Roles for Histones H4 Serine 1 Phosphorylation in DNA Double Strand Break Repair and Chromatin Compaction: A Dissertation

The study of DNA templated events is not complete without considering the chromatin environment. Histone modifications help to regulate gene expression, chromatin compaction and DNA replication. Because DNA damage repair must occur within the context of chromatin, many remodeling enzymes and histone modifications work in concert to enable access to the DNA and aid in restoration of chromatin after repair is complete. CK2 has recently been identified as a histone modifying enzyme. In this study we identify CK2 as a histone H3 tail kinase in vitro, identify the phospho-acceptor site in vitro, and characterize the modification in vivo in S. cerevisiae. We also characterize the DNA damage phenotype of a strain lacking a single catalytic subunit of CK2. We further characterize the CK2- dependent phosphorylation of serine 1 of histone H4 in vivo. We find that it is recruited directly to the site of a DSB and this recruitment requires the SIN3/RPD3 histone deacetylase complex. We also characterize the contribution of H4 serine 1 phosphorylation in chromatin compaction by using reconstituted nucleosomal arrays to study folding in the analytical ultracentrifuge

Academic Incivility: Can the Dark Triad Personality Traits Predict Academic Entitlement?

Academic entitlement is a view held by students that can cause dissent and student incivility. Academic entitlement can be driven by various factors, including the personality traits of the Dark Triad (personality traits of Machiavellianism, psychopathy, and narcissism). Other researchers have examined the relationship between these traits and academic entitlement, but further research on this subject is needed. Adams’ equity theory, which proposes that people experience distress when they identify as either under- or over rewarded individuals, provided the theoretical foundation for this study. Using a quantitative approach, 160 participants were recruited using online methods and asked to complete a survey comprised of the Academic Entitlement Scale, the Short Dark Triad Scale, and the Marlowe-Crowne Social Desirability Scale. Hierarchical multiple regression was used to examine the relationship between the data gathered on the Dark Triad personality traits and academic entitlement. The results indicated Machiavellianism and psychopathy traits contained in the Dark Triad personalities do predict academic entitlement. This knowledge promotes positive social change by providing educators and support staff with insight into the millennial generation of students. A greater understanding of the link between personality traits allows professors and support staff to mitigate these behaviors by adapting their teaching styles to diminish the chance of academic-entitled behaviors to manifest

The Ras-Erk-ETS-signaling pathway is a drug target for longevity

Summary Identifying the molecular mechanisms that underlie aging and their pharmacological manipulation are key aims for improving lifelong human health. Here, we identify a critical role for Ras-Erk-ETS signaling in aging in Drosophila. We show that inhibition of Ras is sufficient for lifespan extension downstream of reduced insulin/IGF-1 (IIS) signaling. Moreover, direct reduction of Ras or Erk activity leads to increased lifespan. We identify the E-twenty six (ETS) transcriptional repressor, Anterior open (Aop), as central to lifespan extension caused by reduced IIS or Ras attenuation. Importantly, we demonstrate that adult-onset administration of the drug trametinib, a highly specific inhibitor of Ras-Erk-ETS signaling, can extend lifespan. This discovery of the Ras-Erk-ETS pathway as a pharmacological target for animal aging, together with the high degree of evolutionary conservation of the pathway, suggests that inhibition of Ras-Erk-ETS signaling may provide an effective target for anti-aging interventions in mammals. Video Abstrac

Aquatic Ecosystems in a Shifting Indiana Climate: A Report from the Indiana Climate Change Impacts Assessment

Indiana is home to many types of aquatic ecosystems, including lakes, rivers, streams, wetlands and temporary (ephemeral) pools, which provide habitats for a wide range of plants and animals. These ecosystems will experience changes in water quantity, water temperature, ice cover, water clarity and oxygen content as the state’s temperature and rainfall patterns shift. The plants and animals living in these aquatic ecosystems will undergo changes that will vary based on the species and the specific places they inhabit. It is challenging to know precisely how organisms will respond to changes in climate. Effects on one species create a difficult-to-predict chain reaction that potentially influences other species in the same ecosystem. Some organisms will adapt and evolve to survive, or even thrive, as the climate changes, but they will have to adjust to more than just the changes in climate. They will also respond to changes in a wide variety of other environmental factors that affect them, including invasive species, habitat destruction, contaminants, nutrient runoff, and land management decisions. While these complicated interactions make it challenging to predict the long-term fate of Indiana’s aquatic species, enough is known about climate-related stressors to help managers develop strategies to avoid the most critical outcomes, hopefully avoiding species loss. This report from the Indiana Climate Change Impacts Assessment (IN CCIA) uses climate projections for the state to explore the potential threats to Indiana’s aquatic ecosystems and describes potential management implications and opportunities

The Multi-Epoch Nearby Cluster Survey: type Ia supernova rate measurement in z~0.1 clusters and the late-time delay time distribution

We describe the Multi-Epoch Nearby Cluster Survey (MENeaCS), designed to measure the cluster Type Ia supernova (SN Ia) rate in a sample of 57 X-ray selected galaxy clusters, with redshifts of 0.05 < z < 0.15. Utilizing our real time analysis pipeline, we spectroscopically confirmed twenty-three cluster SN Ia, four of which were intracluster events. Using our deep CFHT/Megacam imaging, we measured total stellar luminosities in each of our galaxy clusters, and we performed detailed supernova detection efficiency simulations. Bringing these ingredients together, we measure an overall cluster SN Ia rate within R_{200} (1 Mpc) of 0.042^{+0.012}_{-0.010}^{+0.010}_{-0.008} SNuM (0.049^{+0.016}_{-0.014}^{+0.005}_{-0.004} SNuM) and a SN Ia rate within red sequence galaxies of 0.041^{+0.015}_{-0.015}^{+0.005}_{-0.010} SNuM (0.041^{+0.019}_{-0.015}^{+0.005}_{-0.004} SNuM). The red sequence SN Ia rate is consistent with published rates in early type/elliptical galaxies in the `field'. Using our red sequence SN Ia rate, and other cluster SNe measurements in early type galaxies up to $z\sim1$, we derive the late time (>2 Gyr) delay time distribution (DTD) of SN Ia assuming a cluster early type galaxy star formation epoch of z_f=3. Assuming a power law form for the DTD, \Psi(t)\propto t^s, we find s=-1.62\pm0.54. This result is consistent with predictions for the double degenerate SN Ia progenitor scenario (s\sim-1), and is also in line with recent calculations for the double detonation explosion mechanism (s\sim-2). The most recent calculations of the single degenerate scenario delay time distribution predicts an order of magnitude drop off in SN Ia rate \sim 6-7 Gyr after stellar formation, and the observed cluster rates cannot rule this out.Comment: 35 pages, 14 figures, ApJ accepte

Changes in Kelp and Other Seaweeds Following Elwha Dam Removal

Kelps are ecologically important seaweeds that dominated the nearshore vegetation community prior to dam removal on the Elwha River. Dam removal is expected to trigger a shift from kelps to vegetation types that are characteristic of soft-sediment communities through restoring natural sediment supply. This study is investigating how nearshore vegetation responds to restoration of the natural sediment regime, both initially when large amounts of sediment entrained in the reservoirs are released and over longer time periods. We assessed vegetation at multiple spatial scales using three approaches. First, we measured floating kelp canopy area using aerial photography. Second, we assessed the abundance of understory kelp and seagrasses with towed videography along 50 km of shoreline. Third, scuba divers recorded density of kelp species and other seaweeds along 10 km of shoreline bracketing the river mouth. Results show profound changes in vegetation and a strong gradient in magnitude of impact related to distance from the river mouth. Floating kelp canopy area decreased 74% in the Elwha Drift Cell in the first year following project initiation (year 1), with lower magnitude losses throughout the Strait of Juan de Fuca. Area of prostrate kelps decreased by 45% (400 ha) and of stipitate kelps by 30% (130 ha) in the Elwha Drift Cell in year 1. Mean kelp density near the river mouth decreased 77% in year 1 and 95% in year 2. While all 10 kelp species declined, annuals were more impacted than perennials. In contrast to the general decline, juveniles of several kelp species appeared in late August of year 2, a substantial delay compared to typical spring timing of juvenile growth. What caused the large kelp losses and apparent delay of juvenile growth? Likely candidates include light reduction from the river plume and scour, burial or settlement inhibition from deposition. These candidates will be explored using physical data from the multidisciplinary research effort

The Grizzly, March 20, 1981

Special Olympics at Ursinus This Weekend • IFC All Set for Dance • Basketball Team Shootin\u27 for National Title • St. Andrews Scholarship Applications Being Taken • McQuillan Warns of Student Loan Cuts • USGA Notes • Evening Student Awarded Phillips Prize • Departmental Focus: Economics / Business Administration • Texan in New York • Rush Clarifies Itself in Moving Pictures • Positive Rock Radio • Midsummer Night\u27s Dream in Final Preparation • UC Secretaries: Service Beyond the Call of Duty • Classics Club Announces Movie • Course Offerings 1981-1982 • Ursinus Basketball in Final Four • All-American Giff Earns Third • Gymnastics Season Seen as a Successhttps://digitalcommons.ursinus.edu/grizzlynews/1055/thumbnail.jp

Habitat alteration in coastal and marine habitats following dam removal on the Elwha River

The ongoing removal of the Elwha and Glines Canyon dams on the Elwha River have mobilized a massive amount of sediment that has accumulated and altered habitats throughout the watershed. Accumulation has been particularly high in the estuaries and nearshore, significantly altering physical and biological conditions. We have been measuring a suite of parameters since 2010 to better understand how sediment accumulation and suspended sediment alter physical and biological conditions, and how those changes alter habitat conditions. In estuarine and nearshore habitats we are measuring salinity, temperature, turbidity, primary productivity, light availability, and nutrient concentration. In the estuary we are additionally measuring pH, dissolved oxygen concentration; in the nearshore we are additionally measuring current direction and speed, wave height and direction, and sediment deposition and residence time. Our data show that conditions in the estuary changed from a tidally influenced, brackish estuary to a freshwater estuary that is episodically isolated from the river within one year of dam removal. In addition to the fine sediment that has accumulated in the estuary, this hydrologic change has resulted in ecological changes to the estuary, including a shift in species composition of fish and invertebrates. In the nearshore, light availability has decreased during the dam removal process, and the incidence of seafloor sedimentation has increased, which is ephemeral owing to winnowing from periodic strong currents. Burial, scouring, and reduced light availability caused by increased sedimentation are likely negatively impacting algal communities in the nearshore that are within the Elwha River plume. This study advances our understanding of how the timing and magnitude of sediment delivery affects habitat availability, species persistence, and community composition change with implications to future land-use changes

Identifying a Novel Role for Fractalkine (CX3CL1) in Memory CD8(+) T Cell Accumulation in the Omentum of Obesity-Associated Cancer Patients

The omentum is enriched with pro-inflammatory effector memory CD8+ T cells in patients with the obesity-associated malignancy, esophagogastric adenocarcinoma (EAC) and we have identified the chemokine macrophage inflammatory protein-1alpha as a key player in their active migration to this inflamed tissue. More recently, others have established that subsets of memory CD8+ T cells can be classified based on their surface expression of CX3CR1; the specific receptor for the inflammatory chemokine fractalkine. CD8+ T cells expressing intermediate levels (CX3CR1INT) are defined as peripheral memory, those expressing the highest levels (CX3CR1HI) are effector memory/terminally differentiated and those lacking CX3CR1 (CX3CR1NEG) are classified as central memory. To date, the fractalkine:CX3CR1 axis has not been examined in the context of CD8+ T cell enrichment in the omentum and here we examine this chemokines involvement in the accumulation of memory CD8+ T cells in the omentum of EAC patients. Our data show that fractalkine is significantly enriched in the omentum of EAC patients and drives migration of T cells derived from EAC patient blood. Furthermore, CX3CR1 is endocytosed specifically by CD8+ T cells upon encountering fractalkine, which is consistent with the significantly diminished frequencies of CX3CR1INT and CX3CR1HI CD8+ T cells in the fractalkine-rich environment of omentum in EAC, relative to matched blood. Fractalkine-mediated endocytosis of CX3CR1 by CD8+ T cells is sustained and is followed by enhanced surface expression of L-selectin (CD62L). These novel data align with our findings that circulating CX3CR1NEG CD8+ T cells express higher levels of L-selectin than CX3CR1INT CD8+ T cells. This is consistent with previous reports and implicates fractalkine in the conversion of CX3CR1INT CD8+ T cells to a CX3CR1NEG phenotype characterized by alterations in the migratory capacity of these T cells. For the first time, these findings identify fractalkine as a driver of T cell migration to the omentum in EAC and indicate that CD8+ T cells undergo sequenced fractalkine-mediated alterations in CX3CR1 and L-selectin expression. These data implicate fractalkine as more than a chemotactic cytokine in obesity-associated meta-inflammation and reveal a role for this chemokine in the maintenance of the CX3CR1NEG CD8+ T cell populations