81 research outputs found

    Process Drama: A Creative Way To Assess ELA Understanding

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    With increasing demands and decreasing amounts of instructional time, teachers are constantly looking for creative ways to integrate, assess, and target instruction to meet the needs of each student. This article takes a look at how one teacher employed the use of a highly engaging process drama to teach and assess multiple subject area content standards. A process drama is remarkably creative, social, and applicable so can be easily adapted to meet the needs of any grade level. The low floor, high ceiling project allows students multiple avenues to demonstrate understanding of skills and concepts

    Deposition and fate of trace metals in Finnish bogs and implications for the use of bogs as geological archives

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    Vier Probenahmestellen mit bekannter atmosphärischer Spurenmetall-Deposition wurden beprobt: Hietajärvi (HIJ) als Referenz für die Hintergrundbelastung; Outokumpu, in der Nähe einer ehemaligen Cu-Ni-Mine; Harjavalta (HAR), nahe eines Cu und Ni Hüttenwerks und Alkkia, wo 1962 in einer Feldstudie Metallsalze aufgetragen wurden. Ziel dieser Arbeit ist es herauszufinden, in welchem Ausmaß die atmosphärische Cu, Ni, Co, Zn und Cd Deposition in Torfprofilen aus Hochmooren aufgezeichnet wird. Dies wurde mittels zweier unabhängiger Herangehensweisen studiert: Metall-Akkumulationsraten in Torfproben wurden mit der tatsächlichen Deposition verglichen, und Metallkonzentrationen im Porenwasser wurden mit Gesamtkonzentrationen verglichen. Spurenmetall-Konzentrationen wurden mittels ICP-SF-MS bestimmt. Ein neues Gerät zur Entnahme von Porenwasser-Proben in Hochmooren sowie ein vollständiges Probenahme-Protokoll wurde entwickelt, mit folgenden Blindwerten: (in µg L-1): Cd 0.001, Co 0.009, Cr 0.05, Cu 0.07, Mn 0.2, Mo 0.02, Ni 0.10, Pb 0.004, Sc 0.011, V 0.01, Zn 1. Die manuelle Filtration an der Probenahmestelle führte zu einer signifikanten Erhöhung der Cr, Cu und Zn Blindwerte. Der hohe Gehalt an Huminstoffen in den Porenwässern führte zu starken Filtrationsartefakten. In HIJ und OUT wurden zusätzlich Porenwasser-Proben mittels Dialyse gewonnen (sog. „Hesslein peeper“). Diese Probenahme-Technik ist weniger anfällig für Filtrationsartefakte, jedoch konnte damit keine zuverlässigen Konzentrationsprofile gewonnen werden (Ausnahme: Co und Mn). Folgende Hintergrund-Konzentrationen wurden in tiefen Torfschichten in HIJ bestimmt (in µg g-1): Cu 1.3 ± 0.2 (n=62), Co 0.25 ± 0.04 (n=71), Cd 0.08 ± 0.01 (n=23) und Zn 4 ± 2 (n=40). Ähnliche Konzentrationen wurden auch in den tieferen Torfschichten der anderen Probenahme-Stellen gefunden, während obere Torflagen erhöhte Metall-Konzentrationen aufwiesen. Die Metallkonzentrationen waren unabhängig vom Bodenstaub-Eintrag, vom Zersetzungsgrad der Torfschichten und von den S und Fe Konzentrationen. Die Cu und Co Akkumulationsraten spiegelten die atmosphärische Deposition in OUT hervorragend wider. Nickel, Zn und Cd wurden dagegen nach der Ablagerung mobilisiert. Trotz Schwierigkeiten bei der Altersbestimmung der Torfproben deuteten die Metall-Akkumulationsraten in HAR auf eine Mobilisierung aller Metalle hin. Porenwasser-Konzentrationen in HIJ und OUT waren niedrig (< 8 nM Cu and Ni, < 1.4 nM Co, < 250 nM Zn). Trotz Anzeichen einer gewissen Freisetzung von Ni und Zn in OUT deuteten sie auf eine Umverteilung der Metalle im Anfangsstadium hin. Hohe Cd bzw. niedrige Cu Konzentrationen im Porenwasser bestätigten die Ergebnisse der ersten Herangehensweise. Die unterschiedliche Mobilität der Metalle basiert vermutlich auf der unterschiedlichen Resistenz der abgelagerten Sulfiderze gegen Oxidation an der Oberfläche des Moores. Porenwasser-Konzentrationen in HAR sind stark gegenüber HIJ und OUT erhöht, vermutlich da dort leichtlösliche Metall-Oxide abgelagert wurden

    Age-dependent rise in IFN-γ competence undermines effective type 2 responses to nematode infection

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    The efficient induction of type 2 immune responses is central to the control of helminth infections. Previous studies demonstrated that strong Th1 responses driven by intracellular pathogens as well as a bias for type 1 activity in senescent mice impedes the generation of Th2 responses and the control of intestinal nematode infections. Here, we show that the spontaneous differentiation of Th1 cells and their expansion with age restrains type 2 immunity to infection with the small intestinal nematode H. polygyrus much earlier in life than previously anticipated. This includes the more extensive induction of IFN-γ competent, nematode-specific Th2/1 hybrid cells in BALB/c mice older than three months compared to younger animals. In C57BL/6 mice, Th1 cells accumulate more rapidly at steady state, translating to elevated Th2/1 differentiation and poor control of parasite fitness in primary infections experienced at a young age. Blocking of early IFN-γ and IL-12 signals during the first week of nematode infection leads to sharply decreased Th2/1 differentiation and promotes resistance in both mouse lines. Together, these data suggest that IFN-γ competent, type 1 like effector cells spontaneously accumulating in the vertebrate host progressively curtail the effectiveness of anti-nematode type 2 responses with rising host age

    A minimal model of peptide binding predicts ensemble properties of serum antibodies

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    <p/> <p>Background</p> <p>The importance of peptide microarrays as a tool for serological diagnostics has strongly increased over the last decade. However, interpretation of the binding signals is still hampered by our limited understanding of the technology. This is in particular true for arrays probed with antibody mixtures of unknown complexity, such as sera. To gain insight into how signals depend on peptide amino acid sequences, we probed random-sequence peptide microarrays with sera of healthy and infected mice. We analyzed the resulting antibody binding profiles with regression methods and formulated a minimal model to explain our findings.</p> <p>Results</p> <p>Multivariate regression analysis relating peptide sequence to measured signals led to the definition of amino acid-associated weights. Although these weights do not contain information on amino acid position, they predict up to 40-50% of the binding profiles' variation. Mathematical modeling shows that this position-independent ansatz is only adequate for highly diverse random antibody mixtures which are not dominated by a few antibodies. Experimental results suggest that sera from healthy individuals correspond to that case, in contrast to sera of infected ones.</p> <p>Conclusions</p> <p>Our results indicate that position-independent amino acid-associated weights predict linear epitope binding of antibody mixtures only if the mixture is random, highly diverse, and contains no dominant antibodies. The discovered ensemble property is an important step towards an understanding of peptide-array serum-antibody binding profiles. It has implications for both serological diagnostics and B cell epitope mapping.</p

    Parasitic Nematodes Exert Antimicrobial Activity and Benefit From Microbiota-Driven Support for Host Immune Regulation

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    Intestinal parasitic nematodes live in intimate contact with the host microbiota. Changes in the microbiome composition during nematode infection affect immune control of the parasites and shifts in the abundance of bacterial groups have been linked to the immunoregulatory potential of nematodes. Here we asked if the small intestinal parasite Heligmosomoides polygyrus produces factors with antimicrobial activity, senses its microbial environment and if the anti-nematode immune and regulatory responses are altered in mice devoid of gut microbes. We found that H. polygyrus excretory/secretory products exhibited antimicrobial activity against gram+/− bacteria. Parasites from germ-free mice displayed alterations in gene expression, comprising factors with putative antimicrobial functions such as chitinase and lysozyme. Infected germ-free mice developed increased small intestinal Th2 responses coinciding with a reduction in local Foxp3+RORγt+ regulatory T cells and decreased parasite fecundity. Our data suggest that nematodes sense their microbial surrounding and have evolved factors that limit the outgrowth of certain microbes. Moreover, the parasites benefit from microbiota-driven immune regulatory circuits, as an increased ratio of intestinal Th2 effector to regulatory T cells coincides with reduced parasite fitness in germ-free mice.Peer Reviewe

    Multiplexed Quantitative Assessment of the Fate of Taurine and Sulfoquinovose in the Intestinal Microbiome

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    (1) Introduction: Sulfonates, which can be diet- or host-derived, are a class of compounds detected in the gut, are involved in host–microbiome interactions and have several health effects. Our aim was to develop a method to quantify five of the sulfonates in the intestine and apply it in a simplified human microbiome model. These were taurine, its metabolic precursor cysteate and one of its degradation products isethionate, as well as sulfoquinovose and one of its most relevant degradation products 2,3-dihydroxy-1-propanesulfonate. (2) Methods: An extraction and sample preparation method was developed, without the need for derivatization. To detect and quantify the extracted sulfonates, a multiplexed LC-MS/MS-MRM method was established. (3) Results: The accuracy and precision of the method were within GLP-accepted parameters. To apply this method in a pilot study, we spiked either taurine or sulfoquinovose into an in vitro simplified human microbiota model with and without Bilophila wadsworthia, a known sulfonate utilizer. The results revealed that only the culture with B. wadsworthia was able to degrade taurine, with isethionate as an intermediate. After spiking the communities with sulfoquinovose, the results revealed that the simplified human microbiome model was able to degrade sulfoquinovose to 2,3-dihydroxypropane-1-sulfonate, which was probably catalyzed by Escherichia coli. In the community with B. wadsworthia, the 2,3-dihydroxypropane-1-sulfonate produced was further degraded by B. wadsworthia to sulfide. (4) Conclusions: We successfully developed a method for sulfonate quantification and applied it in a first pilot study

    Parasitic Nematodes Exert Antimicrobial Activity and Benefit From Microbiota-Driven Support for Host Immune Regulation

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    Intestinal parasitic nematodes live in intimate contact with the host microbiota. Changes in the microbiome composition during nematode infection affect immune control of the parasites and shifts in the abundance of bacterial groups have been linked to the immunoregulatory potential of nematodes. Here we asked if the small intestinal parasite Heligmosomoides polygyrus produces factors with antimicrobial activity, senses its microbial environment and if the anti-nematode immune and regulatory responses are altered in mice devoid of gut microbes. We found that H. polygyrus excretory/secretory products exhibited antimicrobial activity against gram+/− bacteria. Parasites from germ-free mice displayed alterations in gene expression, comprising factors with putative antimicrobial functions such as chitinase and lysozyme. Infected germ-free mice developed increased small intestinal Th2 responses coinciding with a reduction in local Foxp3+RORγt+ regulatory T cells and decreased parasite fecundity. Our data suggest that nematodes sense their microbial surrounding and have evolved factors that limit the outgrowth of certain microbes. Moreover, the parasites benefit from microbiota-driven immune regulatory circuits, as an increased ratio of intestinal Th2 effector to regulatory T cells coincides with reduced parasite fitness in germ-free mice

    Consensus molecular subtype classification of colorectal adenomas

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    Consensus molecular subtyping is an RNA expression-based classification system for colorectal cancer (CRC). Genomic alterations accumulate during CRC pathogenesis, including the premalignant adenoma stage, leading to changes in RNA expression. Only a minority of adenomas progress to malignancies, a transition that is associated with specific DNA copy number aberrations or microsatellite instability (MSI). We aimed to investigate whether colorectal adenomas can already be stratified into consensus molecular subtype (CMS) classes, and whether specific CMS classes are related to the presence of specific DNA copy number aberrations associated with progression to malignancy. RNA sequencing was performed on 62 adenomas and 59 CRCs. MSI status was determined with polymerase chain reaction-based methodology. DNA copy number was assessed by low-coverage DNA sequencing (n = 30) or array-comparative genomic hybridisation (n = 32). Adenomas were classified into CMS classes together with CRCs from the study cohort and from The Cancer Genome Atlas (n = 556), by use of the established CMS classifier. As a result, 54 of 62 (87%) adenomas were classified according to the CMS. The CMS3 ‘metabolic subtype’, which was least common among CRCs, was most prevalent among adenomas (n = 45; 73%). One of the two adenomas showing MSI was classified as CMS1 (2%), the ‘MSI immune’ subtype. Eight adenomas (13%) were classified as the ‘canonical’ CMS2. No adenomas were classified as the ‘mesenchymal’ CMS4, consistent with the fact that adenomas lack invasion-associated stroma. The distribution of the CMS classes among adenomas was confirmed in an independent series. CMS3 was enriched with adenomas at low risk of progressing to CRC, whereas relatively more high-risk adenomas were observed in CMS2. We conclude that adenomas can be stratified into the CMS classes. Considering that CMS1 and CMS2 expression signatures may mark adenomas at increased risk of progression, the distribution of the CMS classes among adenomas is consistent with the proportion of adenomas expected to progress to CRC

    Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

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    Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts
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