Functional analysis of DcpS as a candidate cutaneous squamous cell carcinoma susceptibility gene

DCPS is a candidate cutaneous squamous cell carcinoma (SCC) susceptibility gene as determined by allelic imbalance mapping of paired SCC and genomic blood DNA samples. DCPS shows no protein expression in 23% of human SCCs on a tissue microarray, and reduced protein expression in another 30%. This is in contrast to strong staining for DCPS in 100% of normal tissue samples. DCPS, a decapping scavenger enzyme, influences the pool of available cap-binding proteins and, in turn, impacts aspects of mRNA metabolism like pre-mRNA splicing and decay. The hypothesis driving this research is that DCPS acts as a tumor suppressor. To test this hypothesis, functional effects of increasing and decreasing expression of DcpS in a mouse keratinocyte cell line have been studied. First intron splicing and exon skipping is enhanced in DcpS overexpression cell lines, while splicing of the second intron is not affected by DcpS expression. DcpS knockdown cell lines were found to have more stable mRNA compared to a control cell line. DcpS knockdown cell lines exhibit less growth than normal and overexpression cell lines. Cell migration is not affected by DcpS expression. DcpS knockdown cell lines exhibit more apoptosis than normal and overexpression cell lines. Finally, there is a greater percentage of cells in the S and G2-M phases of the cell cycle in DcpS knockdown cell lines compared to mock and overexpression cell lines. From these studies it appears that while DcpS may affect mRNA splicing and stability, decreased levels of DcpS do not result in a cancer phenotype. Rather, decreased levels of DcpS seem to lead to an anti-tumorigenic phenotype. Future directions may include examining the effect of UV radiation on these phenotypes and determining other proteins with which DcpS interacts.Pelotonia Undergraduate Research FellowshipSchool of Allied Medical Professions ScholarshipA one-year embargo was granted for this item

Monastic Teaching and Metacognition

Each new student is thrust into the unknown of a different situation. Kelsey Gray... explores the best way to adapt to a rapidly changing environment

Virtual EQ – the talent differentiator in 2020?

In an increasingly competitive, globalised world, knowledge-intensive industries/ services are seen as engines for success. Key to this marketplace is a growing army of ‘talent’ i.e. skilled and dedicated knowledge workers. These knowledge workers engage in non-routine problem solving through combining convergent, divergent and creative thinking across organizational and company boundaries - a process often facilitated though the internet and social media, consequently forming networks of expertise. For knowledge workers, sharing their learning with others through communities of practice embedded in new information media becomes an important element of their personal identity and the creation of their individual brand or e-social reputation. Part of the new knowledge/skills needed for this process becomes not only emotional intelligence (being attuned to the emotional needs of others) but being able to do this within and through new media, thus the emergence of virtual emotional intelligence (EQ). Our views of current research found that HRD practitioners in 2020 might need to consider Virtual EQ as part of their talent portfolio. However it seems that new technology has created strategies for capturing and managing knowledge that are readily duplicated and that a talent differentiator in 2020 might simply be the ability and willingness to learn

The Emory-Tibet Science Initiative: Rethinking Cross-Cultural Science and Teaching

The Emory-Tibet Science Initiative was founded when the Dalai Lama invited Emory to develop and teach a comprehensive curriculum in modern science to Tibetan Buddhist monks and nuns. The project was built to grow and nurture a two-way exchange between complementary systems of knowledge. In the 10 years since the first days of the pilot, the interactions between people and places and the scientific and learning processes have served as a platform for exploring teaching across cultures and enriching approaches to teaching and science more generally. As a result of these interactions, we expand our definition of inclusivity in the classroom and the practice of science, emphasize connections and tensions between science and other systems of knowledge, and create space for student and instructor reflection and learning. The next phase of the project will engage students in research projects as tools for learning and as a means to contribute knowledge to the project and the larger science education community

Hygiene of Hand and Mind During the Pandemic

Making handwashing a meditative practice can help us focus on humanity’s interconnectedness with the environment

Skeletal Evidence for Leprosy in India by the Second Millenium B.C.

Leprosy is a chronic infectious disease caused by _Mycobacterium leprae_ that affects almost 500,000 people worldwide^1^. The timing of first infection, geographic origin, and pattern of transmission of the disease are unknown^1-3^. Comparative genomics research has recently suggested _M. leprae_ evolved in East Africa or South Asia before spreading to Europe and the rest of the World^4-5^. The earliest accepted textual evidence indicates that leprosy existed in India by at least 600 B.C. and was known in Europe by 400 B.C.^6-7^. The earliest skeletal evidence was dated 300-200 B.C. in Egypt^8^ and Thailand^9^. Here, we report the presence of lepromatous leprosy in skeletal remains from Balathal, a Chalcolithic site (2300-1550 B.C.) in India^10-11^. A middle aged adult male skeleton demonstrates manifestations of facies leprosa and rhinomaxillary syndrome, degenerative joint disease, infectious involvement of the tibia (periostitis), and injury to the peripheral skeleton, often the result of skin anaesthesia. Paleopathological analysis indicates that lepromatous leprosy was present in India by 1800 B.C., a result which supports some translations of the Atharva Veda that reference leprosy and its treatment in hymns composed before the first millennium B.C.^12^. The presence of leprosy in Chalcolithic India suggests _M. leprae_ may have been transmitted during the second or third millennium B.C., at a time when there was substantial interaction between South Asia, West Asia, and Northeastern Africa^13^. This evidence should be impetus to look for additional skeletal and molecular evidence of leprosy in human remains from this time period in India and Africa to confirm the origin of the disease

Survival Motor Neuron protein interaction partners in Drosophila melanogster

Spinal Muscular Atrophy (SMA) is a neuromuscular disorder that results from biallelic loss-of-function mutations in the human survival motor neuron 1 (SMN1) gene. Tissue-specific and housekeeping functions have been ascribed to SMN; however, their relevance to SMA pathology is not well understood. We generated transgenic Drosophila melanogaster that express only flag-tagged wild-type SMN. Our objective is to characterize novel protein-protein interactions of SMN. We collected embryos and analyzed Flag-purified lysates by mass spectrometry. We identified Flag-SMN along with other known interactors such as the Sm proteins and the Gemins. We also identified Slmb, SkpA, and Cullin 1 as being highly enriched in Flag-SMN samples as compared to the control sample. Together, these proteins comprise the SCFSlmb E3 ubiquitin ligase. These interactions were verified in Drosophila S2 cells and human cells. In vitro experiments revealed Slmb and SMN can directly interact. Identification of a putative Slmb degron in the self-oligomerization domain of SMN led us to generate a serine to alanine mutation that stabilizes full length and truncated SMN, with strongest effects on SMN with poor self-oligomerization capability. This same point mutation decreases SMN’s interaction with Slmb, demonstrating the putative Slmb degron is indeed mediating degradation of SMN. Finally, expression of truncated SMN stabilized by the mutation modifies viability of a mild SMA mouse model. We identified additional protein interactions of SMN with CG2941, nucleosome assembly protein 1 (Nap1), and Bendless (Ben). Each of these interactions was verified in cell culture or using antibodies generated specifically for the protein of interest. Preliminary investigation of CG2941 has revealed it is an essential gene that produces protein that localizes to both the nucleus and the cytoplasm. We have examined SMN protein interactions in the context of developing Drosophila melanogaster embryos, with follow-up studies in mouse, and human systems. When SMN is unable to self-oligomerize, the Slmb degron is highly accessible, and thus SMN is degraded. SMN also interacts with previously unknown partners that may be relevant to SMA pathology. This work elucidates a disease-relevant mechanism where SMN levels are regulated by self-multimerization and identifies candidate proteins for further study of the molecular mechanisms underlying SMA.Doctor of Philosoph

Quantitative Phenotyping of Brain Endothelial Cell-Cell Junctions for Physiological and Pathophysiological Applications

The integrity of endothelial cell-cell junctions is required for the maintenance of normal physiological processes. The expression of junctional proteins is particularly important in the endothelial cells of the blood-brain barrier (BBB), the cellular unit that protects the brain via regulated transport between the peripheral blood and the central nervous system. Dysfunction of the BBB is linked with decreased junctional protein localization and is implicated in several diseases including Alzheimer’s disease and multiple sclerosis. On the other hand, the tight junctions of the BBB impede the delivery of medications targeting the brain. Therefore, understanding the key players driving junction stability could hold significant promise for therapeutic discovery and drug delivery applications. Despite this, the mechanisms underlying junction disruption aren’t fully understood. While several studies have linked different junction protein patterns with altered barrier function, the quantification of this parameter remains limited due to the lack of efficient measurement techniques. Here, we aimed to investigate the influence of junction phenotype on brain endothelial barrier properties. To accomplish this, we developed the Junction Analyzer Program (JAnaP) to semi-automatically calculate edge-localization protein phenotypes. Application of the JAnaP to measure the junctional proteins VE-cadherin and ZO-1 in different physiological and pathophysiological conditions revealed that discontinuous junctions contribute more to barrier permeability compared to continuous, linear junctions. Continuous junctions were also increased in endothelial cells with decreased contractility, mediated biochemically or by lowered subendothelial matrix stiffness. Finally, breast cancer cell secreted factors increased immature adherens junctions, likely through VEGF signaling, but minimally affected tight junction presentation. Thus far, the development and application of the JAnaP has revealed insights into the effects of junction patterns on barrier function, the mechanobiology of endothelial cells, and the response of brain endothelial cells to biochemical cues involved in breast cancer metastasis. Understanding the conditions driving altered junction presentation, and the resultant effects on barrier integrity, could lead to the development of therapeutics capable of traversing the BBB for delivery to the brain or for diseases associated with BBB dysfunction. Future use of this program holds significant potential for physiological and pathophysiological study in various endothelial and epithelial cell systems

SMN - A chaperone for nuclear RNP social occasions?

Survival Motor Neuron (SMN) protein localizes to both the nucleus and the cytoplasm. Cytoplasmic SMN is diffusely localized in large oligomeric complexes with core member proteins, called Gemins. Biochemical and cell biological studies have demonstrated that the SMN complex is required for the cytoplasmic assembly and nuclear transport of Sm-class ribonucleoproteins (RNPs). Nuclear SMN accumulates with spliceosomal small nuclear (sn)RNPs in Cajal bodies, sub-domains involved in multiple facets of snRNP maturation. Thus, the SMN complex forms stable associations with both nuclear and cytoplasmic snRNPs, and plays a critical role in their biogenesis. In this review, we focus on potential functions of the nuclear SMN complex, with particular emphasis on its role within the Cajal body

Development of a \u3cem\u3eMen’s Health\u3c/em\u3e Course for First-Year Undergraduates Using Culturally Responsive Teaching Strategies

Purpose A novel first-year experience course was developed using culturally responsive teaching strategies at an undergraduate liberal arts college in the southeastern USA to promote health advocacy and to provide students with an overview of male health. The course focuses on the biological, sociocultural, economic and gender influences that shape men\u27s health beliefs and practices. It also emphasizes health disparities in the USA among Black/African American men compared to other racial groups and intervention strategies to improve health outcomes. Design/methodology/approach The lecture and laboratory components of the course were designed as a blended learning environment with a modified flipped class model. Culturally relevant strategies guided the course design with three focus domains: academic success, cultural competence and sociopolitical consciousness. A community engagement model and service-learning activities were also incorporated in the design. The authors used course grades to gauge learning and implemented a survey to assess students\u27 perception of the knowledge gained in three realms: men\u27s health, health sciences and physical sciences. Findings This report describes the course design, highlights the value of using culturally responsive teaching strategies and service-learning projects to encourage students\u27 active learning. Course activity examples are discussed with student responses. The authors found that students\u27 perception of their knowledge in men\u27s health, health sciences and physical sciences increased and the students performed well in the course. Originality/value This is one of few biology courses in the nation that intentionally focuses on the unique health challenges of Black men, while empowering college students to develop culturally competent strategies to improve their health outcomes. The findings suggest that the students learned the material and that their perceived knowledge on men\u27s health increased. The authors urge other academic institutions and healthcare providers to consider implementation of similar courses in an effort to enhance male health equity