Digital Commons Network^™

Digital, Social Micro-Interventions To Promote Physical Activity Among Midlife Adults With Elevated Cardiovascular Risk: An Ambulatory Feasibility Study With Momentary Randomization., Danielle Arigo, Leah M Schumacher, Kiri Baga, Jacqueline A Mogle

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Although regular physical activity (PA) mitigates the risk for cardiovascular disease (CVD) during midlife, existing PA interventions are minimally effective. Harnessing social influences in daily life shows promise: digital micro-interventions could effectively engage these influences on PA and require testing.

PURPOSE: This feasibility study employed ecological momentary assessment with embedded micro-randomization to activate two types of social influences (i.e., comparison, support; NCT04711512).

METHODS: Midlife adults (N = 30, MAge = 51, MBMI = 31.5 kg/m2, 43% racial/ethnic minority) with ≥1 CVD risk conditions completed four mobile surveys per day for 7 days while wearing PA monitors. After 3 days …

Decentralized Clinical Trials (Dcts): Facilitators & Barriers For A Pediatric Research Site, Abby Kietzman

Presentations

In 2020, the COVID-19 pandemic drastically altered the way clinical research is conducted through a widespread adoption of telemedicine practices. Using telehealth/telemedicine services allowed researchers to conduct “decentralized clinical trials”, or DCTs, for all or portions of study protocol procedures while maintaining safety measures implemented for pandemic control. However, current review of available literature details the explosion in use of decentralized clinical trials, resulting in gaps in evidence-based outcomes and lack of standardization across research entities. While sponsors and contract research organizations (CROs) tend to lead the charge around adoption of DCTs, research sites are hesitant to make the transition …

Pclaf-Dream Drives Alveolar Cell Plasticity For Lung Regeneration, Bongjun Kim, Yuanjian Huang, Kyung-Pil Ko, Shengzhe Zhang, Gengyi Zou, Jie Zhang, Moon Jong Kim, Danielle Little, Lisandra Vila Ellis, Margherita Paschini, Sohee Jun, Kwon-Sik Park, Jichao Chen, Carla Kim, Jae-Il Park

Faculty, Staff and Student Publications

Cell plasticity, changes in cell fate, is crucial for tissue regeneration. In the lung, failure of regeneration leads to diseases, including fibrosis. However, the mechanisms governing alveolar cell plasticity during lung repair remain elusive. We previously showed that PCLAF remodels the DREAM complex, shifting the balance from cell quiescence towards cell proliferation. Here, we find that PCLAF expression is specific to proliferating lung progenitor cells, along with the DREAM target genes transactivated by lung injury. Genetic ablation of Pclaf impairs AT1 cell repopulation from AT2 cells, leading to lung fibrosis. Mechanistically, the PCLAF-DREAM complex transactivates CLIC4, triggering TGF-β signaling activation, …

Tick-Borne Diseases And Pregnancy: A Narrative Review Evaluating Pregnancy Complications Caused By Tick-Borne Diseases, Michael W Curtis, Job E Lopez

Faculty, Staff and Students Publications

Ticks are vectors of public health concern because the pathogens they transmit can cause detrimental diseases in humans. Lyme disease, tick-borne relapsing fever, human granulocytic anaplasmosis, Rocky Mountain spotted fever, tick-borne encephalitis, Crimean-Congo hemorrhagic fever, and babesiosis are some of the most common diseases caused by the pathogens transmitted by ticks. The overlap between human activities and tick habitats is growing, contributing to an increase in tick-borne disease cases. Unfortunately, pregnancy as a risk factor for tick-borne diseases is largely ignored. In this narrative review we use case reports, epidemiological studies, and animal studies to evaluate the maternal, pregnancy, and …

Neuregulin1 Nuclear Signaling Influences Adult Neurogenesis And Regulates A Schizophrenia Susceptibility Gene Network Within The Mouse Dentate Gyrus, Prithviraj Rajebhosale, Alice Jone, Kory R Johnson, Rohan Hofland, Camille Palarpalar, Samara Khan, Lorna W Role, David A Talmage

Faculty, Staff and Student Publications

Neuregulin1 (Nrg1) signaling is critical for neuronal development and function from fate specification to synaptic plasticity. Type III Nrg1 is a synaptic protein which engages in bidirectional signaling with its receptor ErbB4. Forward signaling engages ErbB4 phosphorylation, whereas back signaling engages two known mechanisms: (1) local axonal PI3K-AKT signaling and (2) cleavage by γ-secretase resulting in cytosolic release of the intracellular domain (ICD), which can traffic to the nucleus (Bao et al., 2003; Hancock et al., 2008). To dissect the contribution of these alternate signaling strategies to neuronal development, we generated a transgenic mouse with a missense mutation (V

Personalized Copd Care: The Future Of Precision-Based Therapies, Leslie K Appleton, Nicola A Hanania, Muhammad Adrish

Faculty, Staff and Students Publications

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory illness characterized by long-standing respiratory symptoms and airflow limitation. It is a major contributor to respiratory disease-related deaths and currently ranked as the sixth leading cause of mortality in the United States. Approved pharmacological therapies for the stable disease primarily consist of inhaled short and long-acting bronchodilators, inhaled corticosteroids, azithromycin, and roflumilast. In recent years, significant progress has been made in the management of COPD through the identification of different COPD phenotypes and endotypes, which allows for a more personalized treatment approach. While earlier studies investigating targeted therapies were less promising, …

Recovery After Human Bone Marrow Mesenchymal Stem Cells (Hbm-Mcs)-Derived Extracellular Vesicles (Evs) Treatment In Post-Mcao Rats Requires Repeated Handling, Yolanda Gomez-Galvez, Malvika Gupta, Mandeep Kaur, Salvatore Fusco, Maria Vittoria Podda, Claudio Grassi, Amit K. Srivastava, Lorraine Iacovitti, Elena Blanco-Suarez

Farber Institute for Neuroscience Faculty Papers

Rehabilitation is the only current intervention that improves sensorimotor function in ischemic stroke patients, similar to task-specific intensive training in animal models of stroke. Bone marrow mesenchymal stem cells (BM-MSCs)-derived extracellular vesicles (EVs) are promising in restoring brain damage and function in stroke models. Additionally, the non-invasive intranasal route allows EVs to reach the brain and target specific ischemic regions. Yet unclear is how handling might enhance recovery or influence other therapies such as EVs after stroke. We used the transient middle cerebral artery occlusion (MCAO) model of stroke in rats to assess how intensive handling alone, in the form …

Identification Of New Leads Against Ubiquitin Specific Protease-7 (Usp7): A Step Towards The Potential Treatment Of Cancers, Sumaira Javaid, Seema Zadi, Muhammad Awais, Atai-Tul Wahab, Humaira Zafar, Innokentiy Maslennikov, M. Iqbal Choudhary

Pharmacy Faculty Articles and Research

Ubiquitin-specific protease-7 (USP7) is an important drug target as it regulates multiple proteins and genes (such as MDM2 and p53) with roles in cancer progression. Its inhibition can hinder the function of oncogenes, increase tumor suppression, and enhance immune response. The current study was designed to express USP7 in a prokaryotic system, followed by screening of small molecules against it using biophysical methods, primarily STD-NMR technique. Among them, 12 compounds showed interaction with USP7 as inferred from NMR-based screening. These compounds further caused destabilization of USP7 by reducing its melting temperature (T_m) up to 6 °C in …

Tobacco Smoke Exposure Is A Driver Of Altered Oxidative Stress Response And Immunity In Head And Neck Cancer, Y Li, P Yadollahi, F Essien, V Putluri, Sra Chandra, K R Kami Reddy, Ahm Kamal, N Putluri, L M Abdurrahman, E Ruiz-Echartea, K Ernste, A Trivedi, J Vazquez-Perez, W H Hudson, W Decker, R Patel, A A Osman, F Kheradmand, S Y Lai, J N Myers, H D Skinner, C Coarfa, K Lee, A Jain, A Malovannaya, M J Frederick, V C Sandulache

Faculty, Staff and Students Publications

Purpose: Exposomes are critical drivers of carcinogenesis. However, how they modulate tumor behavior remains unclear. Extensive clinical data link cigarette smoke as a key exposome that promotes aggressive tumors, higher rates of metastasis, reduced response to chemoradiotherapy, and suppressed anti-tumor immunity. We sought to determine whether smoke itself can modulate aggressive tumor behavior in head and neck squamous cell carcinoma (HNSCC) through reprogramming the cellular reductive state.

Experimental design: Using established human and murine HNSCC cell lines and syngeneic mouse models, we utilized conventional western blotting, steady state and flux metabolomics, RNA sequencing, quantitative proteomics and flow cytometry to analyze …

Excess Potassium Promotes Autophagy To Maintain The Immunosuppressive Capacity Of Myeloid-Derived Suppressor Cells Independent Of Arginase 1, Ramesh Thylur Puttalingaiah, Matthew J. Dean, Liqin Zheng, Phaethon Philbrook, Dorota Wyczechowska, Timothy Kayes, Luis Del Valle, Denise Danos, Maria Dulfary Sanchez-Pino

School of Medicine Faculty Publications

Potassium ions (K+) are critical electrolytes that regulate multiple functions in immune cells. Recent studies have shown that the elevated concentration of extracellular potassium in the tumor interstitial fluid limits T cell effector function and suppresses the anti-tumor capacity of tumor-associated macrophages (TAMs). The effect of excess potassium on the biology of myeloid-derived suppressor cells (MDSCs), another important immune cell component of the tumor microenvironment (TME), is unknown. Here, we present data showing that increased concentrations of potassium chloride (KCl), as the source of K+ ions, facilitate autophagy by increasing the expression of the autophagosome marker LC3β. Simultaneously, excess potassium …

Policy-Relevant Differences Between Secondhand And Thirdhand Smoke: Strengthening Protections From Involuntary Exposure To Tobacco Smoke Pollutants, Georg E Matt, Lydia Greiner, Rachael A Record, Heather Wipfli, Jamie Long, Nathan G Dodder, Eunha Hoh, Nicolas Lopez Galvez, Thomas E Novotny, Penelope J E Quintana, Hugo Destaillats, Xiaochen Tang, Antoine M Snijders, Jian-Hua Mao, Bo Hang, Suzaynn Schick, Peyton Jacob, Prue Talbot, E Melinda Mahabee-Gittens, Ashley L Merianos, Thomas F Northrup, Lara Gundel, Neal L Benowitz

Faculty, Staff and Student Publications

Starting in the 1970s, individuals, businesses and the public have increasingly benefited from policies prohibiting smoking indoors, saving thousands of lives and billions of dollars in healthcare expenditures. Smokefree policies to protect against secondhand smoke exposure, however, do not fully protect the public from the persistent and toxic chemical residues from tobacco smoke (also known as thirdhand smoke) that linger in indoor environments for years after smoking stops. Nor do these policies address the economic costs that individuals, businesses and the public bear in their attempts to remediate this toxic residue. We discuss policy-relevant differences between secondhand smoke and thirdhand …

A Student-Community Partnership To Enhance Cancer Research Training, Rebecca J. Melillo, Christiane El Khoury, Amy L. Shaver, Moriah L. Cunningham, Nathalia Benavides, Quezia Lacerda, Felix J. Kim, Amy E. Leader

Kimmel Cancer Center Faculty Papers

BACKGROUND: Despite the importance of community involvement in research, little formal training in community outreach and engagement (COE) is offered to cancer research trainees. A collaboration between the Office of COE and the Office of Cancer Research Training and Education Coordination (CRTEC) at the Sidney Kimmel Comprehensive Cancer Center at Jefferson led to the COE-CRTEC Trainee Working Group, a unique program in which trainees in cancer research each created a novel COE initiative.

METHODS: Four cancer research trainees were selected to serve as COE Program Liaisons (CPLs), each aligned with one of the four cancer center research programs. Each CPL …

Neighborhood Effects On Acute Pediatric Asthma: Race, Greenspace, And Pm2.5, Elizabeth Wesley, Nathaniel A. Brunsell, David R. Rahn, Jarron M. Saint Onge, Natalie J. Kane, Kevin F. Kennedy

Manuscripts, Articles, Book Chapters and Other Papers

Urbanization produces spatially variable landscapes where climatic, environmental, and social systems interact in complex ways that affect public health. Environmental exposure along with the associated health risks are unevenly distributed and communities of color are often disproportionately affected by poor health outcomes. Acute pediatric asthma is the most common chronic condition of childhood in developed nations and is especially prevalent in minority and low-income children. In this study, we analyze the spatial variability of neighborhood-level acute pediatric asthma emergency department (ED) visits across the Kansas City Metro Area. Using Bayesian negative binomial regression, we describe the relationships and interactions between …

Molecular Mechanisms Of Biofilm Formation In Helicobacter Pylori, Kartika Afrida Fauzia, Wiwin Is Effendi, Ricky Indra Alfaray, Hoda M Malaty, Yoshio Yamaoka, Muhammad Mifthussurur

Faculty, Staff and Students Publications

BACKGROUND: Biofilm formation in

METHODS: We conducted a literature review analysis of the published articles on the

RESULTS: The results showed that biofilm formation starts as adhesion and progresses through micro-colonies, maturation, and dispersion in a planktonic form. Moreover, specific genes modulate each phase of biofilm formation. Few studies have shown that mechanisms, such as quorum sensing and diffusible signal factors, enhance coordination among bacteria when switching from biofilm to planktonic states. Different protein expressions were also observed between planktonic and biofilm strains, and the biofilm architecture was supported by exopolysaccharides, extracellular DNA, and outer membrane vesicles.

CONCLUSIONS: This infrastructure …

“Ups And Downs, Joys And Sorrows” – Assessment And Clinical Relevance Of Patient Priorities In An Interdisciplinary Parkinson’S Disease Clinic, Esme D. Trahair, Allison M. Allen, Sneha Mantri

Journal of Patient-Centered Research and Reviews

Purpose: Barriers to communication and inaccurate provider assumptions about patient priorities limit the delivery of comprehensive, high-quality, patient-centered care (PCC) to people with Parkinson’s (PWP). This study aimed to analyze priorities of PWP using a qualitative, unstructured single-question survey and to test associations with validated quality of life (QOL) measures.

Methods: During appointments at a subspecialty, interdisciplinary clinic, PWP (n = 139) provided written responses to the prompt: “What is important for your care team to know about you?” Patient Health Questionnaire, Montreal Cognitive Assessment, and Hoehn and Yahr scales were obtained through retrospective chart review. Key qualitative themes were …

“It Is What It Is” – The Lived Experience Of Women With Breast Cancer Undergoing Axillary Lymph Node Dissection, Eva Vikhe Patil, Anna Forsberg, Carina Wennerholm, Jenny Drott

Journal of Patient-Centered Research and Reviews

Purpose: The lived experience of women undergoing axillary procedures as part of their breast cancer (BC) treatment remains unexplored. This lack of in-depth understanding could hamper implementation of person-centred care, which is concerning because BC is the most common form of cancer in women. The aim of this study was therefore to explore the lived experiences of women undergoing axillary lymph node dissection (ALND) due to BC.

Methods: Twelve women with a mean age of 59 years were interviewed about their lived experiences of axillary procedures as part of their BC treatment. The interviews were recorded, transcribed verbatim, and analysed …

Biochemical And Structural Insights Into A 5′ To 3′ Rna Ligase Reveal A Potential Role In Trna Ligation, Yingjie Hu, Victor A Lopez, Hengyi Xu, James P Pfister, Bing Song, Kelly A Servage, Masahiro Sakurai, Benjamin T Jones, Joshua T Mendell, Tao Wang, Jun Wu, Alan M Lambowitz, Diana R Tomchick, Krzysztof Pawłowski, Vincent S Tagliabracci

Faculty, Staff and Student Publications

ATP-grasp superfamily enzymes contain a hand-like ATP-binding fold and catalyze a variety of reactions using a similar catalytic mechanism. More than 30 protein families are categorized in this superfamily, and they are involved in a plethora of cellular processes and human diseases. Here, we identify C12orf29 (RLIG1) as an atypical ATP-grasp enzyme that ligates RNA. Human RLIG1 and its homologs autoadenylate on an active site Lys residue as part of a reaction intermediate that specifically ligates RNA halves containing a 5’-phosphate and a 3’-hydroxyl. RLIG1 binds tRNA in cells and can ligate tRNA within the anticodon loop in vitro. Transcriptomic …

Yap1 Status Defines Two Intrinsic Subtypes Of Lcnec With Distinct Molecular Features And Therapeutic Vulnerabilities, C Allison Stewart, Lixia Diao, Yuanxin Xi, Runsheng Wang, Kavya Ramkumar, Alejandra G Serrano, Azusa Tanimoto, B Leticia Rodriguez, Benjamin B Morris, Li Shen, Bingnan Zhang, Yan Yang, Samera H Hamad, Robert J Cardnell, Alberto Duarte, Moushumi Sahu, Veronica Y Novegil, Bernard E Weissman, Michael Frumovitz, Neda Kalhor, Luisa Solis Soto, Pedro Da Rocha, Natalie Vokes, Don L Gibbons, Jing Wang, John V Heymach, Bonnie Glisson, Lauren Averett Byers, Carl M Gay

Faculty, Staff and Student Publications

Purpose: Large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine malignancy that, like small cell lung cancer (SCLC), is associated with the absence of druggable oncogenic drivers and dismal prognosis. In contrast to SCLC, however, there is little evidence to guide optimal treatment strategies, which are often adapted from SCLC and non-small cell lung cancer approaches.

Experimental design: To better define the biology of LCNEC, we analyzed cell line and patient genomic data and performed IHC and single-cell RNA sequencing of core needle biopsies from patients with LCNEC and preclinical models.

Results: In this study, we demonstrate that the presence …

Cdk12 Loss Drives Prostate Cancer Progression, Transcription-Replication Conflicts, And Synthetic Lethality With Paralog Cdk13, Jean Ching-Yi Tien, Jie Luo, Yu Chang, Yuping Zhang, Yunhui Cheng, Xiaoju Wang, Jianzhang Yang, Rahul Mannan, Somnath Mahapatra, Palak Shah, Xiao-Ming Wang, Abigail J Todd, Sanjana Eyunni, Caleb Cheng, Ryan J Rebernick, Lanbo Xiao, Yi Bao, James Neiswender, Rachel Brough, Stephen J Pettitt, Xuhong Cao, Stephanie J Miner, Licheng Zhou, Yi-Mi Wu, Estefania Labanca, Yuzhuo Wang, Abhijit Parolia, Marcin Cieslik, Dan R Robinson, Zhen Wang, Felix Y Feng, Jonathan Chou, Christopher J Lord, Ke Ding, Arul M Chinnaiyan

Faculty, Staff and Student Publications

Biallelic loss of cyclin-dependent kinase 12 (CDK12) defines a metastatic castration-resistant prostate cancer (mCRPC) subtype. It remains unclear, however, whether CDK12 loss drives prostate cancer (PCa) development or uncovers pharmacologic vulnerabilities. Here, we show Cdk12 ablation in murine prostate epithelium is sufficient to induce preneoplastic lesions with lymphocytic infiltration. In allograft-based CRISPR screening, Cdk12 loss associates positively with Trp53 inactivation but negatively with Pten inactivation. Moreover, concurrent Cdk12/Trp53 ablation promotes proliferation of prostate-derived organoids, while Cdk12 knockout in Pten-null mice abrogates prostate tumor growth. In syngeneic systems, Cdk12/Trp53-null allografts exhibit luminal morphology and immune checkpoint blockade sensitivity. Mechanistically, Cdk12 inactivation …

High-Sensitivity Cardiac Troponin [Hs-Ctn] As A Valuable Biomarker For Pulmonary Hypertension Risk Stratification: A Contemporary Review Of The Literature, Vijay Durga Pradeep Ganipineni, Sahas Reddy Jitta, Mohan Chandra Vinay Bharadwaj Gudiwada, Jaswanth Rao Jasti, Chaitra Janga, Bhavyasri Merugu, Revanth Reddy Bandaru, Srikanth Puli, Vikramaditya Samala Venkata, Advait Vasavada, Rupak Desai

Abington Jefferson Health Papers

Background: Pulmonary hypertension (PH) can lead to cardiac failure, thereby signif- icantly affecting life expectancy and quality of life. Due to inadequate disease surveillance and risk assessment, clinical challenges persist despite advances in diagnosis and treatment. We aimed to review the potential of high-sensitivity cardiac troponin (hs-cTn) as a biomarker for predicting outcomes in PH patients. Methods: A thorough examination of the PubMed and Google Scholar databases was conducted through March 2023. Studies involving adult PH patients and hsTn as a prognostic indicator of outcomes such as mortality, hospitalization, and disease progression were included, after screening their titles and abstracts. …

Memory Modulation: Dominance Of Negative Visual Context Over Neutral Verbal Memory, Stas Kozak, Noa Herz, Maya Tocker, Yair Bar-Haim, Nitzan Censor

Department of Neurology Faculty Papers

Neutral memories can be modulated via intentional memory control paradigms such as directed forgetting. In addition, previous studies have shown that neutral visual memories can be modulated indirectly, via remember and forget instructions towards competing verbal memories. Here we show that direct modulation of neutral verbal memory strength is impaired by negative visual context, and that negative visual context is resistant to indirect memory modulation. Participants were directly instructed to intentionally remember or forget newly encoded neutral verbal information. Importantly, this verbal information was interleaved with embedded negative visual context. Results showed that negative visual context eliminated the well-documented effect …

Bi-Directional Allosteric Pathway In Nmda Receptor Activation And Modulation, Paula A Bender, Subhajit Chakraborty, Ryan J Durham, Vladimir Berka, Elisa Carrillo, Vasanthi Jayaraman

Faculty, Staff and Student Publications

N-methyl-D-aspartate (NMDA) receptors are ionotropic glutamate receptors involved in learning and memory. NMDA receptors primarily comprise two GluN1 and two GluN2 subunits. The GluN2 subunit dictates biophysical receptor properties, including the extent of receptor activation and desensitization. GluN2A- and GluN2D-containing receptors represent two functional extremes. To uncover the conformational basis of their functional divergence, we utilize single-molecule fluorescence resonance energy transfer to probe the extracellular domains of these receptor subtypes under resting and ligand-bound conditions. We find that the conformational profile of the GluN2 amino-terminal domain correlates with the disparate functions of GluN2A- and GluN2D-containing receptors. Changes at the pre-transmembrane …

A Feasibility Study Of A Music Enrichment Program On Relative Reinforcing Value Of Food And Home Environmental Enrichment Among Families Of Low Socioeconomic Status., Kai Ling Kong, Amy R. Smith, Brenda Salley, Deanna Hanson-Abromeit, Hideko Engel, Catherine Serwatka

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Emerging evidence suggests that low socioeconomic status (SES) home environments may play a role by promoting excess energy intake through a lack of access to non-food reinforcers. Because of the deleterious effects of SES-related disparities on child health and development, feasible and culturally acceptable interventions are urgently needed. Community-based music enrichment programs may be an ideal intervention strategy.

METHODS: In collaboration with a local non-profit organization and music studio, we conducted a pilot randomized controlled trial to assess the effects of a music enrichment program versus a play date control in a group of 9-24-month-old healthy infants (N = …

A Unique Advantage Of A 24-Hour Surgical Delay In Autologous Breast Reconstruction, Devin M. Melancon, Daniel Yoo, Zachary Stern-Buchbinder, Samantha Morin, Hugo St. Hilaire, Robert J. Allen

School of Medicine Faculty Publications

Summary: The surgical delay technique can be used effectively in autologous breast reconstruction when there is unfavorable flap vascular anatomy or when the reconstruction necessitates a larger volume of donor tissue to obtain optimal results. The length of time between surgically delaying the flap to pedicle division and inset of the flap often varies based on surgeon preference but is typically approximately a week or longer. The authors present a case in which a 24-hour surgical delay was successfully used to augment deep inferior epigastric perforator flaps for autologous reconstruction. This technique is beneficial as it does not allow time …

Pandemic Perspectives From Detained Youth During Covid-19: Bridging The Knowledge Gap For Future Safeguards., April Mcneill-Johnson, Zuri Hudson, Brittany Moore, Dumebi Okocha, Megha Ramaswamy, Kimberly Randell

Manuscripts, Articles, Book Chapters and Other Papers

Despite the worsening health disparities among youth in detention during the COVID-19 pandemic, there has been minimal exploration into the pandemic experiences of detained youth and opportunities for pandemic mitigation. This paper analyzes the perspectives of youth in detention on the pandemic, including the effect of the pandemic on their detention experience and their perceptions about COVID-19 vaccination. The study used purposive sampling to recruit 16 participants (aged 14-17 years) from two juvenile detention centers in the urban Midwest. We conducted semi-structured interviews and analyzed verbatim transcripts using a hybrid deductive-inductive approach and thematic analysis. Four themes emerged: 1) personal …

Flagellar Motility Is Mutagenic, Souvik Bhattacharyya, Shelby Lopez, Abhyudai Singh, Rasika M Harshey

Faculty, Staff and Student Publications

Flagella are highly complex rotary molecular machines that enable bacteria to not only migrate to optimal environments but also to promote range expansion, competitiveness, virulence, and antibiotic survival. Flagellar motility is an energy-demanding process, where the sum of its production (biosynthesis) and operation (rotation) costs has been estimated to total ~10% of the entire energy budget of an

Atr Inhibition Radiosensitizes Cells Through Augmented Dna Damage And G2 Cell Cycle Arrest Abrogation, Scott J Bright, Mandira Manandhar, David B Flint, Rishab Kolachina, Mariam Ben Kacem, David Kj Martinus, Broderick X Turner, Ilsa Qureshi, Conor H Mcfadden, Poliana C Marinello, Simona F Shaitelman, Gabriel O Sawakuchi

Faculty, Staff and Student Publications

Ataxia telangiectasia and Rad3-related protein (ATR) is a key DNA damage response protein that facilitates DNA damage repair and regulates cell cycle progression. As such, ATR is an important component of the cellular response to radiation, particularly in cancer cells, which show altered DNA damage response and aberrant cell cycle checkpoints. Therefore, ATR's pharmacological inhibition could be an effective radiosensitization strategy to improve radiotherapy. We assessed the ability of an ATR inhibitor, AZD6738, to sensitize cancer cell lines of various histologic types to photon and proton radiotherapy. We found that radiosensitization took place through persistent DNA damage and abrogated G2 …

Tca Metabolism Regulates Dna Hypermethylation In Lps And Mycobacterium Tuberculosis–Induced Immune Tolerance, Abhimanyu, Santiago Carrero Longlax, Tomoki Nishiguchi, Malik Ladki, Daanish Sheikh, Amera L Martinez, Emily M Mace, Sandra L Grimm, Thaleia Caldwell, Alexandra Portillo Varela, Rajagopal V Sekhar, Anna M Mandalakas, Mandla Mlotshwa, Sibuse Ginidza, Jeffrey D Cirillo, Robert S Wallis, Mihai G Netea, Reinout Van Crevel, Cristian Coarfa, Andrew R Dinardo

Faculty, Staff and Students Publications

Severe and chronic infections, including pneumonia, sepsis, and tuberculosis (TB), induce long-lasting epigenetic changes that are associated with an increase in all-cause postinfectious morbidity and mortality. Oncology studies identified metabolic drivers of the epigenetic landscape, with the tricarboxylic acid (TCA) cycle acting as a central hub. It is unknown if the TCA cycle also regulates epigenetics, specifically DNA methylation, after infection-induced immune tolerance. The following studies demonstrate that lipopolysaccharide and Mycobacterium tuberculosis induce changes in DNA methylation that are mediated by the TCA cycle. Infection-induced DNA hypermethylation is mitigated by inhibitors of cellular metabolism (rapamycin, everolimus, metformin) and the TCA …

Alzheimer’S Disease Risk Gene Cd2ap Is A Dose-Sensitive Determinant Of Synaptic Structure And Plasticity, Matea Pavešković, Ruth B De-Paula, Shamsideen A Ojelade, Evelyne K Tantry, Mikhail Y Kochukov, Suyang Bao, Surabi Veeraragavan, Alexandra R Garza, Snigdha Srivastava, Si-Yuan Song, Masashi Fujita, Duc M Duong, David A Bennett, Philip L De Jager, Nicholas T Seyfried, Mary E Dickinson, Jason D Heaney, Benjamin R Arenkiel, Joshua M Shulman

Duncan NRI Faculty and Staff Publications

CD2-Associated protein (CD2AP) is a candidate susceptibility gene for Alzheimer's disease, but its role in the mammalian central nervous system remains largely unknown. We show that CD2AP protein is broadly expressed in the adult mouse brain, including within cortical and hippocampal neurons, where it is detected at pre-synaptic terminals. Deletion of Cd2ap altered dendritic branching and spine density, and impaired ubiquitin-proteasome system activity. Moreover, in mice harboring either one or two copies of a germline Cd2ap null allele, we noted increased paired-pulse facilitation at hippocampal Schaffer-collateral synapses, consistent with a haploinsufficient requirement for pre-synaptic release. Whereas conditional Cd2ap knockout in …

The Fundamentals Of Antiseizure Medications: A Through Z, Timothy E Welty, Jeannine M Conway, Jacquelyn Bainbridge, Kristen Park, David G Vossler, Archana A Patel, Alica Goldman

Faculty, Staff and Students Publications

Since bromides were first used in 1857 to treat epilepsy, numerous antiseizure medications (ASM) have been developed. Many of these are available for the treatment of epilepsy and status epilepticus today. With so many ASM available, questions arise as to whether all of these medications are needed and when should they be used. As precision medicine begins to play a larger role in determining targeted treatments for specific types of epilepsy, a complete understanding of various medications is needed. Additionally, access to several of these medications can be limited in the United States and are especially limited globally. All these …