Getting that Sinking Feeling: Analysis and Impacts of Sea Level Rise on Three National Parks along the East Coast, USA

Due to global climate change, sea level rise (SLR) has become a threat for future generations, but the extent of this danger is unknown. To help understand the possible effects of SLR on the east coast of the United States, we studied three national parks: Acadia National Park (ACAD), Assateague Island National Seashore (ASIS) and Everglades National Park (EVER). We predicted that ACAD would be less affected by SLR than ASIS and EVER due to the construction of its beach profile. By measuring the beach profile, we found that Sand Beach in ACAD was reflective with an average slope of 3.2 cm/m while South Ocean Beach in ASIS had an intermediate morphology with an average slope of 1.57 cm/m. The Snake Bight Channel beach in EVER was dissipative and had no slope. Using historical Landsat imagery from 1984 to 2016, we estimated that ACAD’s water area increased by 1.61%, that ASIS’s water area increased by 2.47%, and that the EVER’s water area decreased by 0.22% between 1992 and 2011. Using RCP scenarios from the latest IPCC report, we estimated future inundation levels in each park along with the percent change between the best and worst-case scenarios. Under the RCP8.5 scenario, ACAD had 1.36 km2 of inundation, ASIS had 37.11 km2, and EVER had 366.47 km2. ACAD had the highest percent change between the worst and best RCP scenario at 15.70%. ASIS had a slightly smaller percent change at 14.25% and EVER had even less at 10.42%. This study suggests that continued SLR will cause national parks billions of dollars in property damage and the loss of their inherent ecological value

Heterologous prion-forming proteins interact to cross-seed aggregation in Saccharomyces cerevisiae

AbstractThe early stages of protein misfolding remain incompletely understood, as most mammalian proteinopathies are only detected after irreversible protein aggregates have formed. Cross-seeding, where one aggregated protein templates the misfolding of a heterologous protein, is one mechanism proposed to stimulate protein aggregation and facilitate disease pathogenesis. Here, we demonstrate the existence of cross-seeding as a crucial step in the formation of the yeast prion [PSI+], formed by the translation termination factor Sup35. We provide evidence for the genetic and physical interaction of the prion protein Rnq1 with Sup35 as a predominant mechanism leading to self-propagating Sup35 aggregation. We identify interacting sites within Rnq1 and Sup35 and determine the effects of breaking and restoring a crucial interaction. Altogether, our results demonstrate that single-residue disruption can drastically reduce the effects of cross-seeding, a finding that has important implications for human protein misfolding disorders.</jats:p

The Experiences of International and Foreign-Born Students in an Accelerated Nursing Program

More international and foreign-born people are choosing to live in America than ever before, many permanently. During the past decade, both education and healthcare have been acutely affected by this change in the national population. To address the need to provide effective healthcare to all ages of a diverse population as well as provide quality educational experiences for international and foreign-born students who enroll in American nursing programs, professional nursing has consistently revised and updated healthcare delivery practices and nursing program curricula. Research consistently addresses the provision of healthcare delivery to a diverse population, but in comparison little has been written about the international and foreign-born student who is in the United States studying and preparing to become a professional nurse. The aim of this study was to report and analyze the experiences of international and foreign-born nursing students who were currently enrolled in an accelerated, second degree program (ABSN) in the Midwest. The findings support prior studies relating to experiences of international and foreign-born students in multiple specialties in the United States, although none in accelerated baccalaureate nursing programs. Davis & Nichols (2001), Sanner, Wilson, & Samson (2002) and Chow (2011) attest to the determination, dedication, and the coping skills of the participants to adapt to and appropriately respond in culturally diverse situations in all venues as did this study. Further, the findings point to the successful development of cultural competence during the one-year ABSN program. The program resulted in positive personal change, also described as transformation for the study participants. An important additional finding was that as the participants mastered the intricacies of professional nursing, they became seriously intent on pursuing advanced degrees in various nursing specialties. This qualitative study will contribute to multiple fields of study as it revealed the individualism of the participants, the meaning they attributed to their year-long higher education experiences and their intention for service in our nation’s communities and around the world as professional nurses

Prion-associated toxicity is rescued by elimination of cotranslational chaperones

The nascent polypeptide-associated complex (NAC) is a highly conserved but poorly characterized triad of proteins that bind near the ribosome exit tunnel. The NAC is the first cotranslational factor to bind to polypeptides and assist with their proper folding. Surprisingly, we found that deletion of NAC subunits in Saccharomyces cerevisiae rescues toxicity associated with the strong [PSI+] prion. This counterintuitive finding can be explained by changes in chaperone balance and distribution whereby the folding of the prion protein is improved and the prion is rendered nontoxic. In particular, the ribosome-associated Hsp70 Ssb is redistributed away from Sup35 prion aggregates to the nascent chains, leading to an array of aggregation phenotypes that can mimic both overexpression and deletion of Ssb. This toxicity rescue demonstrates that chaperone modification can block key steps of the prion life cycle and has exciting implications for potential treatment of many human protein conformational disorders

Prion protein insertional mutations increase aggregation propensity but not fiber stability

<p>Abstract</p> <p>Background</p> <p>Mutations in the <it>PRNP </it>gene account for ~15% of all prion disease cases. Little is understood about the mechanism of how some of these mutations in <it>PRNP </it>cause the protein to aggregate into amyloid fibers or cause disease. We have taken advantage of a chimeric protein system to study the oligopeptide repeat domain (ORD) expansions of the prion protein, PrP, and their effect on protein aggregation and amyloid fiber formation. We replaced the ORD of the yeast prion protein Sup35p with that from wild type and expanded ORDs of PrP and compared their biochemical properties <it>in vitro</it>. We previously determined that these chimeric proteins maintain the [PSI⁺] yeast prion phenotype <it>in vivo</it>. Interestingly, we noted that the repeat expanded chimeric prions seemed to be able to maintain a stronger strain of [<it>PSI</it>⁺] and convert from [<it>psi</it>^-] to [<it>PSI</it>⁺] with a much higher frequency. In this study we have attempted to understand the biochemical properties of these chimeric proteins and to establish a system to study the properties of the ORD of PrP both <it>in vivo </it>and <it>in vitro</it>.</p> <p>Results</p> <p>Investigation of the chimeric proteins <it>in vitro </it>reveals that repeat-expansions increase aggregation propensity and that the kinetics of fiber formation depends on the number of repeats. The fiber formation reactions are promiscuous in that the chimeric protein containing 14 repeats can readily cross-seed fiber formation of proteins that have the wild type number of repeats. Morphologically, the amyloid fibers formed by repeat-expanded proteins associate with each other to form large clumps that were not as prevalent in fibers formed by proteins containing the wild type number of repeats. Despite the increased aggregation propensity and lateral association of the repeat expanded proteins, there was no corresponding increase in the stability of the fibers formed. Therefore, we predict that the differences in fibers formed with different repeat lengths may not be due to gross changes in the amyloid core.</p> <p>Conclusion</p> <p>The biochemical observations presented here explain the properties of these chimeric proteins previously observed in yeast. More importantly, they suggest a mechanism for the observed correlation between age of onset and disease severity with respect to the length of the ORD in humans.</p

The [RNQ+] prion: A model of both functional and pathological amyloid

The formation of fibrillar amyloid is most often associated with protein conformational disorders such as prion diseases, Alzheimer disease and Huntington disease. Interestingly, however, an increasing number of studies suggest that amyloid structures can sometimes play a functional role in normal biology. Several proteins form self-propagating amyloids called prions in the budding yeast Saccharomyces cerevisiae. These unique elements operate by creating a reversible, epigenetic change in phenotype. While the function of the non-prion conformation of the Rnq1 protein is unclear, the prion form, [RNQ(+)], acts to facilitate the de novo formation of other prions to influence cellular phenotypes. The [RNQ(+)] prion itself does not adversely affect the growth of yeast, but the overexpression of Rnq1p can form toxic aggregated structures that are not necessarily prions. The [RNQ(+)] prion is also involved in dictating the aggregation and toxicity of polyglutamine proteins ectopically expressed in yeast. Thus, the [RNQ(+)] prion provides a tractable model that has the potential to reveal significant insight into the factors that dictate how amyloid structures are initiated and propagated in both physiological and pathological contexts

Extensive diversity of prion strains is defined by differential chaperone interactions and distinct amyloidogenic regions

Amyloidogenic proteins associated with a variety of unrelated diseases are typically capable of forming several distinct self-templating conformers. In prion diseases, these different structures, called prion strains (or variants), confer dramatic variation in disease pathology and transmission. Aggregate stability has been found to be a key determinant of the diverse pathological consequences of different prion strains. Yet, it remains largely unclear what other factors might account for the widespread phenotypic variation seen with aggregation-prone proteins. Here, we examined a set of yeast prion variants of the [RNQ+] prion that differ in their ability to induce the formation of another yeast prion called [PSI+]. Remarkably, we found that the [RNQ+] variants require different, non-contiguous regions of the Rnq1 protein for both prion propagation and [PSI+] induction. This included regions outside of the canonical prion-forming domain of Rnq1. Remarkably, such differences did not result in variation in aggregate stability. Our analysis also revealed a striking difference in the ability of these [RNQ+] variants to interact with the chaperone Sis1. Thus, our work shows that the differential influence of various amyloidogenic regions and interactions with host cofactors are critical determinants of the phenotypic consequences of distinct aggregate structures. This helps reveal the complex interdependent factors that influence how a particular amyloid structure may dictate disease pathology and progression

Low activity of select Hsp104 mutants is sufficient to propagate unstable prion variants

The molecular chaperone network plays a critical role in the formation and propagation of self-replicating yeast prions. Not only do individual prions differ in their requirements for certain chaperones, but structural variants of the same prion can also display distinct dependences on the chaperone machinery, specifically Hsp104. The AAA+ ATPase Hsp104 is a disaggregase required for the maintenance of most known yeast prions. As a key component in the propagation of prions, understanding how Hsp104 differs in its interaction with specific variants is crucial to understanding how prion variants may be selected or evolve. Here, we investigate two novel mutations in Hsp104, hsp104-G254D, and hsp104-G730D, which allow us to elucidate some mechanistic features of Hsp104 disaggregation and its requirement for activity in propagating specific prion variants. Both Hsp104 mutants propagate the [PSI+] prion to some extent, but show a high rate of prion loss. Both Hsp104-G254D and Hsp104-G730D display reduced biochemical activity, yet differ in their ability to efficiently resolubilize disordered, heat-aggregated substrates. Additionally, both mutants impair weak [PSI+] propagation, but are capable of propagating the less stable strong [PSI+] variant to some extent. One of the Hsp104 mutants also has the ability to propagate one variant of the [RNQ+] prion. Thus, our data suggest that changes in Hsp104 activity limit substrate disaggregation in a manner that depends more on the stability of the substrate than the nature of the aggregated species

An e-Commerce Systems Integration Framework

The success of e-commerce activity is directly affected by system integration efforts associated with traditional back office and web-based systems. The potential benefits of enterprise-wide e-commerce activities to an organization emphasize the need for system integration beyond individual sales transactions. Unfortunately, many organizations are not capitalizing on the synergistic advantages of integrated systems. Despite the apparent lack of integration, some organizations are attempting to coordinate such customer activities. Planning for and integrating e-commerce technologies are essential to an organization\u27s survival