Reconstructing Surface Water Carbonate Ion Concentration Changes in the Eastern Equatorial Pacific Across Glacial Transitions

Today, the eastern equatorial Pacific (EEP) plays a critical role in the global CO2 budget as a major source of CO2 to the atmosphere, but recent studies suggest the region may shift to a sink for atmospheric CO2 under different climate states. Here, I focus on two transitional periods, the last deglaciation (25 kyr to present) and last glaciation (the Marine Isotope Stage (MIS) 5a-4 transition, 96 to 60 kyr), to investigate how the carbon system in the EEP responds to major climate changes. I measured B/Ca ratios in the planktic foraminifera Globigerina bulloides from core MV1014-17JC (00º10.83’S, 85º52.00’W; 2846 m water depth) as a proxy for changes in surface water carbonate ion concentration ([CO32-]) in the EEP across both climate transitions. Because calcification rate (controlled by [CO32-]) drives the uptake of boron in foraminiferal tests, [CO32-] can be calculated from B/Ca ratios. In addition to the B/Ca proxy, the relationship between δ13C values in the planktic foraminifera Globigerinoides ruber and Trilobatus sacculifer to surface water [CO32-] differ in response to changes in seawater [CO32-]. Therefore, I also measured δ13C in these two species as another proxy for surface water Δ[CO32-] change. Because surface water [CO32-] is linked to surface water CO2 concentrations and thus atmospheric pCO2, I use reconstructed [CO32-] to indicate if the EEP was more or less of a source of CO2 to the atmosphere in the past. Results indicate that across both the deglaciation and glaciation, the EEP remained as much or more of a source of CO2 than today. Enhanced upwelling across these glacial transitions coupled with an expansion of the oxygen minimum zone (OMZ) likely delivered CO2- and nutrient-rich water to the surface. However, this increase in nutrient concentrations coupled with dust fertilization across cold Heinrich events failed to stimulate biological productivity to the point where the region switched to being a sink for atmospheric CO2. Sustained lower-than-modern surface water [CO32-] across both climate transitions indicate that the EEP may remain a source of CO2 to the atmosphere across anthropogenic climate changes in the future

Low Cost Evolution in Materio

This thesis describes a method of using a Low-Cost computer to program Low-Cost materials to perform a computation. The work demonstrates that an evolutionary algorithm running on a Raspberry Pi can exploit physical properties of graphene and sets of resistors to solve simple travelling salesman problems. The work goes on to investigate the use of the platform to evolve a simple electro-magnetic sensor to show the applicability of the platform to solving other problems which cannot be solved in any other way

Liquid-Liquid Phase Separation in Physiology and Pathophysiology of the Nervous System

Molecules within cells are segregated into functional domains to form various organelles. While some of those organelles are delimited by lipid membranes demarcating their constituents, others lack a membrane enclosure. Recently, liquid-liquid phase separation (LLPS) revolutionized our view of how segregation of macromolecules can produce membraneless organelles. While the concept of LLPS has been well studied in the areas of soft matter physics and polymer chemistry, its significance has only recently been recognized in the field of biology. It occurs typically between macromolecules that have multivalent interactions. Interestingly, these features are present in many molecules that exert key functions within neurons. In this review, we cover recent topics of LLPS in different contexts of neuronal physiology and pathology

A central role for dityrosine crosslinking of Amyloid-β in Alzheimer’s disease

Background Alzheimer’s disease (AD) is characterized by the deposition of insoluble amyloid plaques in the neuropil composed of highly stable, self-assembled Amyloid-beta (Aβ) fibrils. Copper has been implicated to play a role in Alzheimer’s disease. Dimers of Aβ have been isolated from AD brain and have been shown to be neurotoxic. Results We have investigated the formation of dityrosine cross-links in Aβ42 formed by covalent ortho-ortho coupling of two tyrosine residues under conditions of oxidative stress with elevated copper and shown that dityrosine can be formed in vitro in Aβ oligomers and fibrils and that these links further stabilize the fibrils. Dityrosine crosslinking was present in internalized Aβ in cell cultures treated with oligomeric Aβ42 using a specific antibody for dityrosine by immunogold labeling transmission electron microscopy. Results also revealed the prevalence of dityrosine crosslinks in amyloid plaques in brain tissue and in cerebrospinal fluid from AD patients. Conclusions Aβ dimers may be stabilized by dityrosine crosslinking. These results indicate that dityrosine cross-links may play an important role in the pathogenesis of Alzheimer’s disease and can be generated by reactive oxygen species catalyzed by Cu2+ ions. The observation of increased Aβ and dityrosine in CSF from AD patients suggests that this could be used as a potential biomarker of oxidative stress in AD

Impact of Inventory Control Reduction on Customer Satisfaction and Partial Fill Costs

Class of 2005 AbstractObjectives: To determine the impact of tightly controlled inventory reduction on customer satisfaction and partial fill costs. Methods: The project was a cross-sectional study employing two survey instruments and a time in motion analysis to determine the number of “we-owes” filled by pharmacies due to inventory reduction, the costs that arise from such reductions, and the impact on customer satisfaction. The first survey instrument was sent to four pharmacies in the Fry’s Food and Drug chain. The survey assessed number of “we-owes” per pharmacy and reasons for having them. The second survey consisted of several statements concerning customer satisfaction. The participants were asked to rate their agreement with each statement using a response scale from 1 (strongly disagree) to 5 (strongly agree). A time-in-motion analysis was performed at two pharmacies averaging 350 prescriptions per day to record the amount of labor involved in filling “we-owes". Results: Medium to high volume Fry’s pharmacy fills an average of forty “we owes” each week. The average yearly costs for filling the “we owes” ranges from $171,579 to$568,796 per year depending on the job status of people filling the “we owes.” The main reason for these partially filled prescriptions was the minimum order point was incorrect accounted for 53.8% of the “we owes Almost half of customers owed medication felt it was not inconvenient them to pick the remainder of their prescription and that over half have had this happen more than once. Implications: The costs of tight inventory control need to be compared with the savings obtained from maintaining marginal inventories.This item is part of the Pharmacy Student Research Projects collection, made available by the College of Pharmacy and the University Libraries at the University of Arizona. For more information about items in this collection, please contact Jennifer Martin, Librarian and Clinical Instructor, Pharmacy Practice and Science, [email protected]

Lyme Neuroborreliosis: Mechanisms of B. burgdorferi Infection of the Nervous System

Lyme borreliosis is the most prevalent tick-borne disease in the United States, infecting ~476,000 people annually. Borrelia spp. spirochetal bacteria are the causative agents of Lyme disease in humans and are transmitted by Ixodes spp ticks. Clinical manifestations vary depending on which Borrelia genospecies infects the patient and may be a consequence of distinct organotropism between species. In the US, B. burgdorferi sensu stricto is the most commonly reported genospecies and infection can manifest as mild to severe symptoms. Different genotypes of B. burgdorferi sensu stricto may be responsible for causing varying degrees of clinical manifestations. While the majority of Lyme borreliae-infected patients fully recover with antibiotic treatment, approximately 15% of infected individuals experience long-term neurological and psychological symptoms that are unresponsive to antibiotics. Currently, long-term antibiotic treatment remains the only FDA-approved option for those suffering from these chronic effects. Here, we discuss the current knowledge pertaining to B. burgdorferi sensu stricto infection in the central nervous system (CNS), termed Lyme neuroborreliosis (LNB), within North America and specifically the United States. We explore the molecular mechanisms of spirochete entry into the brain and the role B. burgdorferi sensu stricto genotypes play in CNS infectivity. Understanding infectivity can provide therapeutic targets for LNB treatment and offer public health understanding of the B. burgdorferi sensu stricto genotypes that cause long-lasting symptoms

Fundamentals of Leadership for Emergency Service Managers

Presentation given at Georgia Association of Emergency Medical Service

Aß’s effect on long term memory: a top-down approach in Lymnaea stagnalis

Amyloid ß(Aß)-induced synaptic and neuronal degeneration has been linked to the memory loss observed in Alzheimer’s disease (AD). Although Aß-induced impairment of synaptic and nonsynaptic plasticity is known to occur before any cell death, the links between these neurophysiological changes and the loss of specific types of behavioural memory are not fully understood. This thesis introduces a behaviourally and physiologically tractable animal model to the Aß field for the first time, allowing for an in-depth approach to investigating Aß-induced memory loss to be explored. In Aß 1-42- and Aß 25-35-treated Lymnaea stagnalis, retrieval of consolidated memory is disrupted after single-trial conditioning and single-injection of synthetic peptide. All succeeding work builds upon these findings using a top-down approach to investigate how Aß disrupts retrieval of consolidated memory. Neuronal and synaptic health were monitored over a 24 hour in vivo incubation period and other memory stages were considered to determine time points of memory vulnerability. In brains that displayed healthy neurons and degenerating synapses, only animals that were exposed to Aß during the 24-48 hour post-training time points exhibited any behavioural deficits. All other behavioural responses remained normal. Focus then shifted to investigate the peptide, as opposed to behaviour, involved in the above mentioned experiments. After systemic injection, Aß was found to penetrate the ganglia, enter cells, and localise to specific organelles by 24 hours exposure. Aß morphology and structure were also monitored over the 24 hour incubation period, using transmission electron microscopy (TEM), formic acid extraction, silver stain, and western blot. A large distinction between the two peptides, Aß 1-42 and Aß 25-35, became apparent at this point and even when peptides were prepared using the same procedure, their effects on behaviour became drastically different. However, it is interesting to note that although the two peptides used are very different, under different preparation procedures they will both produce predominantly tetramer species after 24 hour in vivo incubation. Finally, investigations into disruptions of molecular signalling cascades were considered in order to correlate these disruptions to the observed Aß-induced behavioural deficits. Specifically, molecular, pharmacological, and biochemical techniques were used to measure protein alterations and post-translational modifications, and to inhibit key protein components, involved in cAMP response element binding protein (CREB)-signalling pathways in Lymnaea brain after 24 hour in vivo incubation of Aß. Phosphorylated CREB was found to be decreased in both Aß-treated groups; this decrease pattern was also found in active protein kinase A (PKA) experiments. These experiments correlate memory deficits to Aß-induced disruptions in PKA and CREB activity; however, PKA inhibition experiments indicate that this molecular cascade disruption is not sufficient to cause the observed behavioural deficits. Taken together, this work correlates Aß-induced changes from a wide range of components involved in learning and memory, with Aß-disrupted memory recall. Importantly as well, this work develops Lymnaea stagnalis as a novel model for Aß research and continues to distinguish the two commonly used peptides, Aß 1-42 and Aß 25-35. By linking the effects of Aß on defined neuronal circuits to behavioural deficits in a novel model, the Aß field has been further developed in an important and unique way