Digital Commons Network^™

Patterned Magnetic And Plasmonic Nanostructures In Microfluidics For Extracellular Vesicle Screening And Drug Loading, John H. Molinski

Dartmouth College Ph.D Dissertations

Extracellular vesicles (EVs), once dismissed as shuttles for cellular waste, have emerged as vital nanoscale biomolecules, facilitating intercellular communication through transfer of host-cell specific molecular cargo. Tumor-derived EVs, released by cancer cells, hold potential as diagnostic biomolecules due to their links to cancer cells, abundance within biofluids, and potential for direct extraction and detection. More broadly, EVs from a wide array of cellular origins have been explored as therapeutic carriers, stemming from their innate function as cargo carriers, high biocompatibility, and their ability to evade immune detection. However, harnessing EVs for diagnostic or therapeutic applications necessitates efficient isolation, purification, and …

Alpha 7 Nicotinic Acetylcholine Receptor Expression In The Hippocampus Of Patients With Schizophrenia, Shruti Varshney, Ananya Nethikunta, Minjal Patel, Mary Kosciuk, Randel L. Swanson, Venkat Venkataraman, Robert Nagele, Eric Goldwaser, Nimish K. Acharya

Rowan-Virtua Research Day

Background: Schizophrenia (SZ) is a heterogenous psychiatric condition characterized by disruptions in cognition, social activity, affect, and perception often associated with a varied combination of positive and negative symptoms. The pathophysiology behind SZ remains poorly elucidated. Earlier reports have cited the importance of the alpha 7 nicotinic acetylcholine receptors (α7nAChR) in the hippocampus and the receptor’s association with auditory sensory gating and cognitive function. Specifically, variations in the expression and functionality of α7nAChR can be linked to auditory hallucinations experienced by patients with SZ and several therapies have been researched that target α7nAChRs. However, there are very few primary research …

Neoadjuvant Versus Adjuvant Therapy For Stage Iiib-Iiid Melanoma, Bhumik Patel, Sangnya Upadhyaya

Rowan-Virtua Research Day

The treatment landscape for advanced stage melanoma is rapidly evolving due to advancements in our understanding of melanoma biology and the emergence of novel therapies. This necessitates a comprehensive review to guide clinicians in adopting evidence based and patient centric approaches to treat stage IIIB-IIID melanoma. A literature review was conducted to synthesize current information on the most optimal treatment available. Data available from different clinical trials found that neoadjuvant therapy was a more effective treatment compared to adjuvant therapies alone. Furthermore, neoadjuvant therapy with combination therapy was more efficacious in producing a complete pathological response compared to monotherapy. A …

Cut The Pressure: Blood Pressure Screening In A Community Based Setting, Harold Kareem Knight Jr., Katharine Milani

Rowan-Virtua Research Day

This study addresses the pressing issue of cardiovascular health disparities in African American males through community-based interventions, specifically blood pressure screenings and surveys conducted in a local barbershop setting. Despite a preference among participants for clinical settings, an overwhelming 97.7% expressed high comfort levels in the community-based environment, highlighting the importance of culturally sensitive approaches in healthcare delivery. With 92.5% indicating willingness to return for future screenings, the study underscores the efficacy of non-traditional settings in fostering healthcare engagement. Findings suggest the potential for broader impact through scalable, community-centric initiatives, offering promising avenues for improving health outcomes in underserved populations.

Michigan Water Supply: Analysis Of Health Violations, Gabriela Guzman Reyes '24

Biology Student Scholarship

The presence of toxins in water sources poses a significant public health challenge. In Michigan, this issue has garnered widespread attention due to its adverse effects on human health and well-being. The contaminants found in water, including but not limited to lead, industrial pollutants, and agricultural runoff, stem from a variety of sources such as aging infrastructure, industrial activities, and agricultural practices. News articles and Government officials have reported the adverse affects and impact toxin exposure has on Michigan residents. However, there is little research examining the relationship between water quality violations and socioeconomic factors like poverty levels. I predict …

The Effect Of Integrated Pest Management On Nutrition Of Bee Collected Pollen, Kaitlyn Bresnahan '25

Biology Student Scholarship

Honey bees are the world’s most commercially valuable pollinators, and they face many threats. The greatest challenge facing honey bees is Varroa mites, parasitic mites that feed on bees’ fat bodies, killing bees and spreading diseases. While chemical treatments are available to stop the spread of mites, these treatments are insecticides, which are not ideal to put in a hive of insects. A popular organic method of mite management is using drone comb. Drone brood is preferentially chosen by mites for ovipositing and development because of its larger size and longer development time, so removing drone brood can drastically reduce …

Interspecific Venom Variation Among Three Shades Of Aphonopelma Tarantulas: A. Gabeli, A. Hentzi, And A. Anax, Jorjia Elmore

Honors Theses

Phenotypic variation is a common occurrence throughout the animal kingdom and can occur both interspecifically and intraspecifically. Interspecific variation evolves in response to differential selection between species whereas intraspecific variation is commonly expressed as sex-based or population-based differences. Both interspecific and intraspecific phenotypic differences occur frequently in venomous species including arachnids, and can often result in differences in venom yield, potency, and protein. The North American tarantulas (Theraphosidae: Aphonopelma), include approximately 35 species and little is known about their venom. To test for interspecific and intraspecific venom variation, we collected individuals from three species and generated proteomic profiles and Illumina …

Serum Antibodies To Periodontal Pathogens And Anti-Malondialdehyde-Acetaldehyde: Potential Role In The Interrelationship Between The Periodontium And Rheumatoid Arthritis, Joyce Lee

Theses & Dissertations

Objectives: Study 1 – To quantify associations between anti-Porphyromonas gingivalis, anti-Prevotella intermedia, and anti-Fusobacterium nucleatum serum antibody concentrations and risk of developing rheumatoid arthritis (RA). Study 2 – To test if periodontal clinical measures, alveolar bone loss (ABL), and the aforementioned serum anti-bacterial antibody concentrations are associated with anti-malondialdehyde-acetaldehyde (MAA) serum antibody concentrations.

Methods: Study 1 – Serum samples pre- and post- RA diagnosis (n=214 cases, 210 matched controls) from the U.S. Department of Defense Serum Repository were utilized to compare timing of elevations of anti-bacterial antibody concentrations relative to RA diagnosis and associations …

Cytotoxic Sigma-2 Ligands Trigger Cancer Cell Death Via Cholesterol-Induced-Er-Stress, Rony Takchi, Bethany C Prudner, Qingqing Gong, Takaomi Hagi, Kenneth F Newcomer, Linda X Jin, Suwanna Vangveravong, Brian A Van Tine, William G Hawkins, Dirk Spitzer

2020-Current year OA Pubs

Sigma-2-ligands (S2L) are characterized by high binding affinities to their cognate sigma-2 receptor, overexpressed in rapidly proliferating tumor cells. As such, S2L were developed as imaging probes (ISO1) or as cancer therapeutics, alone (SV119 [C6], SW43 [C10]) and as delivery vehicles for cytotoxic drug cargoes (C6-Erastin, C10-SMAC). However, the exact mechanism of S2L-induced cytotoxicity remains to be fully elucidated. A series of high-affinity S2L were evaluated regarding their cytotoxicity profiles across cancer cell lines. While C6 and C10 displayed distinct cytotoxicities, C0 and ISO1 were essentially non-toxic. Confocal microscopy and lipidomics analysis in cellular and mouse models revealed that C10 …

Awareness In The Brain: A Mechanistic And Descriptive Account, Jacob Fried, Roy Pereira

Honors Thesis

An exploration of the different aspects of consciousness and their biological underpinnings, followed by a review of existing theories of awareness in the brain and a critique of the existing research. This paper conducts a review and critique of the contemporary research and finds that no existing theory currently offers an account of awareness in the brain that is both mechanistic and descriptive in nature. Thus, this paper proposes a new theory of the process of awareness in the brain, wherein Attention Schema Theory is considered as the mechanism of awareness and Global Neuronal Workspace Theory as its nature.

Growth From Within, Raevenne Zackery

Graduate Artistry Projects and Performances

My intersection of art and biology and the body of work that I created transcends who I am as a person not only an artist, but my appreciation in the love for science. Specifically, nature impacts the entire world. The simplicity of thinking about nature is the cycle of life I found myself, beginning a career as a biology major, wanting to do biomedical research with life developing vitamins and skin care, but ideally, I wanted to be different and every possible way the genre of display nature or the impact of an environment shows more complexity to the way …

Fiddler Crab Gut Microbiomes As An Indicator For Eutrophication Due To Waste-Water Contamination In Estuaries, Madison L. Geraci

Honors Theses

Estuaries are unique biogeochemical zones in coastal systems that provide a myriad of ecological functions: providing habitat for critically important fishery species, diverse species of plants and animals, and contributing to nutrient cycling. Estuaries are vulnerable to anthropogenic stressors as they are intersections between marine and terrestrial communities and are often the hotspot of coastal development and activity. Estuarine sediments act as repositories for anthropogenic contaminants, including excess nutrient runoffs and waste-water pollution that can cause states of eutrophication. Microorganisms are sensitive to these environmental changes, presenting a unique opportunity of being useful bioindicators of environmental stress. Isolating microorganisms from …

The Effect Of Diabetes Mellitus On Differentiation Of Mesenchymal Stem Cells Into Insulin-Producing Cells, Mohamed M. Kamal, Omar I. Badr, Shohda A. El-Maraghy, Heba R. Ghaiad

Pharmacy

Background

Diabetes mellitus (DM) is a global epidemic with increasing incidences. DM is a metabolic disease associated with chronic hyperglycemia. Aside from conventional treatments, there is no clinically approved cure for DM up till now. Differentiating mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) is a promising approach for curing DM. Our study was conducted to investigate the effect of DM on MSCs differentiation into IPCs in vivo and in vitro.

Methods

We isolated adipose-derived mesenchymal stem cells (Ad-MSCs) from the epididymal fat of normal and STZ-induced diabetic Sprague–Dawley male rats. Afterwards, the in vitro differentiation of normal-Ad-MSCs (N-Ad-MSCs) and …

Using Genome And Transcriptome Data From African-Ancestry Female Participants To Identify Putative Breast Cancer Susceptibility Genes, Jie Ping, Guochong Jia, Qiuyin Cai, Xingyi Guo, Ran Tao, Christine Ambrosone, Dezheng Huo, Stefan Ambs, Mollie E Barnard, Yu Chen, Montserrat Garcia-Closas, Jian Gu, Jennifer J Hu, Esther M John, Christopher I Li, Katherine Nathanson, Barbara Nemesure, Olufunmilayo I Olopade, Tuya Pal, Michael F Press, Maureen Sanderson, Dale P Sandler, Toshio Yoshimatsu, Prisca O Adejumo, Thomas Ahearn, Abenaa M Brewster, Anselm J M Hennis, Timothy Makumbi, Paul Ndom, Katie M O'Brien, Andrew F Olshan, Mojisola M Oluwasanu, Sonya Reid, Song Yao, Ebonee N Butler, Maosheng Huang, Atara Ntekim, Bingshan Li, Melissa A Troester, Julie R Palmer, Christopher A Haiman, Jirong Long, Wei Zheng

Faculty, Staff and Student Publications

African-ancestry (AA) participants are underrepresented in genetics research. Here, we conducted a transcriptome-wide association study (TWAS) in AA female participants to identify putative breast cancer susceptibility genes. We built genetic models to predict levels of gene expression, exon junction, and 3' UTR alternative polyadenylation using genomic and transcriptomic data generated in normal breast tissues from 150 AA participants and then used these models to perform association analyses using genomic data from 18,034 cases and 22,104 controls. At Bonferroni-corrected P < 0.05, we identified six genes associated with breast cancer risk, including four genes not previously reported (CTD-3080P12.3, EN1, LINC01956 and NUP210L). Most of these genes showed a stronger association with risk of estrogen-receptor (ER) negative or triple-negative than ER-positive breast cancer. We also replicated the associations with 29 genes reported in previous TWAS at P < 0.05 (one-sided), providing further support for an association of these genes with breast cancer risk. Our study sheds new light on the genetic basis of breast cancer and highlights the value of conducting research in AA populations.

Kras G12c Inhibitor Combination Therapies: Current Evidence And Challenge, Hirotaka Miyashita, Shumei Kato, David S Hong

Faculty, Staff and Student Publications

Although KRAS G12C inhibitors have proven that KRAS is a "druggable" target of cancer, KRAS G12C inhibitor monotherapies have demonstrated limited clinical efficacy due to primary and acquired resistance mechanisms. Multiple combinations of KRAS G12C inhibitors with other targeted therapies, such as RTK, SHP2, and MEK inhibitors, have been investigated in clinical trials to overcome the resistance. They have demonstrated promising efficacy especially by combining KRAS G12C and EGFR inhibitors for KRAS G12C-mutated colorectal cancer. Many clinical trials of combinations of KRAS G12C inhibitors with other targeted therapies, such as SOS1, ERK, CDK4/6, and wild-type RAS, are ongoing. Furthermore, preclinical …

Melting Premenstrual Dysphoric Disorder/ Premenstrual Exacerbation Symptoms With Metalsmithing: A Group Process, Maureen Bella Russo

Art Therapy Counseling Final Research Projects

People experiencing Premenstrual Dysphoric Disorder/Premenstrual Exacerbation, PMDD/PME, frequently live with debilitating symptoms that can arrest their daily life functions (Barker-Smith, 2020). Finding art to process and transform painful emotions that align with PMDD/PME hormonal depression/anxiety, may assist in supporting people to keep choosing life, especially when these art practices involve group settings and community artmaking (Phillips & Rosal, 1989; Robb, 2022). Metalsmithing requires significant cognitive awareness and promotes mind/body connections in its elemental art form (Carlson, 2015). This proposal outlines a group process involving 8-12 people who will receive a beginner’s metalsmithing, 12-week studio art program at Hyde Park Arts …

Characterization Of The Potential Of Mouse Mammary Tumor Virus (Mmtv) To Disrupt Mammary Epithelial Cell Gene Expression And Its Consequences, Neena G. Panicker

Thesis/ Dissertation Defenses

The mouse mammary tumor virus (MMTV) is a betaretrovirus known to induce breast cancer in mice. Unlike most other tumorigenic retroviruses that target hematopoietic cells, MMTV primarily targets mammary epithelial cells for infection and transformation. This makes it a valuable model for studying human breast cancer, which also originates from mammary epithelial cells. MMTV is transmitted through milk, with the highest expression occurring in lactating mammary glands due to the mammary gland enhancer and hormone-responsive elements (HREs) in its promoter. However, not much is known about how MMTV affects these cells at the molecular level. Since elevated hormonal induction during …

Identification Of Compounds That Cause Axonal Dieback Without Cytotoxicity In Dorsal Root Ganglia Explants And Intervertebral Disc Cells With Potential To Treat Pain Via Denervation, Fei San Lee, Uyen N. Nguyen, Eliza J. Munns, Rebecca A. Wachs

Department of Agricultural and Biological Systems Engineering: Faculty Publications

Low back pain, knee osteoarthritis, and cancer patients suffer from chronic pain. Aberrant nerve growth into intervertebral disc, knee, and tumors, are common pathologies that lead to these chronic pain conditions. Axonal dieback induced by capsaicin (Caps) denervation has been FDA-approved to treat painful neuropathies and knee osteoarthritis but with shortterm efficacy and discomfort. Herein, we propose to evaluate pyridoxine (Pyr), vincristine sulfate (Vcr) and ionomycin (Imy) as axonal dieback compounds for denervation with potential to alleviate pain. Previous literature suggests Pyr, Vcr, and Imy can cause undesired axonal degeneration, but no previous work has evaluated axonal dieback and cytotoxicity …

Traditional Dowry In Repressing Papuan Women’S Political Representation Jayapura City Legislative 2014-2019, Ferinandus Leonardo Snanfi

Jurnal Wacana Politik

This research investigated the impact of traditional dowry payments on the low political representation of indigenous Papuan women in the Jayapura City legislature from 2014 to 2019. Despite the election of four indigenous Papuan women to the Jayapura City legislature in 2014, there remains a significant gap in representation. This qualitative research gathered data through interviews with 30 respondents, including seven influential community figures, seven husbands of indigenous Papuan women, six Papuan students, two lecturers, three members of political parties, two female Papuan legislators, one representative from the General Election Commission, one member of the Papuan People’s Council, and the …

Tsyn-Seq: A T-Cell Synapse-Based Antigen Identification Platform, Yimei Jin, Takahiko Miyama, Alexandria Brown, Tomo Hayase, Xingzhi Song, Anand K Singh, Licai Huang, Ivonne I Flores, Lauren K Mcdaniel, Israel Glover, Taylor M Halsey, Rishika Prasad, Valerie Chapa, Saira Ahmed, Jianhua Zhang, Kunal Rai, Christine B Peterson, Gregory Lizee, Jennifer Karmouch, Eiko Hayase, Jeffrey J Molldrem, Chia-Chi Chang, Wen-Bin Tsai, Robert R Jenq

Faculty, Staff and Student Publications

Tools for genome-wide rapid identification of peptide-major histocompatibility complex targets of T-cell receptors (TCR) are not yet universally available. We present a new antigen screening method, the T-synapse (Tsyn) reporter system, which includes antigen-presenting cells (APC) with a Fas-inducible NF-κB reporter and T cells with a nuclear factor of activated T cells (NFAT) reporter. To functionally screen for target antigens from a cDNA library, productively interacting T cell-APC aggregates were detected by dual-reporter activity and enriched by flow sorting followed by antigen identification quantified by deep sequencing (Tsyn-seq). When applied to a previously characterized TCR specific for the E7 antigen …

Fam86a Methylation Of Eef2 Links Mrna Translation Elongation To Tumorigenesis, Joel William Francis, Simone Hausmann, Sabeen Ikram, Kunlun Yin, Robert Mealey-Farr, Natasha Mahealani Flores, Annie Truc Trinh, Tourkian Chasan, Julia Thompson, Pawel Karol Mazur, Or Gozani

Faculty, Staff and Student Publications

eEF2 post-translational modifications (PTMs) can profoundly affect mRNA translation dynamics. However, the physiologic function of eEF2K525 trimethylation (eEF2K525me3), a PTM catalyzed by the enzyme FAM86A, is unknown. Here, we find that FAM86A methylation of eEF2 regulates nascent elongation to promote protein synthesis and lung adenocarcinoma (LUAD) pathogenesis. The principal physiologic substrate of FAM86A is eEF2, with K525me3 modeled to facilitate productive eEF2-ribosome engagement during translocation. FAM86A depletion in LUAD cells causes 80S monosome accumulation and mRNA translation inhibition. FAM86A is overexpressed in LUAD and eEF2K525me3 levels increase through advancing LUAD disease stages. FAM86A knockdown attenuates LUAD cell proliferation and suppression …

Microglial Dynamics And Mechanisms Underlying The Phagocytosis Of Dying Oligodendrocytes, Genaro E. Olveda

Dartmouth College Ph.D Dissertations

Myelin is a complex multilamellar structure, generated by oligodendrocytes, that ensheaths axons and is a vital component for neural processing. Degeneration of both oligodendrocytes and their myelin sheaths is a common pathological feature associated with aging and neurodegenerative diseases. Efficient removal of the cellular and myelin debris is crucial for remyelination and prevention of further degeneration. Microglia, the primary phagocytes of the CNS, are thought to play a key role in this process. To investigate the cellular dynamics underlying microglia-mediated clearance of degenerating oligodendrocytes and myelin sheaths, at the single cell level, we developed a novel model for inducible cortical …

Dual-Systems And Fuzzy-Trace Theory Predictions Of Covid-19 Risk Taking In Young Adults, Sarah M. Edelson, Valerie F. Reyna, Bridget B. Hayes, David M. N. Garavito

Articles

Risk-reduction behaviors are the first line of defense in viral epidemics. Choosing to not engage in risk-reduction behaviors produced millions of preventable deaths from COVID-19. Understanding why this happens and how to predict it is important for theory development and public policy. We took four approaches to this problem: experimentally varying theory-driven predictors (social rewards, transmission risk, and mandatory/voluntary regulations) in choice scenarios, further probing choices in specific scenarios predicted to elicit risk taking, conducting hierarchical regressions with demographic and theory-driven predictors for both scenario types, and conducting corresponding regressions for self-reported protective behaviors. The sample consisted of 247 young …

Spartan Daily, May 2, 2024, San Jose State University, School Of Journalism And Mass Communications

Spartan Daily, 2024

Volume 162, Issue 40

Mdm2 Inhibitors For Cancer Therapy: The Past, Present, And Future, Wei Wang, Najah Albadari, Yi Du, Josef F Fowler, Hannah T Sang, Wa Xian, Frank Mckeon, Wei Li, Jia Zhou, Ruiwen Zhang

Faculty, Staff and Student Publications

Since its discovery over 35 years ago, MDM2 has emerged as an attractive target for the development of cancer therapy. MDM2's activities extend from carcinogenesis to immunity to the response to various cancer therapies. Since the report of the first MDM2 inhibitor more than 30 years ago, various approaches to inhibit MDM2 have been attempted, with hundreds of small-molecule inhibitors evaluated in preclinical studies and numerous molecules tested in clinical trials. Although many MDM2 inhibitors and degraders have been evaluated in clinical trials, there is currently no Food and Drug Administration (FDA)-approved MDM2 inhibitor on the market. Nevertheless, there are …

May 2, 2024, The Daily Mississippian

Daily Mississippian (all digitized issues)

No abstract provided.

Understanding Gene Regulation By Non-Cg Dna Methylation And Mecp2 At Cellular Resolution In The Brain, Mati Nemera

Arts & Sciences Graduate Student Theses and Dissertations

The mammalian brain features a variety of cell types with distinct functions and properties. This cellular diversity is maintained by epigenomic regulation of gene expression. Neurons in particular express long genes and are uniquely enriched for non-CG methylation, especially methylation at CA dinucleotides (mCA). MeCP2, whose mutation results in Rett syndrome, regulates gene expression by binding to mCA. However, the function of this mCA-MeCP2 pathway in the regulation of fine-tuned neuronal gene expression programs has not been investigated. Here, we provide evidence that mCA-MeCP2 pathway plays a role in the maintenance of neuron type-specific gene expression programs at a high …

Integrated Transcriptomics And Histopathology Approach Identifies A Subset Of Rejected Donor Livers With Potential Suitability For Transplantation, Ankita Srivastava, Alexandra Manchel, John Waters, Manju Ambelil, Benjamin K. Barnhart, Jan B. Hoek, Ashesh P. Shah, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Liver transplantation is an effective treatment for liver failure. There is a large unmet demand, even as not all donated livers are transplanted. The clinical selection criteria for donor livers based on histopathological evaluation and liver function tests are variable. We integrated transcriptomics and histopathology to characterize donor liver biopsies obtained at the time of organ recovery. We performed RNA sequencing as well as manual and artificial intelligence-based histopathology (10 accepted and 21 rejected for transplantation).

RESULTS: We identified two transcriptomically distinct rejected subsets (termed rejected-1 and rejected-2), where rejected-2 exhibited a near-complete transcriptomic overlap with the accepted livers, …

May 2, 2024, James Madison University

The Breeze, 2020-

The Breeze is the student newspaper of James Madison University in Harrisonburg, Virginia.

The Spectrum Of Pneumonia Among Intubated Neonates In The Neonatal Intensive Care Unit, Dayle J. Bondarev, Rita M. Ryan, Devashis Mukherjee

Faculty Scholarship

We review the pathophysiology, epidemiology, diagnosis, treatment, and prevention of ventilator-associated pneumonia (VAP) in neonates. VAP has been studied primarily in adult ICU patients, although there has been more focus on pediatric and neonatal VAP (neo-VAP) in the last decade. The definition as well as diagnosis of VAP in neonates remains a challenge to date. The neonatal intensivist needs to be familiar with the current diagnostic tools and prevention strategies available to treat and reduce VAP to reduce neonatal morbidity and the emergence of antibiotic resistance. This review also highlights preventive strategies and old and emerging treatments available.