79 research outputs found

    Student Experimental Farm Smart Pathway Lighting System

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    This project works together with the Student Experimental Farm (SEF) and the DC House in order to install a smart lighting pathway system. This system will run off of DC power supplied by the solar panels connected to the DC House. This project tested and explored the group’s abilities to design and implement a full system run off of 48V DC. By installing this system it will greatly improve the ease for students to work at the SEF beyond daylight hours. The system will allow continuous dull lighting and will switch to full brightness once a person is detected. This feature goes along with the ideals of the DC House, saving energy. This project helped to show the capabilities of a DC system and can impact the lives of those in communities with no access to an AC grid. The results of this system were not as successful as planned. The wiring within the junction boxes proved to be quite tricky so the system does not work at its full potential, however this does lead to further improvements by students to come

    Growth rate and resource imbalance interactively control biomass stoichiometry and elemental quotas of aquatic bacteria

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    The effects of resource stoichiometry and growth rate on the elemental composition of biomass have been examined in a wide variety of organisms, but the interaction among these effects is often overlooked. To determine how growth rate and resource imbalance affect bacterial carbon (C): nitrogen (N): phosphorus (P) stoichiometry and elemental content, we cultured two strains of aquatic heterotrophic bacteria in chemostats at a range of dilution rates and P supply levels (C:P of 100:1 to 10,000:1). When growing below 50% of their maximum growth rate, P availability and dilution rate had strong interactive effects on biomass C:N:P, elemental quotas, cell size, respiration rate, and growth efficiency. In contrast, at faster growth rates, biomass stoichiometry was strongly homeostatic in both strains (C:N:P of 70:13:1 and 73:14:1) and elemental quotas of C, N, and P were tightly coupled (but not constant). Respiration and cell size increased with both growth rate and P limitation, and P limitation induced C accumulation and excess respiration. These results show that bacterial biomass stoichiometry is relatively constrained when all resources are abundant and growth rates are high, but at low growth rates resource imbalance is relatively more important than growth rate in controlling bacterial biomass composition.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136292/1/ecy1705_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136292/2/ecy1705.pd

    Structural Basis for a Neutralizing Antibody Response Elicited by a Recombinant Hantaan Virus Gn Immunogen

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    Hantaviruses are a group of emerging pathogens capable of causing severe disease upon zoonotic transmission to humans. The mature hantavirus surface presents higher-order tetrameric assemblies of two glycoproteins, Gn and Gc, which are responsible for negotiating host cell entry and constitute key therapeutic targets. Here, we demonstrate that recombinantly derived Gn from Hantaan virus (HTNV) elicits a neutralizing antibody response (serum dilution that inhibits 50% infection [ID50], 1:200 to 1:850) in an animal model. Using antigen-specific B cell sorting, we isolated monoclonal antibodies (mAbs) exhibiting neutralizing and non-neutralizing activity, termed mAb HTN-Gn1 and mAb nn-ITN-Gn2, respectively. Crystallographic analysis reveals that these mAbs target spatially distinct epitopes at disparate sites of the N-terminal region of the HTNV Gn ectodomain. Epitope mapping onto a model of the higher order (Gn-Gc)(4) spike supports the immune accessibility of the mAb HTN-Gn1 epitope, a hypothesis confirmed by electron cryo-tomography of the antibody with virus-like particles. These data define natively exposed regions of the hantaviral Gn that can be targeted in immunogen design. IMPORTANCE The spillover of pathogenic hantaviruses from rodent reservoirs into the human population poses a continued threat to human health. Here, we show that a recombinant form of the Hantaan virus (HTNV) surface-displayed glycoprotein, Gn, elicits a neutralizing antibody response in rabbits. We isolated a neutralizing (HTN-Gn1) and a non-neutralizing (nn-ITN-Gn2) monoclonal antibody and provide the first molecular-level insights into how the Gn glycoprotein may be targeted by the antibody-mediated immune response. These findings may guide rational vaccine design approaches focused on targeting the hantavirus glycoprotein envelope.Peer reviewe

    Adaptation of Microelectrode Array Technology for the Study of Anesthesia-Induced Neurotoxicity in the Intact Piglet Brain

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    Every year, millions of children undergo anesthesia for a multitude of procedures. However, studies in both animals and humans have called into question the safety of anesthesia in children, implicating anesthetics as potentially toxic to the brain in development. To date, no studies have successfully elucidated the mechanism(s) by which anesthesia may be neurotoxic. Animal studies allow investigation of such mechanisms, and neonatal piglets represent an excellent model to study these effects due to their striking developmental similarities to the human brain. This protocol adapts the use of enzyme-based microelectrode array (MEA) technology as a novel way to study the mechanism(s) of anesthesia-induced neurotoxicity (AIN). MEAs enable real-time monitoring of in vivo neurotransmitter activity and offer exceptional temporal and spatial resolution. It is hypothesized that anesthetic neurotoxicity is caused in part by glutamate dysregulation and MEAs offer a method to measure glutamate. The novel implementation of MEA technology in a piglet model presents a unique opportunity for the study of AIN

    Northern Bobwhite Demographics and Resource Selection Are Explained by Prescribed Fire with Grazing and Woody Cover in Southwest Missouri

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    Understanding the effects of landscape management on northern bobwhite (Colinus virginianus; hereafter, bobwhite) population growth requires information about seasonal- and stage-specific demographic parameters linked across the annual cycle. We review results to date from 3 years (2016–2018) of an intensive field study evaluating drivers of bobwhite population dynamics and resource selection during the breeding and non-breeding season in southwest Missouri, USA using data from adult and juvenile bobwhite fitted with radio-transmitters. Land cover of our study sites ranged from large blocks of native grasslands maintained with prescribed fire and grazing to more traditional management resulting in small patches of grasslands interspersed with food plots, disked idle areas, and woody cover. During the breeding season, relative probability of selection by broods increased in relation to proportion of native grass managed by grazing and burning and proportion of cropland. Brood survival was also greatest on native grasslands burned and grazed within the past 2 growing seasons. During the fall and winter, relative probability of selection by adults increased as woody edge density increased. Fall and winter survival increased as distance from trees increased and decreased as distance to shrubs increased. Our integrated population model indicated that the number of young hatched per female and adult breeding season survival were greatest on sites with the most native grassland managed by prescribed fire with grazing. However, non-breeding season survival was greater on sites with more agriculture or food plots and woody cover. Abundance declined across all sites from 2016 to 2019. Our work suggests that native grasslands managed by prescribed fire with grazing can provide quail habitat superior to traditional management that strived for a mixture of agriculture, woody cover, and grassland. The combination of conservation grazing and fire in native grasslands interspersed with shrubs may provide the greatest chance for bobwhite populations to persist in southwest Missouri and similar landscapes

    Trends in RED Blood CELL Transfusions within the Biologics Effectiveness and Safety (BEST) Initiative Network, 2012-2018

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    The U.S. FDA Center for Biologics Evaluation and Research (CBER) recently established the Biologics Effectiveness and Safety (BEST) Initiative which is an active surveillance system for all CBER regulated products, including blood components, and which also allows for investigation of patterns in utilization. The 2015 National Blood Collection& Utilization Survey (NBCUS) Report found an overall decrease in the number of units of red blood cells (RBCs) transfused in recent years. The aim of this study is to describe the utilization of RBCs from 2012 through 2018 using electronic health records (EHR) from three data sources participating in the BEST Initiative

    Salmonella Strains Isolated from Galápagos Iguanas Show Spatial Structuring of Serovar and Genomic Diversity

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    It is thought that dispersal limitation primarily structures host-associated bacterial populations because host distributions inherently limit transmission opportunities. However, enteric bacteria may disperse great distances during food-borne outbreaks. It is unclear if such rapid long-distance dispersal events happen regularly in natural systems or if these events represent an anthropogenic exception. We characterized Salmonella enterica isolates from the feces of free-living Galápagos land and marine iguanas from five sites on four islands using serotyping and genomic fingerprinting. Each site hosted unique and nearly exclusive serovar assemblages. Genomic fingerprint analysis offered a more complex model of S. enterica biogeography, with evidence of both unique strain pools and of spatial population structuring along a geographic gradient. These findings suggest that even relatively generalist enteric bacteria may be strongly dispersal limited in a natural system with strong barriers, such as oceanic divides. Yet, these differing results seen on two typing methods also suggests that genomic variation is less dispersal limited, allowing for different ecological processes to shape biogeographical patterns of the core and flexible portions of this bacterial species' genome

    ST6GAL1-mediated aberrant sialylation promotes prostate cancer progression.

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    Aberrant glycosylation is a universal feature of cancer cells, and cancer-associated glycans have been detected in virtually every cancer type. A common change in tumour cell glycosylation is an increase in α2,6 sialylation of N-glycans, a modification driven by the sialyltransferase ST6GAL1. ST6GAL1 is overexpressed in numerous cancer types, and sialylated glycans are fundamental for tumour growth, metastasis, immune evasion, and drug resistance, but the role of ST6GAL1 in prostate cancer is poorly understood. Here, we analyse matched cancer and normal tissue samples from 200 patients and verify that ST6GAL1 is upregulated in prostate cancer tissue. Using MALDI imaging mass spectrometry (MALDI-IMS), we identify larger branched α2,6 sialylated N-glycans that show specificity to prostate tumour tissue. We also monitored ST6GAL1 in plasma samples from >400 patients and reveal ST6GAL1 levels are significantly increased in the blood of men with prostate cancer. Using both in vitro and in vivo studies, we demonstrate that ST6GAL1 promotes prostate tumour growth and invasion. Our findings show ST6GAL1 introduces α2,6 sialylated N-glycans on prostate cancer cells and raise the possibility that prostate cancer cells can secrete active ST6GAL1 enzyme capable of remodelling glycans on the surface of other cells. Furthermore, we find α2,6 sialylated N-glycans expressed by prostate cancer cells can be targeted using the sialyltransferase inhibitor P-3FAX -Neu5Ac. Our study identifies an important role for ST6GAL1 and α2,6 sialylated N-glycans in prostate cancer progression and highlights the opportunity to inhibit abnormal sialylation for the development of new prostate cancer therapeutics. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

    In-situ mechanical weakness of subducting sediments beneath a plate boundary décollement in the Nankai Trough

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    © 2018, The Author(s). The study investigates the in-situ strength of sediments across a plate boundary décollement using drilling parameters recorded when a 1180-m-deep borehole was established during International Ocean Discovery Program (IODP) Expedition 370, Temperature-Limit of the Deep Biosphere off Muroto (T-Limit). Information of the in-situ strength of the shallow portion in/around a plate boundary fault zone is critical for understanding the development of accretionary prisms and of the décollement itself. Studies using seismic reflection surveys and scientific ocean drillings have recently revealed the existence of high pore pressure zones around frontal accretionary prisms, which may reduce the effective strength of the sediments. A direct measurement of in-situ strength by experiments, however, has not been executed due to the difficulty in estimating in-situ stress conditions. In this study, we derived a depth profile for the in-situ strength of a frontal accretionary prism across a décollement from drilling parameters using the recently established equivalent strength (EST) method. At site C0023, the toe of the accretionary prism area off Cape Muroto, Japan, the EST gradually increases with depth but undergoes a sudden change at ~ 800 mbsf, corresponding to the top of the subducting sediment. At this depth, directly below the décollement zone, the EST decreases from ~ 10 to 2 MPa, with a change in the baseline. This mechanically weak zone in the subducting sediments extends over 250 m (~ 800–1050 mbsf), corresponding to the zone where the fluid influx was discovered, and high-fluid pressure was suggested by previous seismic imaging observations. Although the origin of the fluids or absolute values of the strength remain unclear, our investigations support previous studies suggesting that elevated pore pressure beneath the décollement weakens the subducting sediments. [Figure not available: see fulltext.]

    Nicotine dependence produces hyperalgesia: Role of corticotropin-releasing factor-1 receptors (CRF1Rs) in the central amygdala (CeA)

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    Because tobacco use has a large negative health and financial impact on society, it is critical to identify the factors that drive excessive use. These factors include the aversive withdrawal symptoms that manifest upon cessation of tobacco use, and may include increases in nociceptive processing. Corticotropin-releasing factor (CRF) signalling in the central amygdala (CeA) has been attributed an important role in: (1) central processing of pain, (2) excessive nicotine use that results in nicotine dependence, and (3) in mediating the aversive symptoms that manifest following cessation of tobacco exposure. Here, we describe three experiments in which the main hypothesis was that CRF/CRF1 receptor (CRF1R) signalling in the CeA mediates nicotine withdrawal-induced increases in nociceptive sensitivity in rats that are dependent on nicotine. In Experiment 1, nicotine-dependent rats withdrawn from chronic intermittent (14-h/day) nicotine vapor exhibited decreased hind paw withdrawal latencies in response to a painful thermal stimulus in the Hargreaves test, and this effect was attenuated by systemic administration of the CRF1R antagonist, R121919. In Experiment 2, nicotine-dependent rats withdrawn from nicotine vapor exhibited robust increases in mRNA for CRF and CRF1Rs in CeA. In Experiment 3, intra-CeA administration of R121919 reduced thermal nociception only in nicotine-dependent rats. Collectively, these results suggest that nicotine dependence increases CRF/CRF1R signaling in the CeA that mediates withdrawal-induced increases in sensitivity to a painful stimulus. Future studies will build on these findings by exploring the hypothesis that nicotine withdrawal-induced reduction in pain thresholds drive excessive nicotine use via CRF/CRF1R signalling pathways
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