First imaging of corotating interaction regions using the STEREO spacecraft

Plasma parcels are observed propagating from the Sun out to the large coronal heights monitored by the Heliospheric Imagers (HI) instruments onboard the NASA STEREO spacecraft during September 2007. The source region of these out-flowing parcels is found to corotate with the Sun and to be rooted near the western boundary of an equatorial coronal hole. These plasma enhancements evolve during their propagation through the HI cameras’ fields of view and only becoming fully developed in the outer camera field of view. We provide evidence that HI is observing the formation of a Corotating Interaction Region(CIR) where fast solar wind from the equatorial coronal hole is interacting with the slow solar wind of the streamer belt located on the western edge of that coronal hole. A dense plasma parcel is also observed near the footpoint of the observed CIR at a distance less than 0.1AU from the Sun where fast wind would have not had time to catch up slow wind. We suggest that this low-lying plasma enhancement is a plasma parcel which has been disconnected from a helmet streamer and subsequently becomes embedded inside the corotating interaction region.

Taxonomical vs. functional responses of bee communities to fire in two contrasting climatic regions

Valuable insights into mechanisms of community responses to environmental change can be gained by analysing in tandem the variation in functional and taxonomic composition along environmental gradients. We assess the changes in species and functional trait composition (i.e. dominant traits and functional diversity) of diverse bee communities in contrasting fire-driven systems in two climatic regions: Mediterranean (scrub habitats in Israel) and temperate (chestnut forests in southern Switzerland). In both climatic regions, there were shifts in species diversity and composition related to post-fire age. In the temperate region, functional composition responded markedly to fire; however, in the Mediterranean, the taxonomic response to fire was not matched by functional replacement. These results suggest that greater functional stability to fire in the Mediterranean is achieved by replacement of functionally similar species (i.e. functional redundancy) which dominate under different environmental conditions in the heterogeneous landscapes of the region. In contrast, the greater functional response in the temperate region was attributed to a more rapid post-fire vegetation recovery and shorter time-window when favourable habitat was available relative to the Mediterranean. Bee traits can be used to predict the functional responses of bee communities to environmental changes in habitats of conservation importance in different regions with distinct disturbance regimes. However, predictions cannot be generalized from one climatic region to another where distinct habitat configurations occur.

Prevalence and determinants of Cryptosporidium spp. infection in smallholder dairy cattle in Iringa and Tanga Regions of Tanzania

The prevalence of Cryptosporidium spp. infection in a cross-sectional study of dairy cattle, from two contrasting dairying regions in Tanzania, were determined by staining smears of faecal samples with the modified Ziehl-Neelsen technique. Of the 1126 faecal samples screened, 19.7% were positive for Cr\yptosporidium spp. The prevalence was lower in Tanga Region than in Iringa Region. The prevalence of affected farms was 20% in Tanga and 21 % in Iringa. In both regions, the probability of detecting Cryptosporidium oocysts in faeces varied with animal class, but these were not consistent in both regions. In Tanga Region, Cryptosporidium oocysts were significantly more likely to be found in the faeces of milking cows. In Iringa Region, the likelihood that cattle had Cryptosporidium-positive faeces declined with age, and milking cattle were significantly less likely to have Cryptosporidium-positive faeces. In this region, 7% of cattle were housed within the family house at night, and this was marginally associated with a higher likelihood that animals had Ctyptosporidium-positive faeces. Our study suggests that even though herd sizes are small, Cryptosporidium spp. are endemic on many Tanzanian smallholder dairy farms. These protozoa may impact on animal health and production, but also on human health, given the close associations between the cattle and their keepers. Further studies are required to assess these risks in more detail, and understand the epidemiology of Cryptosporidium spp. in this management system.

Measuring bee diversity in different European habitats and biogeographical regions

Bee pollinators are currently recorded with many different sampling methods. However, the relative performances of these methods have not been systematically evaluated and compared. In response to the strong need to record ongoing shifts in pollinator diversity and abundance, global and regional pollinator initiatives must adopt standardized sampling protocols when developing large-scale and long-term monitoring schemes. We systematically evaluated the performance of six sampling methods (observation plots, pan traps, standardized and variable transect walks, trap nests with reed internodes or paper tubes) that are commonly used across a wide range of geographical regions in Europe and in two habitat types (agricultural and seminatural). We focused on bees since they represent the most important pollinator group worldwide. Several characteristics of the methods were considered in order to evaluate their performance in assessing bee diversity: sample coverage, observed species richness, species richness estimators, collector biases (identified by subunit-based rarefaction curves), species composition of the samples, and the indication of overall bee species richness (estimated from combined total samples). The most efficient method in all geographical regions, in both the agricultural and seminatural habitats, was the pan trap method. It had the highest sample coverage, collected the highest number of species, showed negligible collector bias, detected similar species as the transect methods, and was the best indicator of overall bee species richness. The transect methods were also relatively efficient, but they had a significant collector bias. The observation plots showed poor performance. As trap nests are restricted to cavity-nesting bee species, they had a naturally low sample coverage. However, both trap nest types detected additional species that were not recorded by any of the other methods. For large-scale and long-term monitoring schemes with surveyors with different experience levels, we recommend pan traps as the most efficient, unbiased, and cost-effective method for sampling bee diversity. Trap nests with reed internodes could be used as a complementary sampling method to maximize the numbers of collected species. Transect walks are the principal method for detailed studies focusing on plant-pollinator associations. Moreover, they can be used in monitoring schemes after training the surveyors to standardize their collection skills.

Point estimates and confidence regions for sequential trials involving selection

A number of authors have proposed clinical trial designs involving the comparison of several experimental treatments with a control treatment in two or more stages. At the end of the first stage, the most promising experimental treatment is selected, and all other experimental treatments are dropped from the trial. Provided it is good enough, the selected experimental treatment is then compared with the control treatment in one or more subsequent stages. The analysis of data from such a trial is problematic because of the treatment selection and the possibility of stopping at interim analyses. These aspects lead to bias in the maximum-likelihood estimate of the advantage of the selected experimental treatment over the control and to inaccurate coverage for the associated confidence interval. In this paper, we evaluate the bias of the maximum-likelihood estimate and propose a bias-adjusted estimate. We also propose an approach to the construction of a confidence region for the vector of advantages of the experimental treatments over the control based on an ordering of the sample space. These regions are shown to have accurate coverage, although they are also shown to be necessarily unbounded. Confidence intervals for the advantage of the selected treatment are obtained from the confidence regions and are shown to have more accurate coverage than the standard confidence interval based upon the maximum-likelihood estimate and its asymptotic standard error.

A functional proteomic method for the enrichment of peripheral membrane proteins reveals the collagen binding protein Hsp47 is exposed on the surface of activated human platelets

Platelets are small blood cells vital for hemostasis. Following vascular damage, platelets adhere to collagens and activate, forming a thrombus that plugs the wound and prevents blood loss. Stimulation of the platelet collagen receptor glycoprotein VI (GPVI) allows recruitment of proteins to receptor-proximal signaling complexes on the inner-leaflet of the plasma membrane. These proteins are often present at low concentrations; therefore, signaling-complex characterization using mass spectrometry is limited due to high sample complexity. We describe a method that facilitates detection of signaling proteins concentrated on membranes. Peripheral membrane proteins (reversibly associated with membranes) were eluted from human platelets with alkaline sodium carbonate. Liquid-phase isoelectric focusing and gel electrophoresis were used to identify proteins that changed in levels on membranes from GPVI-stimulated platelets. Immunoblot analysis verified protein recruitment to platelet membranes and subsequent protein phosphorylation was preserved. Hsp47, a collagen binding protein, was among the proteins identified and found to be exposed on the surface of GPVI-activated platelets. Inhibition of Hsp47 abolished platelet aggregation in response to collagen, while only partially reducing aggregation in response to other platelet agonists. We propose that Hsp47 may therefore play a role in hemostasis and thrombosis.

Chemical characterisation of wild populations of Thymus from different climatic regions in southeast Spain

Thymus is taxonomically a very complex genus with a high frequency of hybridisation and introgression among sympatric species. The variation in accumulation of leaf-surface flavonoids was investigated in 71 wild populations of Thymus front different putative hybrid swarm areas in Andalucia, Spain. Twenty-two flavones, five flavanones, two dihydroflavonols, a flavonol and two unknowns were detected by HPLC-DAD combined with LC-APCI-MS analysis. The majority of compounds were flavones with a lutelin-type substitution of the B-ring, in contrast to previous reports on Macedonian taxa, which predominantly accumulate flavones with apigenin-type substitution of the B-ring. Anatomical and morphometric studies, supported by cluster analysis, identified pure Thymus hyemalis and Thymus baeticus populations, and a large number of putative hybrids. Flavonoid variation was closely related to morphological variation in all populations and is suspected to be a result of genetic polymorphism. Principal component analysis identified the presence of species-specific and geographically linked chemotypes and putative hybrids with mixed morphological and chemical characteristics. Qualitative and quantitative flavonoid accumulation appears to be genetically regulated, while external factors play a secondary role. Flavonoid profiles can thus provide diagnostic markers for the taxonomy of Thymus and are also useful in detecting hybridising taxa. (C) 2007 Elsevier Ltd. All rights reserved.

Peripheral tachykinins and the neurokinin receptor NK1 are required for platelet thrombus formation

Platelets play an important role in hemostasis, with inappropriate platelet activation being a major contributor to debilitating and often fatal thrombosis by causing myocardial infarction and stroke. Although current antithrombotic treatment is generally well tolerated and effective, many patients still experience cardiovascular problems, which may reflect the existence of alternative underlying regulatory mechanisms in platelets to those targeted by existing drugs. In this study, we define a role for peripherally distributed members of the tachykinin family of peptides, namely substance P and the newly discovered endokinins A and B that are present in platelets, in the activation of platelet function and thrombus formation. We have reported previously that the preferred pharmacologically characterized receptor for these peptides, the NK1 receptor, is present on platelets. Inhibition or deficiency of the NK1 receptor, or SP agonist activity, resulted in substantially reduced thrombus formation in vitro under arterial flow conditions, increased bleeding time in mice, and a decrease in experimentally induced thromboembolism. Inhibition of the NK1 receptor may therefore provide benefit in patients vulnerable to thrombosis and may offer an alternative therapeutic target.

The role of Wnt signalling in the development of somites and neural crest

The Wnt family of secreted signalling molecules controls a wide range of developmental processes in all metazoans. In this investigation we concentrate on the role that members of this family play during the development of (1) the somites and (2) the neural crest. (3) We also isolate a novel component of the Wnt signalling pathway called Naked cuticle and investigate the role that this protein may play in both of the previously mentioned developmental processes. (1) In higher vertebrates the paraxial mesoderm undergoes a mesenchymal-to-epithelial transformation to form segmentally organised structures called somites. Experiments have shown that signals originating from the ectoderm overlying the somites or from midline structures are required for the formation of the somites, but their identity has yet to be determined. Wnt6 is a good candidate as a somite epithelialisation factor from the ectoderm since it is expressed in this tissue. In this study we show that injection of Wnt6-producing cells beneath the ectoderm at the level of the segmental plate or lateral to the segmental plate leads to the formation of numerous small epithelial somites. We show that Wnts are indeed responsible for the epithelialisation of somites by applying Wnt antagonists which result in the segmental plate being unable to form somites. These results show that Wnt6, the only member of this family to be localised to the chick paraxial ectoderm, is able to regulate the development of epithelial somites and that cellular organisation is pivotal in the execution of the differentiation programmes. (2) The neural crest is a population of multipotent progenitor cells that arise from the neural ectoderm in all vertebrate embryos and form a multitude of derivatives including the peripheral sensory neurons, the enteric nervous system, Schwann cells, pigment cells and parts of the craniofacial skeleton. The induction of the neural crest relies on an ectodermally derived signal, but the identity of the molecule performing this role in amniotes is not known. Here we show that Wnt6, a protein expressed in the ectoderm, induces neural crest production. (3) The intracellular response to Wnt signalling depends on the choice of signalling cascade activated in the responding cell. Cells can activate either the canonical pathway that modulates gene expression to control cellular differentiation and proliferation, or the non-canonical pathway that controls cell polarity and movement (Pandur et al. 2002b). Recent work has identified the protein Naked cuticle as an intracellular switch promoting the non-canonical pathway at the expense of the canonical pathway. We have cloned chick Naked cuticle-1 (cNkd1) and demonstrate that it is expressed in a dynamic manner during early embryogenesis. We show that it is expressed in the somites and in particular regions where cells are undergoing movement. Lastly our study shows that the expression of cNkd1 is regulated by Wnt expression originating from the neural tube. This study provides evidence that non-canonical Wnt signalling plays a part in somite development.

Modelling the formation of necrotic regions in avascular tumours

The mechanisms underlying the formation of necrotic regions within avascular tumours are not well understood. In this paper, we examine the relative roles of nutrient deprivation and of cell death, from both the proliferating phase of the cell cycle via apoptosis and from the quiescent phase via necrosis, in changing the structure within multicellular tumour spheroids and particularly the accumulation of dead cell material in the centre. A mathematical model is presented and studied that accounts for nutrient diffusion, changes in cell cycling rates, the two different routes to cell death as well as active motion of cells and passive motion of the dead cell material. In studying the accumulation of dead cell matter we do not distinguish between the route by which each was formed. The resulting mathematical model is examined for a number of scenarios. Results show that in many cases the size of the necrotic core is closely correlated with low levels in nutrient concentration. However, in certain cases, particularly where the rate of necrosis is large, the resulting necrotic core can lead to regions of non-negligible nutrient concentration-dependent upon the mode of cell death.

A system for studying epithelial-stromal interactions reveals distinct inductive abilities of stromal cells from benign prostatic hyperplasia and prostate cancer

The development of normal and abnormal glandular structures in the prostate is controlled at the endocrine and paracrine levels by reciprocal interactions between epithelium and stroma. To study these processes it is useful to have an efficient method of tissue acquisition for reproducible isolation of cells from defined histologies. Here we assessed the utility of a standardized system for acquisition and growth of prostatic cells from different regions of the prostate with different pathologies, and we compared the abilities of stromal cells from normal peripheral zone (PZ-S), benign prostatic hyperplasia (BPH-S), and cancer (CA-S) to induce the growth of a human prostatic epithelial cell line (BPH-1) in vivo. Using the tissue recombination method, we showed that grafting stromal cells (from any histology) alone, or BPH-1 epithelial cells alone produced no visible grafts. Recombining PZ-S with BPH-1 cells also produced no visible grafts (n = 15). Recombining BPH-S with BPH-1 cells generated small, well-organized and sharply demarcated grafts approximately 3-4 mm in diameter (n = 9), demonstrating a moderate inductive ability of BPH-S. Recombining CA-S with BPH-1 cells generated highly disorganized grafts that completely surrounded the host kidney and invaded into adjacent renal tissue, demonstrating induction of an aggressive phenotype. We conclude that acquisition of tissue from toluidine blue dye stained specimens is an efficient method to generate high quality epithelial and/or stromal cultures. Stromal cells derived by this method from areas of BPH and cancer induce epithelial cell growth in vivo which mimics the natural history of these diseases.

The structure of interrupted human AC microsatellites

Microsatellite lengths change over evolutionary time through a process of replication slippage. A recently proposed model of this process holds that the expansionary tendencies of slippage mutation are balanced by point mutations breaking longer microsatellites into smaller units and that this process gives rise to the observed frequency distributions of uninterrupted microsatellite lengths. We refer to this as the slippage/point-mutation theory. Here we derive the theory's predictions for interrupted microsatellites comprising regions of perfect repeats, labeled segments, separated by dinucleotide interruptions containing point mutations. These predictions are tested by reference to the frequency distributions of segments of AC microsatellite in the human genome, and several predictions are shown not to be supported by the data, as follows. The estimated slippage rates are relatively low for the first four repeats, and then rise initially linearly with length, in accordance with previous work. However, contrary to expectation and the experimental evidence, the inferred slippage rates decline in segments above 10 repeats. Point mutation rates are also found to be higher within microsatellites than elsewhere. The theory provides an excellent fit to the frequency distribution of peripheral segment lengths but fails to explain why internal segments are shorter. Furthermore, there are fewer microsatellites with many segments than predicted. The frequencies of interrupted microsatellites decline geometrically with microsatellite size measured in number of segments, so that for each additional segment, the number of microsatellites is 33.6% less. Overall we conclude that the detailed structure of interrupted microsatellites cannot be reconciled with the existing slippage/point-mutation theory of microsatellite evolution, and we suggest that microsatellites are stabilized by processes acting on interior rather than on peripheral segments.

Trinuclear cu(ll) complexes containing peripheral ketonic oxygen bridges and a mu(3)-OH core: Syntheses, crystal structures, spectroscopic and magnetic properties

Four new trinuclear copper(II) complexes, [(CuL1)(3)(mu(3)-OH)](ClO4)(2)center dot H2O (1), [(CuL2)(3)(mu(3)-OH)](CIO4)(2) (2), [(CuL3)(3)-(mu(3)-OH)](ClO4)(4)center dot H2O (3), and [(CuL4)(3)(mu(3)-OH)](ClO4)(2)center dot H2O (4), where HL1 = 8-amino-4,7,7-trimethyl-5-azaoct-3-en-2-one, HL2 = 7-amino-4-methyl-5-azaoct-3-en-2-one, HL3 = 7(ethylamino)-4-methyl-5-azahept-3-en-2-one, and HL4 = 4-methyl-7-(methylamino)-5-azahept-3-en-2-one, have been derived from the four tridentate Schiff bases (HL1, HL2, HL3, and HL4) and structurally characterized by X-ray crystallography. For all compounds, the cationic part is trinuclear with a CU3OH core held by three carbonyl oxygen bridges between each pair of copper(II) atoms. The copper atoms are five-coordinate with a distorted square-pyramidal geometry; the equatorial plane consists of the bridging oxygen atom of the central OH group together with three atoms (N, N, O) from one ligand whereas an oxygen atom of a second ligand occupies the axial position. Magnetic measurements have been performed in the 2-300 K temperature range. The experimental data could be satisfactorily reproduced by using an isotropic exchange model, H = -J(S1S2+S2S3+S1S3) yielding as best-fit parameters: J = -66.7 and g = 2.19 for 1, J = -36.6 and g = 2.20 for 2, J = -24.5 and g = 2.20 for 3, and J = -14.9 and g = 2.05 for 4. EPR spectra at low temperature show the existence of spin frustration in complexes 3 and 4, but it has not been possible to carry out calculations of the antisymmetric exchange parameter, G, from magnetic data. In frozen methanolic solution, at 4 K, hyperfine splitting in all complexes and spin frustration in complex 4 seem to be confirmed. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Trinuclear Cu(II) complexes containing peripheral ketonic oxygen bridges and a mu(3)-OH core: steric influence on their structures and existence

Two tridentate Schiff bases, HL1(6-amino-3-methyl-1-phenyl-4-azahex-2-en-1-one), and HL2 (6-atnino-3,6-dimethyl-1-phenyl-4-azahex-2-en-1-one) on reaction with Cu(II) perchlorate in the presence of triethyl amine yielded two new trinuclear copper(II) complexes, [(CuL1)(3)(mu(3)-OH)](ClO4)(2) (1) and [(CuL2)(3)(mu(3)-OH)](ClO4)(2) center dot 0.75H(2)O (2), whereas another tridentate ligand HL3 (7-amino-3-methyl-1-phenyl-4-azahept-2-en-1-one) underwent hydrolysis under the same reaction conditions to result in the formation of a mononuclear complex, [Cu(bn)(pn)ClO4] (3) [where bn = 1-benzoylacetonate and pn = 1,3-propanediamine]. All three complexes have been characterized by X-ray crystallography. For both 1 and 2 the cationic part is trinuclear with a [Cu3OH] core held by three carbonyl oxygen bridges between each pair of copper(II) atoms. The structure of 3 is a monomer with a chelating 1,3-propanediamine and a benzoyl acetone moiety. Magnetic measurements of I and 2 have been performed in the 2-300 K temperature range. The experimental data could be satisfactorily reproduced by using an isotropic exchange model, H = -J(S1S2 + S2S3 + S1S3), yielding as best fit parameters: J = -25.6 cm(-1), g = 2.21 for 1 and J = 11.2 cm(-1), g = 2.10 for 2. The EPR spectra at low temperature could be indicative of spin frustration in complex 1. (C) 2006 Elsevier Ltd. All rights reserved.