926 research outputs found

    Sedimentary ancient DNA sequences reveal marine ecosystem shifts and indicator taxa for glacial-interglacial sea ice conditions

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    Sedimentary ancient DNA (sedaDNA) analysis is a promising new approach for reconstructing the impact of past climate and environmental changes on marine paleobiodiversity. By recovering, amplifying, and sequencing taxonomically informative sedaDNA fragments preserved in sediments, it is possible to assess the response of a broad range of eukaryote taxa, including non-fossilizing lineages, to past climate change. Here we present a unique marine derived sedaDNA metabarcoding record, spanning the penultimate glacial-interglacial transition across Marine Isotope Stages 6 to 5d (>135–107 ka) from an Eirik Drift core-site in the Labrador Sea. We identified a range of marine groups including dinoflagellates, diatoms, coccolithophores, chlorophytes, and copepods. There were representatives of primary/secondary producers, grazers, and parasites, which may represent remnants of complex ecosystems and ancient food webs. There were significant biodiversity shifts following the penultimate deglaciation and changing sea ice conditions throughout the Last Interglacial. These shifts reflected the striking increase in community richness during periods of seasonal sea ice and reduction under extensive perennial sea ice cover and open ocean. We identify two potential sedaDNA indicator taxa sequences associated with past seasonal sea ice which are most likely pico-eukaryote representatives of Micromonas and Pyramimonas, both green algae with known sea ice associations in modern ecosystems. Our work demonstrates the importance of high resolution marine sedaDNA metabarcoding for unravelling climate-ecosystem linkages and strengthens the potential of sedaDNA signals for past sea ice reconstructions through indicator sequences.publishedVersio

    Multiparametric MRI for assessment of early response to neoadjuvant sunitinib in renal cell carcinoma.

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    Funder: NIHR Cambridge Biomedical Research CentreFunder: Addenbrooke’s Charitable TrustFunder: National Institute for Health Research (NIHR)Funder: Mark Foundation For Cancer ResearchFunder: Cambridge Commonwealth, European and International TrustFunder: Cancer Research UKFunder: Cambridge Clinical Trials UnitFunder: Cancer Research UK Cambridge CentreFunder: Engineering and Physical Sciences Research Council Cancer Imaging Centre in Cambridge and ManchesterFunder: Cambridge Experimental Cancer Medicine CentrePURPOSE: To detect early response to sunitinib treatment in metastatic clear cell renal cancer (mRCC) using multiparametric MRI. METHOD: Participants with mRCC undergoing pre-surgical sunitinib therapy in the prospective NeoSun clinical trial (EudraCtNo: 2005-004502-82) were imaged before starting treatment, and after 12 days of sunitinib therapy using morphological MRI sequences, advanced diffusion-weighted imaging, measurements of R2* (related to hypoxia) and dynamic contrast-enhanced imaging. Following nephrectomy, participants continued treatment and were followed-up with contrast-enhanced CT. Changes in imaging parameters before and after sunitinib were assessed with the non-parametric Wilcoxon signed-rank test and the log-rank test was used to assess effects on survival. RESULTS: 12 participants fulfilled the inclusion criteria. After 12 days, the solid and necrotic tumor volumes decreased by 28% and 17%, respectively (p = 0.04). However, tumor-volume reduction did not correlate with progression-free or overall survival (PFS/OS). Sunitinib therapy resulted in a reduction in median solid tumor diffusivity D from 1298x10-6 to 1200x10-6mm2/s (p = 0.03); a larger decrease was associated with a better RECIST response (p = 0.02) and longer PFS (p = 0.03) on the log-rank test. An increase in R2* from 19 to 28s-1 (p = 0.001) was observed, paralleled by a decrease in Ktrans from 0.415 to 0.305min-1 (p = 0.01) and a decrease in perfusion fraction from 0.34 to 0.19 (p<0.001). CONCLUSIONS: Physiological imaging confirmed efficacy of the anti-angiogenic agent 12 days after initiating therapy and demonstrated response to treatment. The change in diffusivity shortly after starting pre-surgical sunitinib correlated to PFS in mRCC undergoing nephrectomy, however, no parameter predicted OS. TRIAL REGISTRATION: EudraCtNo: 2005-004502-82

    Volume 15

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    Introduction Dr. Amorette Barber, Director, Office of Student Research From the Editor Dr. Hannah Dudley-Shotwell Artist’s Statement Connor Thompson On mentorship Dr. John Miller The Meat of the Matter: Allen, Human and Animal in Terry Blsson’s “They’re Made of Out of Meat” by Emily Steffenhagen “Please REBLOG!”: An Ethical analysis of Doxxing, Internet Vigilantism and Racists Getting Fired by Emily Robertson Journaling: Paper Has More Patience Than People by Luis Fernando Dos Reis The Effects of Climate Change on the Archeological World by Emily Farmer Lowered Seat Height Does Not Impair Wingate Performance in Untrained Cyclists by Samuel Villa, Robert Allison, and Zachary Chessor Intentions, Interpretations, and the Paradoxes of Asimov’s Laws of Robotics by Meagan Borden How Trans-Exclusionary Radical Feminists Define and Defend Women’s Spaces by Austin Burnett The Impeachment of Andrew Johnson by Larry W. Grant, Jr. “unsex me here”: Lady Macbeth’s Performance of Female Masculinity by Tristan Marowski Monstrosity, Queer Desire, and écriture féminine in Sherldan le Fanu’s Carmilla by Emma Moore The Surfaces of Loathsome Beauty in the Picture of Dorian Gray by Pearl Sif

    sgsR: a structurally guided sampling toolbox for LiDAR-based forest inventories

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    Establishing field inventories can be labor intensive, logistically challenging and expensive. Optimizing a sample to derive accurate forest attribute predictions is a key management-level inventory objective. Traditional sampling designs involving pre-defined, interpreted strata could result in poor selection of within-strata sampling intensities, leading to inaccurate estimates of forest structural variables. The use of airborne laser scanning (ALS) data as an applied forest inventory tool continues to improve understanding of the composition and spatial distribution of vegetation structure across forested landscapes. The increased availability of wall-to-wall ALS data is promoting the concept of structurally guided sampling (SGS), where ALS metrics are used as an auxiliary data source driving stratification and sampling within management-level forest inventories. In this manuscript, we present an open-source R package named sgsR that provides a robust toolbox for implementing various SGS approaches. The goal of this package is to provide a toolkit to facilitate better optimized allocation of sample units and sample size, as well as to assess and augment existing plot networks by accounting for current forest structural conditions. Here, we first provide justification for SGS approaches and the creation of the sgsR toolbox. We then briefly describe key functions and workflows the package offers and provide two reproducible examples. Avenues to implement SGS protocols according to auxiliary data needs are presented

    Arctic Paleoceanography Cruise KH21-234 with R/V Kronprins Haakon

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    We set sail from Longyearbyen on 30.6.2021 to collect surface sediments, long sediment archives, water and plankton samples. The study area is located north of Svalbard, within the seasonal and permanent sea ice covered Arctic Ocean. We took stations N of Svalbard, near Nordaustlandet, Sophia Basin, Yermak Plateau and on the shelf east of Svalbard. In total, we had 52 stations. We deployed the multicorer at least once at every station and sampled the core tops already onboard. These samples will be included in the Arctic Surface Sediment DNA Database, which we will use to establish new aDNA based sea ice proxies. We recovered gravity cores from 12 stations that can be used to reconstruct the Arctic sea ice history in the Holocene, last glacial and likely also Last Interglacial. We collected ice and water and filtered these for eDNA and biomarkers, and water for tracing the isotope signal of the different water masses in the region (Atlantic Water, Polar Water).publishedVersio

    Tuning MPL signaling to influence hematopoietic stem cell differentiation and inhibit essential thrombocythemia progenitors

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    Thrombopoietin (TPO) and the TPO-receptor (TPO-R, or c-MPL) are essential for hematopoietic stem cell (HSC) maintenance and megakaryocyte differentiation. Agents that can modulate TPO-R signaling are highly desirable for both basic research and clinical utility. We developed a series of surrogate protein ligands for TPO-R, in the form of diabodies (DBs), that homodimerize TPO-R on the cell surface in geometries that are dictated by the DB receptor binding epitope, in effect "tuning" downstream signaling responses. These surrogate ligands exhibit diverse pharmacological properties, inducing graded signaling outputs, from full to partial TPO agonism, thus decoupling the dual functions of TPO/TPO-R. Using single-cell RNA sequencing and HSC self-renewal assays we find that partial agonistic diabodies preserved the stem-like properties of cultured HSCs, but also blocked oncogenic colony formation in essential thrombocythemia (ET) through inverse agonism. Our data suggest that dampening downstream TPO signaling is a powerful approach not only for HSC preservation in culture, but also for inhibiting oncogenic signaling through the TPO-R

    The ClinGen Epilepsy Gene Curation Expert Panel—Bridging the divide between clinical domain knowledge and formal gene curation criteria

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    The field of epilepsy genetics is advancing rapidly and epilepsy is emerging as a frequent indication for diagnostic genetic testing. Within the larger ClinGen framework, the ClinGen Epilepsy Gene Curation Expert Panel is tasked with connecting two increasingly separate fields: the domain of traditional clinical epileptology, with its own established language and classification criteria, and the rapidly evolving area of diagnostic genetic testing that adheres to formal criteria for gene and variant curation. We identify critical components unique to the epilepsy gene curation effort, including: (a) precise phenotype definitions within existing disease and phenotype ontologies; (b) consideration of when epilepsy should be curated as a distinct disease entity; (c) strategies for gene selection; and (d) emerging rules for evaluating functional models for seizure disorders. Given that de novo variants play a prominent role in many of the epilepsies, sufficient genetic evidence is often awarded early in the curation process. Therefore, the emphasis of gene curation is frequently shifted toward an iterative precuration process to better capture phenotypic associations. We demonstrate that within the spectrum of neurodevelopmental disorders, gene curation for epilepsy-associated genes is feasible and suggest epilepsy-specific conventions, laying the groundwork for a curation process of all major epilepsy-associated genes
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