129 research outputs found

    Leaf and whole tree adaptations to mild salinity in field grown Populus euphratica

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    Populus euphratica Oliv. is a highly salt tolerant tree species, and this study represents the first comprehensive investigation of salt tolerance mechanisms of mature trees of P. euphratica in the field. We measured NaCl concentration in xylem sap, NaCl accumulation in leaves, the effect of NaCl on leaf physiological parameters and osmotic adjustment and the allocation and distribution of NaCl between different plant organs on a whole plant level in trees exposed to mild saline groundwater (around 30 mM) in China. Populus euphratica showed three key mechanisms of salt tolerance. The primary mechanism had a strong control over Na+ and Cl- uptake with effective exclusion mechanisms for Cl- with up to 99% of the external NaCl being excluded from the xylem. Secondly, the trees allocated large proportions of NaCl into the leaves, which served as a salt elimination mechanism as the leaves are ultimately shed at the end of the growing season. Thirdly, the trees tolerated high foliar Na+ concentrations through a combination of osmotic adjustment using sucrose and probable sequestering of Na+ in the apoplast. Our results indicate that the control of Na+ and Cl- uptake and the regulation of Na+ and Cl- delivery to the shoot are key to salt tolerance of P. euphratica in the field with tolerance of high Na+ concentrations in leaves being a critical component

    Cutaneous Head and Neck Squamous Cell Carcinoma with Regional Metastases: The Prognostic Importance of Soft Tissue Metastases and Extranodal Spread

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    Extranodal spread (ENS) is an established adverse prognostic factor in metastatic cutaneous squamous cell carcinoma (cSCC); however, the clinical significance of soft tissue metastases (STM) is unknown. The aim of this study was to evaluate the prognosis of patients with STM from head and neck cSCC, and to compare this with that of node metastases with and without ENS. Patients with cSCC metastatic to the parotid and/or neck treated by primary surgical resection between 1987 and 2007 were included. Metastatic nodes > 3 cm in size were an exclusion criterion. A Cox proportional hazard model was used to determine the effect of STM adjusting for other relevant prognostic factors. The population included 164 patients with a median follow-up of 26 months. There were 8 distant and 37 regional recurrences. There were 22 were cancer-specific deaths, and 29 patients died. STM was a significant predictor of reduced overall (hazard ratio 3.3; 95% confidence interval 1.6-6.4; P = 0.001) and disease-free survival (hazard ratio 2.4; 95% confidence interval 1.4-4.1; P = 0.001) when compared to patients with node disease with or without ENS. After adjusting for covariates, STM and number of involved nodes were significant independent predictors of overall and disease-free survival. In metastatic cSCC of the head and neck, the presence of STM is an independent predictor of reduced survival and is associated with a greater adverse effect than ENS alone

    MCAM: Multiple Clustering Analysis Methodology for Deriving Hypotheses and Insights from High-Throughput Proteomic Datasets

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    Advances in proteomic technologies continue to substantially accelerate capability for generating experimental data on protein levels, states, and activities in biological samples. For example, studies on receptor tyrosine kinase signaling networks can now capture the phosphorylation state of hundreds to thousands of proteins across multiple conditions. However, little is known about the function of many of these protein modifications, or the enzymes responsible for modifying them. To address this challenge, we have developed an approach that enhances the power of clustering techniques to infer functional and regulatory meaning of protein states in cell signaling networks. We have created a new computational framework for applying clustering to biological data in order to overcome the typical dependence on specific a priori assumptions and expert knowledge concerning the technical aspects of clustering. Multiple clustering analysis methodology (‘MCAM’) employs an array of diverse data transformations, distance metrics, set sizes, and clustering algorithms, in a combinatorial fashion, to create a suite of clustering sets. These sets are then evaluated based on their ability to produce biological insights through statistical enrichment of metadata relating to knowledge concerning protein functions, kinase substrates, and sequence motifs. We applied MCAM to a set of dynamic phosphorylation measurements of the ERRB network to explore the relationships between algorithmic parameters and the biological meaning that could be inferred and report on interesting biological predictions. Further, we applied MCAM to multiple phosphoproteomic datasets for the ERBB network, which allowed us to compare independent and incomplete overlapping measurements of phosphorylation sites in the network. We report specific and global differences of the ERBB network stimulated with different ligands and with changes in HER2 expression. Overall, we offer MCAM as a broadly-applicable approach for analysis of proteomic data which may help increase the current understanding of molecular networks in a variety of biological problems.National Institutes of Health (U.S.) (NIH-U54-CA112967 )National Institutes of Health (U.S.) (NIH-R01-CA096504

    Investigating the Willingness to Pay for a Contributory National Health Insurance Scheme in Saudi Arabia:A Cross-sectional Stated Preference Approach

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    Background: The Saudi Healthcare System is universal, financed entirely from government revenue principally derived from oil, and is ‘free at the point of delivery’ (non-contributory). However, this system is unlikely to be sustainable in the medium to long term. This study investigates the feasibility and acceptability of healthcare financing reform by examining households’ willingness to pay (WTP) for a contributory national health insurance scheme. Methods: Using the contingent valuation method, a pre-tested interviewer-administered questionnaire was used to collect data from 1187 heads of household in Jeddah province over a 5-month period. Multi-stage sampling was employed to select the study sample. Using a double-bounded dichotomous choice with the follow-up elicitation method, respondents were asked to state their WTP for a hypothetical contributory national health insurance scheme. Tobit regression analysis was used to examine the factors associated with WTP and assess the construct validity of elicited WTP. Results: Over two-thirds (69.6%) indicated that they were willing to participate in and pay for a contributory national health insurance scheme. The mean WTP was 50 Saudi Riyal (US$13.33) per household member per month. Tobit regression analysis showed that household size, satisfaction with the quality of public healthcare services, perceptions about financing healthcare, education and income were the main determinants of WTP. Conclusions: This study demonstrates a theoretically valid WTP for a contributory national health insurance scheme by Saudi people. The research shows that willingness to participate in and pay for a contributory national health insurance scheme depends on participant characteristics. Identifying and understanding the main influencing factors associated with WTP are important to help facilitate establishing and implementing the national health insurance scheme. The results could assist policy-makers to develop and set insurance premiums, thus providing an additional source of healthcare financing

    Adsorption at cell surface and cellular uptake of silica nanoparticles with different surface chemical functionalizations: impact on cytotoxicity

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    International audienceSilica nanoparticles are particularly interesting for medical applications because of the high inertness and chemical stability of silica material. However, at the nanoscale their innocuousness must be carefully verified before clinical use. The aim of this study was to investigate the in vitro biological toxicity of silica nanoparticles depending on their surface chemical functionalization. To that purpose, three kinds of 50 nm fluorescent silica-based nanoparticles were synthesized: 1) sterically stabilized silica nanoparticles coated with neutral polyethylene glycol (PEG) molecules, 2) positively charged silica nanoparticles coated with amine groups and 3) negatively charged silica nanoparticles coated with carboxylic acid groups. RAW 264.7 murine macrophages were incubated for 20 hours with each kind of nanoparticles. Their cellular uptake and adsorption at the cell membrane were assessed by a fluorimetric assay and cellular responses were evaluated in terms of cytotoxicity, pro-inflammatory factor production and oxidative stress. Results showed that the highly positive charged nanoparticle, were the most adsorbed at cell surface and triggered more cytotoxicity than other nanoparticles types. To conclude, this study clearly demonstrated that silica nanoparticles surface functionalization represents a key parameter in their cellular uptake and biological toxicity

    Polarization Transfer in the ^4He(\vec e,e'\vec p)^3H Reaction up to Q^2 = 2.6 (GeV/c)^2

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    We have measured the proton recoil polarization in the ^4He(\vec e,e'\vec p)^3H reaction at Q^2 = 0.5, 1.0, 1.6, and 2.6 (GeV/c)^2. The measured ratio of polarization transfer coefficients differs from a fully relativistic calculation, favoring the inclusion of a predicted medium modification of the proton form factors based on a quark-meson coupling model. In contrast, the measured induced polarizations agree reasonably well with the fully relativistic calculation indicating that the treatment of final-state interactions is under control.Comment: 5 pages, 3 figures, uses revtex.sty, submitted to Physical Review Letter

    The use of airborne laser scanning to develop a pixel-based stratification for a verified carbon offset project

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    Background The voluntary carbon market is a new and growing market that is increasingly important to consider in managing forestland. Monitoring, reporting, and verifying carbon stocks and fluxes at a project level is the single largest direct cost of a forest carbon offset project. There are now many methods for estimating forest stocks with high accuracy that use both Airborne Laser Scanning (ALS) and high-resolution optical remote sensing data. However, many of these methods are not appropriate for use under existing carbon offset standards and most have not been field tested. Results This paper presents a pixel-based forest stratification method that uses both ALS and optical remote sensing data to optimally partition the variability across an ~10,000 ha forest ownership in Mendocino County, CA, USA. This new stratification approach improved the accuracy of the forest inventory, reduced the cost of field-based inventory, and provides a powerful tool for future management planning. This approach also details a method of determining the optimum pixel size to best partition a forest. Conclusions The use of ALS and optical remote sensing data can help reduce the cost of field inventory and can help to locate areas that need the most intensive inventory effort. This pixel-based stratification method may provide a cost-effective approach to reducing inventory costs over larger areas when the remote sensing data acquisition costs can be kept low on a per acre basis

    DSIF and RNA Polymerase II CTD Phosphorylation Coordinate the Recruitment of Rpd3S to Actively Transcribed Genes

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    Histone deacetylase Rpd3 is part of two distinct complexes: the large (Rpd3L) and small (Rpd3S) complexes. While Rpd3L targets specific promoters for gene repression, Rpd3S is recruited to ORFs to deacetylate histones in the wake of RNA polymerase II, to prevent cryptic initiation within genes. Methylation of histone H3 at lysine 36 by the Set2 methyltransferase is thought to mediate the recruitment of Rpd3S. Here, we confirm by ChIP–Chip that Rpd3S binds active ORFs. Surprisingly, however, Rpd3S is not recruited to all active genes, and its recruitment is Set2-independent. However, Rpd3S complexes recruited in the absence of H3K36 methylation appear to be inactive. Finally, we present evidence implicating the yeast DSIF complex (Spt4/5) and RNA polymerase II phosphorylation by Kin28 and Ctk1 in the recruitment of Rpd3S to active genes. Taken together, our data support a model where Set2-dependent histone H3 methylation is required for the activation of Rpd3S following its recruitment to the RNA polymerase II C-terminal domain

    A Validated Age-Related Normative Model for Male Total Testosterone Shows Increasing Variance but No Decline after Age 40 Years

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    The diagnosis of hypogonadism in human males includes identification of low serum testosterone levels, and hence there is an underlying assumption that normal ranges of testosterone for the healthy population are known for all ages. However, to our knowledge, no such reference model exists in the literature, and hence the availability of an applicable biochemical reference range would be helpful for the clinical assessment of hypogonadal men. In this study, using model selection and validation analysis of data identified and extracted from thirteen studies, we derive and validate a normative model of total testosterone across the lifespan in healthy men. We show that total testosterone peaks [mean (2.5-97.5 percentile)] at 15.4 (7.2-31.1) nmol/L at an average age of 19 years, and falls in the average case [mean (2.5-97.5 percentile)] to 13.0 (6.6-25.3) nmol/L by age 40 years, but we find no evidence for a further fall in mean total testosterone with increasing age through to old age. However we do show that there is an increased variation in total testosterone levels with advancing age after age 40 years. This model provides the age related reference ranges needed to support research and clinical decision making in males who have symptoms that may be due to hypogonadism.Publisher PDFPeer reviewe
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