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Concern about salt levels in freshwater habitats receiving road de-icer runoff has inspired the development of “eco-friendly” formulations that are intended to be less toxic to aquatic organisms, but few experiments have determined that these products are environmentally benign. Mesocosms containing lake water were established for 6 weeks to compare traditional road salt with two newer de-icers, one an inorganic mixture of chloride salts and the second of beet extract and brine. Amplicon sequencing and algal blocking sequences facilitated the identification of differentially impacted bacterial taxa. Ironically, although there was only a minor effect on bacterial structure at high road-salt concentrations, there was an increased relative abundance of salt-resistant genera in the mixed-salt formulation. After amendment with the beet brine de-icer, there was a turnover of taxa coincident with a 68-fold decrease in dissolved oxygen, with decreased diversity and displacement by anaerobic genera indicating a shift across a threshold to a new, apparently stable state, suggesting mesocosm recovery was unlikely. Overall, although we applaud the sentiment behind the formulation of less-damaging “eco-friendly” de-icers, they appear to have more negative environmental impacts than the traditional road salt that they were made to replace.

My dissertation addresses ethics in social professions through a conceptual and empirical study of how professional boundaries and codes organize relationship. Central research questions include: \"How might one's sense of responsibility to another person shrink under professional codes, procedures or good boundaries? Does professionalism lower the stakes of professional relationship by restricting involvement and avoiding risk?\" After developing an interdisciplinary, theoretical account of professionalism and normative ethics, I bring care ethics and postmodern critique together to challenge the foundations of professional ethics. While providing important protections, professional norms and codes of ethics narrow the scope of what is \"ethical\" and limit ethical possibility. Emphases on \"do no harm\" and risk-aversion lower the stakes of professional relationship. My queer reading of ethics code discloses how professional ethics are treated as stable knowledge. I argue that professionalism ascribes the condition of being ethical rather than promoting active social processes and pragmatic ways of doing ethics. My qualitative study of professional teachers and social workers who became \"parents\" to youth they met in professional contexts grounds my theoretical and philosophical inquiry in experiential narrative. I describe an ethical periphery where practitioners make \"positive boundary crossings\" and suggest that professional ethics is a matter of deliberated action rather than identity. Mutual relations and \"elastic boundaries\" invite more creative and pragmatic problem solving and make ethical discourse more relevant and meaningful in everyday professional practice

This volume seeks to advance the discusison of Paul's relationship to Greek epistolary traditions by evaluating the nature of ancient letters as well as the individual letter components. These features are evaluated alongside Paul's letters to better understand Paul's use and adaptations of these traditions in order to meet his communicative needs.

Processing multiple sensory modalities is critical for executing complex behaviors. This study finds that single cerebellar granule cells integrate inputs from both vestibular and visual input pathways, each exhibiting characteristic synaptic strengths and plasticities. These are translated into output dynamics that enhance the network's representation of complex sensory contexts. The ability of the brain to rapidly process information from multiple pathways is critical for reliable execution of complex sensory-motor behaviors, yet the cellular mechanisms underlying a neuronal representation of multimodal stimuli are poorly understood. Here we explored the possibility that the physiological diversity of mossy fiber (MF) to granule cell (GC) synapses in the mouse vestibulocerebellum may contribute to the processing of coincident multisensory information at the level of individual GCs. We found that the strength and short-term dynamics of individual MF-GC synapses can act as biophysical signatures for primary vestibular, secondary vestibular and visual input pathways. Most GCs receive inputs from different modalities, which, when coactivated, produced enhanced GC firing rates and distinct first spike latencies. Thus, pathway-specific synaptic response properties permit temporal coding of correlated multisensory inputs by single GCs, thereby enriching sensory representation and facilitating pattern separation.

CRISPR-based gene activation (CRISPRa) is a strategy for upregulating gene expression by targeting promoters or enhancers in a tissue/cell-type specific manner. Here, we describe an experimental framework that combines highly multiplexed perturbations with single-cell RNA sequencing (sc-RNA-seq) to identify cell-type-specific, CRISPRa-responsive cis- regulatory elements and the gene(s) they regulate. Random combinations of many gRNAs are introduced to each of many cells, which are then profiled and partitioned into test and control groups to test for effect(s) of CRISPRa perturbations of both enhancers and promoters on the expression of neighboring genes. Applying this method to a library of 493 gRNAs targeting candidate cis- regulatory elements in both K562 cells and iPSC-derived excitatory neurons, we identify gRNAs capable of specifically upregulating intended target genes and no other neighboring genes within 1 Mb, including gRNAs yielding upregulation of six autism spectrum disorder (ASD) and neurodevelopmental disorder (NDD) risk genes in neurons. A consistent pattern is that the responsiveness of individual enhancers to CRISPRa is restricted by cell type, implying a dependency on either chromatin landscape and/or additional trans- acting factors for successful gene activation. The approach outlined here may facilitate large-scale screens for gRNAs that activate genes in a cell type-specific manner. Scalable CRISPRa screening of cis-regulatory elements in non-cancer cell lines has proved challenging. Here, the authors describe a scalable, CRISPR activation screening framework to identify regulatory element-gene pairs in diverse cell types including cancer cells and neurons.

• Sun-induced fluorescence in the far-red region (SIF) is increasingly used as a remote and proximal-sensing tool capable of tracking vegetation gross primary production (GPP). However, the use of SIF to probe changes in GPP is challenged during extreme climatic events, such as heatwaves. • Here, we examined how the 2018 European heatwave (HW) affected the GPP–SIF relationship in evergreen broadleaved trees with a relatively invariant canopy structure. To do so, we combined canopy-scale SIF measurements, GPP estimated from an eddy covariance tower, and active pulse amplitude modulation fluorescence. • The HW caused an inversion of the photosynthesis–fluorescence relationship at both the canopy and leaf scales. The highly nonlinear relationship was strongly shaped by nonphotochemical quenching (NPQ), that is, a dissipation mechanism to protect from the adverse effects of high light intensity. During the extreme heat stress, plants experienced a saturation of NPQ, causing a change in the allocation of energy dissipation pathways towards SIF. • Our results show the complex modulation of the NPQ–SIF–GPP relationship at an extreme level of heat stress, which is not completely represented in state-of-the-art coupled radiative transfer and photosynthesis models.

In this study, we explored the use of statistical machine learning and long-term groundwater nitrate monitoring data to estimate vadose zone and saturated zone lag times in an irrigated alluvial agricultural setting. Unlike most previous statistical machine learning studies that sought to predict groundwater nitrate concentrations within aquifers, the focus of this study was to leverage available groundwater nitrate concentrations and other environmental variables to determine mean regional vertical velocities (transport rates) of water and solutes in the vadose zone and saturated zone (3.50 and 3.75 m yr−1, respectively). The statistical machine learning results are consistent with two primary recharge processes in this western Nebraska aquifer, namely (1) diffuse recharge from irrigation and precipitation across the landscape and (2) focused recharge from leaking irrigation conveyance canals. The vadose zone mean velocity yielded a mean recharge rate (0.46 m yr−1) consistent with previous estimates from groundwater age dating in shallow wells (0.38 m yr−1). The saturated zone mean velocity yielded a recharge rate (1.31 m yr−1) that was more consistent with focused recharge from leaky irrigation canals, as indicated by previous results of groundwater age dating in intermediate-depth wells (1.22 m yr−1). Collectively, the statistical machine learning model results are consistent with previous observations of relatively high water fluxes and short transit times for water and nitrate in the primarily oxic aquifer. Partial dependence plots from the model indicate a sharp threshold in which high groundwater nitrate concentrations are mostly associated with total travel times of 7 years or less, possibly reflecting some combination of recent management practices and a tendency for nitrate concentrations to be higher in diffuse infiltration recharge than in canal leakage water. Limitations to the machine learning approach include the non-uniqueness of different transport rate combinations when comparing model performance and highlight the need to corroborate statistical model results with a robust conceptual model and complementary information such as groundwater age.

Subpopulations of B-lymphocytes traffic to different sites and organs to provide diverse and tissue-specific functions. Here, we provide evidence that epigenetic differences confer a neuroinvasive phenotype. An EBV+ B cell lymphoma cell line (M14) with low frequency trafficking to the CNS was neuroadapted to generate a highly neuroinvasive B-cell population (MUN14). MUN14 B cells efficiently infiltrated the CNS within one week and produced neurological pathologies. We compared the gene expression profiles of viral and cellular genes using RNA-Seq and identified one viral (EBNA1) and several cellular gene candidates, including secreted phosphoprotein 1/osteopontin (SPP1/OPN), neuron navigator 3 (NAV3), CXCR4, and germinal center-associated signaling and motility protein (GCSAM) that were selectively upregulated in MUN14. ATAC-Seq and ChIP-qPCR revealed that these gene expression changes correlated with epigenetic changes at gene regulatory elements. The neuroinvasive phenotype could be attenuated with a neutralizing antibody to OPN, confirming the functional role of this protein in trafficking EBV+ B cells to the CNS. These studies indicate that B-cell trafficking to the CNS can be acquired by epigenetic adaptations and provide a new model to study B-cell neuroinvasion associated CNS lymphoma and autoimmune disease of the CNS, including multiple sclerosis (MS).

Proliferating eukaryotic cells undergo a finite number of cell divisions before irreversibly exiting mitosis. Yet pathways that normally limit the number of cell divisions remain poorly characterized. Here we describe a screen of a collection of 3762 single gene mutants in the yeast Saccharomyces cerevisiae, accounting for 2/3 of annotated yeast ORFs, to search for mutants that undergo an atypically high number of cell divisions. Many of the potential longevity genes map to cellular processes not previously implicated in mitotic senescence, suggesting that regulatory mechanisms governing mitotic exit may be broader than currently anticipated. We focused on an ER-Golgi gene cluster isolated in this screen to determine how these ubiquitous organelles integrate into mitotic longevity. We report that a chronic increase in ER protein load signals an expansion in the assembly of autophagosomes in an Ire1-independent manner, accelerates trafficking of high molecular weight protein aggregates from the cytoplasm to the vacuoles, and leads to a profound enhancement of daughter cell production. We demonstrate that this catabolic network is evolutionarily conserved, as it also extends reproductive lifespan in the nematode Caenorhabditis elegans. Our data provide evidence that catabolism of protein aggregates, a natural byproduct of high protein synthesis and turn over in dividing cells, is among the drivers of mitotic longevity in eukaryotes.