Anticancer and Anti-metastatic Effects of Supercritical Extracts of Hops (Humulus lupulus L.) and Mango ginger (Curcuma amada Roxb.) in Human Glioblastoma

Glioblastoma is one of the most aggressive, lethal and incurable primary brain tumors with a dismal prognosis in humans. Mango ginger (Curcuma amada) and hops (Humulus lupulus) are two botanicals containing phytochemicals with potential anticancer effects. We have investigated the anticancer and antimetastatic properties of supercritical CO2 extract of mango ginger (CA) and ethanol extract of hops (HL) in the U-87MG human glioblastoma cell line. Both CA and HL individually demonstrate strong cytotoxicity against glioblastoma cells. CompuSyn analysis of cytotoxicity data confirms that CA and HL are synergistic for cytotoxicity with combination index (CI) values of <1.0. Additionally, CA and HL individually as well as the combination significantly inhibit MMP-2 and MMP-9 activity, tumor cell migration (transendothelial cell migration assay) and AKT phosphorylation in U-87MG cells. CA and HL inhibit glycolysis in U-87MG cells as indicated by the inhibition of ATP and lactate synthesis with the CA+HL combination demonstrating strong inhibition of glycolysis via the reduction of ATP and lactate synthesis compared to cells treated by each extract alone. CA and HL treatment down regulates the expression of proteins associated with metastasis, MMP-2 and MMP-9 and up regulates the expression of TIMP1. Proteins associated with apoptosis, inflammation and energy metabolism were also modulated by CA and HL treatment of glioblastoma cells. These results suggest that CA and HL can be combined for the therapeutic management of glioblastomas

Deep CCD Surface Photometry of Galaxy Clusters I: Methods and Initial Studies of Intracluster Starlight

We report the initial results of a deep imaging survey of galaxy clusters. The primary goals of this survey are to quantify the amount of intracluster light as a function of cluster properties, and to quantify the frequency of tidal debris. We outline the techniques needed to perform such a survey, and we report findings for the first two galaxy clusters in the survey: Abell 1413, and MKW 7 . These clusters vary greatly in richness and structure. We show that our surface photometry reliably reaches to a surface brightness of \mu_v = 26.5 mags per arcsec. We find that both clusters show clear excesses over a best-fitting r^{1/4} profile: this was expected for Abell 1413, but not for MKW 7. Both clusters also show evidence of tidal debris in the form of plumes and arc-like structures, but no long tidal arcs were detected. We also find that the central cD galaxy in Abell 1413 is flattened at large radii, with an ellipticity of $\approx 0.8$, the largest measured ellipticity of any cD galaxy to date.Comment: 58 pages, 24 figures, accepted for publication in the Astrophysical Journal. Version has extremely low resolution figures to comply with 650k limit. High resolution version is available at http://burro.astr.cwru.edu/johnf/icl1.ps.gz Obtaining high resolution version is strongly reccomende

Genome resequencing reveals multiscale geographic structure and extensive linkage disequilibrium in the forest tree Populus trichocarpa

This is the publisher’s final pdf. The article is copyrighted by the New Phytologist Trust and published by John Wiley & Sons, Inc. It can be found at: http://onlinelibrary.wiley.com/journal/10.1111/%28ISSN%291469-8137. To the best of our knowledge, one or more authors of this paper were federal employees when contributing to this work.•Plant population genomics informs evolutionary biology, breeding, conservation and bioenergy feedstock development. For example, the detection of reliable phenotype–genotype associations and molecular signatures of selection requires a detailed knowledge about genome-wide patterns of allele frequency variation, linkage disequilibrium and recombination.\ud •We resequenced 16 genomes of the model tree Populus trichocarpa and genotyped 120 trees from 10 subpopulations using 29 213 single-nucleotide polymorphisms.\ud •Significant geographic differentiation was present at multiple spatial scales, and range-wide latitudinal allele frequency gradients were strikingly common across the genome. The decay of linkage disequilibrium with physical distance was slower than expected from previous studies in Populus, with r² dropping below 0.2 within 3–6 kb. Consistent with this, estimates of recent effective population size from linkage disequilibrium (N[subscript e] ≈ 4000–6000) were remarkably low relative to the large census sizes of P. trichocarpa stands. Fine-scale rates of recombination varied widely across the genome, but were largely predictable on the basis of DNA sequence and methylation features.\ud •Our results suggest that genetic drift has played a significant role in the recent evolutionary history of P. trichocarpa. Most importantly, the extensive linkage disequilibrium detected suggests that genome-wide association studies and genomic selection in undomesticated populations may be more feasible in Populus than previously assumed

Training of Instrumentalists and Development of New Technologies on SOFIA

This white paper is submitted to the Astronomy and Astrophysics 2010 Decadal Survey (Astro2010)1 Committee on the State of the Profession to emphasize the potential of the Stratospheric Observatory for Infrared Astronomy (SOFIA) to contribute to the training of instrumentalists and observers, and to related technology developments. This potential goes beyond the primary mission of SOFIA, which is to carry out unique, high priority astronomical research. SOFIA is a Boeing 747SP aircraft with a 2.5 meter telescope. It will enable astronomical observations anywhere, any time, and at most wavelengths between 0.3 microns and 1.6 mm not accessible from ground-based observatories. These attributes, accruing from the mobility and flight altitude of SOFIA, guarantee a wealth of scientific return. Its instrument teams (nine in the first generation) and guest investigators will do suborbital astronomy in a shirt-sleeve environment. The project will invest $10M per year in science instrument development over a lifetime of 20 years. This, frequent flight opportunities, and operation that enables rapid changes of science instruments and hands-on in-flight access to the instruments, assure a unique and extensive potential - both for training young instrumentalists and for encouraging and deploying nascent technologies. Novel instruments covering optical, infrared, and submillimeter bands can be developed for and tested on SOFIA by their developers (including apprentices) for their own observations and for those of guest observers, to validate technologies and maximize observational effectiveness.Comment: 10 pages, no figures, White Paper for Astro 2010 Survey Committee on State of the Professio

Exploratory Case‐Control Analysis of Psychosocial Factors and Adult Periodontitis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141163/1/jper1060.pd

Activation of Human T-Helper/Inducer Cell, T-Cytotoxic Cell, B-Cell, and Natural Killer (NK)-Cells and induction of Natural Killer Cell Activity against K562 Chronic Myeloid Leukemia Cells with Modified Citrus Pectin

<p>Abstract</p> <p>Background</p> <p>Modified citrus pectin (MCP) is known for its anti-cancer effects and its ability to be absorbed and circulated in the human body. In this report we tested the ability of MCP to induce the activation of human blood lymphocyte subsets like T, B and NK-cells.</p> <p>Methods</p> <p>MCP treated human blood samples were incubated with specific antibody combinations and analyzed in a flow cytometer using a 3-color protocol. To test functionality of the activated NK-cells, isolated normal lymphocytes were treated with increasing concentrations of MCP. Log-phase PKH26-labeled K562 leukemic cells were added to the lymphocytes and incubated for 4 h. The mixture was stained with FITC-labeled active form of caspase 3 antibody and analyzed by a 2-color flow cytometry protocol. The percentage of K562 cells positive for PKH26 and FITC were calculated as the dead cells induced by NK-cells. Monosaccharide analysis of the MCP was performed by high-performance anion-exchange chromatography with pulse amperometric detection (HPAEC-PAD).</p> <p>Results</p> <p>MCP activated T-cytotoxic cells and B-cell in a dose-dependent manner, and induced significant dose-dependent activation of NK-cells. MCP-activated NK-cells demonstrated functionality in inducing cancer cell death. MCP consisted of oligogalacturonic acids with some containing 4,5-unsaturated non-reducing ends.</p> <p>Conclusions</p> <p>MCP has immunostimulatory properties in human blood samples, including the activation of functional NK cells against K562 leukemic cells in culture. Unsaturated oligogalacturonic acids appear to be the immunostimulatory carbohydrates in MCP.</p

The Politics of Environmental Dispute Resolution

Also PCMA Working Paper #17.http://deepblue.lib.umich.edu/bitstream/2027.42/51148/1/380.pd

Investigation of G72 (DAOA) expression in the human brain

<p>Abstract</p> <p>Background</p> <p>Polymorphisms at the G72/G30 locus on chromosome 13q have been associated with schizophrenia or bipolar disorder in more than ten independent studies. Even though the genetic findings are very robust, the physiological role of the predicted G72 protein has thus far not been resolved. Initial reports suggested G72 as an activator of D-amino acid oxidase (DAO), supporting the glutamate dysfunction hypothesis of schizophrenia. However, these findings have subsequently not been reproduced and reports of endogenous human G72 mRNA and protein expression are extremely limited. In order to better understand the function of this putative schizophrenia susceptibility gene, we attempted to demonstrate G72 mRNA and protein expression in relevant human brain regions.</p> <p>Methods</p> <p>The expression of G72 mRNA was studied by northern blotting and semi-quantitative SYBR-Green and Taqman RT-PCR. Protein expression in human tissue lysates was investigated by western blotting using two custom-made specific anti-G72 peptide antibodies. An in-depth <it>in silico </it>analysis of the G72/G30 locus was performed in order to try and identify motifs or regulatory elements that provide insight to G72 mRNA expression and transcript stability.</p> <p>Results</p> <p>Despite using highly sensitive techniques, we failed to identify significant levels of G72 mRNA in a variety of human tissues (e.g. adult brain, amygdala, caudate nucleus, fetal brain, spinal cord and testis) human cell lines or schizophrenia/control post mortem BA10 samples. Furthermore, using western blotting in combination with sensitive detection methods, we were also unable to detect G72 protein in a number of human brain regions (including cerebellum and amygdala), spinal cord or testis. A detailed <it>in silico </it>analysis provides several lines of evidence that support the apparent low or absent expression of G72.</p> <p>Conclusion</p> <p>Our results suggest that native G72 protein is not normally present in the tissues that we analysed in this study. We also conclude that the lack of demonstrable G72 expression in relevant brain regions does not support a role for G72 in modulation of DAO activity and the pathology of schizophrenia via a DAO-mediated mechanism. <it>In silico </it>analysis suggests that G72 is not robustly expressed and that the transcript is potentially labile. Further studies are required to understand the significance of the G72/30 locus to schizophrenia.</p

Genome resequencing reveals multiscale geographic structure and extensive linkage disequilibrium in the forest tree Populus trichocarpa

•Plant population genomics informs evolutionary biology, breeding, conservation and bioenergy feedstock development. For example, the detection of reliable phenotype–genotype associations and molecular signatures of selection requires a detailed knowledge about genome-wide patterns of allele frequency variation, linkage disequilibrium and recombination. •We resequenced 16 genomes of the model tree Populus trichocarpa and genotyped 120 trees from 10 subpopulations using 29 213 single-nucleotide polymorphisms. •Significant geographic differentiation was present at multiple spatial scales, and range-wide latitudinal allele frequency gradients were strikingly common across the genome. The decay of linkage disequilibrium with physical distance was slower than expected from previous studies in Populus, with r² dropping below 0.2 within 3–6 kb. Consistent with this, estimates of recent effective population size from linkage disequilibrium (N[subscript e] ≈ 4000–6000) were remarkably low relative to the large census sizes of P. trichocarpa stands. Fine-scale rates of recombination varied widely across the genome, but were largely predictable on the basis of DNA sequence and methylation features. •Our results suggest that genetic drift has played a significant role in the recent evolutionary history of P. trichocarpa. Most importantly, the extensive linkage disequilibrium detected suggests that genome-wide association studies and genomic selection in undomesticated populations may be more feasible in Populus than previously assumed.This is the publisher’s final pdf. The article is copyrighted by the New Phytologist Trust and published by John Wiley & Sons, Inc. It can be found at: http://onlinelibrary.wiley.com/journal/10.1111/%28ISSN%291469-8137Keywords: recombination., allele frequency gradients, linkage disequilibrium (LD), population structure, black cottonwood (Populus trichocarpa), genome resequencin

System-wide transcriptome damage and tissue identity loss in COVID-19 patients

The molecular mechanisms underlying the clinical manifestations of coronavirus disease 2019 (COVID-19), and what distinguishes them from common seasonal influenza virus and other lung injury states such as acute respiratory distress syndrome, remain poorly understood. To address these challenges, we combine transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues to define body-wide transcriptome changes in response to COVID-19. We then match these data with spatial protein and expression profiling across 357 tissue sections from 16 representative patient lung samples and identify tissue-compartment-specific damage wrought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, evident as a function of varying viral loads during the clinical course of infection and tissue-type-specific expression states. Overall, our findings reveal a systemic disruption of canonical cellular and transcriptional pathways across all tissues, which can inform subsequent studies to combat the mortality of COVID-19 and to better understand the molecular dynamics of lethal SARS-CoV-2 and other respiratory infections., • Across all organs, fibroblast, and immune cell populations increase in COVID-19 patients • Organ-specific cell types and functional markers are lost in all COVID-19 tissue types • Lung compartment identity loss correlates with SARS-CoV-2 viral loads • COVID-19 uniquely disrupts co-occurrence cell type clusters (different from IAV/ARDS) , Park et al. report system-wide transcriptome damage and tissue identity loss wrought by SARS-CoV-2, influenza, and bacterial infection across multiple organs (heart, liver, lung, kidney, and lymph nodes) and provide a spatiotemporal landscape of COVID-19 in the lung