Digital Commons Network^™

Use Of Kcc2 Dna Plasmid Transfection To Modulate Chloride Homeostasis In Cultured Dopamine-Neuron Like Cells, Jacqueline N. Farolan Ms., Ashlee Szwedko, Mason Terry, Andrew Payne Phd., Dario Mizrachi Phd.

Annual Research Symposium

Potassium-chloride cotransporter 2 (KCC2) works in opposition to Na-K-Cl cotransporter 1 (NKCC1) to maintain low intracellular chloride concentrations in neurons. In immature neurons, there are high levels of NKCC1 and low levels of KCC2, which creates a high intracellular chloride concentration. Increased KCC2, therefore decreased chloride concentration, creates a GABA switch, switching immature neurons to mature neurons. This changes the activity of GABA from excitatory to inhibitory. Decreased KCC2 has been found to be correlated with reward seeking behaviors in the dopaminergic circuitry. Our study aims to artificially upregulate KCC2 and therefore decrease chloride concentrations in neurons. In the future, …

Collaborative Learning In Clinical Education As A Catalyst To Support Foundational Professional Competencies In Speech-Language Pathology: A Theoretical Framework, Lori-Ann Ferraro

Teaching and Learning in Communication Sciences & Disorders

As a part of every speech-language pathology graduate program in the US, clinical education is an integral and required element for both academic accreditation and the eventual clinical certification for students. Clinical education is significantly important when considering overall educational models because it is an aspect of a student’s education that contributes to their ability to make connections between what is learned in the classroom and its real-world clinical application while contributing to the acquisition of competencies. The 2:1 collaborative learning model is supported by sound learning theories and evidence from the literature. A theoretical framework was created to demonstrate …

Recent Advances In The Pharmacological Properties Of Scutellarin: Mechanistic Insights And Therapeutic Potential, Hind A. Satar, Emad Yousif, Ahmed Ahmed, Muna Bufaroosha

AUIQ Complementary Biological System

Scutellarin, a flavonoid glycoside primarily derived from Scutellaria baicalensis, has garnered increasing scientific interest for its multifaceted pharmacological properties. This review summarizes recent advances in our understanding of scutellarin's therapeutic effects, including its antioxidant, anti-inflammatory, neuroprotective, cardioprotective and anticancer activities. Emphasis is placed on elucidating its molecular mechanisms of action, such as modulation of the NF-κB, Nrf2, and PI3K/Akt pathways, and its role in regulating oxidative stress, inflammation, and apoptosis. Additionally, we discuss formulation innovations, including nanoparticle and liposomal delivery systems, aimed at overcoming scutellarin's poor oral bioavailability and enhancing therapeutic performance. Key limitations in current research …

Ns5-Targeting Nucleoside Analogs Inhibit Dengue Virus And Other Flaviviruses, Priyanka Bhakt, Swechha Pokharel, Yue Li, Tamanna Srivastava, Jesse Miller, Mark Dittmar, Yongqing Zhu, David Nguyen, Zachary Walter, Kasirajan Ayyanathan, Matthew Tudor, Chenguang Yu, Arnab Chatterjee, Holly Ramage, David Schultz, Sara Cherry

Department of Microbiology and Immunology Faculty Papers

Dengue virus (DENV) is a mosquito-transmitted flavivirus that circulates globally as four distinct serotypes and poses a substantial threat to public health. There are an estimated ~96 million symptomatic infections yearly, including severe cases of dengue fever, underscoring the urgency of identifying effective therapeutics targeting all four serotypes. Nucleoside analogs, which mimic endogenous nucleosides to inhibit viral RNA replication, offer a promising strategy for broad-spectrum antiviral development. Here, we conducted a high-throughput screen of 1,101 nucleoside analogs against DENV serotype 2 (DENV2) in a panel of human cell models, including human epithelial cells, hepatocytes, and fibroblasts. Candidates that were active …

S6k1 Modulates Stat3 Activation To Promote Resistance To Radiotherapy In Lung Cancer, Ali Calderon-Aparicio, Noelle Francois, Tyler Grenda, Shan Xu, Olugbenga Okusanya, Jun He, Nicole L Simone

Department of Radiation Oncology Faculty Papers

Radiotherapy is a mainstay in the management of locally advanced lung cancer; however, intrinsic and acquired radioresistance contribute to poor prognosis. S6K1, a serine/threonine kinase, regulates cell growth, protein synthesis, and survival, and is increased in tumors, which is linked to enhanced survival under therapeutic stress, including radiation. The mechanisms, however, are not fully understood. This study investigates the role of S6K1 in lung cancer radioresistance and the mechanisms involved. Intrinsic radioresistance in lung cancer cells was associated with increased S6K1 activation. Pharmacologic inhibition or genetic deletion of S6K1 enhanced radiosensitivity both in vitro and in vivo, highlighting the therapeutic …

Syndecan-1-Targeted Therapeutic Antibody Impairs Macropinocytosis And Elicits Antitumor Immunity In Pancreatic Cancer, Zecheng Yang, Madelaine S Theardy, Shuaitong Chen, Yongkun Wei, Mitsunobu Takeda, Yue Zeng, Xiaofei Wang, Jun Yao, Jennifer Li, Prapassorn Thirasastr, Jangho Park, Yangxi Zheng, Long T Vien, Khalida M Wani, Huamin Wang, Sisi Gao, Tim Heffernan, Lawrence Kwong, Ignacio I Wistuba, Laura Bover, Giulio F Draetta, Haoqiang Ying, Wantong Yao

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with a 5-year survival rate of just 13%. While the development and early clinical use of small molecules targeting oncogenic KRAS mutations, key drivers of PDAC, have shown promise, resistance to these targeted therapies remains a significant challenge. We recently identified Syndecan-1 (SDC1), a highly expressed heparan sulfate proteoglycan, as a critical KRAS effector protein that promotes nutrient salvage and tumor growth. Here, we report the development of a human-specific monoclonal antibody (anti-SDC1 mAb) that inhibits PDAC cell proliferation in vitro and suppresses PDAC tumor growth in vivo. Mechanistically, …

Larval Zebrafish Minimize Energy Consumption During Hunting Via Adaptive Movement Selection, Thomas Darveniza, Robert Wong, Shuyu I Zhu, Zac Pujic, Biao Sun, Matthew Levendosky, Ramesh Agarwal, Michael H Mccullough, Geoffrey J Goodhill

2020-Current year OA Pubs

Animals must balance behavioral goals with the energetic costs of movement. How such trade-offs are implemented algorithmically during natural behavior, and how they adapt to changing energetic constraints, remains poorly understood. Here we show that larval zebrafish adjust their motor strategies during prey hunting to minimize energy expenditure. Using high-speed video tracking and 3D computational fluid dynamics simulations, we quantified the energy costs (in Joules) of different movement types across three developmental stages. While the structure of discrete movement types ("bouts") remained stable with age, their selection probabilities changed depending on their energetic cost, such that more expensive bouts were …

Long-Acting Interleukin-7 Improves The Efficacy Of Oncolytic Viral Therapy In Glioblastoma, Yuping Derek Li, David A Giles, Yi Huang, Ashwani Kesarwani, Tong Hu, Logan Page, Amanda De Andrade Costa, Jingqin Luo, Mai T Dang, Albert H Kim, John F Dipersio, David T Curiel, Michael S Diamond, Milan G Chheda, Et Al.

2020-Current year OA Pubs

Despite advances in immunotherapy, the prognosis for patients with glioblastoma (GBM) remains poor. The efficacy of GBM-targeted immunotherapies is limited by the paucity of functional T cells in the tumor microenvironment, a consequence of the local and systemic immunosuppression prevalent in patients with GBM. To overcome these challenges, here we develop a treatment strategy we term "expand and pull," which uses systemic administration of rhIL-7-hyFc, a long-acting recombinant human interleukin-7, to increase peripheral T cell abundance ("expand"), followed by intratumoral oncolytic virus treatment to recruit these cells to the tumor microenvironment ("pull"). We show that rhIL-7-hyFc improves the efficacy of …

Spatiotemporal Histogenesis Of The Developing Human Cerebellum Reveals Dynamic Layering Of Bergmann Glia, Guanyi He, Simon Du, Henry Tan, Sri Yellampally, Anders W Erickson, Virginia Fernandez, Ferechte Encha-Razavi, Kimberley A Phillips, Christine Haberler, Nicole Amberg, Victor Borrell, Paul A Northcott, Michael D Taylor, Kathleen J Millen, Parthiv Haldipur

Faculty, Staff and Students Publications

Bergmann glia (BG) are a specialized glial population essential for cerebellar development, yet their developmental timeline and molecular identity in the human cerebellum remain poorly understood. Here, we combined detailed histopathological analysis with spatial transcriptomics and single-nucleus RNA sequencing to generate a developmental atlas of human cerebellar BG. Histology revealed that BG emerge around 11 post-conception weeks (PCW), initially serving as a scaffold for Purkinje cells (PCs) migrating into the PC layer of the cerebellar cortex. Following the establishment of a multilayered PC arrangement, BG form a distinct parallel layer separated from the PCs by the lamina dissecans (LD), with …

Accurate Interpretation Of Within-Host Dissemination Using Barcoded Bacteria, Rachel T Giorgio, My T Le, Ting Zhang, Caitlyn L Holmes, Karthik Hullahalli

2020-Current year OA Pubs

Bacterial dissemination across tissues is a critically important process influencing infection outcomes. Monitoring within-host dissemination is challenging because conventional measures of bulk bacterial burden cannot distinguish between lineages that are shared between tissues and those that replicate locally. This limitation can be overcome using barcoded bacteria, where deep sequencing of the barcode locus and comparisons of barcodes between tissues define which lineages spread within the host. Numerous studies have used barcoded bacteria to generate high-resolution maps of dissemination. However, since multiple cells in the infectious inoculum can contain identical barcodes, inferences about dissemination can be confounded when distinct lineages from …

Variable And Conserved Features Of Copy-Back Viral Genome Populations Generated De Novo During Sendai Virus Infection, Yanling Yang, Yuchen Wang, Carolina B López

2020-Current year OA Pubs

Copy-back viral genomes (cbVGs) are generated during the replication of negative-sense RNA viruses when the polymerase drops off from the genome and reattaches to the nascent strand. cbVGs have strong immunostimulatory properties and impact infection outcomes. Despite their importance, the composition and mechanisms of

Engineering Chimeric Antigen Receptor Cd4 T Cells For Alzheimer's Disease, Pavle Boskovic, Rotem Shalita, Wenqing Gao, Hailey Vernon, Yu Lin Deng, Marco Colonna, Robbie G Majzner, Ido Amit, Jonathan Kipnis

2020-Current year OA Pubs

Alzheimer's disease (AD) is the prevailing cause of age-associated dementia worldwide. Current standard of care relies on antibody-based immunotherapy. However, antibody-based approaches carry risks for patients, and their effects on cognition are marginal. Increasing evidence suggests that T cells contribute to AD onset and progression. Unlike the cytotoxic effects of CD8

The Impact Of Physical Activity And Diet On The Potassium-Chloride Cotransporter 2 In The Central Nervous System: A Literature Review, Benjamin M. Latey, Dustin Bowers, Andrew J. Payne

Annual Research Symposium

No abstract provided.

Sting-Induced Blood-Brain Barrier Opening Combined With Radiotherapy Potentiates Antitumor Response In A High-Grade Glioma Model, Shashwat Tripathi, Hinda Najem, Lisa Hurley, Ruochen Du, Crismita Dmello, Heba Ali, Kathleen Mccortney, Karl J Habashy, Peng Zhang, Craig M Horbinski, Lara Leoni, Ryan J Avery, Rimas V Lukas, Timothy L Sita, David R Raleigh, Sean Sachdev, Roger Stupp, Maciej S Lesniak, David M Ashley, Daniele Procissi, Michael A Curran, Irina Balyasnikova, Amy B Heimberger

Faculty, Staff and Student Publications

Radiation therapy (RT) is the standard of care for glioblastoma but is not curative. Triggering the cGAS/stimulator of interferon genes (STING) pathway with potent agonists, such as 8803, exerts activity across high-grade glioma preclinical models. To determine if the combination of 8803 with RT warrants consideration in the up-front treatment setting and to clarify the underlying mechanisms of therapeutic activity, C57BL/6J mice harboring intracerebral CT-2A or QPP8v gliomas were treated with RT, intratumoral 8803, or both. The treatment with the combination resulted in 80% long-term survival in the CT-2A model but not in the radiation-resistant QPP8v model. This therapeutic effect …

Mutant Kras In Brain Endothelial Cells Promotes Vascular Inflammation And Impairs Vascular Integrity In Brain Arteriovenous Malformation, Jung-Eun Park, Bridger H Freeman, Hyejin Park, Sehee Kim, Adrian E Bafor, Ohnmar Myint, Song Gao, Zhen Xu, Jakob Körbelin, Jaroslaw Aronowski, Peng Roc Chen, Eunhee Kim, Eun S Park

Faculty, Staff and Student Publications

Somatic KRAS (KRASG12V) mutation in endothelial cells (EC) induces brain arteriovenous malformation (bAVM) that could lead to vascular instability and ultimately bleeding. However, the causes of bAVM instability remain unclear. Here we demonstrate that KRASG12V expressing cultured ECs (KRAS-G12V-EC) have increased expression of pro-inflammatory mediators and reduced expression of blood-brain-barrier (BBB) junction constituents. The conditioned medium from KRAS-G12V-EC can activate BV2-microglia (BV2-MG) and conditioned media from this primed BV2-MG can compromise the expression of EC-junction constituents when added to wild-type ECs. In an in vitro BBB model, KRAS-G12V-EC form a dysfunctional EC barrier that is further disrupted, leading to lower …

Non-Canonical Role Of Dna Mismatch Repair On Sensory Processing In Mice, Sadia N Rahman, Demetrios Neophytou, Siboney Oviedo-Gray, Bao Q Vuong, Hysell V Oviedo

2020-Current year OA Pubs

DNA repair mechanisms are essential for cellular development and function. In post-mitotic neurons, deficiencies in DNA damage response proteins can lead to severe neurodegenerative and neurodevelopmental disorders. One highly conserved factor involved in DNA repair is MutS Homolog 2 (Msh2), which is responsible for correcting base-base mismatches and insertion/deletion loops during cell proliferation. However, its role in mature neurons remains poorly understood. This study investigates the impact of Msh2 loss on sensory processing in mice. Using electrophysiological and molecular assays, we identifiedsignificant deficits in cortical and thalamic sound processing in Msh2

The Feminist Impostor Phenomenon Approach (Fipa): A Feminist Approach To Addressing Impostor Phenomenon In Novice Counselors, Isabel Springer, Kelly Emelianchik-Key

Journal of Counselor Preparation and Supervision

Impostor Phenomenon (IP) is known to affect new professionals in health professions, yet there is little to no academic literature available on how it affects early career counselors and how it can be addressed. Novice counselors (NC) frequently experience extreme anxiety and feelings of fraudulence around their professional performance. Feminist mentorship and interventions can help alleviate IP and foster self-efficacy and confidence in new counseling professionals. The Feminist Impostor Phenomenon Approach (FIPA) consists of a three-hour workshop educating participants through a feminist lens about IP and relevant coping strategies, and subsequent weekly consciousness-raising groups where coping strategies are reinforced, and …

Evolving Strategies In Prostate Cancer: Emerging Approaches And Unmet Needs From The Bridging The Gaps In Prostate Cancer Expert Panel, Rana Mckay, Benjamin Maughan, Alicia Morgans, Neal Shore, Evan Yu, Ravi Madan, Jacob Berchuck, Bradley Carthon, Steven Finkelstein, Leonard Gomella, Michael Gorin, Andrew Hahn, Stacy Loeb, Vivek Narayan, Daniel Petrylak, Charles Ryan, Karine Tawagi, Phuoc Tran, Tanya Dorff

Department of Urology Faculty Papers

BACKGROUND: The expansion of treatment options for prostate cancer (PC) has improved disease-specific and overall survival outcomes but has also raised questions about the optimal level of treatment needed for patients based on their individual prognosis and accounting for potential toxicity, incorporating quality of life considerations.

METHODS: A panel of experts met to discuss current controversies in the care of patients with PC across the disease continuum. Multidisciplinary experts review advances and persistent uncertainties in biomarker-guided assessment, imaging, and systemic therapy for prostate cancer. The discussion outlines priority gaps in evidence that must be addressed to optimize individualized patient care. …

Investigating Tau Pathology In The Retina And Anterior Segment Structures Of The Eye In A 3-Nitropropionic Acid–Induced Tauopathy Mouse Model, Mohamed Sayed Ahmed Abdel-Kader Qasem

Theses and Dissertations

Background and Objectives: Alzheimer's disease, the most prevalent neurodegenerative disorder in older adults, is characterized by accumulation of hyperphosphorylated tau and amyloid-beta (Aβ) plaques in the central nervous system. Given the retina's shared embryological origin with the brain, its direct neural connectivity via the optic nerve, and similarities in vasculature and age-related degeneration patterns, retinal pathology may serve as an early, non-invasive biomarker for Alzheimer's disease. This study employed 3-nitropropionic acid (3NP) as a pathway-specific tauopathy model driven by mitochondrial dysfunction. The study particularly aimed to investigate whether retinal and corneal tau pathology reflects underlying tau-related neurodegeneration triggered by …

Prephiral Bacterial Infectious Agent Triggers Neuroinflammatory Responses And Neurobehavioral Impairment In Wild-Type Mice, Hadeer Atalah

Theses and Dissertations

Neurodegenerative diseases, including Alzheimer's and Parkinson's, present an increasing global challenge, with chronic neuroinflammation identified as a principal factor alongside genetic, environmental, and infectious influences (Boyd et al., 2022).  Epidemiological data associate bacterial infections with a 40% heightened risk of Parkinson's disease; however, the mechanisms—especially the direct connection between peripheral sepsis and the silent onset of central nervous system pathology absent acute meningitis—are inadequately investigated (Smeyne et al., 2021), particularly concerning common pathogens like Klebsiella pneumoniae in high-burden areas such as Egyptian ICUs, where it constitutes 30% of cases (Alkompoz et al., 2023). This study filled the gap by creating …

Uncovering Potential Therapeutic Targets For Spinal Cord Injury; Insights From Single-Cell And Cross-Species Transcriptomics, Sara Samy Abouzekry

Theses and Dissertations

Central nervous system (CNS) injury remains a devastating healthcare problem. Despite years of research, it remains almost impossible to achieve meaningful functional repair following traumatic brain injury (TBI) and spinal cord injury (SCI). Spinal cord injury (SCI), a highly devastating subset of CNS trauma, is considered a challenge due to the extremely limited regenerative capacity of the nervous system in adult mammals. In contrast, certain species display remarkable repair abilities followed by moderate regenerative ability in neonatal mammals, indicating that regeneration is shaped by the evolutionary context as well as the developmental age.

To uncover the core molecular mediators of …

Leo Ii...A Remembrance, The Flor-Ala

Documents

A special edition issue of The Flor-Ala in remembrance of Leo II.

New Honor For Leo Ii: May Be First In Nation, Cheri Shipper, Dr. J. R. Holladay, Dr. Wayne Cotton

Documents

This news release announces the exciting news that Leo II was selected as "Honorary ChairAnimal for National Pet Week" May 7-13 in the Shoals.

Tv Helps Leo Overcome Boredom, Karen Jackson

Documents

TV always makes people (and animals) happy!

*Article from The TimesDaily*

See The Lion At Una, Vacation Guide

Documents

A short write-up about the only African lion which serves as a school mascot-Leo II.

King Of The Jungle, Scott Burcham/Staff

Documents

Leo II playing with his new toy pig on the eve of UNA's game against Texas A & M Kingsville in Florence.

Leo I Versus Leo Ii, Dr. Joe Wallace

Documents

Personal account of Leo I versus Leo II written by Dr. Joe Wallace in Shoal Magazine.

Lion Talk: Vocabulary 101, Elise Cofield

Documents

Information about the Lions Fund at the University of North Alabama in the Spring edition of the UNA Magazine.

Leo Ii's Passing Leaves Large Void Around Una Campus, Una Sports Information

Documents

A fitting tribute to Leo II in the Lion's Roar.

The Story Of Leo The Lion, Joe Wallace

Documents

This souvenir edition magazine details the relationship between author Joe Wallace and Leo I at UNA.