acquired long QT (LQT) syndrome, provide a substrate for life‐threatening cardiac arrhythmias. In this article, we use computational biology to link HERG mutations mechanistically to the resulting abnormalities of the whole‐cell action potential. We study how the kinetic properties of IKs (the slow delayed rectifier) that are conferred by molecular subunit interactions, facilitate its role in repolarization and ‘repolarization reserve’. A new noninvasive imaging modality (electrocardiographic imaging) is shown to image cardiac repolarization on the epicardial surface, suggesting its possible role in risk stratification, diagnosis and treatment of LQT syndrome.
Amplification of spatial dispersion of repolarization underlies sudden cardiac death associated with catecholaminergic polymorphic VT, long QT, short QT and Brugada syndromes
Authors: ANTZELEVITCH C. , OLIVA A.
Published: November 2005

This review examines the hypothesis that amplification of spatial dispersion of repolarization in the form of transmural dispersion of repolarization (TDR) underlies the development of life‐threatening ventricular arrhythmias associated with inherited ion channelopathies including the long QT, short QT and Brugada syndromes as well as catecholaminergic polymorphic ventricular tachycardia. In the long QT syndrome, amplification of TDR is often secondary to preferential prolongation of the action potential duration (APD) of M cells, whereas in the Brugada syndrome, it is thought to be because of selective abbreviation of the APD of right ventricular epicardium. Preferential abbreviation of APD of either endocardium or epicardium appears to be responsible for amplification of TDR in the short QT syndrome. In catecholaminergic polymorphic VT, the reversal of the direction of activation of the ventricular wall is responsible for the increase in TDR. In conclusion, the long QT, short QT, Brugada and catecholaminergic VT syndromes are pathologies with very different phenotypes and aetiologies, but which share a common final pathway in causing sudden death.
Molecular/genetic determinants of repolarization and their modification by environmental stress
Authors: ROSEN M. R. , COHEN I. S.
Published: November 2005

Although a variety of factors, inherited or environmental, can influence expression of ion channel proteins to impact on repolarization, that environment can affect genetic determinants of repolarization for intervals of varying duration is a concept that is not as generally appreciated as it should be. In the following pages we review the molecular/genetic determinants of cardiac repolarization and summarize how pathologic events and environmental intrusions can affect these determinants. Understanding the chains of events involved should yield insights into both the causes and potential avenues of treatment for abnormalities of repolarization.
Estimating population size of endangered brush‐tailed rock‐wallaby (Petrogale penicillata) colonies using faecal DNA
Authors: PIGGOTT M. P. , BANKS S. C. , STONE N. , BANFFY C. , TAYLOR A. C.
Published: November 2005

The brush‐tailed rock‐wallaby (Petrogale penicillata) is an endangered species in southeastern Australia and many of the remaining populations are declining. The steep rocky habitat and shy nature of the species make it difficult to obtain data on population parameters such as abundance and recruitment. Faecal pellet counts from scat plots are commonly used to monitor population trends but these are imprecise and difficult to relate to absolute population size. We conducted a noninvasive genetic sampling ‘mark–recapture’ study over a 2‐year period to identify individuals from faecal DNA samples and estimate the population size of four brush‐tailed rock‐wallaby colonies located in Wollemi National Park, New South Wales. Scat plots in rock‐wallaby colonies were used as sample collection points for this study. Two separate population estimates were carried out for three of the colonies to determine if we could detect recruitment and changes in population size. We determined that there was one large colony of an estimated 67 individuals (95% confidence interval: 55–91) and three smaller colonies. Monitoring of the smaller colonies also detected possible population size increases in all three. Our results indicate that faecal DNA analysis may be a promising method for estimating and monitoring population trends in this species particularly when used with a traditional field survey method.
Microsatellites reveal a lack of structure in Australian populations of the diamondback moth, Plutella xylostella (L.)
Authors: ENDERSBY N. M. , MCKECHNIE S. W. , RIDLAND P. M. , WEEKS A. R.
Published: November 2005

The diamondback moth, Plutella xylostella, is renowned for developing resistance to insecticides and causing significant economic damage to Brassica vegetable crops throughout the world. Yet despite its economic importance, little is known about the population structure and movement patterns of this pest both at local and regional scales. In Australia, the movement patterns and insecticide resistance status of P. xylostella infesting canola, vegetables, forage brassicas and weeds have fundamental implications for the management of this pest. Here we use six polymorphic microsatellite loci to investigate population structure and gene flow in Australian populations of P. xylostella. Samples of P. xylostella from New Zealand, Malaysia, Indonesia and Kenya were also scored at these loci. We found no evidence of population structure within Australia, with most populations having low inbreeding coefficients and in Hardy–Weinberg equilibrium. In addition, a sample from the North Island of New Zealand was indistinguishable from the Australian samples. However, large genetic differences were found between the Australia/New Zealand samples and samples from Kenya, Malaysia and Indonesia. There was no relationship between genetic distance and geographic distance among Australian and New Zealand samples. Two of the loci were found to have null alleles, the frequency of which was increased in the populations outside the Australia/New Zealand region. We discuss these results with reference to insecticide resistance management strategies for P. xylostella in Australia.
Effect of genotype and environment on branching in weedy green millet (Setaria viridis) and domesticated foxtail millet (Setaria italica) (Poaceae)
Authors: DOUST ANDREW N. , KELLOGG ELIZABETH A.
Published: November 2005

Many domesticated crops are derived from species whose life history includes weedy characteristics, such as the ability to vary branching patterns in response to environmental conditions. However, domesticated crop plants are characterized by less variable plant architecture, as well as by a general reduction in vegetative branching compared to their progenitor species. Here we examine weedy green millet and its domesticate foxtail millet that differ in the number of tillers (basal branches) and axillary branches along each tiller. Branch number in F2:3 progeny of a cross between the two species varies with genotype, planting density, and other environmental variables, with significant genotype–environment interactions (GEI). This is shown by a complex pattern of reaction norms and by variation in the pattern of significant quantitative trait loci (QTL) amongst trials. Individual and joint analyses of high and low density trials indicate that most QTL have significant GEI. Dominance and epistasis also explain some variation in branching. Likely candidate genes underlying the QTL (based on map position and phenotypic effect) include teosinte branched1 and barren stalk1. Phytochrome B, which has been found to affect response to shading in other plants, explains little or no variation. Much variation in branching is explained by QTL that do not have obvious candidate genes from maize or rice.
Mycoplasma mycoides ssp. mycoides Biotype Small Colony‐Secreted Components Induce Apoptotic Cell Death in Bovine Leucocytes
Authors: Dedieu L. , Chapey E. , Balcer‐Rodrigues V.
Published: November 2005

Contagious bovine pleuropneumonia, caused by Mycoplasma mycoides ssp. mycoides biotype small colony (MmmSC), is one of the most serious cattle diseases in Africa. Several observations suggested that MmmSC had evolved an efficient way to escape the bovine immune responses by triggering host‐cell cytotoxicity. This study was implemented to determine whether the cytotoxic effect was due to apoptotic cell death. To that end, bovine blood cells were cultured for up to 3 days in the presence of viable or heat‐killed MmmSC compared to unstimulated cultures. The findings provided evidence for a viable MmmSC‐induced, time‐dependent apoptosis in bovine blood leucocytes, whereas heat‐killed MmmSC had no effect. Morphological and physiological changes (evidenced by TUNEL and annexin V staining) typical of apoptosis were observed in response to viable MmmSC. All the lymphocyte subsets as well as the monocyte/granulocyte subset exhibited extensive apoptosis after exposure to viable MmmSC. Our results demonstrated a potential role for MmmSC‐secreted components as pathogenic factors able to induce programmed cell death in bovine blood leucocytes.
Detection of an Autologous Ligand for Mannan‐Binding Lectin on Human B Lymphocytes
Authors: Downing I. , MacDonald S. L. , Turner M. L. , Kilpatrick D. C.
Published: November 2005

Mannan‐binding lectin (MBL) is a collectin and a major soluble pattern‐recognition protein. MBL can distinguish self from nonself and altered self using its C‐type carbohydrate recognition domain and may also interact via its collagen‐like region with autologous cells. Recently, it was found that MBL could bind to adherent cells (monocytes) and dendritic cells in a specific and sugar‐sensitive manner. We have now investigated the interaction of MBL with fresh human peripheral blood cells and report binding to B lymphocytes and natural killer cells. The binding to B lymphocytes was studied in detail and was compared with the binding of MBL to monocytes and dendritic cells. Binding of MBL to B cells was evident at physiological MBL and calcium concentrations but was optimal at supraphysiological MBL concentrations. It was readily inhibited by autologous serum, mannan, mannose, GlcNAc and (to a lesser extent) galactose but not by C1q. A similar, but not identical, inhibition profile was observed with dendritic cells, but monocytes were not sensitive to mannose or mannan. We conclude that MBL is capable of binding to differently glycosylated ligands on several autologous cell types via its carbohydrate‐recognition domain. We speculate that this could have functional significance at extravascular sites, but perhaps only in individuals possessing MBL genotypes conferring MBL sufficiency.
Analysis of Epitopes on the Unrelated Proteins Thyrotropin Receptor and α1‐Antitrypsin which are Recognized by A10 Monoclonal Antibody
Authors: Piotrowska U. , Adler G.
Published: November 2005

In a previous study, we noticed an unexpected reaction of an antithyrotropin receptor ectodomain (ETSHR)‐reactive monoclonal antibody, A10, with α1‐antitrypsin (antitrypsin). Presently, we decided to probe the structural basis of this cross‐reactivity. Recombinant ETSHR, antitrypsin, synthetic peptides corresponding to the region of similarity in these proteins (EEDFRV and EEDFHV, respectively) and a set of peptides related to this region, N‐ and C‐terminally elongated, were used in the study. Comparing the values of the dissociation constants, we found that the affinity of peptides corresponding to the region of similarity to monoclonal antibody A10 was the same in spite of a difference in one residue (R 38 in ETSHR and H 209 in antitrypsin), whereas a change of E 206 to R in antitrypsin‐related peptide dramatically decreased the affinity. The whole binding site of A10 in ETSHR as well as in antitrypsin was larger than the region of similarity. We propose that residues ECHQEEDFV represent the monoclonal antibody A10 epitope. They form an almost continuous sequence of residues 30–37 and 39 in ETSHR. The monoclonal antibody A10 binding site on antitrypsin is shorter. It comprises amino acids 205–208 and 210, from the region of similarity with, probably, additional two residues, H‐287 and E 363.