The role of ATP and adenosine in the control of hepatic blood flow in the rabbit liver in vivo

BACKGROUND: The role of adenosine and ATP in the regulation of hepatic arterial blood flow in the "buffer response" was studied in vitro and in a new in vivo model in the rabbit. The model achieves portal-systemic diversion by insertion of a silicone rubber prosthesis between the portal vein and inferior vena cava and avoids alterations in systemic haemodynamics. RESULTS: Hepatic arterial (HA) blood flow increased in response to reduced portal venous (PV) blood flow, the "buffer response", from 19.4 (3.3) ml min(-1 )100 g(-1 )to 25.6 (4.3) ml min(-1 )100 g(-1 )(mean (SE), p < 0.05, Student's paired t-test). This represented a buffering capacity of 18.7 (5.2) %. Intra-portal injections of ATP or adenosine (1 micrograms kg(-1)-0.5 mg kg(-1)) elicited immediate increases in HA blood flow to give -log ED(50 )values of 2.0 and 1.7 mg kg(-1 )for ATP and adenosine respectively. Injection of ATP and adenosine had no measurable effect on PV flow. In vitro, using an isolated dual-perfused rabbit liver preparation, the addition of 8-phenyltheophylline (10 MicroMolar) to the HA and PV perfusate significantly inhibited the HA response to intra-arterial adenosine and to mid-range doses of intra-portal or intra-arterial ATP (p < 0.001). CONCLUSIONS: It is suggested that HA vasodilatation elicited by ATP may be partially mediated through activation of P(1)-purinoceptors following catabolism of ATP to adenosine

PEGylation of polypropylenimine dendrimers: effects on cytotoxicity, DNA condensation, gene delivery and expression in cancer cells

Diaminobutyric polypropylenimine (DAB) dendrimers have been shown to be highly efficient non-viral gene delivery systems for cancer therapy. However, their cytotoxicity currently limits their applications. To overcome this issue, PEGylation of DAB dendrimer, using various PEG molecular weights and dendrimer generations, has been attempted to decrease the cytotoxicity and enhance the DNA condensation, size and zeta potential, cellular uptake and transfection efficacy of these dendriplexes. Among all the PEGylated dendrimers synthesized, generation 3- and generation 4-DAB conjugated to low molecular weight PEG (2 kDa) at a dendrimer: DNA ratio of 20:1 and 10:1 resulted in an increase in gene expression on almost all tested cancer cells lines (by up to 3.2-fold compared to unmodified dendrimer in A431 cells). The highest level of β-galactosidase gene expression (10.07 × 10−3 ± 0.09 × 10−3 U/mL) was obtained following treatment of B16F10-Luc cells with G4-dendrimer PEGylated with PEG2K at a dendrimer: DNA ratio of 20:1. These delivery systems significantly decreased cytotoxicity on B16F10-Luc cells, by more than 3.4-fold compared to unmodified dendrimer. PEGylated generations 3- and 4-DAB dendrimers are therefore promising gene delivery systems for cancer therapy, combining low cytotoxicity and high transfection efficacy

A Partially Supervised Bayesian Image Classification Model with Applications in Diagnosis of Sentinel Lymph Node Metastases in Breast Cancer

A method has been developed for the analysis of images of sentinel lymph nodes generated by a spectral scanning device. The aim is to classify the nodes, excised during surgery for breast cancer, as normal or metastatic. The data from one node constitute spectra at 86 wavelengths for each pixel of a 20*20 grid. For the analysis, the spectra are reduced to scores on two factors, one derived externally from a linear discriminant analysis using spectra taken manually from known normal and metastatic tissue, and one derived from the node under investigation to capture variability orthogonal to the external factor. Then a three-group mixture model (normal, metastatic, non-nodal background) using multivariate t distributions is fitted to the scores, with external data being used to specify informative prior distributions for the parameters of the three distributions. A Markov random field prior imposes smoothness on the image generated by the model. Finally, the node is classified as metastatic if any one pixel in this smoothed image is classified as metastatic. The model parameters were tuned on a training set of nodes, and then the tuned model was tested on a separate validation set of nodes, achieving satisfactory sensitivity and specificity. The aim in developing the analysis was to allow flexibility in the way each node is modelled whilst still using external information. The Bayesian framework employed is ideal for this.Comment: 31 pages, 7 figure

PEGylation of polypropylenimine dendrimers : effects on cytotoxicity, DNA condensation, gene delivery and expression in cancer cells

Diaminobutyric polypropylenimine (DAB) dendrimers have been shown to be highly efficient non-viral gene delivery systems for cancer therapy. However, their cytotoxicity currently limits their applications. To overcome this issue, PEGylation of DAB dendrimer, using various PEG molecular weights and dendrimer generations, has been attempted to decrease the cytotoxicity and enhance the DNA condensation, size and zeta potential, cellular uptake and transfection efficacy of these dendriplexes. Among all the PEGylated dendrimers synthesized, generation 3- and generation 4-DAB conjugated to low molecular weight PEG (2 kDa) at a dendrimer: DNA ratio of 20:1 and 10:1 resulted in an increase in gene expression on almost all tested cancer cells lines (by up to 3.2-fold compared to unmodified dendrimer in A431 cells). The highest level of β-galactosidase gene expression (10.07x10E-3 ± 0.09x10E-3 U/mL) was obtained following treatment of B16F10-Luc cells with G4-dendrimer PEGylated with PEG2K at a dendrimer: DNA ratio of 20:1. These delivery systems significantly decreased cytotoxicity on B16F10-Luc cells, by more than 3.4-fold compared to unmodified dendrimer. PEGylated generations 3- and 4-DAB dendrimers are therefore promising gene delivery systems for cancer therapy, combining low cytotoxicity and high transfection efficacy

Aeolianite and barrier dune construction spanning the last two glacial-interglacial cycles from the southern Cape coast, South Africa

The southern Cape region of South Africa has extensive coastal aeolianites and barrier dunes. Whilst previously reported, limited knowledge of their age has precluded an understanding of their relationship with the climatic and sea-level fluctuations that have taken place during the Late Quaternary. Sedimentological and geomorphological studies combined with an optical dating programme reveal aeolianite development and barrier dune construction spanning at least the last two glacial–interglacial cycles. Aeolianite deposition has occurred on the southern Cape coast at ca 67–80, 88–90, 104–128, 160–189 and >200 ka before the present. Using this and other published data coupled with a better understanding of Late Quaternary sea-level fluctuations and palaeocoastline configurations, it is concluded that these depositional phases appear to be controlled by interglacial and subsequent interstadial sea-level high stands. These marine transgressions and regressions allowed onshore carbonate-rich sediment movement and subsequent aeolian reworking to occur at similar points in the landscape on a number of occasions. The lack of carbonates in more recent dunes (Oxygen Isotope Stages 1/2 and 4/5) is attributed not to leaching but to changes to carbonate production in the sediment source area caused by increased terrigenous material and/or changes in the balance between the warm Agulhas and nutrient-rich Benguela ocean current

Image-guided Placement of Magnetic Neuroparticles as a Potential High-Resolution Brain-Machine Interface

We are developing methods of noninvasively delivering magnetic neuroparticles™ via intranasal administration followed by image-guided magnetic propulsion to selected locations in the brain. Once placed, the particles can activate neurons via vibrational motion or magnetoelectric stimulation. Similar particles might be used to read out neuronal electrical pulses via spintronic or liquid-crystal magnetic interactions, for fast bidirectional brain-machine interface. We have shown that particles containing liquid crystals can be read out with magnetic resonance imaging (MRI) using embedded magnetic nanoparticles and that the signal is visible even for voltages comparable to physiological characteristics. Such particles can be moved within the brain (e.g., across midline) without causing changes to neurological firing

An analysis of national target groups for monovalent 2009 pandemic influenza vaccine and trivalent seasonal influenza vaccines in 2009-10 and 2010-11

<p>Abstract</p> <p>Background</p> <p>Vaccination is generally considered to be the best primary prevention measure against influenza virus infection. Many countries encourage specific target groups of people to undertake vaccination, often with financial subsidies or a priority list. To understand differential patterns of national target groups for influenza vaccination before, during and after the 2009 influenza pandemic, we reviewed and analyzed the country-specific policies in the corresponding time periods.</p> <p>Methods</p> <p>Information on prioritized groups targeted to receive seasonal and pandemic influenza vaccines was derived from a multi-step internet search of official health department websites, press releases, media sources and academic journal articles. We assessed the frequency and consistency of targeting 20 different groups within populations which are associated with age, underlying medical conditions, role or occupations among different countries and vaccines. Information on subsidies provided to specific target groups was also extracted.</p> <p>Results</p> <p>We analyzed target groups for 33 (seasonal 2009 and 2009-10 vaccines), 72 (monovalent pandemic 2009-10 vaccine) and 34 (seasonal 2010 and 2010-11 vaccines) countries. In 2009-10, the elderly, those with chronic illness and health care workers were common targets for the seasonal vaccine. Comparatively, the elderly, care home residents and workers, animal contacts and close contacts were less frequently targeted to receive the pandemic vaccine. Pregnant women, obese persons, essential community workers and health care workers, however, were more commonly targeted. After the pandemic, pregnant women, obese persons, health care and care home workers, and close contacts were more commonly targeted to receive the seasonal vaccine compared to 2009-10, showing continued influence from the pandemic. Many of the countries provided free vaccines, partial subsidies, reimbursements or national health insurance coverage to specific target groups and over one-third of the countries offered universal subsidy regarding the pandemic vaccine. There was also some inconsistency between countries in target groups.</p> <p>Conclusions</p> <p>Differences in target groups between countries may reflect variable objectives as well as uncertainties regarding the transmission dynamics, severity and age-specific immunity against influenza viruses before and after vaccination. Clarification on these points is essential to elucidate optimal and object-oriented vaccination strategies.</p

Climate seasonality limits leaf carbon assimilation and wood productivity in tropical forests

The seasonal climate drivers of the carbon cycle in tropical forests remain poorly known, although these forests account for more carbon assimilation and storage than any other terrestrial ecosystem. Based on a unique combination of seasonal pan-tropical data sets from 89 experimental sites (68 include aboveground wood productivity measurements and 35 litter productivity measurements), their associated canopy photosynthetic capacity (enhanced vegetation index, EVI) and climate, we ask how carbon assimilation and aboveground allocation are related to climate seasonality in tropical forests and how they interact in the seasonal carbon cycle. We found that canopy photosynthetic capacity seasonality responds positively to precipitation when rainfall is < 2000ĝ€-mmĝ€-yrĝ'1 (water-limited forests) and to radiation otherwise (light-limited forests). On the other hand, independent of climate limitations, wood productivity and litterfall are driven by seasonal variation in precipitation and evapotranspiration, respectively. Consequently, light-limited forests present an asynchronism between canopy photosynthetic capacity and wood productivity. First-order control by precipitation likely indicates a decrease in tropical forest productivity in a drier climate in water-limited forest, and in current light-limited forest with future rainfall < 2000ĝ€-mmĝ€-yrĝ'1. Author(s) 2016.Fil: Wagner, Fabien H.. Instituto Nacional de Pesquisas Espaciais; BrasilFil: Hérault, Bruno. Ecologie Des Forets de Guyane; BrasilFil: Bonal, Damien. Institut National de la Recherche Agronomique; FranciaFil: Stahl, Clment. Universiteit Antwerp; BélgicaFil: Anderson, Liana O.. National Center For Monitoring And Early Warning Of Natural Disasters; BrasilFil: Baker, Timothy R.. University Of Leeds; Reino UnidoFil: Sebastian Becker, Gabriel. Universidad de Hohenheim; AlemaniaFil: Beeckman, Hans. Royal Museum For Central Africa; BélgicaFil: Boanerges Souza, Danilo. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Cesar Botosso, Paulo. Ministerio da Agricultura Pecuaria e Abastecimento de Brasil. Empresa Brasileira de Pesquisa Agropecuaria; BrasilFil: Bowman, David M. J. S.. University of Tasmania; AustraliaFil: Bräuning, Achim. Universitat Erlangen-Nuremberg; AlemaniaFil: Brede, Benjamin. Wageningen University And Research Centre; Países BajosFil: Irving Brown, Foster. Universidade Federal Do Acre; BrasilFil: Julio Camarero, Jesus. Instituto Boliviano de Investigacion Forestal Bolivia; BoliviaFil: Camargo, Plnio Barbosa. Universidade de Sao Paulo; BrasilFil: Cardoso, Fernanda C.G.. Universidade Federal do Paraná; BrasilFil: Carvalho, Fabrcio Alvim. Universidade Federal de Juiz de Fora; BrasilFil: Castro, Wendeson. Universidade Federal Do Acre; BrasilFil: Koloski Chagas, Rubens. Universidade de Sao Paulo; BrasilFil: Chave, Jrome. Centre National de la Recherche Scientifique; FranciaFil: Chidumayo, Emmanuel N.. University Of Zambia; ZambiaFil: Clark, Deborah A.. University Of Missouri-st. Louis; Estados UnidosFil: Regina Capellotto Costa, Flavia. Ministério da Ciência, Tecnologia, Inovações. Instituto Nacional de Pesquisas da Amazônia; BrasilFil: Couralet, Camille. Royal Museum For Central Africa; BélgicaFil: Henrique Da Silva Mauricio, Paulo. Universidade Federal Do Acre; BrasilFil: Dalitz, Helmut. Universidad de Hohenheim; AlemaniaFil: Resende De Castro, Vinicius. Universidade Federal de Vicosa; BrasilFil: Milani, Jaanan Eloisa De Freitas. Universidade Federal do Paraná; BrasilFil: Roig Junent, Fidel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla | Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla | Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla; Argentin