The regulation of integrin-linked kinase in human platelets: evidence for involvement in the regulation of integrin alpha(2)beta(1)

Background: Activation of the platelet integrin alpha(2)beta(1) is closely regulated due to the high thrombogenicity of its ligand. As a beta(1) interacting kinase, ILK represents a candidate intracellular regulator of alpha(2)beta(1) in human platelets. Objectives We investigated the regulation of ILK in human platelets and the role of ILK in regulating alpha(2)beta(1) activation in HEL cells, a megakaryocytic cell line. Methods: An in-vitro kinase assay was used to determine the effect of platelet agonists on ILK kinase activity together with the contribution of PI3K and PKC on ILK activation. Interaction of ILK with beta(1)-integrin subunits was investigated by coimmunoprecipitation and the role of ILK in regulating alpha(2)beta(1) function assessed by overexpression studies in HEL cells. Results: We report that collagen and thrombin modulate ILK kinase activity in human platelets in an aggregation-independent manner. Furthermore, ILK activity is dually regulated by PI3K and PKC in thrombin-stimulated platelets and regulated by PI3K in collagen-stimulated cells. ILK associates with the beta(1)-integrin subunits immunoprecipitated from platelet cell lysates, an association which increased upon collagen stimulation. Overexpression of ILK in HEL cells enhanced alpha(2)beta(1)-mediated adhesion whereas overexpression of kinase-dead ILK reduced adhesion, indicating a role for this kinase in the positive regulation of alpha(2)beta(1). Conclusions: Our findings that ILK regulates alpha(2)beta(1) in HEL cells, is activated in platelets and associates with beta(1)-integrins, raise the possibility that it may play a key role in adhesion events upon agonist stimulation of platelets.

X-ray crystallographic study of DNA duplex cross-linking: simultaneous binding to two d(CGTACG)(2) molecules by a bis(9-aminoacridine-4-carboxamide) derivative

Acridine-4-carboxamides form a class of known DNA mono-intercalating agents that exhibit cytotoxic activity against tumour cell lines due to their ability to inhibit topoisomerases. Previous studies of bis-acridine derivatives have yielded equivocal results regarding the minimum length of linker necessary between the two acridine chromophores to allow bis-intercalation of duplex DNA. We report here the 1.7 angstrom resolution X-ray crystal structure of a six-carbon-linked bis(acridine-4-carboxamide) ligand bound to d(CGTACG)(2) molecules by non-covalent duplex cross-linking. The asymmetric unit consists of one DNA duplex containing an intercalated acridine-4-carboxamide chromophore at each of the two CG steps. The other half of each ligand is bound to another DNA molecule in a symmetry-related manner, with the alkyl linker threading through the minor grooves. The two crystallographically independent ligand molecules adopt distinct side chain interactions, forming hydrogen bonds to either O6 or N7 on the major groove face of guanine, in contrast to the semi-disordered state of mono-intercalators bound to the same DNA molecule. The complex described here provides the first structural evidence for the non-covalent cross-linking of DNA by a small molecule ligand and suggests a possible explanation for the inconsistent behaviour of six-carbon linked bis-acridines in previous assays of DNA bis-intercalation.

Reconstruction of historical pollination rates reveals linked declines of pollinators and plants

Widespread reports of low pollination rates suggest a recent anthropogenic decline in pollination that could threaten natural and agricultural ecosystems. Nevertheless, unequivocal evidence for a decline in pollination over time has remained elusive because it was not possible to determine historical pollination rates. Here we demonstrate a widely applicable method for reconstructing historical pollination rates, thus allowing comparison with contemporary rates from the same sites. We focused on the relationship between the oil-collecting bee Rediviva peringueyi (Melittidae) and the guild of oil-secreting orchid species (Coryciinae) that depends on it for pollination. The guild is distributed across the highly transformed and fragmented lowlands of the Cape Region of South Africa. We show that rehydrated herbarium specimens of Pterygodium catholicum, the most abundant member of the guild, contain a record of past pollinator activity in the form of pollinarium removal rates. Analysis of a pollination time series showed a recent decline in pollination on Signal Hill, a small urban conservation area. The same herbaria contain historical species occurrence data. We analyzed this data and found that there has been a contemporaneous shift in orchid guild composition in urban areas due to the local extirpation of the non-clonal species, consistent with their greater dependence on seeds and pollination for population persistence.

Synthesis and properties of tetra-μ-acetatodiruthenium(II,III) phenylphosphinate and phenylphosphonate complexes: X-ray crystal structures of [Ru2(μ-O2CCH3)4(HPhPO2)2]H and [Ru2(μ-O2CCH3)4(PhPO3H)2]H·H2O

Phenylphosphinic acid (HPhPO2H) and phenylphosphonic acid (PhPO3H2) react with a methanolic solution of [Ru2(μ-O2CCH3)4(O2CCH3)2]H·0.7H2O at room temperature to give [Ru2(μ-O2CCH3)4(HPhPO2)2H (1) and [Ru2(μ-O2CCH3)4 (PhPO3H)2]H·H2O (2), respectively. The X-ray crystal structures of 1 and 2 each show the RuRu core to be ligated by four bridging bidentate acetate ligands [RuRu distances: 1 = 2.272(1) Å; 2 = 2.267(2) Å] and two axial phenylphosphinate and phenylphosphonate ligands, respectively. In each complex the individual bimetallic molecules are linked together by a hydrogen ion which bridges the oxygen atoms of neighbouring axial ligands. In 2 the water molecule is also hydrogen-bonded to one of the axial phenylphosphonate groups. Spectroscopic, magnetic and cyclic voltammetric data for the complexes are given.

Synthesis of water-soluble and ether-soluble tetra-μ-acetatodiruthenium(II,III) complexes and X-ray crystal structure of [Ru2(μ-O2CC6H5)4(C2H5OH)2][Ru2(μ-O2CC6H5)4(HSO4)2]

[Ru2(μ-O2CCH3)4Cl] reacts readily with aqueous Ag2SO4 (2: 1 molar ratio) to give the sulphate salt [Ru2(μ-O2CCH3)4(H2O)2]2(SO4) (1). Addition of NaBPh4 to an aqueous solution of 1 produces the ether-soluble tetraphenylborate salt [Ru2(μ-O2CCH3)4(H2O)2][BPh4] (2). A methanolic solution of 1 reacts with Ba(C6H5CCCO2)2 · H2O to give the tetraacetatemonophenylpropynoate complex [Ru2(μ-O2CCH3)4(O2CCCC6H5)] · H2O (3). The reaction of an ethanolic suspension of [Ru2(μ-O2CC6H5)4Cl] with Ag2SO4 and H2SO4 (2 : 1 : 1 molar ratio) leads to the tetra-μ-benzoatodiruthenium(II,III) double complex salt [Ru2(μ-O2CC6H5)4(C2H5OH)2][Ru2(μ-O2CC6H5)4(HSO4)2] (4). Complex 4 is also obtained by reacting an ethanolic solution of 1 with an excess of benzoic acid in the presence of H2SO4. The X-ray crystal structure of 4 shows it to consist of [Ru2(μ-O2CC6H5)4(C2H5OH)2]+ and [Ru2(μ-O2CC6H5)4(HSO4)2]− ions, which are linked together by hydrogen bonds into an infinite polymeric chain. The RuRu distances in the cation and anion are very similar [2.265(2) and 2.272(2) Å, respectively]. Spectroscopic, magnetic, conductivity and cyclic voltammetry data are given for the complexes.

Stepwise construction of [Os6(CO)18(μ6-P)]-, a hexanuclear osmium cluster monoanion with trigonal-prismatic co-ordination for phosphorus: X-ray crystal structures of [Os6(μ-H)2(CO)20(MeCN)(μ3-PH)] and [PPh3Me][Os6(CO)18(μ6-P)]

Treatment of the labile cluster [Os3(CO)11(MeCN)] with PH3 affords the substituted product [Os3(CO)11(PH3)](1) in high yield. Subsequent reaction of (1) with Na2CO3 in MeOH, followed by acidification, gives the hydrido phosphido cluster [Os3(µ-H)(CO)10(µ-PH2)](2). When (2) is heated to 45–60 °C in the presence of [Os3(CO)11(MeCN)] a hexanuclear complex with the formulation [Os6(µ-H)2(CO)21(µ3-PH)](3) is obtained. If this reaction is repeated using [Os3(CO)10(MeCN)2] instead of [Os3(CO)11(MeCN)], an acetonitrile-containing product, [Os6(µ-H)2(CO)20(MeCN)(µ3-PH)](4), is obtained. An X-ray analysis of (4) shows that two Os3 triangular units are linked by a µ3-phosphinidene ligand, which symmetrically bridges an Os–Os edge of one triangle and is terminally co-ordinated to one Os atom of the second triangle. When (3) is treated with a weak base, such as [N(PPh3)2]Cl or [PPh3Me] Br, deprotonation to the corresponding cluster monoanion [Os6(µ-H)(CO)21(µ3-PH)]–(5) occurs. Treatment of (5) with a weak acid regenerates (3) in quantitative yield. Thermolysis of (3) leads to a closing up of the metal framework, affording the cluster [Os6(µ-H)(CO)18(µ6-P)], which readily deprotonates to give the anion [Os6(CO)18(µ6-P)]–(7) in the presence of [N(PPh3)2] Cl or [PPh3Me]Br. The same anion (7) may also be obtained by direct thermolysis of (5). An X-ray analysis of the [PPh3Me]+ salt of (7) confirms that the phosphorus occupies an interstitial site in a trigonal-prismatic hexaosmium framework, and co-ordinates to all six metal atoms with an average Os–P distance of 2.31 (1)Å. Proton and 31P n.m.r. data on all the new clusters are presented, and the position of the phosphorus resonance in the 31P n.m.r. spectrum is related to the changes in the environment of the phosphorus atom.

Tensor regression based on linked multiway parameter analysis

Classical regression methods take vectors as covariates and estimate the corresponding vectors of regression parameters. When addressing regression problems on covariates of more complex form such as multi-dimensional arrays (i.e. tensors), traditional computational models can be severely compromised by ultrahigh dimensionality as well as complex structure. By exploiting the special structure of tensor covariates, the tensor regression model provides a promising solution to reduce the model’s dimensionality to a manageable level, thus leading to efficient estimation. Most of the existing tensor-based methods independently estimate each individual regression problem based on tensor decomposition which allows the simultaneous projections of an input tensor to more than one direction along each mode. As a matter of fact, multi-dimensional data are collected under the same or very similar conditions, so that data share some common latent components but can also have their own independent parameters for each regression task. Therefore, it is beneficial to analyse regression parameters among all the regressions in a linked way. In this paper, we propose a tensor regression model based on Tucker Decomposition, which identifies not only the common components of parameters across all the regression tasks, but also independent factors contributing to each particular regression task simultaneously. Under this paradigm, the number of independent parameters along each mode is constrained by a sparsity-preserving regulariser. Linked multiway parameter analysis and sparsity modeling further reduce the total number of parameters, with lower memory cost than their tensor-based counterparts. The effectiveness of the new method is demonstrated on real data sets.

The use and usefulness of a parent questionnaire to help schools identify disability

The Equality Act 2010 will be implemented in full in 2011, and schools in the UK will have to provide special aids or services for children with disabilities where this provision is considered reasonable. This paper reports on staff perspectives on the use and usefulness of a parental questionnaire on disability from a sample of 49 schools (mainstream and special) located in 12 local authorities. Most schools found the process of administering the parent questionnaire undemanding; just under half of the sample indicated that they would take some action as a result of the data collected from the parental questionnaire (e.g., to inform plans for targeting or monitoring support for children, and to contact parents and follow-up issues they had mentioned); and about one-third of schools recorded unanticipated findings from the parental questionnaire, that is, the identification of children whose disabilities were not previously known to the school. Implications for schools are discussed.

Resources, staff beliefs and organizational culture: factors in the use of information and communication technology for adults with intellectual disabilities

Background  Access to, and the use of, information and communication technology (ICT) is increasingly becoming a vital component of mainstream life. First-order (e.g. time and money) and second-order factors (e.g. beliefs of staff members) affect the use of ICT in different contexts. It is timely to investigate what these factors may be in the context of service provision for adults with intellectual disabilities given the role ICT could play in facilitating communication and access to information and opportunities as suggested in Valuing People. Method  Taking a qualitative approach, nine day service sites within one organization were visited over a period of 6 months to observe ICT-related practice and seek the views of staff members working with adults with intellectual disabilities. All day services were equipped with modern ICT equipment including computers, digital cameras, Internet connections and related peripherals. Results  Staff members reported time, training and budget as significant first-order factors. Organizational culture and beliefs about the suitability of technology for older or less able service users were the striking second-order factors mentioned. Despite similar levels of equipment, support and training, ICT use had developed in very different ways across sites. Conclusion  The provision of ICT equipment and training is not sufficient to ensure their use; the beliefs of staff members and organizational culture of sites play a substantial role in how ICT is used with and by service users. Activity theory provides a useful framework for considering how first- and second-order factors are related. Staff members need to be given clear information about the broader purpose of activities in day services, especially in relation to the lifelong learning agenda, in order to see the relevance and usefulness of ICT resources for all service users.

High-throughput phenotyping (HTP) identifies seedling root traits linked to variation in seed yield and nutrient capture in field-grown oilseed rape (Brassica napusL.)

Background and Aims Root traits can be selected for crop improvement. Techniques such as soil excavations can be used to screen root traits in the field, but are limited to genotypes that are well-adapted to field conditions. The aim of this study was to compare a low-cost, high-throughput root phenotyping (HTP) technique in a controlled environment with field performance, using oilseed rape (OSR; Brassica napus) varieties. Methods Primary root length (PRL), lateral root length and lateral root density (LRD) were measured on 14-d-old seedlings of elite OSR varieties (n = 32) using a ‘pouch and wick’ HTP system (∼40 replicates). Six field experiments were conducted using the same varieties at two UK sites each year for 3 years. Plants were excavated at the 6- to 8-leaf stage for general vigour assessments of roots and shoots in all six experiments, and final seed yield was determined. Leaves were sampled for mineral composition from one of the field experiments. Key Results Seedling PRL in the HTP system correlated with seed yield in four out of six (r = 0·50, 0·50, 0·33, 0·49; P < 0·05) and with emergence in three out of five (r = 0·59, 0·22, 0·49; P < 0·05) field experiments. Seedling LRD correlated positively with leaf concentrations of some minerals, e.g. calcium (r = 0·46; P < 0·01) and zinc (r = 0·58; P < 0·001), but did not correlate with emergence, general early vigour or yield in the field. Conclusions Associations between PRL and field performance are generally related to early vigour. These root traits might therefore be of limited additional selection value, given that vigour can be measured easily on shoots/canopies. In contrast, LRD cannot be assessed easily in the field and, if LRD can improve nutrient uptake, then it may be possible to use HTP systems to screen this trait in both elite and more genetically diverse, non-field-adapted OSR.

Gestão organizacional X educação a distância: um estudo de caso da gestão da EAD na Faculdade Ideal-Faci

A presente pesquisa de caráter qualitativo, realizada no ano de 2009, teve como objetivo examinar o processo de Gestão da Educação a Distância, promovido na Instituição de Ensino Superior Faculdade Ideal, a fim de averiguar à satisfação dos clientes (alunos) e da equipe gestora (funcionários da administração, professores e diretores) em relação à qualidade (eficiência e eficácia) do processo. Nesse sentido, mediante um estudo de caso, procedeu-se a pesquisa em duas etapas: na primeira desenvolveu-se uma pesquisa bibliográfica e documental para a fundamentação teórica e apropriação documental que possibilitou o conhecimento da IES em questão; na segunda etapa foram realizadas a observação participante, as entrevistas e a aplicação dos questionários na IES objeto deste estudo ao envolvidos no processo, o que proporcionou a coleta dos dados e subsidiou a elaboração do referencial textual e as análises realizadas. Após a investigação, chegaram-se as considerações de que a IES desenvolve algumas estratégias de gestão do conhecimento que viabilizam o desenvolvimento e a sustentação de competências capazes de promovê-Ia. Também se observou que o modelo de gestão adotado promove uma educação (EAD) de qualidade (eficiente e eficaz), satisfazendo os participes do processo, os quais avaliaram os domlnios de competência como bom e ótimo. Além disso, detectou-se que o ponto forte do modelo de gestão adotado está sustentado nos domlnios de qualidade associado à tecnologia. A análise dos dados permitiu algumas inferências: os domlnios qualidade e tecnologia apresentaram altos nlveis de aprovação pela equipe gestora; já os alunos avaliaram o domlnio qualidade como ótimo e os demais como bons, isto é, três em cada quatro alunos estão satisfeitos ou muito satisfeitos com a qualidade da EAD ofertada na IES, disso resulta que se sentem atendidos e satisfeitos como clientes em relação à qualidade dos serviços ofertados e as suas necessidades educacionais. Entretanto, detectou-se que os respondentes não conseguiram identificar o tipo de gestão adotado na IES. Também se verificou que a empresa não possui nenhuma forma de recompensa ou reconhecimento para gerir o conhecimento do capital intelectual institucional. Conclui-se, portanto, que este trabalho possibilitou a esta pesquisadora reflexões intensas, levando-a a repensar o seu próprio exerclcio profissionalacadêmico. Faz-se necessário também informar que não se teve pretensão em abordar a totalidade das questões que permeiam a discussão deste assunto, intentando-se, tão-somente, apontá-Ias como relacionais. Assim, espera-se que esta pesquisa sirva de orientação para outros pesquisadores na área da gestão educacional da EAD e que a mesma, diferentemente de se tornar mais uma produção nas prateleiras da academia, suscite novas discussões e novos debates na área, inquietando alguns e em outros despertando "novos olhares" em direção a uma educação a distância de qualidade (eficiente e eficaz).

Autonomy Markers in Brazilian Adults With Intellectual Disabilities

The objective of the study was to investigate the relationship between autonomy markers in adult people with intellectual disabilities (ID) and variables such as intelligence quotient (IQ), early aging, and literacy. Participants were 47 adults with ID (33 men; aged 28-58 years with nonspecific etiology, 34 literate). All participants were trainees at the Center for Training of Capacity and Orientation for Employment at Associação de Pais e Amigos dos Excepcionais de São Paulo, São Paulo State, Brazil. They were divided into two age groups: younger (n = 27, mean age 31.85; +/- 2.23), and older (n = 38, mean age 41.84; +/- 5.54). They were administered intelligence scales twice, and answered questions related to social participation, community integration, and choice-making; the percentage of item responses leaning toward self-determination and freedom in choice-making was considered in defining the autonomy score. For both groups, IQ declined from the first to the second assessment. Autonomy scores were more determined by IQ classification than by literacy. Authors concluded that autonomy in people with ID is a multifactorial phenomenon associated with cognitive decline.

Susceptibility to Yersinia pseudotuberculosis Infection is Linked to the Pattern of Macrophage Activation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Physical properties of pectin-high amylose starch mixtures cross-linked with sodium trimetaphosphate

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)