Supporting Inclusivity and Social Justice Literacy in Nursing Education Programs

Healthcare in the United States is not meeting the needs of its citizens. Inequality based on race and economics has been well documented in recent years. Nurses have the power to positively influence healthcare inequities and change the landscape of today’s healthcare system. Nursing education programs can be a catalyst for this change. Through the creation of supportive practices, nursing education programs can be instrumental in helping future nurses increase their awareness and understanding of culture, race, and social justice in healthcare

Visualizing mRNA Translation in situ in Single Cells

Translation of mRNA is tightly regulated in cells to ensure that proteins are synthesized at the right time, in the right location, and at appropriate levels. Single-molecule fluorescence in situ hybridization (smFISH) is a simple and widely used method to measure mRNA transcription through determining the abundance and localization of mRNAs in single cells. A comparable single-molecule in situ method to measure mRNA translation would enable a more complete understanding of gene regulation. In this thesis, we describe the development and characterization of a fluorescence assay to detect ribosome interactions with mRNA (FLARIM). The method adapts smFISH to visualize and characterize translation of single molecules of mRNA in fixed cells. To visualize ribosome-mRNA interactions, we use pairs of oligonucleotide probes that bind separately to ribosomes (via ribosomal RNA) and to the mRNA of interest, and that produce strong fluorescence signals via the hybridization chain reaction (HCR) when the probes are in close proximity. FLARIM does not require genetic manipulation, is applicable to practically any endogenous mRNA transcript, and provides both spatial and temporal information. We first characterize FLARIM in mouse fibroblast cells. We show that FLARIM is sensitive to changes in ribosome association with mRNA upon inhibition of global translation with puromycin. We also show that FLARIM detects changes in ribosome association with an mRNA whose translation is upregulated in response to increased concentrations of iron. Finally, we demonstrate FLARIM in mouse hippocampal neurons, in which local translation of mRNA in the neuronal processes is essential to cell growth and development. We first demonstrate FLARIM in neurons using probes for β-actin mRNA. We then show that FLARIM detects increased transcription and translation of activity regulated cytoskeletal protein (Arc) mRNA in response to neuronal activation with brain-derived neurotrophic factor (BDNF). We also compare the cellular distribution between the major microtubule-associated protein 2 (MAP2) mRNA isoforms, whose translation will be characterized in future FLARIM experiments. Overall, this work expands the capability of smFISH to study mRNA translation in addition to transcription, and it shows the utility of in situ translation analysis in characterizing single-cell gene expression.</p

A natural histone H2A variant lacking the Bub1 phosphorylation site and regulated depletion of centromeric histone CENP-A foster evolvability in Candida albicans.

Eukaryotes have evolved elaborate mechanisms to ensure that chromosomes segregate with high fidelity during mitosis and meiosis, and yet specific aneuploidies can be adaptive during environmental stress. Here, we identify a chromatin-based system required for inducible aneuploidy in a human pathogen. Candida albicans utilizes chromosome missegregation to acquire tolerance to antifungal drugs and for nonmeiotic ploidy reduction after mating. We discovered that the ancestor of C. albicans and 2 related pathogens evolved a variant of histone 2A (H2A) that lacks the conserved phosphorylation site for kinetochore-associated Bub1 kinase, a key regulator of chromosome segregation. Using engineered strains, we show that the relative gene dosage of this variant versus canonical H2A controls the fidelity of chromosome segregation and the rate of acquisition of tolerance to antifungal drugs via aneuploidy. Furthermore, whole-genome chromatin precipitation analysis reveals that Centromere Protein A/ Centromeric Histone H3-like Protein (CENP-A/Cse4), a centromeric histone H3 variant that forms the platform of the eukaryotic kinetochore, is depleted from tetraploid-mating products relative to diploid parents and is virtually eliminated from cells exposed to aneuploidy-promoting cues. We conclude that genetically programmed and environmentally induced changes in chromatin can confer the capacity for enhanced evolvability via chromosome missegregation

Treatment Options for Paediatric Anaplastic Large Cell Lymphoma (ALCL): Current Standard and beyond.

Anaplastic Lymphoma Kinase (ALK)-positive Anaplastic Large Cell Lymphoma (ALCL), remains one of the most curable cancers in the paediatric setting; multi-agent chemotherapy cures approximately 65-90% of patients. Over the last two decades, major efforts have focused on improving the survival rate by intensification of combination chemotherapy regimens and employing stem cell transplantation for chemotherapy-resistant patients. More recently, several new and 'renewed' agents have offered the opportunity for a change in the paradigm for the management of both chemo-sensitive and chemo-resistant forms of ALCL. The development of ALK inhibitors following the identification of the EML4-ALK fusion gene in Non-Small Cell Lung Cancer (NSCLC) has opened new possibilities for ALK-positive ALCL. The uniform expression of CD30 on the cell surface of ALCL has given the opportunity for anti-CD30 antibody therapy. The re-evaluation of vinblastine, which has shown remarkable activity as a single agent even in the face of relapsed disease, has led to the consideration of a revised approach to frontline therapy. The advent of immune therapies such as checkpoint inhibition has provided another option for the treatment of ALCL. In fact, the number of potential new agents now presents a real challenge to the clinical community that must prioritise those thought to offer the most promise for the future. In this review, we will focus on the current status of paediatric ALCL therapy, explore how new and 'renewed' agents are re-shaping the therapeutic landscape for ALCL, and identify the strategies being employed in the next generation of clinical trials

Sleep Health Education to Promote Public Health: Attitudes and Desired Learning Goals among Social Work Students

Social workers are often front line behavioral health providers for underserved populations, many of whom experience sleep disturbances. Inadequate sleep presents a public health challenge and is associated with many adverse physical health and mental health consequences. Social workers are uniquely positioned to promote sleep health among individuals experiencing health inequities. However, sleep is rarely included as part of the curricula in social work programs in the U.S. We conducted qualitative formative research to investigate social work students’ perceptions of sleep education and desired sleep learning objectives. Twenty-five social work students were recruited via a listserv e-mail to participate in one of three focus groups. Participants believed sleep education could be beneficial in promoting client health and well-being. Desired learning goals included: (1) the importance of sleep; (2) identify symptoms of sleep deprivation and sleep disorders; (3) environmental and lifestyle factors that impact sleep; (4) behaviors to promote optimal sleep; and (5) sleep health as it relates to special populations (e.g., homelessness, substance using). Social work students expressed a desire to aquire knowledge on sleep health promotion as part of the social work curricula. Sleep education could be of considerable relevance to social work students, practitioners, and the clients they serve

Resistance to Targeted Agents Used to Treat Paediatric ALK-Positive ALCL.

Non-Hodgkin lymphoma (NHL) is the third most common malignancy diagnosed in children. The vast majority of paediatric NHL are either Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), anaplastic large cell lymphoma (ALCL), or lymphoblastic lymphoma (LL). Multi-agent chemotherapy is used to treat all of these types of NHL, and survival is over 90% but the chemotherapy regimens are intensive, and outcomes are generally poor if relapse occurs. Therefore, targeted therapies are of interest as potential solutions to these problems. However, the major problem with all targeted agents is the development of resistance. Mechanisms of resistance are not well understood, but increased knowledge will facilitate optimal management strategies through improving our understanding of when to select each targeted agent, and when a combinatorial approach may be helpful. This review summarises currently available knowledge regarding resistance to targeted therapies used in paediatric anaplastic lymphoma kinase (ALK)-positive ALCL. Specifically, we outline where gaps in knowledge exist, and further investigation is required in order to find a solution to the clinical problem of drug resistance in ALCL

Growing in generosity?:The effects of giving magnitude, target, and audience on the neural signature of giving in adolescence

Giving is essential for forming and maintaining social relationships, which is an important developmental task for adolescents. This pre-registered fMRI study investigated behavioral and neural correlates of adolescents’ (N = 128, ages 9 – 19 years) small versus large size giving in different social contexts related to target (i.e., giving to a friend or unfamiliar peer) and peer presence (i.e., anonymous versus audience giving). Participants gave more in the small size than large size condition, more to friends than to unfamiliar peers, and more in the audience compared to anonymous condition. Giving very small or large amounts was associated with increased activity in the medial prefrontal cortex (mPFC) and anterior insula (AI), and older adolescents showed increased lateral and anterior PFC activation for small size giving. We observed activity in the intraparietal cortex (IPL), dorsolateral prefrontal cortex, and AI for giving to friends, but no age-related differences in this activity. Behaviorally, in contrast, we observed that older adolescents differentiated more in giving between friends and unfamiliar peers. Finally, we observed interactions between peer presence and target in the AI, and between giving magnitude and target in the precuneus. Together, findings reveal higher context-dependency of giving and more lateral PFC activity for small versus large giving in older adolescents

Engaging Teachers and Students in STEM Instruction through Service-Learning

GreenSTEM at VCU integrates science, technology, engineering and math (STEM) education with a focus on energy and the environment using service-learning techniques for middle school science, mathematics and technology teachers