306 research outputs found

    Water Age, Water Chemistry, and Microbial Populations in a Drinking Water Distribution System

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    Microbes in tap water play a crucial role in pipe corrosion, human health, and water aesthetics. Because instances of tap water borne illnesses are on the rise in the USA, and many water distribution systems are reaching the end of their design lifespan, research leading to a better understanding of microbial growth and colonization is being actively pursued by many labs (EPA 2002; Miller et al. 2012). In the past decade, several studies have tracked the microbial community change of entire water distribution systems using high throughput sequencing technology (Ma et al. 2020; Perrin et al. 2019). System-scale community microbiology data has shown clear seasonal trends in microbial drinking water taxa. This study utilized similar genomic methods to characterize the planktonic (free-floating) microbial community in the drinking water of the North Shore Water Commission distribution system, just north of Milwaukee, Wisconsin.As treated water moves through a pipe system, residual microbes from the source water may multiply, or microbes may enter the flowing water from the biofilm covering the pipe wall (Rittman and Snoeyink 1984). American treatment plants seek to deactivate all microbes in the finished water; whereas, European systems focus on removing nutrients from the finished water, especially ammonia, manganese, and dissolved oxygen: As a result, microbes sloughing from the biofilm tend to regrow quicker in American systems, i .e., the water is more unstable, than microbial growth in European systems. The overall effect of retention time, or water age, on microbial communities is not clearly understood in American or European systems. As disinfectant residuals decline, and exposure to pipe biofilms rises, microbial regrowth and microbial deposition are hypothesized to cause the total microbial load to rise (Wang et al. 2014). Furthermore, certain taxa such as Sphingomonas, Nitrospira, Mycobacterium, and Hyphomicrobium, have been shown to positively correlate to water age (Chan et al. 2019). However, because water age (retention time) is typically only inferred from spatial data, greater precision in water age measurements will help to characterize microbial community changes with age, and thus improve the understanding of engineering design that impact potential health risks. For example, by identifying regions of a distribution system with chronically high water age, engineers could schedule more frequent hydrant flushing to prevent biofilm formation. Elucidating water age is a difficult task: Hydrologic models can be used to estimate water age; however, few drinking water systems have models, and those that exist are rarely calibrated with chemical tracers and are based on several untested assumptions (Waples et al. 2015). This study employed a newly designed protocol to measure water age using naturally-occurring radionuclides (Waples et al. 2015). These temporal data combined with 16S rRNA gene sequencing offer insights into microbial growth in a full-scale drinking water system

    Improving Estimates of Phytoplankton Populations in the Chesapeake Bay Using Hyperspectral Radiometers

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    In coastal and estuarine waters, high turbidity and land interference severely diminish the utility of satellite data. This study tested the accuracy of hyperspectral inversion algorithms to better resolve chlorophyll a estimates in the Chesapeake Bay. Hyperspectral instruments measure reflected light with much greater spectral resolution than the multispectral instruments currently deployed on ocean-observing satellites. Increased spectral resolution allows for better approximation of phytoplankton concentrations in optically complex waters. This research seeks to test optical inversion algorithms designed for turbid waters like the Chesapeake Bay. By pairing in situ measurements of chlorophyll with electromagnetic spectrum measurements, we determined the most accurate algorithms for use in the Chesapeake Bay. These algorithms can then be employed in future remote sensing studies to yield accurate chlorophyll measurements in fine temporal, and spatial time scales

    Dogbane Under Stress: Habitat Differentiation of Anthocyanins in Apocynum cannabinum

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    The quarry in DePauw’s Nature Park, which was previously stripped of soil and layers of bedrock, offers an ideal study system for understanding how plants adapt to disturbances. The quarry bottom is particularly stressful for plants because of this loss in soil, high variability in water availability due to the poor porosity of the bedrock, and high light intensity. Therefore, plants that live there must have traits suitable for this harsh environment. One response elicited to stress in plants is the production of red pigments called anthocyanins. Anthocyanins are versatile and have been found to be protective in a multitude of ways; among their many functions, they have been shown to protect against tissue damage at high light levels and increase herbivore resistance. Using Hemp Dogbane, Apocynum cannabinum, as a study system, we asked whether anthocyanin content in stems differs between quarry and non quarry environments, if there is a relationship between pigmentation and herbivory, and how pigmentation is selected on in the two habitats

    Ein Beitrag zur Kenntnis der Lingua geographica

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    http://tartu.ester.ee/record=b1964710~S1*es

    A Combined Score of Circulating miRNAs Allows Outcome Prediction in Critically Ill Patients

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    Background and aims: Identification of patients with increased risk of mortality represents an important prerequisite for an adapted adequate and individualized treatment of critically ill patients. Circulating micro-RNA (miRNA) levels have been suggested as potential biomarkers at the intensive care unit (ICU), but none of the investigated miRNAs displayed a sufficient sensitivity or specificity to be routinely employed as a single marker in clinical practice. Methods and results: We recently described alterations in serum levels of 7 miRNAs (miR-122, miR-133a, miR-143, miR-150, miR-155, miR-192, and miR-223) in critically ill patients at a medical ICU. In this study, we re-analyzed these previously published data and performed a combined analysis of these markers to unravel their potential as a prognostic scoring system in the context of critical illness. Based on the Youden’s index method, cut-off values were systematically defined for dysregulated miRNAs, and a “miRNA survival score” was calculated. Patients with high scores displayed a dramatically impaired prognosis compared to patients with low values. Additionally, the predictive power of our score could be further increased when the patient’s age was additionally incorporated into this score. Conclusions: We describe the first miRNA-based biomarker score for prediction of medical patients’ outcome during and after ICU treatment. Adding the patients’ age into this score was associated with a further increase in its predictive power. Further studies are needed to validate the clinical utility of this score in risk-stratifying critically ill patients

    Activin and TGFβ use diverging mitogenic signaling in advanced colon cancer.

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    BackgroundUnderstanding cell signaling pathways that contribute to metastatic colon cancer is critical to risk stratification in the era of personalized therapeutics. Here, we dissect the unique involvement of mitogenic pathways in a TGFβ or activin-induced metastatic phenotype of colon cancer.MethodMitogenic signaling/growth factor receptor status and p21 localization were correlated in primary colon cancers and intestinal tumors from either AOM/DSS treated ACVR2A (activin receptor 2) -/- or wild type mice. Colon cancer cell lines (+/- SMAD4) were interrogated for ligand-induced PI3K and MEK/ERK pathway activation and downstream protein/phospho-isoform expression/association after knockdown and pharmacologic inhibition of pathway members. EMT was assessed using epithelial/mesenchymal markers and migration assays.ResultsIn primary colon cancers, loss of nuclear p21 correlated with upstream activation of activin/PI3K while nuclear p21 expression was associated with TGFβ/MEK/ERK pathway activation. Activin, but not TGFβ, led to PI3K activation via interaction of ACVR1B and p85 independent of SMAD4, resulting in p21 downregulation. In contrast, TGFβ increased p21 via MEK/ERK pathway through a SMAD4-dependent mechanism. While activin induced EMT via PI3K, TGFβ induced EMT via MEK/ERK activation. In vivo, loss of ACVR2A resulted in loss of pAkt, consistent with activin-dependent PI3K signaling.ConclusionAlthough activin and TGFβ share growth suppressive SMAD signaling in colon cancer, they diverge in their SMAD4-independent pro-migratory signaling utilizing distinct mitogenic signaling pathways that affect EMT. p21 localization in colon cancer may determine a dominant activin versus TGFβ ligand signaling phenotype warranting further validation as a therapeutic biomarker prior to targeting TGFβ family receptors

    Whole genome and exome sequencing of monozygotic twins discordant for Crohn's disease

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    Background Crohn's disease (CD) is an inflammatory bowel disease caused by genetic and environmental factors. More than 160 susceptibility loci have been identified for IBD, yet a large part of the genetic variance remains unexplained. Recent studies have demonstrated genetic differences between monozygotic twins, who were long thought to be genetically completely identical. Results We aimed to test if somatic mutations play a role in CD etiology by sequencing the genomes and exomes of directly affected tissue from the bowel and blood samples of one and the blood-derived exomes of two further monozygotic discordant twin pairs. Our goal was the identification of mutations present only in the affected twins, pointing to novel candidates for CD susceptibility loci. We present a thorough genetic characterization of the sequenced individuals but detected no consistent differences within the twin pairs. An estimate of the CD susceptibility based on known CD loci however hinted at a higher mutational load in all three twin pairs compared to 1,920 healthy individuals. Conclusion Somatic mosaicism does not seem to play a role in the discordance of monozygotic CD twins. Our study constitutes the first to perform whole genome sequencing for CD twins and therefore provides a valuable reference dataset for future studies. We present an example framework for mosaicism detection and point to the challenges in these types of analyses

    A functional methylome map of ulcerative colitis

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    The etiology of inflammatory bowel diseases is only partially explained by the current genetic risk map. It is hypothesized that environmental factors modulate the epigenetic landscape and thus contribute to disease susceptibility, manifestation, and progression. To test this, we analyzed DNA methylation (DNAm), a fundamental mechanism of epigenetic long-term modulation of gene expression. We report a three-layer epigenome-wide association study (EWAS) using intestinal biopsies from 10 monozygotic twin pairs (n = 20 individuals) discordant for manifestation of ulcerative colitis (UC). Genome-wide expression scans were generated using Affymetrix UG 133 Plus 2.0 arrays (layer 1). Genome-wide DNAm scans were carried out using Illumina 27k Infinium Bead Arrays to identify methylation variable positions (MVPs, layer 2), and MeDIP-chip on Nimblegen custom 385k Tiling Arrays to identify differentially methylated regions (DMRs, layer 3). Identified MVPs and DMRs were validated in two independent patient populations by quantitative real-time PCR and bisulfite-pyrosequencing (n = 185). The EWAS identified 61 disease-associated loci harboring differential DNAm in cis of a differentially expressed transcript. All constitute novel candidate risk loci for UC not previously identified by GWAS. Among them are several that have been functionally implicated in inflammatory processes, e.g., complement factor CFI, the serine protease inhibitor SPINK4, and the adhesion molecule THY1 (also known as CD90). Our study design excludes nondisease inflammation as a cause of the identified changes in DNAm. This study represents the first replicated EWAS of UC integrated with transcriptional signatures in the affected tissue and demonstrates the power of EWAS to uncover unexplained disease risk and molecular events of disease manifestation

    Lectin-like bacteriocins from pseudomonas spp. utilise D-rhamnose containing lipopolysaccharide as a cellular receptor

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    Lectin-like bacteriocins consist of tandem monocot mannose-binding domains and display a genus-specific killing activity. Here we show that pyocin L1, a novel member of this family from Pseudomonas aeruginosa, targets susceptible strains of this species through recognition of the common polysaccharide antigen (CPA) of P. aeruginosa lipopolysaccharide that is predominantly a homopolymer of d-rhamnose. Structural and biophysical analyses show that recognition of CPA occurs through the C-terminal carbohydrate-binding domain of pyocin L1 and that this interaction is a prerequisite for bactericidal activity. Further to this, we show that the previously described lectin-like bacteriocin putidacin L1 shows a similar carbohydrate-binding specificity, indicating that oligosaccharides containing d-rhamnose and not d-mannose, as was previously thought, are the physiologically relevant ligands for this group of bacteriocins. The widespread inclusion of d-rhamnose in the lipopolysaccharide of members of the genus Pseudomonas explains the unusual genus-specific activity of the lectin-like bacteriocins
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