Dual Targeting of the Mesenchymal and Amoeboid Pathways: A Viable Therapy against Metastatic Breast Cancer

Metastasis from the primary tumor site is the major cause of death in breast cancer, and acquisition of migration capacity is a key element for successful metastasis. Recently, it was found that expression of NEDD9, a focal adhesion associated scaffolding protein, could be used to switch between two types of single cell movement known as mesenchymal and amoeboid. Control of this switch can potentially open up new avenues of treatment against cancer metastasis. Simultaneous inhibition of both types of single cell movement may prevent cancer migration, thus decreasing cancer spreading and increasing survival of cancer patients. For example, forcibly pushing the switch toward amoeboid migration in combination with treatment against the kinase ROCK, a key component of amoeboid movement, might prove to be a vital strategy against metastasis. Currently, such strategies are not available in clinical practice. This project seeks to fill this gap in knowledge and provide new migration-based strategies to treat breast cancer metastases by 1) defining the impact of NEDD9 expression on regulation of mesenchymal invasion in breast cancer cells, 2) deciphering the mechanism and characterizing the key downstream effectors of NEDD9-dependent signaling that contribute to breast cancer mesenchymal migration, and 3) determining the anti-metastatic therapeutic benefit of inhibiting both mesenchymal and amoeboid breast cancer cell movement in vitro and in vivo

Counseling while Black: A critical inquiry exploring the experiences of Black Master’s level counselors in non-academic, predominantly White, mental health settings

As the counseling profession has evolved to embrace multiculturalism, scant research has focused on examining how Black counselors in predominantly White settings navigate the social injustices of white supremacy and patriarchy. This dissertation project is a critical, dialogue-based study of Black, Master\u27s level counselors\u27 race and gender-related challenges in predominantly White, non-academic, mental health settings. It offers two primary contributions to existing empirical literature: a meta-theoretical understanding and a critical qualitative inquiry based on a methodological integration. The meta-theoretical understanding offered in this dissertation is grounded in a theoretical reconstruction of Critical Race Theory (Bell, 1980; Crenshaw, 1989; Delgado, 1984; Freeman, 1978), Glass Barriers Theory (Wingfield, 2009), and the concept of dueling consciousness (Kendi, 2019). The three research questions that guided this empirical investigation were: 1. What are the experiences of being a self-identified Black, Master’s level counselor in a predominantly White, non-academic, mental health setting? 2. What challenges and barriers related to race and gender, if any, are associated with the experiences of being a self-identified Black, Master’s level counseling in a predominantly White, non-academic, mental health setting? 3. How do self-identified Black, Master’s level counselors in predominantly White, non-academic, mental health settings respond to, cope with, and overcome the challenges and barriers related to race and gender in the workplace? Data were generated using semi-structured interviews and analyzed using an integration of Gilligan, Spencer, Weinberg, and Bertsch’s (2003) Listening Guide, a voice-centered relational approach, and Carspecken’s (1996) Critical Qualitative Methodology. Three main themes emerged: visibility problems resulting from participants’ membership to a group in the numerical minority; dueling consciousness, which manifested as participants vacillated between actively rejecting and adopting racist-sexist standards; and role encapsulation, the experience of being limited by the roles assigned to them without their consent, which was only experienced by female participants. This study presents an overarching interactive framework that demonstrates how participants’ meaning-making and engagement with White colleagues is driven by their desire to be treated as fully human within an often dehumanizing context

A new species of \u3cem\u3eKochius\u3c/em\u3e from Avra Valley, southern Arizona (Scorpiones: Vaejovidae)

A new scorpion species, Kochius colluvius sp. n. is described (Scorpiones: Vaejovidae). This small brown species is found in the Avra Valley near Tucson, Arizona, USA. It appears to be most similar to Kochius sonorae (Williams, 1971) and K. hirsuticauda (Banks, 1910). On all fingers examined, the fixed finger has 6 ID denticles and the movable finger has 7. There is no scalloping of the chela fingers. This species differs from all other vaejovids in Arizona by having a coarsely granulated exoskeleton

Neutrinos and Gamma Rays from Galaxy Clusters

The next generation of neutrino and gamma-ray detectors should provide new insights into the creation and propagation of high-energy protons within galaxy clusters, probing both the particle physics of cosmic rays interacting with the background medium and the mechanisms for high-energy particle production within the cluster. In this paper we examine the possible detection of gamma-rays (via the GLAST satellite) and neutrinos (via the ICECUBE and Auger experiments) from the Coma cluster of galaxies, as well as for the gamma-ray bright clusters Abell 85, 1758, and 1914. These three were selected from their possible association with unidentified EGRET sources, so it is not yet entirely certain that their gamma-rays are indeed produced diffusively within the intracluster medium, as opposed to AGNs. It is not obvious why these inconspicuous Abell-clusters should be the first to be seen in gamma-rays, but a possible reason is that all of them show direct evidence of recent or ongoing mergers. Their identification with the EGRET gamma-ray sources is also supported by the close correlation between their radio and (purported) gamma-ray fluxes. Under favorable conditions (including a proton spectral index of 2.5 in the case of Abell 85, and sim 2.3 for Coma, and Abell 1758 and 1914), we expect ICECUBE to make as many as 0.3 neutrino detections per year from the Coma cluster of galaxies, and as many as a few per year from the Abell clusters 85, 1758, and 1914. Also, Auger may detect as many as 2 events per decade at ~ EeV energies from these gamma-ray bright clusters.Comment: Accepted for publication in Ap

Consuming Lines of Difference: The Politics of Wealth and Poverty along the Color Line

Commentators on African American life have often focused on poverty, evaded African American wealth, and ignored the ways genteel affluence and impoverishment were constructed along turn-of-the-century color lines. Documentary research and archaeology at the Madam CJ Walker home in Indianapolis, Indiana illuminates how the continuum of wealth and poverty was defined and negotiated by one of African America’s wealthiest early 20th century entrepreneurs. The project provides an opportunity to compare the ways in which wealth was defined and experienced along the color line in the early 20th century and how such notions of Black affluence shaped racialized definitions of poverty and materialit

Liat1, an arginyltransferase-binding protein whose evolution among primates involved changes in the numbers of its 10-residue repeats

The arginyltransferase Ate1 is a component of the N-end rule pathway, which recognizes proteins containing N-terminal degradation signals called N-degrons, polyubiquitylates these proteins, and thereby causes their degradation by the proteasome. At least six isoforms of mouse Ate1 are produced through alternative splicing of Ate1 pre-mRNA. We identified a previously uncharacterized mouse protein, termed Liat1 (ligand of Ate1), that interacts with Ate1 but does not appear to be its arginylation substrate. Liat1 has a higher affinity for the isoforms Ate1^(1A7A) and Ate1^(1B7A). Liat1 stimulated the in vitro N-terminal arginylation of a model substrate by Ate1. All examined vertebrate and some invertebrate genomes encode proteins sequelogous (similar in sequence) to mouse Liat1. Sequelogs of Liat1 share a highly conserved ∼30-residue region that is shown here to be required for the binding of Liat1 to Ate1. We also identified non-Ate1 proteins that interact with Liat1. In contrast to Liat1 genes of nonprimate mammals, Liat1 genes of primates are subtelomeric, a location that tends to confer evolutionary instability on a gene. Remarkably, Liat1 proteins of some primates, from macaques to humans, contain tandem repeats of a 10-residue sequence, whereas Liat1 proteins of other mammals contain a single copy of this motif. Quantities of these repeats are, in general, different in Liat1 of different primates. For example, there are 1, 4, 13, 13, 17, and 17 repeats in the gibbon, gorilla, orangutan, bonobo, neanderthal, and human Liat1, respectively, suggesting that repeat number changes in this previously uncharacterized protein may contribute to evolution of primates

Feral swine \u3ci\u3eSus scrofa\u3c/i\u3e: a new threat to the remaining breeding wetlands of the Vulnerable reticulated flatwoods salamander \u3ci\u3eAmbystoma bishopi\u3c/i\u3e

Feral swine Sus scrofa have been implicated as a major threat to sensitive habitats and ecosystems as well as threatened wildlife. Nevertheless, direct and indirect impacts on threatened species (especially small, fossorial species) are not well documented. The decline of the U.S. federally endangered reticulated flatwoods salamander Ambystoma bishopi, categorized as Vulnerable on the IUCN Red List, has been rapid and there are few remaining breeding locations for this species. The flatwoods salamander depends on complex herbaceous vegetation in all life stages, including eggs, larvae and adults. Historically sets of hog tracks have been observed only occasionally in the vicinity of monitored reticulated flatwoods salamander breeding wetlands, and damage to the wetlands had never been recorded. However, during the autumn–winter breeding season of 2013-2014 we observed a large increase in hog sign, including extensive rooting damage, in known flatwoods salamander breeding wetlands. Our objective was to assess the amount of hog sign and damage in these wetlands and to take corrective management actions to curb additional impacts. Of 28 wetlands surveyed for hog sign, presence was recorded at 68%, and damage at 54%. Of the 11 sites known to be occupied by flatwoods salamanders in 2013-2014, 64% had presence, and 55% had damage. We found that regular monitoring of disturbance in wetland habitats was a valuable tool to determine when intervention was needed and to assess the effectiveness of intervention. Habitat damage caused by feral hogs poses a potentially serious threat to the salamanders, which needs to be mitigated using methods to control and exclude hogs from this sensitive habitat

Rethinking Committee Work in the Research Enterprise: The Case of Regenerative Gatekeeping

Committees touch nearly every facet in the science, technology, engineering, and mathematics research enterprise. However, the role of gatekeeping through committee work has received little attention in Earth and space sciences. We propose a novel concept called, “regenerative gatekeeping” to challenge institutional inertia, cultivate belonging, accessibility, justice, diversity, equity, and inclusion in committee work. Three examples, a hiring committee process, a seminar series innovation, and an awards committee, highlight the need to self-assess policies and practices, ask critical questions and engage in generative conflict. Rethinking committee work can activate distributed mechanisms needed to promote change

The relationship of social determinants and distress in newly diagnosed cancer patients

Patients with a new cancer diagnosis can experience distress when diagnosed. There are disparities in treatment of cancer patients based on social determinants, but minimal research exists on the relationship of those social determinants and distress after a new cancer diagnosis. Our goals were to determine the social determinants associated with distress after a new cancer diagnosis and determine the relationship of distress with outcome. Patients with a new cancer diagnosis at one institution from January 2019 to December 2020 were analyzed. Patients were given the National Comprehensive Cancer Network (NCCN) distress thermometer during their first visit. Demographics, tumor characteristics, clinical variables and survival were recorded. Patients were also asked to share specific factors that led to distress, including: (1) financial, (2) transportation, (3) childcare and (4) religious. A total of 916 patients returned distress thermometers. Mean age was 59.1 years. Females comprised 71.3 (653/916) percent of the cohort. On Dunn\u27s multiple comparison, the following factors were associated with increased distress level: female (p \u3c 0.01), ages 27 to 45 (p \u3c 0.01), uninsured (p \u3c 0.01) and unemployed (p \u3c 0.01). Patients with higher distress scores also experienced worse overall survival (p \u3c 0.05). Females, young patients, uninsured patients and unemployed patients experience more distress after a new cancer diagnosis. Increased distress is independently associated with worse overall survival. Social determinants can be used to predict which patients may require focused interventions to reduce distress after a new cancer diagnosis

From Spinning Silk to Spreading Saliva: Mouthpart Remodeling in Manduca sexta (Lepidoptera: Sphingidae)

As a model organism, the tobacco hornworm Manduca sexta (Linnaeus 1763) has contributed much to our knowledge of developmental processes in insects, and major developmental changes between different larval instars are generally well understood. Second and later instars of M. sexta do not produce silk, and their spinneret and accessory labial glands (=Lyonet’s glands), structures thought to be key players in silk production in other lepidopterans, are highly reduced. To our knowledge, mouthparts and labial gland morphology of the silk-producing first instar have never been described. In this study, we compared the mouthpart morphology and transcriptome profile of first and later instars of M. sexta to determine whether the loss of silk production correlates with changes in the structure of the spinneret and the labial glands, and with changes in expression of silk-related genes. We found that the first instar, unlike later instars, has a typical, silk-producing spinneret with a tube-like spigot and well developed Lyonet’s glands. Moreover, three known silk protein genes are highly expressed in the first instar but exhibit little to no expression in the embryo or later instars. Thus, the changes in morphology and gene expression presented here, coinciding with changes in larval behavior from silk production to saliva spreading, further our understanding of the developmental processes underlying this transition in this model organism