Digital Commons Network^™

What Is The Intention To Move And When Does It Occur?, Antonio I. Triggiani, Gabriel Kreiman, Cara Lewis, Uri Maoz, Alfred Mele, Liad Mudrik, Adina L. Roskies, Aaron Schurger, Mark Hallett

Psychology Faculty Articles and Research

In 1983 Benjamin Libet and colleagues published a paper apparently challenging the view that the conscious intention to move precedes the brain’s preparation for movement. The experiment initiated debates about the nature of intention, the neurophysiology of movement, and philosophical and legal understanding of free will and moral responsibility. Here we review the concept of “conscious intention” and attempts to measure its timing. Scalp electroencephalographic activity prior to movement, the Bereitschaftspotential, clearly begins prior to the reported onset of conscious intent. However, the interpretation of this finding remains controversial. Numerous studies show that the Libet method for determining intent, W …

Hica Toxin-Based Counterselection Marker For Allelic Exchange Mutations In Fusobacterium Nucleatum, Bibek Gc, Peng Zhou, Chenggang Wu

Faculty, Staff and Student Publications

The study of fusobacterial virulence factors has dramatically benefited from the creation of various genetic tools for DNA manipulation, including galK-based counterselection for in-frame deletion mutagenesis in Fusobacterium nucleatum, which was recently developed. However, this method requires a host lacking the galK gene, which is an inherent limitation. To circumvent this limitation, we explored the possibility of using the hicA gene that encodes a toxin consisting of a HicAB toxin-antitoxin module in Fusobacterium periodonticum as a new counterselective marker. Interestingly, the full-length hicA gene is not toxic in F. nucleatum, but a truncated hicA gene version lacking the first …

Bridging Clinic And Wildlife Care With Ai-Powered Pan-Species Computational Pathology, Khalid Abduljabbar, Simon P Castillo, Katherine Hughes, Hannah Davidson, Amy M Boddy, Lisa M Abegglen, Lucia Minoli, Selina Iussich, Elizabeth P Murchison, Trevor A Graham, Simon Spiro, Carlo C Maley, Luca Aresu, Chiara Palmieri, Yinyin Yuan

Faculty, Staff and Student Publications

Cancers occur across species. Understanding what is consistent and varies across species can provide new insights into cancer initiation and evolution, with significant implications for animal welfare and wildlife conservation. We build a pan-species cancer digital pathology atlas (panspecies.ai) and conduct a pan-species study of computational comparative pathology using a supervised convolutional neural network algorithm trained on human samples. The artificial intelligence algorithm achieves high accuracy in measuring immune response through single-cell classification for two transmissible cancers (canine transmissible venereal tumour, 0.94; Tasmanian devil facial tumour disease, 0.88). In 18 other vertebrate species (mammalia = 11, reptilia = 4, aves …

Overcoming Adaptive Resistance To Anti-Vegf Therapy By Targeting Cd5l, Christopher J Lafargue, Paola Amero, Kyunghee Noh, Lingegowda S Mangala, Yunfei Wen, Emine Bayraktar, Sujanitha Umamaheswaran, Elaine Stur, Santosh K Dasari, Cristina Ivan, Sunila Pradeep, Wonbeak Yoo, Chunhua Lu, Nicholas B Jennings, Vinod Vathipadiekal, Wei Hu, Anca Chelariu-Raicu, Zhiqiang Ku, Hui Deng, Wei Xiong, Hyun-Jin Choi, Min Hu, Takae Kiyama, Chai-An Mao, Rouba Ali-Fehmi, Michael J Birrer, Jinsong Liu, Ningyan Zhang, Gabriel Lopez-Berestein, Vittorio De Franciscis, Zhiqiang An, Anil K Sood

Faculty, Staff and Student Publications

Antiangiogenic treatment targeting the vascular endothelial growth factor (VEGF) pathway is a powerful tool to combat tumor growth and progression; however, drug resistance frequently emerges. We identify CD5L (CD5 antigen-like precursor) as an important gene upregulated in response to antiangiogenic therapy leading to the emergence of adaptive resistance. By using both an RNA-aptamer and a monoclonal antibody targeting CD5L, we are able to abate the pro-angiogenic effects of CD5L overexpression in both in vitro and in vivo settings. In addition, we find that increased expression of vascular CD5L in cancer patients is associated with bevacizumab resistance and worse overall survival. …

Investigating Differences In Iga Antibody Response Against Aspergillus Fumigatus In Wild Type And Tlr7 Protein Deficient Mice, Courtney Folk

Student Academic Conference

Aspergillus fumigatus is a commonly inhaled, respiratory fungal pathogen and an allergen found in flooded indoor environments, household dust, soil, and plant matter. While a competent immune system effectively clears the inhaled fungus, this same fungus poses a significant threat to weakened immune systems due to its potential to invade the lungs, bloodstream and brain tissue. The mouse genome is 99% similar to the human genome and can serve effectively model the effects of inhaled A. fumigatus (Guénet, 2005). Antibodies play a crucial role in neutralizing pathogens and in mediating an allergic response. In this study, we will investigate the …

A Phenomenological Take On Mirror Self-Face Perception In Schizophrenia, Giovanni Pennisi

Journal of Mind and Medical Sciences

Studies concerning social deficits in schizophrenia has often been restrained to exploring facial recognition. Various investigations have shown that those diagnosed with schizophrenia have difficulties in perceiving the identities and emotions of those around them merely through observing their facial features. A few others have also taken into account the issue of self-face recognition in individuals with schizophrenia, finding that their capacity to associate photos or videos of their own face to themselves is hindered due to the illness. However, to my knowledge, only a few studies have so far delved into the intricacies of how individuals with schizophrenia or …

The Inherited Intestinal Microbiota From Myeloid-Specific Zip8ko Mice Impairs Pulmonary Host Defense Against Pneumococcal Pneumonia, Derrick R. Samuelson, Deandra R. Smith, Kelly C. Cunningham, Sabah Haq, Daniel N. Villageliú, Christi Christi Ellis, Niaz Bahar Chowdhury, Amanda E. Ramer-Tait, Jeff Price, Daren L. Knoell

Food for Health: Publications

Intestinal dysbiosis increases susceptibility to infection through the alteration of metabolic profiles, which increases morbidity. Zinc (Zn) homeostasis in mammals is tightly regulated by 24 Zn transporters. ZIP8 is unique in that it is required by myeloid cells to maintain proper host defense against bacterial pneumonia. In addition, a frequently occurring ZIP8 defective variant (SLC39A8 rs13107325) is strongly associated with inflammation-based disorders and bacterial infection. In this study, we developed a novel model to study the effects of ZIP8-mediated intestinal dysbiosis on pulmonary host defense independent of the genetic effects. Cecal microbial communities from a myeloid-specific Zip8 knockout mouse …

Modelling Radiation Cancer Treatment With A Death-Rate Term In Ordinary And Fractional Differential Equations, Nicole Wilson, Corina S Drapaca, Heiko Enderling, Jimmy J Caudell, Kathleen P Wilkie

Faculty, Staff and Student Publications

Fractional calculus has recently been applied to the mathematical modelling of tumour growth, but its use introduces complexities that may not be warranted. Mathematical modelling with differential equations is a standard approach to study and predict treatment outcomes for population-level and patient-specific responses. Here, we use patient data of radiation-treated tumours to discuss the benefits and limitations of introducing fractional derivatives into three standard models of tumour growth. The fractional derivative introduces a history-dependence into the growth function, which requires a continuous death-rate term for radiation treatment. This newly proposed radiation-induced death-rate term improves computational efficiency in both ordinary and …

Cdk5-Prmt1-Wdr24 Signaling Cascade Promotes Mtorc1 Signaling And Tumor Growth, Shasha Yin, Liu Liu, Lauren E Ball, Yalong Wang, Mark T Bedford, Stephen A Duncan, Haizhen Wang, Wenjian Gan

Faculty, Staff and Student Publications

The mammalian target of rapamycin complex1 (mTORC1) is a central regulator of metabolism and cell growth by sensing diverse environmental signals, including amino acids. The GATOR2 complex is a key component linking amino acid signals to mTORC1. Here, we identify protein arginine methyltransferase 1 (PRMT1) as a critical regulator of GATOR2. In response to amino acids, cyclin-dependent kinase 5 (CDK5) phosphorylates PRMT1 at S307 to promote PRMT1 translocation from nucleus to cytoplasm and lysosome, which in turn methylates WDR24, an essential component of GATOR2, to activate the mTORC1 pathway. Disruption of the CDK5-PRMT1-WDR24 axis suppresses hepatocellular carcinoma (HCC) cell proliferation …

Saturated Fatty Acids Dampen The Immunogenicity Of Cancer By Suppressing Sting, Blake R Heath, Wang Gong, Hülya F Taner, Luke Broses, Kohei Okuyama, Wanqing Cheng, Max Jin, Zackary R Fitzsimonds, Andriana Manousidaki, Yuesong Wu, Shaoping Zhang, Haitao Wen, Steven B Chinn, Eric Bartee, Yuying Xie, James J Moon, Yu Leo Lei

Faculty, Staff and Student Publications

Oncogenes destabilize STING in epithelial cell-derived cancer cells, such as head and neck squamous cell carcinomas (HNSCCs), to promote immune escape. Despite the abundance of tumor-infiltrating myeloid cells, HNSCC presents notable resistance to STING stimulation. Here, we show how saturated fatty acids in the microenvironment dampen tumor response to STING stimulation. Using single-cell analysis, we found that obesity creates an IFN-I-deprived tumor microenvironment with a massive expansion of suppressive myeloid cell clusters and contraction of effector T cells. Saturated fatty acids, but not unsaturated fatty acids, potently inhibit the STING-IFN-I pathway in HNSCC cells. Myeloid cells from obese mice show …

Review Of The Tumor Microenvironment In Basal And Squamous Cell Carcinoma, Elizabeth Chiang, Haleigh Stafford, Jane Buell, Uma Ramesh, Moran Amit, Priyadharsini Nagarajan, Michael Migden, Dan Yaniv

Faculty, Staff and Student Publications

It is widely known that tumor cells of basal and squamous cell carcinoma interact with the cellular and acellular components of the tumor microenvironment to promote tumor growth and progression. While this environment differs for basal and squamous cell carcinoma, the cellular players within both create an immunosuppressed environment by downregulating effector CD4+ and CD8+ T cells and promoting the release of pro-oncogenic Th2 cytokines. Understanding the crosstalk that occurs within the tumor microenvironment has led to the development of immunotherapeutic agents, including vismodegib and cemiplimab to treat BCC and SCC, respectively. However, further investigation of the TME will provide …

Beneficial Actions Of Sglt2 Inhibition And H2s Therapy In Heart Failure With Preserved Ejection Fraction, Jake Doiron, Zhen Li, Huijing Xia, Kyle B. Lapenna, Timothy D. Allerton, Daniel R. Kapusta, David J. Lefer

School of Graduate Studies Faculty Publications

Association for Clinical and Translational Science, ACTS 2023, April 18 - 20, 2023, Washington DC

Combined Inhibition Of Bcl-2 And Mcl-1 Overcomes Bax Deficiency-Mediated Resistance Of Tp53-Mutant Acute Myeloid Leukemia To Individual Bh3 Mimetics, Bing Z Carter, Po Yee Mak, Wenjing Tao, Edward Ayoub, Lauren B Ostermann, Xuelin Huang, Sanam Loghavi, Steffen Boettcher, Yuki Nishida, Vivian Ruvolo, Paul E Hughes, Phuong K Morrow, Torsten Haferlach, Steven Kornblau, Muharrem Muftuoglu, Michael Andreeff

Faculty, Staff and Student Publications

TP53-mutant acute myeloid leukemia (AML) respond poorly to currently available treatments, including venetoclax-based drug combinations and pose a major therapeutic challenge. Analyses of RNA sequencing and reverse phase protein array datasets revealed significantly lower BAX RNA and protein levels in TP53-mutant compared to TP53-wild-type (WT) AML, a finding confirmed in isogenic CRISPR-generated TP53-knockout and -mutant AML. The response to either BCL-2 (venetoclax) or MCL-1 (AMG176) inhibition was BAX-dependent and much reduced in TP53-mutant compared to TP53-WT cells, while the combination of two BH3 mimetics effectively activated BAX, circumventing survival mechanisms in cells treated with either BH3 mimetic, and synergistically induced …

A Small Secreted Protein Nicol Regulates Lumicrine-Mediated Sperm Maturation And Male Fertility, Daiji Kiyozumi, Kentaro Shimada, Michael Chalick, Chihiro Emori, Mayo Kodani, Seiya Oura, Taichi Noda, Tsutomu Endo, Martin M Matzuk, Daniel H Wreschner, Masahito Ikawa

Faculty, Staff and Students Publications

The mammalian spermatozoa produced in the testis require functional maturation in the epididymis for their full competence. Epididymal sperm maturation is regulated by lumicrine signalling pathways in which testis-derived secreted signals relocate to the epididymis lumen and promote functional differentiation. However, the detailed mechanisms of lumicrine regulation are unclear. Herein, we demonstrate that a small secreted protein, NELL2-interacting cofactor for lumicrine signalling (NICOL), plays a crucial role in lumicrine signalling in mice. NICOL is expressed in male reproductive organs, including the testis, and forms a complex with the testis-secreted protein NELL2, which is transported transluminally from the testis to the …

Developmental Exposure To Corn Grown On Lake Erie Dredged Material: A Preliminary Analysis, Kaylyn A. S. Flanigan, Madelyn I. Czuba, Victoria R. Riesgo, Megan A. Rúa, Louise M. Stevenson, Jari Willing

Biological Sciences Faculty Publications

While corn is considered to be a healthy food option, common agricultural practices, such as the application of soil amendments, might be introducing contaminants of concern (COC) into corn plants. The use of dredged material, which contain contaminants such as heavy metals, polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs), as a soil amendment is increasing. Contaminants from these amendments can accumulate in corn kernels harvested from plants grown on these sediments and potentially biomagnify in organisms that consume them. The extent to which secondary exposure to such contaminants in corn affect the mammalian central nervous system has been virtually …

Comparative Study Of Adenosine Analogs As Inhibitors Of Protein Arginine Methyltransferases And A Clostridioides Difficile- Specific Dna Adenine Methyltransferase, Jujun Zhou, Youchao Deng, Iredia D Iyamu, John R Horton, Dan Yu, Taraneh Hajian, Masoud Vedadi, Dante Rotili, Antonello Mai, Robert M Blumenthal, Xing Zhang, Rong Huang, Xiaodong Cheng

Faculty, Staff and Student Publications

S-Adenosyl-l-methionine (SAM) analogs are adaptable tools for studying and therapeutically inhibiting SAM-dependent methyltransferases (MTases). Some MTases play significant roles in host–pathogen interactions, one of which is Clostridioides difficile-specific DNA adenine MTase (CamA). CamA is needed for efficient sporulation and alters persistence in the colon. To discover potent and selective CamA inhibitors, we explored modifications of the solvent-exposed edge of the SAM adenosine moiety. Starting from the two parental compounds (6e and 7), we designed an adenosine analog (11a) carrying a 3-phenylpropyl moiety at the adenine N6-amino group, and a 3-(cyclohexylmethyl guanidine)-ethyl moiety at the …

Cross-Dataset Single-Cell Analysis Identifies Temporal Alterations In Cell Populations Of Primary Pancreatic Tumor And Liver Metastasis, Daowei Yang, Rohan Moniruzzaman, Hua Wang, Huamin Wang, Yang Chen

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) has a unique tumor microenvironment composed of various cell populations such as cancer cells, cancer-associated fibroblasts (CAFs), immune cells, and endothelial cells. Recently, single-cell RNA-sequencing analysis (scRNA-seq) has systemically revealed the genomic profiles of these cell populations in PDAC. However, the direct comparison of cell population composition and genomic profile between primary tumors (at both early- and late-stage) and metastatic tumors of PDAC is still lacking. In this study, we combined and analyzed recent scRNA-seq datasets of transgenic KPC mouse models with autochthonous PDAC and matched liver metastasis, revealing the unique tumor ecosystem and cell composition …

Synthetic Errα/Β/Γ Agonist Induces An Errα-Dependent Acute Aerobic Exercise Response And Enhances Exercise Capacity, Cyrielle Billon, Sadichha Sitaula, Subhashis Banerjee, Ryan Welch, Bahaa Elgendy, Lamees Hegazy, Tae Gyu Oh, Melissa Kazantzis, Arindam Chatterjee, John Chrivia, Matthew E Hayes, Weiyi Xu, Angelica Hamilton, Janice M Huss, Lilei Zhang, John K Walker, Michael Downes, Ronald M Evans, Thomas P Burris

Faculty, Staff and Students Publications

Repetitive physical exercise induces physiological adaptations in skeletal muscle that improves exercise performance and is effective for the prevention and treatment of several diseases. Genetic evidence indicates that the orphan nuclear receptors estrogen receptor-related receptors (ERRs) play an important role in skeletal muscle exercise capacity. Three ERR subtypes exist (ERRα, β, and γ), and although ERRβ/γ agonists have been designed, there have been significant difficulties in designing compounds with ERRα agonist activity. Additionally, there are limited synthetic agonists that can be used to target ERRs in vivo. Here, we report the …

Corneal Injury Is Associated With Stromal And Vascular Alterations Within Cranial Dura Mater, Olga V. Glinskii, Vladislav V. Glinsky, Leike Xie, Filiz Bunyak, Vladimir V. Glinskii, Sunilima Sinha, Suneel Gupta, Renato V. Iozzo, Rajiv R. Mohan

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The cornea and cranial dura mater share sensory innervation. This link raises the possibility that pathological impulses mediated by corneal injury may be transmitted to the cranial dura, trigger dural perivascular/connective tissue nociceptor responses, and induce vascular and stromal alterations affecting dura mater blood and lymphatic vessel functionality. In this study, using a mouse model, we demonstrate for the first time that two weeks after the initial insult, alkaline injury to the cornea leads to remote pathological changes within the coronal suture area of the dura mater. Specifically, we detected significant pro-fibrotic changes in the dural stroma, as well as …

Ppgpp And Rna-Polymerase Backtracking Guide Antibiotic-Induced Mutable Gambler Cells, Yin Zhai, P J Minnick, John P Pribis, Libertad Garcia-Villada, P J Hastings, Christophe Herman, Susan M Rosenberg

Faculty, Staff and Students Publications

Antibiotic resistance is a global health threat and often results from new mutations. Antibiotics can induce mutations via mechanisms activated by stress responses, which both reveal environmental cues of mutagenesis and are weak links in mutagenesis networks. Network inhibition could slow the evolution of resistance during antibiotic therapies. Despite its pivotal importance, few identities and fewer functions of stress responses in mutagenesis are clear. Here, we identify the Escherichia coli stringent starvation response in fluoroquinolone-antibiotic ciprofloxacin-induced mutagenesis. Binding of response-activator ppGpp to RNA polymerase (RNAP) at two sites leads to an antibiotic-induced mutable gambler-cell subpopulation. Each activates a stress response …

An Altered Extracellular Matrix-Integrin Interface Contributes To Huntington’S Disease-Associated Cns Dysfunction In Glial And Vascular Cells, Sarah J Hernandez, Ryan G Lim, Tarik Onur, Mark A Dane, Rebecca Smith, Keona Wang, Grace En-Hway Jean, Andrea Reyes-Ortiz, Kaylyn Devlin, Ricardo Miramontes, Jie Wu, Malcolm Casale, David Kilburn, Laura M Heiser, James E Korkola, David Van Vactor, Juan Botas, Katherine L Thompson-Peer, Leslie M Thompson

Faculty, Staff and Students Publications

Astrocytes and brain endothelial cells are components of the neurovascular unit that comprises the blood-brain barrier (BBB) and their dysfunction contributes to pathogenesis in Huntington's disease (HD). Defining the contribution of these cells to disease can inform cell-type-specific effects and uncover new disease-modifying therapeutic targets. These cells express integrin (ITG) adhesion receptors that anchor the cells to the extracellular matrix (ECM) to maintain the integrity of the BBB. We used HD patient-derived induced pluripotent stem cell (iPSC) modeling to study the ECM-ITG interface in astrocytes and brain microvascular endothelial cells and found ECM-ITG dysregulation in human iPSC-derived cells that may …

Mixed Depression In The Post-Covid-19 Syndrome: Correlation Between Excitatory Symptoms In Depression And Physical Burden After Covid-19, Alessio Simonetti, Evelina Bernardi, Stella Margoni, Antonello Catinari, Antonio Restaino, Valentina Ieritano, Marta Palazzetti, Federico Mastrantonio, Delfina Janiri, Matteo Tosato, Francesco Landi, Gabriele Sani

Faculty, Staff and Students Publications

The relationship between depression and post-COVID-19 disease syndrome (post-COVID-19 syndrome) is established. Nevertheless, few studies have investigated the association between post-COVID-19 syndrome and mixed depression, i.e., a specific sub-form of depression characterized by high level of excitatory symptoms. Aims of the present study are: (a) to compare the post-COVID-19 syndrome's burden in depressed and non-depressed patients, and (b) to investigate the correlation between post-COVID-19 syndrome's burden and the severity of mixed depression. One thousand and forty six (n = 1460) subjects with post-COVID-19 syndrome were assessed. Subjects were divided into those with (DEP) or without (CONT) depression. Sociodemographically, post-COVID-19 syndrome's …

Computational Design And Molecular Modeling Of Morphine Derivatives For Preferential Binding In Inflamed Tissue, Makena Augenstein, Nayiri Alexander, Matthew Gartner

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The opioid epidemic has impacted over 10 million Americans in 2019. Opioids, like morphine, bind non-selectively in both peripheral tissue, leading to effective pain relief, and central tissue, resulting in dangerous side effects and addiction. The inflamed conditions of injured tissues have a lower pH (pH = 6–6.5) environment than healthy tissue (pH = 7.4). We aim to design a morphine derivative that binds selectively within inflamed tissue using molecular extension and dissection techniques. Morphine binds to the μ-opioid receptor (MOR) when the biochemically active amine group is protonated. Fluorination of a β-carbon from the tertiary amine group led to …

Circadian Clock Control Of Mrtf/Srf Pathway Suppresses Beige Adipocyte Thermogenic Recruitment, Xuekai Xiong, Weini Li, Ruya Liu, Pradip Saha, Vijay Yechoor, Ke Ma

Faculty, Staff and Students Publications

The morphological transformation of adipogenic progenitors into mature adipocytes requires dissolution of actin cytoskeleton with loss of myocardin-related transcription factor (MRTF)/serum response factor (SRF) activity. Circadian clock confers temporal control in adipogenic differentiation, while the actin cytoskeleton-MRTF/SRF signaling transduces extracellular physical niche cues. Here, we define a novel circadian transcriptional control involved in actin cytoskeleton-MRTF/SRF signaling cascade that modulates beige fat thermogenic function. Key components of actin dynamic-MRTF/SRF pathway display circadian regulation in beige fat depot. The core clock regulator, brain and muscle arnt-like 1 (Bmal1), exerts direct transcriptional control of genes within the actin dynamic-MRTF/SRF cascade that impacts actin …

Sptssa Variants Alter Sphingolipid Synthesis And Cause A Complex Hereditary Spastic Paraplegia, Siddharth Srivastava, Hagar Mor Shaked, Kenneth Gable, Sita D Gupta, Xueyang Pan, Niranjanakumari Somashekarappa, Gongshe Han, Payam Mohassel, Marc Gotkine, Elizabeth Doney, Paula Goldenberg, Queenie K G Tan, Yi Gong, Benjamin Kleinstiver, Brian Wishart, Heidi Cope, Claudia Brito Pires, Hannah Stutzman, Rebecca C Spillmann, Undiagnosed Disease Network, Reza Sadjadi, Orly Elpeleg, Chia-Hsueh Lee, Hugo J Bellen, Simon Edvardson, Florian Eichler, Teresa M Dunn

Faculty, Staff and Students Publications

Sphingolipids are a diverse family of lipids with critical structural and signalling functions in the mammalian nervous system, where they are abundant in myelin membranes. Serine palmitoyltransferase, the enzyme that catalyses the rate-limiting reaction of sphingolipid synthesis, is composed of multiple subunits including an activating subunit, SPTSSA. Sphingolipids are both essential and cytotoxic and their synthesis must therefore be tightly regulated. Key to the homeostatic regulation are the ORMDL proteins that are bound to serine palmitoyltransferase and mediate feedback inhibition of enzymatic activity when sphingolipid levels become excessive. Exome sequencing identified potential disease-causing variants in SPTSSA in three children presenting …

Social Deprivation Induces Astrocytic Trpa1-Gaba Suppression Of Hippocampal Circuits, Yi-Ting Cheng, Junsung Woo, Estefania Luna-Figueroa, Ehson Maleki, Akdes Serin Harmanci, Benjamin Deneen

Faculty, Staff and Students Publications

Social experience is essential for the development and maintenance of higher order brain function. Social deprivation results in a host of cognitive deficits and cellular studies have largely focused on associated neuronal dysregulation; how astrocyte function is impacted by social deprivation is unknown. Here we show that hippocampal astrocytes from juvenile mice subjected to social isolation exhibit increased Ca2+ activity and global changes in gene expression. We found that the Ca2+ channel TRPA1 is upregulated in astrocytes after social deprivation and astrocyte-specific deletion of TRPA1 reverses the physiological and cognitive deficits associated with social deprivation. Mechanistically, TRPA1 inhibition of hippocampal …

Development And Characterization Of Inducible Astrocyte-Specific Aromatase Knockout Mice, Jing Wang, Uday P Pratap, Yujiao Lu, Gangadhara R Sareddy, Rajeshwar R Tekmal, Ratna K Vadlamudi, Darrell W Brann

Faculty, Staff and Student Publications

17β-estradiol (E2) is produced in the brain as a neurosteroid, in addition to being an endocrine signal in the periphery. The current animal models for studying brain-derived E2 include global and conditional non-inducible knockout mouse models. The aim of this study was to develop a tamoxifen (TMX)-inducible astrocyte-specific aromatase knockout mouse line (GFAP-ARO-iKO mice) to specifically deplete the E2 synthesis enzymes and aromatase in astrocytes after their development in adult mice. The characterization of the GFAP-ARO-iKO mice revealed a specific and robust depletion in the aromatase expressions of their astrocytes and a significant decrease in their hippocampal E2 levels after …

Modeling Collective Cell Behavior In Cancer: Perspectives From An Interdisciplinary Conversation, Frederick R Adler, Alexander R A Anderson, Abhinav Bhushan, Paul Bogdan, Jose Javier Bravo-Cordero, Amy Brock, Yun Chen, Edna Cukierman, Kathleen E Delgiorno, Gerald V Denis, Meghan C Ferrall-Fairbanks, Zev Jordan Gartner, Ronald N Germain, Deborah M Gordon, Ginger Hunter, Mohit Kumar Jolly, Loukia Georgiou Karacosta, Karthikeyan Mythreye, Parag Katira, Rajan P Kulkarni, Matthew L Kutys, Arthur D Lander, Ashley M Laughney, Herbert Levine, Emil Lou, Pedro R Lowenstein, Kristyn S Masters, Dana Pe'er, Shelly R Peyton, Manu O Platt, Jeremy E Purvis, Gerald Quon, Jennifer K Richer, Nicole C Riddle, Analiz Rodriguez, Joshua C Snyder, Gregory Lee Szeto, Claire J Tomlin, Itai Yanai, Ioannis K Zervantonakis, Hannah Dueck

Faculty, Staff and Student Publications

Collective cell behavior contributes to all stages of cancer progression. Understanding how collective behavior emerges through cell-cell interactions and decision-making will advance our understanding of cancer biology and provide new therapeutic approaches. Here, we summarize an interdisciplinary discussion on multicellular behavior in cancer, draw lessons from other scientific disciplines, and identify future directions.

Survey Of Nutrition Education Among Medical Students, Michael P. Duggan, Anahita T. Kodali, Zach A. Panton, Shannon M. Smith, Grant J. Riew, Jack F. Donaghue, Gregory A. Leya, Logan G. Briggs

Journal of Wellness

Introduction: The current literature regarding both specific interventions and the current level of nutrition education in the United States is scarce. The purpose of this paper is to provide medical student perspectives on both the degree and necessity of nutrition education during medical school.

Methods: Medicine in Motion (MM) is a non-profit student-run organization founded in 2018 that aims to address burnout in medicine through physical activity, community service, and philanthropy. MM issued a survey to nine of its chapters in January 2021 to assess a range of topics including burnout, physical activity, and nutrition education.

Results: Of 5500 invited …

Children's And Caregivers' Review Of A Guided Imagery Therapy Mobile App Designed To Treat Children With Functional Abdominal Pain Disorders: Leveraging A Mixed Methods Approach With User-Centered Design, John M Hollier, Tiantá A Strickland, C Michael Fordis, Miranda Al Van Tilburg, Robert J Shulman, Debbe Thompson

Faculty, Staff and Students Publications

BACKGROUND: Functional abdominal pain disorders (FAPDs) are highly prevalent and associated with substantial morbidity. Guided imagery therapy (GIT) is efficacious; however, barriers often impede patient access. Therefore, we developed a GIT mobile app as a novel delivery platform.

OBJECTIVE: Guided by user-centered design, this study captured the critiques of our GIT app from children with FAPDs and their caregivers.

METHODS: Children aged 7 to 12 years with Rome IV-defined FAPDs and their caregivers were enrolled. The participants completed a software evaluation, which assessed how well they executed specific app tasks: opening the app, logging in, initiating a session, setting the …