1,418 research outputs found

    Decoration and Form

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    Genetic Substrates of the Initial Subjective Rewarding Effects of Alcohol in Mice

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    Susceptibility to alcohol use disorders (AUDs) arises from a complex interplay of genetics and environmental experiences. While the initial subjective response predicts susceptibility to AUD, genetic variation is responsible for about 50% of an individual\u27s risk. This study used a single-exposure conditioned place preference paradigm (SE-CPP) to identify phenotypic and genetic correlates of the initial subjective rewarding effects of alcohol (EtOH) in diversity outbred (DO) mice. We assessed the relationship between SE-CPP and anxiety-like behaviors using a marble burying test and light-dark box test. Ninety-six male and female diversity outbred mice were tested in a Marble Burying test at 7-8 weeks, followed by the light-dark box at 9-10 weeks of age. Between 11-12 weeks, subjects were assessed for SE-CPP. Animals received 1.5 g/kg EtOH or equivolume saline on either Day 1 and Day 3 in two distinct contexts (counterbalanced) and were tested for a context preference on Day 5. Overall, SE-CPP was evident in both males and females. In females, there was a correlation between the percentage of time spent in the EtOH-paired context and the number of marbles buried four weeks prior. In males, there was a correlation between the distance traveled during EtOH conditioning and the percentage of time spent in the EtOH-paired context. Genotyping will be used to understand the possible link between the observed phenotypes and genetic variation. This research contributes to a better understanding of the influences of sex and genetic variation in AUD

    Prognosis for Ecosystem Recovery Following Rodent Eradication and Seabird Restoration in an Island Archipelago

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    Invasive species are widespread and can have devastating effects on biota, especially insular biota. Invasive species eradications are increasingly employed to promote island recovery to preinvasion states. However, it remains unclear if additional restoration actions may be required on islands that were once heavily reliant on seabird guano for ecosystem functions. Active seabird augmentation has been suggested as necessary to exact ecosystem recovery on contemporary timescales in some cases. I use two experiments on offshore islands in Cook Strait, New Zealand, to test the hypothesis that seabird restoration will restore island ecosystem functioning following invasive rodent removal. The first is a small-scale single-island fertilization experiment that simulates seabird recovery. This experiment tested the recovery potential of offshore islands and was used to infer the density of seabirds needed to elicit ecosystem recovery. The second is a large-scale natural experiment that takes advantage of eight islands with differing rodent eradication and seabird restoration histories. I compared ecosystem functioning variables (d15N, C:N ratios in soil, plants, and spiders, as well as arthropod abundance and diversity) on two islands that had rodents eradicated and two islands undergoing seabird augmentation with two control islands (never invaded by rodents) and two positive control islands (currently invaded by rodents). The results suggest that islands do have the potential for recovery given nutrient amendments, but that islands with rodents eradicated and islands undergoing seabird augmentation have not recovered most of their ecosystem function. Finer, intra-island analysis showed that seabird restoration projects have the potential to speed the recovery process, but that the projects on the studied seabird restoration islands were not advanced enough to produce island-wide recovery. The results suggest that high seabird densities (5–10 burrows/m2) are needed to promote recovery to never-invaded control levels. Seabird augmentation, through chick translocation and/or social facilitation with decoys, vocalization playbacks, and/or mirrors can supplement passive seabird recovery on islands where seabirds have been extirpated or extremely reduced by invasive predators. Such restoration efforts may be necessary to promote ecosystem recovery on contemporary timescales

    Seabird Islands Take Mere Decades to Recover Following Rat Eradication

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    Islands house a majority of the world’s biodiversity and are thus critical for biodiversity conservation. Seabird nesting colonies provide nutrients that are integral to maintain island biodiversity and ecosystem function. Invasive rats destroy seabird colonies and thus the island ecosystems that depend on seabird-derived nutrients. After rat eradication, it is unclear how long ecosystem recovery may take, although some speculate on the order of centuries. I looked at ecosystem recovery along a chronosequence of islands that had 12–22 years to recover following rat eradication. I show that soil, plant, and spider marine-derived nitrogen levels and C:N ratios take mere decades to recover even after centuries-long rat invasion. Moreover, active seabird restoration could speed recovery even further, giving much hope to quickly conserve many endemic species on islands worldwide

    Elucidation of UBQLN2 liquid-liquid phase separation mechanisms via point mutations and domain deletions

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    Organization, separation, and cellular regulation are all functions of membraneless organelles (MLOs), which arise by a biophysical phenomenon termed liquid-liquid phase separation (LLPS). By this process, macromolecules in a mixed liquid solution condense together to form liquid droplets within a liquid solution, comparable to oil droplets in water. Some known MLOs formed in cells via LLPS include nucleoli, stress granules, Cajal bodies, and processing-bodies, among other membrane-lacking liquid granules. Previous work has shown that many proteins which compose these liquid compartments also undergo LLPS isolated in vitro, and thus have become model systems to investigate the forces that drive these macromolecules to undergo phase transitions. Currently, the LLPS field has identified key features of proteins which contribute to phase separation. Included in this are sequences of intrinsic disorder and structured sequences, prion-like regions, oligomerization, and multivalent interactions. In this thesis, the protein of interest, UBQLN2, contains all such features. Additionally, prior work in the Castañeda lab and others has shown that UBQLN2 is recruited to stress granules, and disease-related inclusion bodies. In vitro, UBQLN2 phase separates into spherical liquid droplets in a concentration and temperature-dependent manner. As UBQLN2 exhibits LLPS both in vitro and in vivo, it serves as a model system to uncover, on a molecular level, the driving forces of phase separation. The studies provided herein, investigate the properties of UBQLN2 phase separation and how they are modified with the introduction of mutations and domain deletions. By identifying how molecular variations modify UBQLN2 LLPS properties, one can identify a molecular code which UBQLN2 follows to drive and modulate its LLPS. Through experimental investigation via turbidity assays, phase diagram construction, microscopy, and self-association studies, we elucidate the molecular foundations of UBQLN2 LLPS. Here, I propose that UBQLN2 LLPS is driven by “sticker” sequences which contribute to interchain interactions, and that hydrophobic and polar interactions are important sequence-intrinsic features which drive LLPS and control material properties of UBQLN2 droplets. Additionally, I look at UBQLN2 on a domain-by-domain level to uncover how sequence features like structure, disorder, and prion propensity may contribute differently to phase separation. Finally, I propose a method of UBQLN2 purification that potentially incorporates native post-translational modifications (PTMs) to create a more physiologically relevant system for study

    Up in Arms: The Hunt to Define the Second Amendment\u27s Scope

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    Up in Arms: The Hunt to Define the Second Amendment\u27s Scope

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    Academic Self-Confidence Scale: A Psychological Study in Two Parts

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