Digital Commons Network^™

Challenges Of Spatially Resolved Metabolism In Cancer Research, Andrew N. Lane, Richard M. Higashi, Teresa W-M Fan

Markey Cancer Center Faculty Publications

Stable isotope-resolved metabolomics comprises a critical set of technologies that can be applied to a wide variety of systems, from isolated cells to whole organisms, to define metabolic pathway usage and responses to perturbations such as drugs or mutations, as well as providing the basis for flux analysis. As the diversity of stable isotope-enriched compounds is very high, and with newer approaches to multiplexing, the coverage of metabolism is now very extensive. However, as the complexity of the model increases, including more kinds of interacting cell types and interorgan communication, the analytical complexity also increases. Further, as studies move further …

A Crisis In Clinical Research, David S Hong, Patricia Lorusso, Mario Sznol

Faculty, Staff and Student Publications

The clinical research pipeline is critical to ensuring continued development of novel treatments that can offer patients with cancer safe and effective options. Unfortunately, progress has slowed since the COVID-19 pandemic due to uncovered, systemic inefficiencies across critical processes. Towards initiating discussion on how to reinvigorate clinical research, the Society for Immunotherapy of Cancer (SITC) hosted a virtual summit that characterized issues and formed potential solutions. This commentary serves to highlight the crisis facing clinical research as well as stimulate field-wide discussion on how to better serve patients into the future.

Parg Is Essential For Polθ-Mediated Dna End-Joining By Removing Repressive Poly-Adp-Ribose Marks, Umeshkumar Vekariya, Leonid Minakhin, Gurushankar Chandramouly, Mrityunjay Tyagi, Tatiana Kent, Katherine Sullivan-Reed, Jessica Atkins, Douglas Ralph, Margaret Nieborowska-Skorska, Anna-Mariya Kukuyan, Hsin-Yao Tang, Richard T. Pomerantz, Tomasz Skorski

Department of Biochemistry and Molecular Biology Faculty Papers

DNA polymerase theta (Polθ)-mediated end-joining (TMEJ) repairs DNA double-strand breaks and confers resistance to genotoxic agents. How Polθ is regulated at the molecular level to exert TMEJ remains poorly characterized. We find that Polθ interacts with and is PARylated by PARP1 in a HPF1- independent manner. PARP1 recruits Polθ to the vicinity of DNA damage via PARylation dependent liquid demixing, however, PARylated Polθ cannot perform TMEJ due to its inability to bind DNA. PARG-mediated de-PARylation of Polθ reactivates its DNA binding and end-joining activities. Consistent with this, PARG is essential for TMEJ and the temporal recruitment of PARG to DNA …

Regioselective Hydroamination Of Unactivated Olefins With Diazirine And Total Synthesis Of Nostodione A And Scytonemin, Qingyu Xing

USF Tampa Graduate Theses and Dissertations

As an atom-economic way of carbon-nitrogen bond formation, hydroaminations are great tool for make amines, hydrazines, and other nitrogen-containing heterocycles. Specifically, radical hydroamination is a useful approach for functionalization of unactivated olefins, especially in sterically hindered environments. Diversification remains a challenge for radical hydroaminated products, since the nitrogen sources are carefully designed. In the first chapter of this dissertation, we report a highly diversifiable radical hydroamination reaction with diazirine as a nitrogen source and its potential applications in synthesis of several pharmaceutical interested compounds. Cobalt catalyzed regioselective hydroamination with diazirine shows wide function group tolerance, like phenyl thioether, ketones, esters, …

Emerging Biomedical And Clinical Applications Of 3d-Printed Poly(Lactic Acid)-Based Devices And Delivery Systems, Allan John R Barcena, Prashanth Ravi, Suprateek Kundu, Karthik Tappa

Faculty, Staff and Student Publications

Poly(lactic acid) (PLA) is widely used in the field of medicine due to its biocompatibility, versatility, and cost-effectiveness. Three-dimensional (3D) printing or the systematic deposition of PLA in layers has enabled the fabrication of customized scaffolds for various biomedical and clinical applications. In tissue engineering and regenerative medicine, 3D-printed PLA has been mostly used to generate bone tissue scaffolds, typically in combination with different polymers and ceramics. PLA's versatility has also allowed the development of drug-eluting constructs for the controlled release of various agents, such as antibiotics, antivirals, anti-hypertensives, chemotherapeutics, hormones, and vitamins. Additionally, 3D-printed PLA has recently been used …

Emergent Emm4 Group A Streptococcus Evidences A Survival Strategy During Interaction With Immune Effector Cells, Chioma M Odo, Luis A Vega, Piyali Mukherjee, Sruti Debroy, Anthony R Flores, Samuel A Shelburne

Faculty, Staff and Student Publications

The major gram-positive pathogen group A Streptococcus (GAS) is a model organism for studying microbial epidemics as it causes waves of infections. Since 1980, several GAS epidemics have been ascribed to the emergence of clones producing increased amounts of key virulence factors such as streptolysin O (SLO). Herein, we sought to identify mechanisms underlying our recently identified temporal clonal emergence among emm4 GAS, given that emergent strains did not produce augmented levels of virulence factors relative to historic isolates. By creating and analyzing isoallelic strains, we determined that a conserved mutation in a previously undescribed gene encoding a putative carbonic …

The Impact Of Clinical Genome Sequencing In A Global Population With Suspected Rare Genetic Disease, Arturo Serize, Jorge Perez

All Publications

There is mounting evidence of the value of clinical genome sequencing (cGS) in individuals with suspected rare genetic disease (RGD), but cGS performance and impact on clinical care in a diverse population drawn from both high-income countries (HICs) and low- and middle-income countries (LMICs) has not been investigated. The iHope program, a philanthropic cGS initiative, established a network of 24 clinical sites in eight countries through which it provided cGS to individuals with signs or symptoms of an RGD and constrained access to molecular testing. A total of 1,004 individuals (median age, 6.5 years; 53.5% male) with diverse ancestral backgrounds …

Characterization Of The Apical Testis And Fusome Patterning In Drosophila Melanogaster, Drosophila Simulans, Drosophila Pseduoobscura, Drosophila Affinis, And Drosophila Sechellia, Crystal L. Calise

Seton Hall University Dissertations and Theses (ETDs)

This study uses five different species across the family of Drosophila as a tool to compare the structures of the stem cell niche and fusome within the testes of these species. Three species from Drosophila melanogaster group, D. melanogaster, D. simulans and D. sechellia, and two species from D. obscura group, D. pseudoobscura and D. affinis were observed using confocal microscopy In addition to a general comparison of male reproductive system structure and anatomy, the species were also analyzed for the presence of Fasciclin-III and α-Spectrin. As expected, species from the D. melanogaster group had the same expression pattern for …

National Narcotics Policy Influence On Youth Substance Abuse In Yendi, Ghana, Imran Abdel-Rahman Gomdah

Walden Dissertations and Doctoral Studies

Possession of small quantities of narcotics for personal use in Ghana could result in years in detention under the Narcotic Drugs Law of 1990, with youth constituting a large number of offenders. The government proposed a drug policy change in 2017 as the prevailing one failed to achieve its goals even with such stringency, resulting in Act 1019’s adoption in May 2020 as a new national drug policy to replace the Narcotic Drugs Law of 1990. The purpose of this generic qualitative study was to assess public perception of the impact of the new policy on the incidences of youth …

Pliocene-Pleistocene Warm-Water Incursions And Water Mass Changes On The Ross Sea Continental Shelf (Antarctica) Based On Foraminifera From Iodp Expedition 374, Iodp Expedition 374 Scientists, Julia L. Seidenstein, R. Mark Leckie, Robert Mckay, Laura De Santis, David Harwood, Jeanine Ash, François Beny, Imogen M. Browne, Giuseppe Cortese, Justin P. Dodd, Oliver M. Esper, Jenny A. Gales, Saki Ishino, Benjamin A. Keisling, Sookwan Kim, Sunghan Kim, Denise K. Kulhanek, Juliane Müller, Molly O. Patterson, Brian W. Romans, Oscar E. Romero, Francesca Sangiorgi, Osamu Seki, Amelia E. Shevenell, Shiv M. Singh, Isabela M. Cordeiro De Sousa, Saiko T. Sugisaki, Tina Van De Flierdt

School of Biological and Marine Sciences

International Ocean Discovery Program (IODP) Expedition 374 sailed to the Ross Sea in 2018 to reconstruct paleoenvironments, track the history of key water masses, and assess model simulations that show warm-water incursions from the Southern Ocean led to the loss of marine-based Antarctic ice sheets during past interglacials. IODP Site U1523 (water depth 828m) is located at the continental shelf break, northeast of Pennell Bank on the southeastern flank of Iselin Bank, where it lies beneath the Antarctic Slope Current (ASC). This site is sensitive to warm-water incursions from the Ross Sea Gyre and modified Circumpolar Deep Water (mCDW) today …

Reflections On The Past, Present, And Potential Futures Of Knowledge Hierarchies In Ocean Biodiversity Governance Research, Holly J. Niner, David Wilson, Kelly Hoareau, Mia Strand, Jennifer Whittingham, Dylan Mcgarry, Bolanle Erinosho, Sulley Ibrahim, Sirkka Tshiningayamwe, Senia Febrica, Alana Malinde S. N. Lancaster, Milica Prokic

School of Biological and Marine Sciences

Governance of the ocean and its biodiversity is deeply entangled within social, political and cultural histories. The evolution of marine science has been subject to similar influences, and we (the authors) consider these factors to create, embed and reinforce knowledge hierarchies in ocean governance processes and associated research that set societal patterns of prioritisation and exclusion. Such knowledge hierarchies have constructed dominant Western-oriented knowledge systems as ‘rational’ and ‘objective’ approaches to environmental governance in contrast to non-Western knowledge systems and have led to a dominance of natural (normal) sciences over centralised biodiversity governance. The extraction and incorporation of traditional knowledge …

Clonal Hematopoiesis Driven By Mutated Dnmt3a Promotes Inflammatory Bone Loss, Hui Wang, Kimon Divaris, Bohu Pan, Xiaofei Li, Jong-Hyung Lim, Gundappa Saha, Marko Barovic, Danai Giannakou, Jonathan M Korostoff, Yu Bing, Souvik Sen, Kevin Moss, Di Wu, James D Beck, Christie M Ballantyne, Pradeep Natarajan, Kari E North, Mihai G Netea, Triantafyllos Chavakis, George Hajishengallis

Faculty, Staff and Student Publications

Clonal hematopoiesis of indeterminate potential (CHIP) arises from aging-associated acquired mutations in hematopoietic progenitors, which display clonal expansion and produce phenotypically altered leukocytes. We associated CHIP-DNMT3A mutations with a higher prevalence of periodontitis and gingival inflammation among 4,946 community-dwelling adults. To model DNMT3A-driven CHIP, we used mice with the heterozygous loss-of-function mutation R878H, equivalent to the human hotspot mutation R882H. Partial transplantation with Dnmt3a

Intrinsically Disordered Membrane Anchors Of Rheb, Rhoa, And Diras3 Small Gtpases: Molecular Dynamics, Membrane Organization, And Interactions, Chase M Hutchins, Alemayehu A Gorfe

Faculty, Staff and Student Publications

Protein structure has been well established to play a key role in determining function; however, intrinsically disordered proteins and regions (IDPs and IDRs) defy this paradigm. IDPs and IDRs exist as an ensemble of structures rather than a stable 3D structure yet play essential roles in many cell-signaling processes. Nearly all Ras superfamily GTPases are tethered to membranes by a lipid tail at the end of a flexible IDR. The sequence of the IDR is a key determinant of membrane localization, and interaction between the IDR and the membrane has been shown to affect signaling in RAS proteins through the …

The Impact Of Clinical Genome Sequencing In A Global Population With Suspected Rare Genetic Disease, Erin Thorpe, Taylor Williams, Chad Shaw, Evgenii Chekalin, Julia Ortega, Keisha Robinson, Jason Button, Marilyn C Jones, Miguel Del Campo, Donald Basel, Julie Mccarrier, Laura Davis Keppen, Erin Royer, Romina Foster-Bonds, Milagros M Duenas-Roque, Nora Urraca, Kerri Bosfield, Chester W Brown, Holly Lydigsen, Henry J Mroczkowski, Jewell Ward, Fabio Sirchia, Elisa Giorgio, Keith Vaux, Hildegard Peña Salguero, Aimé Lumaka, Gerrye Mubungu, Prince Makay, Mamy Ngole, Prosper Tshilobo Lukusa, Adeline Vanderver, Kayla Muirhead, Omar Sherbini, Melissa D Lah, Katelynn Anderson, Jeny Bazalar-Montoya, Richard S Rodriguez, Mario Cornejo-Olivas, Karina Milla-Neyra, Marwan Shinawi, Pilar Magoulas, Duncan Henry, Kate Gibson, Samuel Wiafe, Parul Jayakar, Daria Salyakina, Diane Masser-Frye, Arturo Serize, Jorge E Perez, Alan Taylor, Shruti Shenbagam, Ahmad Abou Tayoun, Alka Malhotra, Maren Bennett, Vani Rajan, James Avecilla, Andrew Warren, Max Arseneault, Tasha Kalista, Ali Crawford, Subramanian S Ajay, Denise L Perry, John Belmont, Ryan J Taft

Center for Medical Ethics and Health Policy Staff Publications

There is mounting evidence of the value of clinical genome sequencing (cGS) in individuals with suspected rare genetic disease (RGD), but cGS performance and impact on clinical care in a diverse population drawn from both high-income countries (HICs) and low- and middle-income countries (LMICs) has not been investigated. The iHope program, a philanthropic cGS initiative, established a network of 24 clinical sites in eight countries through which it provided cGS to individuals with signs or symptoms of an RGD and constrained access to molecular testing. A total of 1,004 individuals (median age, 6.5 years; 53.5% male) with diverse ancestral backgrounds …

Tips, Tools, And Techniques For Generating Innovative Ideas, M. S. Rao

The Journal of Values-Based Leadership

The purpose of this paper is to offer innovative tools and techniques to develop inspiring ideas. It explains the power of the subconscious mind to acquire creative and inventive ideas and unlock hidden potential. It differentiates between creativity and innovation and draws a blueprint to achieve creativity and innovation. It explains and elaborates on innovative leadership. It outlines the characteristics of innovative leaders and illustrates inspiring examples of innovative international leaders including Benjamin Franklin, Thomas Edison, Albert Einstein, Bill Gates, Larry Ellison, Elon Musk, and Mark Zuckerberg. It explains that failure is an integral part of innovation. It directs the …

Rupert Murdoch: Altruism Inverted, Elizabeth Summerfield

The Journal of Values-Based Leadership

American entrepreneur, television producer, media owner and philanthropist, Ted Turner, once described Rupert Murdoch as “the most dangerous man in the world” (Beahm, 1). This is not an unusual judgement. But it is also one which may contribute to sustaining the Murdoch “brand”, his notoriety and appeal to supporters.

This article examines the deep origins of Murdoch’s cynical worldview, and the source of an ambition that drove him from ownership of a small provincial Australian newspaper to global media mogul. What compelled the need to disseminate often dangerously divisive views on as large a stage as possible, while purporting to …

Five Focal Points Of The Ethical Life Practical Knowledge And Ethical Understanding, Joseph P. Hester

The Journal of Values-Based Leadership

No abstract provided.

The Role Of Exogenous Gibberellic Acid (Ga3) Application In Breaking Seed Dormancy In Clematis Hirsutissima​, Ashley Grace Ogle

2024 Symposium

Seed germination in plants is controlled by several mechanisms, including the presence of phytohormones like gibberellins, as well as environmental conditions, such as temperature, light, and moisture. Germination of dormant seeds can be promoted by the exogenous application of Gibberellic Acid (GA3). GA3 acts as a natural endogenous regulator of dormancy. Clematis hirsutissima, commonly known as Sugarbowls, in the plant family Ranunculaceae, is an important perennial species that contributes to biodiversity in western prairie ecosystems by providing habitat for pollinators and wildlife; and it is also a species that shows characteristic embryo dormancy. This native to Washington, has been used …

Alcohol And The Resulting Consequences Of Delirium Tremens, Nicasio L. Santos

2024 Symposium

Alcohol is a depressant drug, inhibiting the function of the central nervous system (CNS) and neurons in the mind (Greenberg, 1953). This results in physiological effects that are typical of an inhibited CNS; slowing of the heartbeat and breathing, and decreasing blood pressure (Scorzelli & Chaudhry, 2009). However, this inhibition of both the CNS and the neural chemistry develops a tolerance, and in turn withdrawal symptoms (Polli et al., 2023). These withdrawal symptoms are the inverse of the inhibition caused by the depressant effects of alcohol (i.e., an overactive CNS, increased activity of neurons; Smith-Alnimer & Watford, 2004). In extreme …

Vol. 13 No. 1, Glen Goodknight

Mythprint

Mythprint is the monthly bulletin of the Mythopoeic Society, a nonprofit educational organization devoted to the study, discussion, and enjoyment of myth and fantasy literature, especially the works of J.R.R. Tolkien, C.S. Lewis, and Charles Williams. To promote these interests, the Society publishes three magazines, maintains a World Wide Web site, and sponsors the annual Mythopoeic Conference and awards for fiction and scholarship, as well as local and written discussion groups.

Microplastic Accumulation In The Marsh Periwinkle (Littoraria Irrorata), Sarah Keaton, Hannah Lukhard, Eli Windy, Manar Hasan

DePaul Discoveries

Contamination of oceans by microplastics (mm) currently poses a major threat to aquatic and terrestrial ecosystems worldwide. Recent attention towards this issue has raised questions about the extent to which microplastics have accumulated in the environment, and has led to an increase in studies on the effects of microplastics in various organisms. However, levels of contamination in protected natural areas are still largely unexplored, yet can offer an important empirical perspective on the issue. In addition, little is known about the potential effects of microplastics on behavior in the field. This research was conducted within the protected ACE Basin National …

Detection And Quantification Of Acetaminophen In Aquatic Samples From Cádiz, Spain, Hannah R. Desmarais, Michelle N. Mikos

DePaul Discoveries

Pharmaceutical contaminants in water are becoming increasingly prevalent. This could have potentially harmful effects on human health and aquatic environments, even at low concentrations. Acetaminophen, the active ingredient of Tylenol ®, was the target compound for this study, and the aim was to determine is presence and concentration in various aquatic samples in and around the city of Cádiz, Spain. It was predicted that acetaminophen would be detected in low concentrations in river water, drain outflow, University of Cádiz saltwater flow, and lagoon water, but undetectable in the University of Cádiz sink water and fountain water. The presence and concentration …

A Seasonal Decomposition Comparison Between Forest And Turf Habitats: Implications For Climate Change, Amanda Shirmer

DePaul Discoveries

Decomposition is an essential ecosystem service in which microorganisms breakdown organic matter. This process improves soil health and acts as a vital step in global carbon cycles. In this study, we examined decomposition rates and associated soil properties in turf and forest habitats across summer and fall seasons in order to determine how land management practices and climate change may be altering local decomposition regimes. Our study determined that there was a statistically significant difference between decomposition rates in turf and forest ecosystems (P=0.003) and a significant difference in decomposition rate across season (P

Postweaning Skull Growth In Living Didelphid Marsupials: The Case Of Gracilinanus Agilis And Cryptonanus Chacoensis, Iveth A. Villalobos Guerrero, Noé U. De La Sancha

DePaul Discoveries

Ontogeny is described as the history of an organism through its lifetime including development, growth, and allometry. The ontogenetic approach in cranial dimensions has proved useful in interpreting evolutionary patterns. Among the largest Didelphidae family of Neotropical marsupials, the species of Gracilinanus agilis and Cryptonanus chacoensis are poorly known. In this study, we address three questions; Is there sexual dimorphism in these species? What is the pattern of allometry? Which allometric patterns best describe the patterns in the skull and mandible? We applied geometric morphometrics to describe and test these differences using MorphoJ. A discriminant function analysis was performed to …

The Impacts Of Urbanization On Soil: The Effect On Decomposition Rates And Microbial Communities, Maximus C. Halekakis

DePaul Discoveries

The anthropogenic impacts of industrialization have left many ecosystems polluted. Soil, being an imperative actor for ecosystem functions, is important to observe under anthropogenic change. My study examined soil organic matter decomposition, microbial biomass carbon(MBC) and the fungal to bacteria ratio(F:B) across an urban-suburban-exurban landuse gradient in San Luis Obispo, California. A cotton strip assay as well as microBIOMETER® testing was performed on three geographic locations in and outside of the city. The cotton strip decomposition acts as an indicator for organic matter breakdown as microorganisms break down the cellulose in the strips causing them to lose mass and tensile …

Disentangling Drivers Of Metacommunity Structure For Small Mammals Throughout Paraguay, William T. Szromba

DePaul Discoveries

Paraguay is home to a unique precipitation gradient, receiving progressively more precipitation from east to west. It has previously been suggested that metacommunity structures for order Chiroptera assemble along precipitation gradients such as this one. Metacommunities have also been shown to assemble along other bioclimatic gradients such as temperature. This study seeks to expand upon other findings by using a larger dataset, partitioned bioclimatic variables, and more mammalian orders. It also seeks to determine how metacommunities assemble along this gradient in Paraguay, investigate the differences between different ecological metacommunity assemblages, and to further understand which bioclimatic variables have the greatest …

Human Second Metacarpal Nanocrystal Analysis, William Abramovich

DePaul Discoveries

Female human bones dated to the 6^th - 8^th century CE were uncovered in Greding Germany after archaeologists discovered a medieval cemetery. Age-at-death estimates have been determined, and data from several techniques are currently being analyzed to learn more about these samples. The purpose of this project is to study the diaphyses of the second metacarpal (mc2) bones excavated using wide-angle x-ray scattering data collected at beamline 1-ID of the Advanced Photon Source at Argonne National Laboratory. The diffraction data were refined using the Rietveld method to obtain lattice (‘a’ and ‘c’) parameter values …

Vol. 6 No. 4, Glen Goodknight

Mythprint

Mythprint is the monthly bulletin of the Mythopoeic Society, a nonprofit educational organization devoted to the study, discussion, and enjoyment of myth and fantasy literature, especially the works of J.R.R. Tolkien, C.S. Lewis, and Charles Williams. To promote these interests, the Society publishes three magazines, maintains a World Wide Web site, and sponsors the annual Mythopoeic Conference and awards for fiction and scholarship, as well as local and written discussion groups.

Developing A Connection To Nature: The Role Of Pet Ownership In Childhood, Alexia Barrable, Samantha Friedman

People and Animals: The International Journal of Research and Practice

Connection to nature is associated with a range of benefits to well-being in both childhood and adulthood. Childhood experiences seem to play a big role in how adult nature connection develops. Among the many predictors of higher connection to nature, relationships with animals, including pets, likely play an important role in facilitating feelings of closeness with nature. In this paper we present two survey studies, one of children (n = 64, age = 6–16 years) and one of adults (n = 356, age = 18–80 years). Our aim was to find out if children who own pets have …

Statistical Analysis Of Lipid Profiles Associated With Coronary Heart Disease In Erbil City-Iraq, Dler Hussein Kadir, Karzan Abdullah, Aziz Muazafar Jafaar, Rebaz Hamza Salih, Shukur Wasman Smail, Gashaw Qasim Rahman, Harem Khdir Awla, Zhikal Omar Khudhur

Polytechnic Journal

Background and objectives: Coronary heart disease (CHD) is one of the most prevalent diseases worldwide. The primary risk factor for coronary heart disease (CHD) lies in the presence of hypertension, elevated levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL) in the bloodstream. Furthermore, a reduction in high-density lipoprotein (HDL) levels is linked to an elevated risk of cardiovascular disease-related mortality.

The current retrospective study was undertaken to evaluate the alterations in the lipid profile of patients with CHD.

Methods: The current survey involved collecting data from 867 patients diagnosed with acute or severe CHD, with an …