DNA methylation-based biomarkers for early detection of non-small cell lung cancer: an update

Lung cancer is the number one cancer killer in the United States. This disease is clinically divided into two sub-types, small cell lung cancer, (10–15% of lung cancer cases), and non-small cell lung cancer (NSCLC; 85–90% of cases). Early detection of NSCLC, which is the more common and less aggressive of the two sub-types, has the highest potential for saving lives. As yet, no routine screening method that enables early detection exists, and this is a key factor in the high mortality rate of this disease. Imaging and cytology-based screening strategies have been employed for early detection, and while some are sensitive, none have been demonstrated to reduce lung cancer mortality. However, mortality might be reduced by developing specific molecular markers that can complement imaging techniques. DNA methylation has emerged as a highly promising biomarker and is being actively studied in multiple cancers. The analysis of DNA methylation-based biomarkers is rapidly advancing, and a large number of potential biomarkers have been identified. Here we present a detailed review of the literature, focusing on DNA methylation-based markers developed using primary NSCLC tissue. Viable markers for clinical diagnosis must be detectable in 'remote media' such as blood, sputum, bronchoalveolar lavage, or even exhaled breath condensate. We discuss progress on their detection in such media and the sensitivity and specificity of the molecular marker panels identified to date. Lastly, we look to future advancements that will be made possible with the interrogation of the epigenome

Evaluation of Novel Imidazotetrazine Analogues Designed to Overcome Temozolomide Resistance and Glioblastoma Regrowth

The cellular responses to two new temozolomide (TMZ) analogues, DP68 and DP86, acting against glioblastoma multi- forme (GBM) cell lines and primary culture models are reported. Dose–response analysis of cultured GBM cells revealed that DP68 is more potent than DP86 and TMZ and that DP68 was effective even in cell lines resistant to TMZ. On the basis of a serial neurosphere assay, DP68 inhibits repop- ulation of these cultures at low concentrations. The efficacy of these compounds was independent of MGMT and MMR func- tions. DP68-induced interstrand DNA cross-links were dem- onstrated with H2O2-treated cells. Furthermore, DP68 induced a distinct cell–cycle arrest with accumulation of cells in S phase that is not observed for TMZ. Consistent with this biologic response, DP68 induces a strong DNA damage response, including phosphorylation of ATM, Chk1 and Chk2 kinases, KAP1, and histone variant H2AX. Suppression of FANCD2 expression or ATR expression/kinase activity enhanced anti- glioblastoma effects of DP68. Initial pharmacokinetic analysis revealed rapid elimination of these drugs from serum. Collec- tively, these data demonstrate that DP68 is a novel and potent antiglioblastoma compound that circumvents TMZ resistance, likely as a result of its independence from MGMT and mismatch repair and its capacity to cross-link strands of DN

Combined proton NMR wideline and NMR relaxometry to study SOM-water interactions of cation-treated soils

Focusing on the idea that multivalent cations affect SOM matrix and surface, we treated peat and soil samples by solutions of NaCl, CaCl2 or AlCl3. Water binding was characterized with low field 1H-NMR-relaxometry (20 MHz) and 1H wideline NMR spectroscopy (400 MHz) and compared to contact angles. From 1H wideline, we distinguished mobile water and water involved in water molecule bridges (WaMB). Large part of cation bridges (CaB) between SOM functional groups are associated with WaMB. Unexpectedly, 1H NMRrelaxometry relaxation rates suggest that cross-linking in the Al-containing peat is not stronger than that by Ca. The relation between percentage of mobile water and WaMB water in the context of wettability and 1H NMR relaxation times confirms that wettability controls the water film surrounding soil particles. Wettability is controlled by WaMB-CaB associations fixing hydrophilic functional groups in the SOM interior. This can lead to severe water repellency. Wettability decreases with increasing involvement of functional groups in CaB-WaMB associations. The results demonstrate the relevance of CaB and WaMB for the dynamics of biogeochemical and hydrological processes under field conditions, as only a few percent of organic matter can affect the physical, chemical, and biological functioning of the entire 3-phase ecosystem

Surface Morphology and Electrical Resistivity in Polycrystalline Au/Cu/Si(100) System

This work describes the analysis of morphology and electrical resistivity (ρ) obtained in the Au/Cu/Si system. The Au/Cu bilayers were deposited by thermal evaporation technique with thicknesses from 50 to 250 nm on SiOx/Si(100) substrates. The Au : Cu concentration ratio of the samples was of 25 : 75 at%. The bilayers were annealed into a vacuum oven with argon atmosphere at 660 K for one hour. The crystalline structures of AuCu and CuSi alloys were confirmed by X-ray diffraction analysis. The scanning electron microscopy (SEM), the atomic force microscopy (AFM), and the energy dispersive spectroscopy (EDS) were used to study the morphology, final thickness, and the atomic concentration of the alloys formed, respectively. The four-point probe technique was used to measure the electrical resistivity (ρ) in the prepared alloys as a function of thickness. The ρ value was measured and it was numerically compared with the Fuchs–Sondheimer (FS) and the Mayadas–Shatzkes (MS) models of resistivity. Results show values of electrical resistivity between 0.9 and 1.9 μΩ-cm. These values are four times smaller than the values of the AuCu systems reported in literature

Virtualized Clinical Studies to Assess the Natural History and Impact of Gut Microbiome Modulation in Non-Hospitalized Patients with Mild to Moderate COVID-19 a Randomized, Open-Label, Prospective Study with a Parallel Group Study Evaluating the Physiologic Effects of KB109 on Gut Microbiota Structure and Function: A Structured Summary of a Study Protocol for a Randomized Controlled Study [preprint]

These 2 parallel studies (K031 and K032) aim to evaluate the safety of KB109 in addition to supportive self-care (SSC) compared with SSC alone in outpatients with mild to moderate coronavirus disease 2019 (COVID-19). KB109 is a novel synthetic glycan that was formulated to modulate the gut microbiome composition and metabolic output in order to increase beneficial short-chain fatty acid (SCFA) production in the gut. The K031 study is designed to evaluate the safety of KB109 and characterize its impact on the natural progression of COVID-19 in patients with mild to moderate disease. The K032 study is evaluating the effect of KB109 on the gut microbiota structure and function in this same patient population. Additionally, both studies are evaluating measures of health care utilization, quality of life (QOL), laboratory indices, biomarkers of inflammation, and serological measures of immunity in patients who received SSC alone or with KB109. Noteworthy aspects of these outpatient studies include study design measures aimed at limiting in-person interactions to minimize the risk of infection spread, such as use of online diaries, telemedicine, and at-home sample collection

Conformational behaviour of humic substances at different depths along a profile of a Lithosol under loblolly (Pinus taeda) plantation.

Published in 6th EGU General Assembly 2009

Conjugated linoleic acid content in milk of Chilean Black Friesian cows under pasture conditions and supplemented with canola seed (Brassica napus) concentrate

At present, there is limited and contradictory information about the effects of the use of canola (Brassica napus) seed as supplement on the contents of conjugated linoleic acid (CLA) in milk of grazing cows. The objective of this study was to evaluate the effect of a dietary supplement with canola seed on the production and composition of milk, and CLA concentration in Chilean Black Friesian cows under pasture conditions. Three experiments were done. Experiment 1: control group was fed 5 kg d–1 of commercial concentrate without canola (0-TC1) and treatment group that was fed 3.75 kg of commercial concentrate plus 1.16 kg of whole canola seed (1.16-TC1). Experiment 2: Control group was fed 8 kg d–1 commercial concentrate without canola (0-TC2) and treatment group that was fed 6.2 kg of commercial concentrate plus 1.2 kg of ground canola seed (1.2-TC2). Experiment 3: control group was fed 6 kg d–1 commercial concentrate without canola (0-TC3) and treatment group was fed 6 kg of commercial concentrate with 20% of whole canola seed (1.2 kg d–1, 1.2-TC3). The duration of each experiment was 60 days. No differences in milk production and quality were observed among the experimental groups in every assay. The CLA isomers trans-10, cis-12 and cis-10, cis-12 were higher than those normally found in the scientific literature. There was no effect of the inclusion of canola seed on total CLA content or the content of cis-9, trans-11, trans-10, cis-12 and cis-10, cis-12 isomers

Immunohistochemical and molecular detection of equine herpesvirus 1 in Uruguay

Equine herpesvirus 1 (EHV-1) is a major cause of epidemic abortion, neonatal mortality, respiratory disease and neurological disorders in horses. In South America, the virus has been isolated in Brazil, Argentina and Colombia. In Chile pathological findings from one aborted foetus have been reported, and in Uruguay only serological data about EHV-1 activity have been found. Some pathological findings were reported in Uruguay several years ago, but these data have never been officially confirmed. The present work describes the relevant findings of a study of EHV-1 infections in the Uruguayan equine population using polymerase chain reaction (PCR) and histological and immunohistochemical analysis techniques. The sequence analysis of a portion of the glycoprotein C gene amplified by PCR confirmed EHV-1 activity. The real-time PCR revealed the association of the virus with the non-neuropathogenic genotype. This study describes for the first time the immunohistochemical and molecular detection of EHV-1 in Uruguay.Facultad de Ciencias Veterinaria

QuickSNP: an automated web server for selection of tagSNPs

Although large-scale genetic association studies involving hundreds to thousands of SNPs have become feasible, the associated cost is substantial. Even with the increased efficiency introduced by the use of tagSNPs, researchers are often seeking ways to maximize resource utilization given a set of SNP-based gene-mapping goals. We have developed a web server named QuickSNP in order to provide cost-effective selection of SNPs, and to fill in some of the gaps in existing SNP selection tools. One useful feature of QuickSNP is the option to select only gene-centric SNPs from a chromosomal region in an automated fashion. Other useful features include automated selection of coding non-synonymous SNPs, SNP filtering based on inter-SNP distances and information regarding the availability of genotyping assays for SNPs and whether they are present on whole genome chips. The program produces user-friendly summary tables and results, and a link to a UCSC Genome Browser track illustrating the position of the selected tagSNPs in relation to genes and other genomic features. We hope the unique combination of features of this server will be useful for researchers aiming to select markers for their genotyping studies. The server is freely available and can be accessed at the URL http://bioinformoodics.jhmi.edu/quickSNP.pl