Electron microscopy analysis of alpha-synuclein and LRRK2 transgenic C. elegans

Thesis (M.A.)--Boston UniversityMutations in alpha-synuclein and leucine-rich repeat kinase 2 (LRRK2) have been implicated in the cause of Parkinson’s disease (PD). These two proteins have been the targets of a great deal of recent research that has transformed our understanding of this disorder. Recent research using C. elegans as a model species has shown that alpha- synuclein expression and the LRRK2-G2019S mutation potentiate neurodegeneration similar to that seen in cases PD. Further exploration revealed that defects in autophagy of dopaminergic neurons may be the cause for the observed pathology. In the current study, the confirmation of autophagy as a possible cause of pathology due to the expression of alpha-synuclein and the LRRK2-G2019S mutation is completed through the use of electron microscopy. We observed that large vacuoles had formed in the cephalic dopaminergic neurons of alpha-synuclein + LRRK2 transgenic samples not seen in wild-type samples. Further, large morphological changes in the nerve ring area of the transgenic nematodes were also observed that may implicate that alpha- synuclein expression in conjunction with the LRRK2-G2019S mutation may have a widespread effect on many neurons that was not previously expected

Exchange rate exposure, foreign currency derivatives and the introduction of the euro : French evidence

We investigate the impact of the introduction of the Euro on exchange rate exposures for French corporations and examine the corporate use of foreign currency derivatives to hedge exchange rate exposure post-Euro. Our findings indicate that the introduction of the Euro is associated with both a reduction in the number of firms that have significant exchange rate exposure and the absolute size of exposure. Consistent with these reduced exposures, French firms use foreign currency derivatives less intensively. Furthermore, the use of foreign currency derivatives is found to be associated with lower exchange rate exposure but there is insufficient evidence that these instruments are more effective in the post-Euro environment

Extended Hubbard model for mesoscopic transport in donor arrays in silicon

Arrays of dopants in silicon are promising platforms for the quantum simulation of the Fermi-Hubbard model. We show that the simplest model with only on-site interaction is insufficient to describe the physics of an array of phosphorous donors in silicon due to the strong intersite interaction in the system. We also study the resonant tunneling transport in the array at low temperature as a mean of probing the features of the Hubbard physics, such as the Hubbard bands and the Mott gap. Two mechanisms of localization which suppresses transport in the array are investigated: The first arises from the electron-ion core attraction and is significant at low filling; the second is due to the sharp oscillation in the tunnel coupling caused by the intervalley interference of the donor electron's wavefunction. This disorder in the tunnel coupling leads to a steep exponential decay of conductance with channel length in one-dimensional arrays, but its effect is less prominent in two-dimensional ones. Hence, it is possible to observe resonant tunneling transport in a relatively large array in two dimensions

Challenges of Blockchain Applications in Digital Health: A Systematic Review

Digital health, an emerging field integrating digital technologies into healthcare, is rapidly evolving and holds the potential to transform medical practices. Blockchain technology has garnered significant attention as a potential solution to various issues within digital health, including data security, automation, interoperability, and patient data ownership. However, despite the numerous advantages, blockchain faces several challenges and unknowns that must be addressed. This systematic literature review aims to explore the challenges of blockchain applications in digital health and provide best practices to overcome current and future roadblocks. Key issues identified include regulatory compliance, energy consumption, network effects, data standards, and the accessibility of the technology to stakeholders. To ensure the successful integration of blockchain within digital health, it is crucial to collaborate with healthcare stakeholders, pursue continued research and innovation, and engage in open discussions about the technology's limitations and potential.Comment: 11 pages, 1 tabl

Evolutionary Innovations In Ants To Thermally Stressful Environments

Temperature is a fundamental environmental force shaping species abundance and distributions through its effects on biochemical reaction rates, metabolism, activity, and reproduction. In light of future climate shifts, mainly driven by temperature increases, how will organisms persist in warmer environments? One molecular mechanism that may play an important role in coping with heat stress is the heat shock response (HSR), which protects against molecular damage. To prevent and repair protein damage specifically, Hsps activate and become up-regulated. However, the functional diversity and relevance of heat shock proteins (Hsps) in extending upper thermal limits in taxonomic groups outside marine and model systems is poorly understood. Ants are a good system to understand the physiological mechanisms for coping with heat stress because they have successfully diversified into thermally stressful environments. To identify and characterize the functional diversity of Hsps in ants, I surveyed Hsp orthologues from published ant genomes to test for signatures of positive selection and to reconstruct their evolutionary history. Within Hymenoptera, ants utilize unique sets of Hsps for the HSR. Stabilizing selection was the prevailing force among Hsp orthologues, suggesting that protein activity is conserved. At the same time, regulatory regions (promoters) governing transcriptional up-regulation diversified: species differ in the number and location of heat shock elements (HSEs). Therefore, Hsp expression patterns may be a target for selection in warm environments. I tested whether Hsp expression corresponded with variation in upper thermal limits in forest ant species within the genus Aphaenogaster. Whole colonies were collected throughout the eastern United States and were lab acclimated. There was a positive relationship between upper thermal limits (Critical Thermal maxima, CTmax) and local temperature extremes. Upper thermal limits were also higher in ant species that lived in open habitats (shrub-oak and long-leaf pine savannah) than species occupying closed habitats (deciduous forest). Ant species with higher CTmax expressed Hsps more slowly, at higher temperatures, and at higher maximum levels than those with low CTmax. Because Hsps sense and repair molecular damage, these results suggest the proteomes of open relative to closed canopy forests are more stable. Although deciduous forest ant species may be buffered from temperature stress, it is likely that temperature interacts with other environmental stressors such as water and nutrient availability that may impact upper thermal limits. I measured the influence of dehydration and nutrition stress on upper thermal limits of forest ants from a single population. Ants that were initially starved were much less thermally tolerant than controls and ants that were initially desiccated. Because ants are likely to experience similar combination of stressors in the wild, upper thermal limits may be severely overestimated in single factor experiments. Therefore, realistic forecasting models need to consider multiple environmental stressors. Overall, adaptive tuning of Hsp expression that reflects better protection and tolerance of protein unfolding may have facilitated ant diversification into warm environments. However, additional stressors and mechanisms may constrain the evolution of upper thermal limits

Using Information Governance to Evaluate Patient Care in Amazon's One Medical

This paper explores the information governance (IG) maturity of Amazon's One Medical (AOM), a digital health and telehealth primary care organization. Combining Amazon's technology expertise with One Medical's healthcare services, AOM aims to transform healthcare through a human-centered, technology-powered model. However, successfully integrating Amazon's disruptive approach into the complex healthcare industry is challenging. To examine AOM's IG maturity, we compare and critique patient care in AOM against the ARMA Maturity Model and AHIMA's IGPHC framework. The study discusses the implications of telehealth on the doctor-patient relationship, rising roles of ancillary service teams, commoditization of healthcare, and potential monopolization. It also addresses security risks, compliance challenges, and the impact of technology on disadvantaged populations. Our analysis highlights the growing importance of information management in the evolving intersection between healthcare and technology and suggests potential areas for improvement in AOM's IG maturity.Comment: 26 pages, 1 figure, 3 table