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Investigation of L-Serine Synthesis and Transport as Stabilizing Feedback Mechanisms within the Tsetse-Wigglesworthia Symbiosis
No full textTsetse flies (Glossina morsitans), which are the obligate vectors of Old-World trypanosomes (Trypanosoma spp.) that cause African trypanosomiasis, have a bacteriome that houses the intracellular endosymbiont Wigglesworthia glossinidia. The ancient coevolution of these species has led to the integration of Wigglesworthia metabolism into tsetse physiology and a subsequent reliance on nutrient exchange for maintaining the fitness of both partners. The establishment of this obligate mutualism has facilitated the emergence of feedback mechanisms that stabilize the symbiosis, such as that which involves the exchange of L-serine and B vitamins. The Gammaproteobacteria Wigglesworthia supplement B vitamins lacking in the hematophagous diet of the tsetse host and, in return, L-serine, which requires B vitamins for its synthesis by tsetse, is provisioned to Wigglesworthia. Here, we identify potential points of weakness in the tsetse-Wigglesworthia symbiosis through L-serine biosynthesis and transport gene expression analyses. L-serine biosynthesis was shown to occur predominantly outside of the bacteriome, indicating the need for B6 to be transported out of its bacteriome origin and into other abdominal tissues. The inhibition of pyridoxal kinase, which converts B6 into its active form following its diffusion into cells, may be used to prevent L-serine synthesis outside of the bacteriome. In hyposymbiotic tsetse, Wigglesworthia do not express SdaC, their sole putative L-serine transporter, despite maintenance of wild-type L-serine biosynthesis levels, which suggests that reduced populations of Wigglesworthia may fail to regulate bacteriome L-serine levels. The bioinformatic characterization of Wigglesworthia SdaC by comparison to other gram-negative bacteria suggests that reduced Wigglesworthia populations may also fail to achieve self-recognition, which could impact vertical transmission. Difficulties in developing treatments for and vaccinations against trypanosome infections has led to a focus on strategies for reducing tsetse populations to prevent trypanosomiasis. These insights into the stability of the tsetse-Wigglesworthia symbiosis provide novel targets for reducing tsetse fitness
Prominin-1 (PROM1) is Needed for the Photoreceptor Outer Segment Development and Vision
No full textProminin 1 (PROM1) is a pentaspan transmembrane glycoprotein localized on the nascent photoreceptor discs. Mutations in PROM1 are linked to various retinal diseases. In this study, we showed that PROM1 depletion causes visual impairment in mice as early as post-natal day 12 (P12). By P30, these animals had irreversible retinal degeneration, evident in photoreceptor cell death. Additionally, PROM1 depletion causes severely malformed outer segments as early as P12 without apparent cell death, indicating the role of PROM1 in outer segment development and maintenance.
Actin network-driven membrane evagination at the base of the outer segment is an indispensable process for forming new discs and maintaining outer segment homeostasis. Structural similarities between the photoreceptor outer segments of actin-network disrupted micePROM1 knock-out mice indicate that PROM1 might also be involved in the photoreceptor outer segments morphogenesis. Thus, we aimed to assess the role of PROM1 C-terminus tail in retinal disorders and photoreceptor development by using murine models. We generated three novel mouse models via CRISPR/Cas9 technology where the C-terminus of endogenous PROM1 is truncated at various lengths (PROM1-Δ42 and PROM1-Δ44) or mutated at a single amino acid level (PROM1-D825N). Electroretinogram analysis showed that all three PROM1-ΔC mouse models have reduced rod and cone function compared to wild-type littermate controls. Surprisingly, PROM1-Δ44 mice had reduced photoreceptor function even with a single copy of mutant PROM1. Our preliminary ultrastructural imaging via transmission electron microscopy revealed that the photoreceptor outer segments of PROM1-Δ42 and PROM1-D825N mice are severely malformed. However, the degree of outer segment defects and overall outer segment disc organization were not identical.
Together, our results highlight the intricate role of the C-terminal tail of PROM1 in photoreceptor function, disc formation, and outer segment morphogenesis. We hypothesize that PROM1 is an essential component of a protein network that orchestrates together to form and maintain photoreceptor outer segments. This study will further aid us in deciphering the mechanism behind PROM1-mediated inherited blindness
Medical Malpractice as Murder? Using Root Cause Analysis as a Guiding Framework for Criminal Medical Malpractice
Get PDFUnprecedented criminal prosecutions for medical errors have increased throughout the nation: A Tennessee nurse was charged with reckless homicide for an isolated medication error; two South Carolina nurses were charged with criminal neglect for failing to change a wound dressing for just two days; and an Ohio pharmacist was charged with involuntary manslaughter for failing to detect that a solution contained too much sodium. Introducing criminal charges for cases of typical medical malpractice, which are most often the result of system failures, will dismantle hospitals’ error-reporting systems and lead to long-term catastrophic results for patient safety. This Note applies system analysis framework, via root cause analysis, to clarify the boundaries between civil and criminal medical malpractice. Root cause analysis uses an undesired event as the starting place for analysis and considers all the contributing factors to make a bright line distinction between latent system errors, which are hidden errors between the system and healthcare provider interface, and active errors, which have a direct causal relationship between the deliberate act of the healthcare provider and the patient. Under this framework, latent system errors should not be criminally penalized. This analysis, with an emphasis on the mental state of the actor, will decrease the inappropriate criminalization of medical malpractice, so that system errors may be properly deterred from recurring. This Note will offer case illustrations to demonstrate when sufficient criminal culpability exists within the scope of medical malpractice to provide a framework that will assist judges, juries, and prosecutors in deciding when criminal charges for medical malpractice are appropriate
Collectible Pricing and Collector Utility: The Role of Production Commitments
Get PDFThis paper investigates the effect of production commitments on consumers of collectable goods. Using data on prices for Magic: The Gathering trading cards, we estimate that the reprinting of certain card varieties caused a 34% decrease in the relative price of reprinted cards. We interpret this estimate with a model of a forward-looking consumer that views collectibles as both a source of enjoyment and a store of wealth. Using a mapping between structural parameters of the model and difference-in-differences regression parameters, we compute lifetime discounted utility decreased by as much as 14% for collectors holding mainly reprinted cards
Seeding Sparks for The Right to Food
Get PDFSeeding Sparks for The Right to Food partnered with Voices of Hunger to disperse a grant to community leaders. These community leaders have projects that are aimed to advance the Right to Food and promote food security. This project interviewed the applicants and pulled out common themes among their responses to further understand their motivations and passions related to food justice
The Impact of Low-Skew on the Ultimate Capacity of Press-Brake-Formed Tub Girders
Get PDFThe development of press-brake-formed tub girders (PBFTGs) has offered innovative solutions for short-span steel bridge applications and helps meet the demand for rapid infrastructure replacement solutions. The Short Span Steel Bridge Alliance (SSSBA) comprises bridge and buried soil structure industry leaders who aim to provide essential educational information to bridge and highway professionals on the design and construction of short-span steel bridge installations (SSSBA, 2020). The American Association of State and Highway Transportation Officials (AASHTO) provides design standards, specifications, and guidance for the analysis and construction of PBFTGs. Currently, the AASHTO Load Resistance and Factor Design Bridge Design Specifications (AASHTO LRFD BDS) classifies PBFTGs as noncompact sections under any skew angle, which places a limit on the flexural capacity to the yield moment (My). This specification greatly limits the applicability of PBFTGs in bridge design, as the plastic moment capacity (Mp) cannot be achieved when designing a PBFTG bridge using the current AASHTO LRFD BDS.
The scope of this research project was to better understand and characterize the flexural behavior of PBFTGs under low-skew angles to expand the applicability of the PBFTG system. This project was performed in four stages. Experimental pseudo-static flexural testing was first performed on two composite 15-degree PBFTGs to collect data and observe the ultimate capacity of each system. A rational methodology based on previous PBFTG research at West Virginia University (WVU) was used to build analytical three-dimensional finite element analysis (FEA) models to benchmark against the experimental test data. A sensitivity study was developed by modeling a matrix of 3,509 PBFTG bridges using the three-dimensional finite element modeling software Abaqus. Girders were modeled with varied parameters before analyzing the impact of each parameter on the ultimate flexural capacities. The analysis specifically was employed to further verify that skewness does not impact the ultimate flexural capacity and that the behavior can be considered compact for PBFTGs with skew angles up to 20 degrees.
Results of this research project show that low-skewed PBFTGs perform with an ultimate flexural resistance exceeding the first yielding moment. This study demonstrates that PBFTGs have a more comprehensive range of applicability and can be a strong competitor in the bridge market if the AASHTO LRFD BDS adopts the recommendation to classify PBFTGs with skews up to 20 degrees as compact sections. Integrating this concept will broaden the applicability of PBFTGs and benefit the design process of shallow steel tub girder bridges
Investigating the Effect of Using Humorous Threats in Recreation Area Rules Signage to Influence Behavioral Intentions
Get PDFCommunicating the importance of rules and warnings to visitors of recreational parks through signage can be difficult. However, it is one of the most important things to keep visitors safe. Oftentimes, these signs use fear of punishment or injury to discourage certain behaviors. According to studies following the Extended Parallel Processing Model (EPPM), using threats can backfire and cause visitors to use maladaptive fear responses to counteract a threat message if the content is too extreme or too psychologically close. Humor is a versatile tool that can be used to grab attention, temper perceptions, and influence decision-making. Comedians like Jon Stewart and George Carlin, for example, have leveraged their position to bring controversial and often difficult-to-digest issues to large audiences through the use of humorous threats.
This study aimed to explore the effect of humorous threats on the reception of messages with the intent of changing behavioral intentions in recreation areas. Participants were asked to complete an online survey about prior attitudes towards rules in recreation areas, past experiences with risk factors, frequency of visitation to recreation areas, and preferred activities. They were then randomly be exposed to one informational rule sign out of four combinations of humor and threat content: normal (control), humor, threat, and humorous threat. After exposure to the sign, they were asked about their emotional and cognitive responses to the content. The study looked for relationships between sign content, perceptions of messages, and behavioral intentions.
The study found that humor, threats, and humorous threats do not have any effect on the behavioral intention decision phase of the EPPM. The study also showed through ANOVA and non-parametric tests that there was a relationship between the sign content and perceptions of risk. The study sheds light on the effectiveness of using humor, fear, and humorous threats for park managers to better communicate with visitors and manage park resources
Life Cycle Cost Model for Transit Bus Fleets
Get PDFAbstract
Life Cycle Cost Model for Transit Buses
Connor Jack
Transit agencies battle with reducing emissions while trying to be cost effective. In 2009, the Transit Cooperative Research Program Report (TCRP) 132 presented a life cycle cost model to aid in procurement evaluation [1]. The model is a life cycle cost analysis tool to estimate the overall costs of procurement and compare alternative technologies [2]. The model concentrates on pre-2007 conventional diesel, diesel hybrid with first generation diesel particulate filters, gasoline hybrid, and compressed natural gas transit buses.
The objectives of this work are to implement battery electric technology into the life cycle cost model and update the model to reflect current cost data for all in-service bus technologies. This life cycle cost model evaluates diesel, diesel hybrid, compressed natural gas, and battery electric buses. Data to update vehicle capital costs, maintenance, infrastructure, training, vehicle maintenance, major powertrain component rebuild/replacements, fuel, one-time purchase, and one-time future costs for all propulsion options were collected and implemented. Electric sections were programmed into the model to account for battery electric technology and the complexities of calculating charging costs.
Battery electric buses (BEB) have higher capital costs and charging infrastructure costs than other in-service bus technologies. On average for a 40-foot bus, BEBs cost 38.8% more than a conventional diesel bus, 30% more than compressed natural gas, and 13% more than diesel hybrid options. Utility rates used for charging costs are either time of use or demand rate schedules. The time of use rate schedule is solely based on the draw of kilowatts per hour. Demand rates are comprised of a time of use section with an accompanying demand charge determined by the highest 15-minute energy draw in a billing cycle. Bus charging utilizes on-route or depot chargers, which impact costs for electricity and infrastructure. Based on collected data, the average depot charger adds 44,000 each. On-route chargers are 228,000 on average. A benefit to BEB technology is zero tailpipe emissions, but the generation of electricity needed by the buses still produces emissions. Evaluated with default model options, BEBs save 25 million for on-route charging for fuel costs compared to diesel technology and 9 million for depot charging compared to compressed natural gas (CNG). Fuel efficiency for BEB is 17.5 miles per diesel gallon equivalent (mpdge) while diesel is 4.5 mpdge, CNG yields 3.75 mpdge, and diesel hybrids have an efficiency of 5.5 mpdge. All these efficiencies are with minimal to no air conditioning or heating impacts.
A model case study shows that variable costs of BEBs are on average 141 million more than that of diesel buses, around 36 million more than diesel hybrid buses. Capital costs consist of purchase price, optional warranty costs, diagnostic equipment for hybrids and BEBs, and spare parts. The main difference between capital and variable costs is that capital costs are the initial one-time costs associated with procurement. Variable costs are associated with recurring expenses throughout the bus’s life. BEBs are less expensive in the long term but the initial costs are higher. Grants and credits may help bring down upfront costs allowing the difference in cost to be more competitive with other propulsion types.
The updates and results of the model provide the ability to evaluate transit buses with current data for evaluation across four different propulsion technologies. BEB is an important option with demand increasing for zero tailpipe emissions. California for example, released legislation that agencies are to be 100% comprised of zero tail pipe emissions technology by 2040 [3]. The drive towards lower emissions gives value to the model being that it has the capability for users to evaluate four different bus technologies and input values for all characteristics evaluated. Additionally, the user could compare multiple scenarios with the same technology type. The complexity of electricity costs makes comparison challenging, output figures and data table provide visual means of comparison
The Impact of Occupational Therapy in Lactation Services
Get PDFMany benefits to breastfeeding exist for both mothers and infants, yet exclusive breastfeeding rates remain low across the nation. These benefits include decreased chance of infections for infants, low infant mortality, and decreased chances of breast and ovarian cancers for mothers (Binns et al., 2016; CDC, 2023). Education strategies have recently become imperative for health organizations to help mothers sustain their ability to breastfeed within the recommended six-month timeframe. Current literature on education supports that women who receive education at some point in their lactation journey are more likely to reach the six-month period and have more confidence in their ability to provide for their infant (Alianmoghaddam et al., 2018; Silva et al., 2016; Tseng et al., 2020). Occupational therapists are experts in role promotion and addressing routines to make them more effective. Therefore, occupational therapists may have a role in breastfeeding promotion to help women reach their occupational goals of breastfeeding and improve health outcomes for mothers and infants on a population level (Pitonyak, 2014; Visser et al., 2016). To demonstrate the need for occupational therapists in the field of lactation, a five-week postpartum breastfeeding course was developed to be implemented in the community. One participant attended all five sessions and completed a pre- and post-survey. Results from the COPM demonstrated an improved sense of importance (pre-average: 6.4, post-average: 8.3) and satisfaction (pre-average: 4.4, post-average: 6.4) in breastfeeding-related occupational performance. The BSES-S also demonstrated a self-reported improved sense of self-efficacy regarding breastfeeding (pre: 49, post: 55). Limitations of the study included a higher level of one-on-one support than the program intended and the lack of diversity in participant experience