Trypanosome invasion of mammalian cells requires activation of the TGFβ signaling pathway

AbstractTrypanosoma cruzi invades most nucleated mammi lian cells by as yet unknown mechanisms. We repoi here that while T. cruzi attaches to epithelial cells lacl ing signaling transforming growth factor β (TGFβ) receptor I or II, the adherent parasites cannot penetrat and replicate inside the mutant cells, as they do i parental cells. Invasion of the mutants is restored by transfection with the TGFβ receptor genes, as are biological responses to TGFβ. Similar rescue of bot TGFβ antiproliferative response and T. cruzi invasio was demonstrated in a hybrid of TGFβ-resistant bladder and colon carcinoma cells. In addition, T. cruzi di not efficiently invade epithelial cells with dysfunctio of the intracellular signaling cascade caused by th constitutive expression of the cyclin-dependent kinas cdk4 or of the oncogene H-ras. Treatment with TGFβ, but not with other anti proliferative agents of nor phagocytic cells, greatly enhances T. cruzi invasior Moreover, infective, but not noninfective, trypanosome strongly induce a TGFβ-responsive reporter gene i TGFβ-sensitive, but not in TGFβ-insensitive, cell line: Thus, T. cruzi itself may directly trigger activation of the TGFβ signaling pathway required for parasite entr into the mammalian cells

Water Saving in the Yellow River Basin, China. 1. Irrigation Demand Scheduling

Rosana G. Moreira, Editor-in-Chief; Texas A&M UniversityThis is a Technical Paper from International Commission of Agricultural Engineering (CIGR, Commission Internationale du Genie Rural) E-Journal Volume 5 (2003): A. Campos, L. Pereira, J. Gonclaves, M. Fabiao, Y. Liu, Y. Li, Z. Mao, and B. Dong. Water Saving in the Yellow River Basin, China. 1. Irrigation Demand Scheduling. Vol. V. July 2003

Water Saving in the Yellow River Basin, China. 2. Assessing the Potential for Improving Basin Irrigation

Rosana G. Moreira, Editor-in-Chief; Texas A&M UniversityThis is a Technical Paper from International Commission of Agricultural Engineering (CIGR, Commission Internationale du Genie Rural) E-Journal Volume 5 (2003): M. Fabiao, J. Gonclaves, L. Pereira, A. Campos, Y. Liu, Y. Li, Z. Mao, and B. Dong. Water Saving in the Yellow River Basin, China. 2. Assessing the Potential for Improving Basin Irrigation. Vol. V. July 2003

Realization of a Tunable Artificial Atom at a Supercritically Charged Vacancy in Graphene

The remarkable electronic properties of graphene have fueled the vision of a graphene-based platform for lighter, faster and smarter electronics and computing applications. One of the challenges is to devise ways to tailor its electronic properties and to control its charge carriers. Here we show that a single atom vacancy in graphene can stably host a local charge and that this charge can be gradually built up by applying voltage pulses with the tip of a scanning tunneling microscope (STM). The response of the conduction electrons in graphene to the local charge is monitored with scanning tunneling and Landau level spectroscopy, and compared to numerical simulations. As the charge is increased, its interaction with the conduction electrons undergoes a transition into a supercritical regime 6-11 where itinerant electrons are trapped in a sequence of quasi-bound states which resemble an artificial atom. The quasi-bound electron states are detected by a strong enhancement of the density of states (DOS) within a disc centered on the vacancy site which is surrounded by halo of hole states. We further show that the quasi-bound states at the vacancy site are gate tunable and that the trapping mechanism can be turned on and off, providing a new mechanism to control and guide electrons in grapheneComment: 18 pages and 5 figures plus 14 pages and 15 figures of supplementary information. Nature Physics advance online publication, Feb 22 (2016

Real-time and label free determination of ligand binding-kinetics to primary cancer tissue specimens; a novel tool for the assessment of biomarker targeting

In clinical oncology, diagnosis and evaluation of optimal treatment strategies are mostly based on histopathological examination combined with immunohistochemical (IHC) expression analysis of cancer-associated antigens in formalin fixed paraffin-embedded (FFPE) tissue biopsies. However, informative IHC analysis depends on both the specificity and affinity of the binding reagent, which are inherently difficult to quantify in situ. Here we describe a label-free method that allows for the direct and real-time assessment of molecular binding kinetics in situ on FFPE tissue specimens using quartz crystal microbalance (QCM) enabled biosensor technology. We analysed the interaction between the rVAR2 protein and its placental-like chondroitin sulfate (pl-CS) receptor in primary human placenta tissue and in breast and prostate tumour specimens in situ. rVAR2 interacted with FFPE human placenta and cancer tissue with an affinity in the nanomolar range, and showed no detectable interaction with pl-CS negative normal tissue. We further validated the method by including analysis with the androgen receptor N-20 antibody (anti-AR). As the KD value produced by this method is independent of the number of epitopes available, this readout offers a quantitative and unbiased readout for in situ binding-avidity and amount of binding epitopes. In summary, this method adds a new and important dimension to classical IHC-based molecular pathology by adding information about the binding characteristics in biologically relevant conditions. This can potentially be used to select optimal biologics for diagnostic and for therapeutic applications as well as guide the development of novel high affinity binding drugs. Keywords: Quartz crystal microscale, Biomarker, Biosensor, VAR2CSA, Cancer, Malari

Assessing the utility of geospatial technologies to investigate environmental change within lake systems

Over 50% of the world's population live within 3. km of rivers and lakes highlighting the on-going importance of freshwater resources to human health and societal well-being. Whilst covering c. 3.5% of the Earth's non-glaciated land mass, trends in the environmental quality of the world's standing waters (natural lakes and reservoirs) are poorly understood, at least in comparison with rivers, and so evaluation of their current condition and sensitivity to change are global priorities. Here it is argued that a geospatial approach harnessing existing global datasets, along with new generation remote sensing products, offers the basis to characterise trajectories of change in lake properties e.g., water quality, physical structure, hydrological regime and ecological behaviour. This approach furthermore provides the evidence base to understand the relative importance of climatic forcing and/or changing catchment processes, e.g. land cover and soil moisture data, which coupled with climate data provide the basis to model regional water balance and runoff estimates over time. Using examples derived primarily from the Danube Basin but also other parts of the World, we demonstrate the power of the approach and its utility to assess the sensitivity of lake systems to environmental change, and hence better manage these key resources in the future

A massive human co-expression-network and its medical applications

Network-based analysis is indispensable in analyzing high throughput biological data. Based on the assumption that the variation of gene interactions under given biological conditions could be better interpreted in the context of a large-scale and wide variety of developmental, tissue, and disease, we leverage the large quantity of publicly-available transcriptomic data \u3e 40,000 HG U133A Affymetrix microarray chips stored in ArrayExpress (http://www.ebi.ac.uk/arrayexpress/) using MetaOmGraph (http://metnet.vrac.iastate.edu/MetNet_MetaOmGraph.htm). From this data, 18,637 chips encompassing over 500 experiments containing high quality data (18637Hu-dataset) were used to create a globally stable gene co-expression network (18637Hu-co-expressionnetwork). Regulons, groups of highly and consistently co-expressed genes, were obtained by partitioning the 18637Hu-co-expression-network using an MCL clustering algorithm. The regulon were demonstrated to be statistically significant using a gene ontology (GO) term overrepresentation test combined with evaluation of the effects of gene permutations. The regulons include approximately 12% of human genes, interconnected by 31,471 correlations. All network data and metadata is publically available (http://metnet.vrac.iastate.edu/ MetNet_MetaOmGraph.htm). Text mining of these metadata, GO term overrepresentation analysis, and statistical analysis of transcriptomic experiments across multiple environmental, tissue, and disease conditions, has revealed novel fingerprints distinguishing central nervous system (CNS)-related conditions. This study demonstrates the value of mega-scale network-based analysis for biologists to further refine transcriptomic data derived from a particular condition, to study the global relationships between genes and diseases, and to develop hypotheses that can inform future research

The C-terminal helix of BubR1 is essential for CENP-E-dependent chromosome alignment

During cell division, misaligned chromosomes are captured and aligned by motors before their segregation. The CENP-E motor is recruited to polar unattached kinetochores, to facilitate chromosome alignment. The spindle checkpoint protein BubR1 has been reported as a CENP-E interacting partner, but to what extent BubR1 contributes to CENP-E localization at kinetochores, has remained controversial. Here we define the molecular determinants that specify the interaction between BubR1 and CENP-E. The basic C-terminal helix of BubR1 is necessary but not sufficient for CENP-E interaction, while a minimal key acidic patch on the kinetochore-targeting domain of CENP-E, is also essential. We then demonstrate that BubR1 is required for the recruitment of CENP-E to kinetochores to facilitate chromosome alignment. This BubR1-CENP-E axis is critical to align chromosomes that have failed to congress through other pathways and recapitulates the major known function of CENP-E. Overall, our studies define the molecular basis and the function for CENP-E recruitment to BubR1 at kinetochores during mammalian mitosis

On the co-evolution of supermassive black holes and their host galaxies since z = 3

[Abridged] To investigate the evolution in the relation between galaxy stellar and central black hole mass we construct a volume limited complete sample of 85 AGN with host galaxy stellar masses M_{*} > 10^{10.5} M_{sol}, and specific X-ray luminosities L_{X} > 2.35 x 10^{43} erg s^{-1} at 0.4 < z < 3. We calculate the Eddington limiting masses of the supermassive black holes residing at the centre of these galaxies, and observe an increase in the average Eddington limiting black hole mass with redshift. By assuming that there is no evolution in the Eddington ratio (\mu) and then that there is maximum possible evolution to the Eddington limit, we quantify the maximum possible evolution in the M_{*} / M_{BH} ratio as lying in the range 700 < M_{*}/M_{BH} < 10000, compared with the local value of M_{*}/M_{BH} ~ 1000. We furthermore find that the fraction of galaxies which are AGN (with L_{X} > 2.35 x 10^{43} erg s^{-1}) rises with redshift from 1.2 +/- 0.2 % at z = 0.7 to 7.4 +/- 2.0 % at z = 2.5. We use our results to calculate the maximum timescales for which our sample of AGN can continue to accrete at their observed rates before surpassing the local galaxy-black hole mass relation. We use these timescales to calculate the total fraction of massive galaxies which will be active (with L_{X} > 2.35 x 10^{43} erg s^{-1}) since z = 3, finding that at least ~ 40% of all massive galaxies will be Seyfert luminosity AGN or brighter during this epoch. Further, we calculate the energy density due to AGN activity in the Universe as 1.0 (+/- 0.3) x 10^{57} erg Mpc^{-3} Gyr^{-1}, potentially providing a significant source of energy for AGN feedback on star formation. We also use this method to compute the evolution in the X-ray luminosity density of AGN with redshift, finding that massive galaxy Seyfert luminosity AGN are the dominant source of X-ray emission in the Universe at z < 3.Comment: 25 pages, 10 figures, accepted for publication in MNRA

Construindo sentidos e possibilidades: a experiência da equipe de incubação de um empreendimento solidário

Esta pesquisa qualitativa teve por objetivo analisar a experiência da equipe de incubação de um empreendimento solidário de usuários de saúde mental. As entrevistas ocorreram com sete membros da equipe, sendo os dados analisados segundo análise de conteúdo. Da análise emergiram quatro categorias: Considerando a incubação como um processo - aprendendo e encontrando os significados de ser apoio; Apontando facilidades e dificuldades no processo de construção do empreendimento; Visualizando resultados da inclusão pelo trabalho - percebendo a melhora dos usuários; Apontando necessidades de mudanças no processo, esperando uma maior autonomia dos usuários e a formalização do empreendimento. A experiência revelou ser um trabalho novo e gratificante para a equipe, possibilitando aprendizado, troca de saberes e vínculo. Identificamos o papel do técnico como educador/facilitador do processo. Além das facilidades e do reconhecimento da relevância do trabalho para a vida dos usuários, a equipe enfrenta desafios para gerar renda satisfatória