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Therapeutic Effects Of Combining Curcumin And Swimming In Osteoarthritis Using A Rat Model, Mona M Saber, Manal Moustafa Mahmoud, Hesham M Amin, Reham M Essam Oct 2023

Therapeutic Effects Of Combining Curcumin And Swimming In Osteoarthritis Using A Rat Model, Mona M Saber, Manal Moustafa Mahmoud, Hesham M Amin, Reham M Essam

Faculty, Staff and Student Publications

Osteoarthritis (OA) is a common debilitating degenerative disease of the elderly. We aimed to study the therapeutic effects of combining curcumin and swimming in monosodium iodoacetate (MIA)-induced OA in a rat model. The rats were divided into 5 groups (n = 9). Group 1 received saline and served as a control group. Groups 2-5 were injected intra-articularly in the right knee with 100 μL MIA. One week later, groups 3 and 5 were started on daily swimming sessions that gradually increased to 20-mins per session, and for groups 4 and 5, oral curcumin was administered at a dose of 200 …


Young-Onset Rectal Cancer: Unique Tumoral Microbiome And Correlation With Response To Neoadjuvant Therapy, Michael G White, Ashish Damania, Jumanah Alshenaifi, Pranoti Sahasrabhojane, Oliver Peacock, Jillian Losh, Matthew C Wong, Zuzana Lutter-Berkova, George J Chang, Andrew Futreal, Jennifer A Wargo, Nadim J Ajami, Scott Kopetz, Y Nancy You Oct 2023

Young-Onset Rectal Cancer: Unique Tumoral Microbiome And Correlation With Response To Neoadjuvant Therapy, Michael G White, Ashish Damania, Jumanah Alshenaifi, Pranoti Sahasrabhojane, Oliver Peacock, Jillian Losh, Matthew C Wong, Zuzana Lutter-Berkova, George J Chang, Andrew Futreal, Jennifer A Wargo, Nadim J Ajami, Scott Kopetz, Y Nancy You

Faculty, Staff and Student Publications

OBJECTIVE: External exposures, the host, and the microbiome interact in oncology. We aimed to investigate tumoral microbiomes in young-onset rectal cancers (YORCs) for profiles potentially correlative with disease etiology and biology.

BACKGROUND: YORC is rapidly increasing, with 1 in 4 new rectal cancer cases occurring under the age of 50 years. Its etiology is unknown.

METHODS: YORC (old) or later-onset rectal cancer (LORC, ≥50 y old) patients underwent pretreatment biopsied of tumor and tumor-adjacent normal (TAN) tissue. After whole genome sequencing, metagenomic analysis quantified microbial communities comparing tumors versus TANs and YORCs versus LORCs, controlling for multiple testing. Response to …


Emphasizing Others’ Persistence Can Promote Unwarranted Social Inferences In Children And Adults, Jamie Amemiya, Gail D Heyman, Caren M Walker Oct 2023

Emphasizing Others’ Persistence Can Promote Unwarranted Social Inferences In Children And Adults, Jamie Amemiya, Gail D Heyman, Caren M Walker

Faculty, Staff and Student Publications

People often hear stories about individuals who persist to overcome their constraints. While these stories can be motivating, emphasizing others’ persistence may promote unwarranted judgments about constrained individuals who do not persist. Using a developmental social inference task (Study 1a: n = 124 U.S. children, 5 to 12 years of age; Study 1b [n = 135] and Study 2 [n = 120]: U.S. adults), the present research tested whether persistence stories lead people to infer that a constrained individual who does not persist, and instead accepts the lower-quality option that is available to them, prefers it over a …


A Machine Learning Approach That Measures Ph Using Acidocest Mri Of Iopamidol, Tianzhe Li, Julio Cárdenas-Rodríguez, Priya N Trakru, Mark D Pagel Oct 2023

A Machine Learning Approach That Measures Ph Using Acidocest Mri Of Iopamidol, Tianzhe Li, Julio Cárdenas-Rodríguez, Priya N Trakru, Mark D Pagel

Faculty, Staff and Student Publications

Tumor acidosis is an important biomarker for aggressive tumors, and extracellular pH (pHe) of the tumor microenvironment can be used to predict and evaluate tumor responses to chemotherapy and immunotherapy. AcidoCEST MRI measures tumor pHe by exploiting the pH-dependent chemical exchange saturation transfer (CEST) effect of iopamidol, an exogenous CT agent repurposed for CEST MRI. However, all pH fitting methodologies for acidoCEST MRI data have limitations. Herein we present results of the application of machine learning for extracting pH values from CEST Z-spectra of iopamidol. We acquired 36,000 experimental CEST spectra from 200 phantoms of iopamidol prepared at five concentrations, …


Innately Expressed Estrogen-Related Receptors In The Skeletal Muscle Are Indispensable For Exercise Fitness, Ashok Kumar, Vihang A Narkar Oct 2023

Innately Expressed Estrogen-Related Receptors In The Skeletal Muscle Are Indispensable For Exercise Fitness, Ashok Kumar, Vihang A Narkar

Faculty, Staff and Student Publications

Peripheral arterial disease (PAD) is a prevalent cardiovascular complication of limb vascular insufficiency, causing ischemic injury, mitochondrial metabolic damage and functional impairment in the skeletal muscle, and ultimately leading to immobility and mortality. While potential therapies have been mostly focussed on revascularization, none of the currently available pharmacological treatments are fully effective in PAD, often leading to amputations, particularly in chronic metabolic diseases. One major limitation of focussed angiogenesis and revascularization as a therapeutic strategy is a limited effect on metabolic restoration and muscle regeneration in the affected limb. Therefore, additional preclinical investigations are needed to discover novel treatment options …


Expert Panel Curation Of 113 Primary Mitochondrial Disease Genes For The Leigh Syndrome Spectrum, Elizabeth M Mccormick, Kierstin Keller, Julie P Taylor, Alison J Coffey, Lishuang Shen, Danuta Krotoski, Brian Harding, Xiaowu Gai, Marni J Falk, Zarazuela Zolkipli-Cunningham, Shamima Rahman Oct 2023

Expert Panel Curation Of 113 Primary Mitochondrial Disease Genes For The Leigh Syndrome Spectrum, Elizabeth M Mccormick, Kierstin Keller, Julie P Taylor, Alison J Coffey, Lishuang Shen, Danuta Krotoski, Brian Harding, Xiaowu Gai, Marni J Falk, Zarazuela Zolkipli-Cunningham, Shamima Rahman

Children’s Nutrition Research Center Staff Publications

Objective: Primary mitochondrial diseases (PMDs) are heterogeneous disorders caused by inherited mitochondrial dysfunction. Classically defined neuropathologically as subacute necrotizing encephalomyelopathy, Leigh syndrome spectrum (LSS) is the most frequent manifestation of PMD in children, but may also present in adults. A major challenge for accurate diagnosis of LSS in the genomic medicine era is establishing gene-disease relationships (GDRs) for this syndrome with >100 monogenic causes across both nuclear and mitochondrial genomes.

Methods: The Clinical Genome Resource (ClinGen) Mitochondrial Disease Gene Curation Expert Panel (GCEP), comprising 40 international PMD experts, met monthly for 4 years to review GDRs for LSS. The GCEP …


Longitudinal Associations Between Cognitive Functioning And Depressive Symptoms Among Couples In The Mexican Health And Aging Study, Joan K Monin, Gail Mcavay, Katie Newkirk, Rafael Samper-Ternent Oct 2023

Longitudinal Associations Between Cognitive Functioning And Depressive Symptoms Among Couples In The Mexican Health And Aging Study, Joan K Monin, Gail Mcavay, Katie Newkirk, Rafael Samper-Ternent

Faculty, Staff and Student Publications

OBJECTIVE: To examine the bidirectional associations between older adult spouses' cognitive functioning and depressive symptoms over time and replicate previous findings from the United States (US) in Mexico.

DESIGN: Longitudinal, dyadic path analysis with the actor-partner interdependence model.

SETTING: Data were from the three most recent interview waves (2012, 2015, and 2018) of the Mexican Health and Aging Study (MHAS), a longitudinal national study of adults aged 50+ years in Mexico.

PARTICIPANTS: Husbands and wives from 905 community-dwelling married couples (N = 1,810).

MEASUREMENTS: The MHAS cognitive battery measured cognitive function. Depressive symptoms were assessed using a modified nine-item Center …


Pirh2-Dependent Dna Damage In Neurons Induced By The G-Quadruplex Ligand Pyridostatin, Rocio Diaz Escarcega, Abhijeet A Patil, Jose F Moruno-Manchon, Akihiko Urayama, Sean P Marrelli, Nayun Kim, David Monchaud, Louise D Mccullough, Andrey S Tsvetkov Oct 2023

Pirh2-Dependent Dna Damage In Neurons Induced By The G-Quadruplex Ligand Pyridostatin, Rocio Diaz Escarcega, Abhijeet A Patil, Jose F Moruno-Manchon, Akihiko Urayama, Sean P Marrelli, Nayun Kim, David Monchaud, Louise D Mccullough, Andrey S Tsvetkov

Faculty, Staff and Student Publications

Noncanonical base pairing between four guanines (G) within single-stranded G-rich sequences leads to formation of а G-quartet. Self-stacking of G-quartets results in a columnar four-stranded DNA structure known as the G-quadruplex (G4 or G4-DNA). In cancer cells, G4-DNA regulates multiple DNA-dependent processes, including transcription, replication, and telomere function. How G4s function in neurons is poorly understood. Here, we performed a genome-wide gene expression analysis (RNA-Seq) to identify genes modulated by a G4-DNA ligand, pyridostatin (PDS), in primary cultured neurons. PDS promotes stabilization of G4 structures, thus allowing us to define genes directly or indirectly responsive to G4 regulation. We found …


Metabolomic Signatures Of Sedentary Behavior And Cardiometabolic Traits In Us Hispanics/Latinos: Results From Hchs/Sol, Jee-Young Moon, Jin Choul Chai, Bing Yu, Rebecca J Song, Guo-Chong Chen, Mariaelisa Graff, Martha L Daviglus, Queenie Chan, Bharat Thyagarajan, Sheila F Castaneda, Megan L Grove, Jianwen Cai, Xiaonan Xue, Yasmin Mossavar-Rahmani, Ramachandran S Vasan, Eric Boerwinkle, Robert C Kaplan, Qibin Qi Oct 2023

Metabolomic Signatures Of Sedentary Behavior And Cardiometabolic Traits In Us Hispanics/Latinos: Results From Hchs/Sol, Jee-Young Moon, Jin Choul Chai, Bing Yu, Rebecca J Song, Guo-Chong Chen, Mariaelisa Graff, Martha L Daviglus, Queenie Chan, Bharat Thyagarajan, Sheila F Castaneda, Megan L Grove, Jianwen Cai, Xiaonan Xue, Yasmin Mossavar-Rahmani, Ramachandran S Vasan, Eric Boerwinkle, Robert C Kaplan, Qibin Qi

Faculty, Staff and Student Publications

PURPOSE: The aim of this study was to understand the serum metabolomic signatures of moderate-to-vigorous physical activity (MVPA) and sedentary behavior, and further associate their metabolomic signatures with incident cardiometabolic diseases.

METHODS: This analysis included 2711 US Hispanics/Latinos from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) aged 18-74 yr (2008-2011). An untargeted, liquid chromatography-mass spectrometry was used to profile the serum metabolome. The associations of metabolites with accelerometer-measured MVPA and sedentary time were examined using survey linear regressions adjusting for covariates. The weighted correlation network analysis identified modules of correlated metabolites in relation to sedentary time, and the modules …


Multi-Ancestry Genome-Wide Study Identifies Effector Genes And Druggable Pathways For Coronary Artery Calcification, Maryam Kavousi, Maxime M Bos, Hanna J Barnes, Christian L Lino Cardenas, Doris Wong, Haojie Lu, Chani J Hodonsky, Lennart P L Landsmeer, Adam W Turner, Minjung Kho, Natalie R Hasbani, Paul S De Vries, Donald W Bowden, Sandesh Chopade, Joris Deelen, Ernest Diez Benavente, Xiuqing Guo, Edith Hofer, Shih-Jen Hwang, Sharon M Lutz, Leo-Pekka Lyytikäinen, Lotte Slenders, Albert V Smith, Maggie A Stanislawski, Jessica Van Setten, Quenna Wong, Lisa R Yanek, Diane M Becker, Marian Beekman, Matthew J Budoff, Mary F Feitosa, Chris Finan, Austin T Hilliard, Sharon L R Kardia, Jason C Kovacic, Brian G Kral, Carl D Langefeld, Lenore J Launer, Shaista Malik, Firdaus A A Mohamed Hoesein, Michal Mokry, Reinhold Schmidt, Jennifer A Smith, Kent D Taylor, James G Terry, Jeroen Van Der Grond, Joyce Van Meurs, Rozemarijn Vliegenthart, Jianzhao Xu, Kendra A Young, Nuno R Zilhão, Robert Zweiker, Themistocles L Assimes, Lewis C Becker, Daniel Bos, J Jeffrey Carr, L Adrienne Cupples, Dominique P V De Kleijn, Menno De Winther, Hester M Den Ruijter, Myriam Fornage, Barry I Freedman, Vilmundur Gudnason, Aroon D Hingorani, John E Hokanson, M Arfan Ikram, Ivana Išgum, David R Jacobs, Mika Kähönen, Leslie A Lange, Terho Lehtimäki, Gerard Pasterkamp, Olli T Raitakari, Helena Schmidt, P Eline Slagboom, André G Uitterlinden, Meike W Vernooij, Joshua C Bis, Nora Franceschini, Bruce M Psaty, Wendy S Post, Jerome I Rotter, Johan L M Björkegren, Christopher J O'Donnell, Lawrence F Bielak, Patricia A Peyser, Rajeev Malhotra, Sander W Van Der Laan, Clint L Miller Oct 2023

Multi-Ancestry Genome-Wide Study Identifies Effector Genes And Druggable Pathways For Coronary Artery Calcification, Maryam Kavousi, Maxime M Bos, Hanna J Barnes, Christian L Lino Cardenas, Doris Wong, Haojie Lu, Chani J Hodonsky, Lennart P L Landsmeer, Adam W Turner, Minjung Kho, Natalie R Hasbani, Paul S De Vries, Donald W Bowden, Sandesh Chopade, Joris Deelen, Ernest Diez Benavente, Xiuqing Guo, Edith Hofer, Shih-Jen Hwang, Sharon M Lutz, Leo-Pekka Lyytikäinen, Lotte Slenders, Albert V Smith, Maggie A Stanislawski, Jessica Van Setten, Quenna Wong, Lisa R Yanek, Diane M Becker, Marian Beekman, Matthew J Budoff, Mary F Feitosa, Chris Finan, Austin T Hilliard, Sharon L R Kardia, Jason C Kovacic, Brian G Kral, Carl D Langefeld, Lenore J Launer, Shaista Malik, Firdaus A A Mohamed Hoesein, Michal Mokry, Reinhold Schmidt, Jennifer A Smith, Kent D Taylor, James G Terry, Jeroen Van Der Grond, Joyce Van Meurs, Rozemarijn Vliegenthart, Jianzhao Xu, Kendra A Young, Nuno R Zilhão, Robert Zweiker, Themistocles L Assimes, Lewis C Becker, Daniel Bos, J Jeffrey Carr, L Adrienne Cupples, Dominique P V De Kleijn, Menno De Winther, Hester M Den Ruijter, Myriam Fornage, Barry I Freedman, Vilmundur Gudnason, Aroon D Hingorani, John E Hokanson, M Arfan Ikram, Ivana Išgum, David R Jacobs, Mika Kähönen, Leslie A Lange, Terho Lehtimäki, Gerard Pasterkamp, Olli T Raitakari, Helena Schmidt, P Eline Slagboom, André G Uitterlinden, Meike W Vernooij, Joshua C Bis, Nora Franceschini, Bruce M Psaty, Wendy S Post, Jerome I Rotter, Johan L M Björkegren, Christopher J O'Donnell, Lawrence F Bielak, Patricia A Peyser, Rajeev Malhotra, Sander W Van Der Laan, Clint L Miller

Faculty, Staff and Student Publications

Coronary artery calcification (CAC), a measure of subclinical atherosclerosis, predicts future symptomatic coronary artery disease (CAD). Identifying genetic risk factors for CAC may point to new therapeutic avenues for prevention. Currently, there are only four known risk loci for CAC identified from genome-wide association studies (GWAS) in the general population. Here we conducted the largest multi-ancestry GWAS meta-analysis of CAC to date, which comprised 26,909 individuals of European ancestry and 8,867 individuals of African ancestry. We identified 11 independent risk loci, of which eight were new for CAC and five had not been reported for CAD. These new CAC loci …


Nuclear Receptors As Potential Therapeutic Targets In Peripheral Arterial Disease And Related Myopathy, Ashok Kumar, Vihang A Narkar Oct 2023

Nuclear Receptors As Potential Therapeutic Targets In Peripheral Arterial Disease And Related Myopathy, Ashok Kumar, Vihang A Narkar

Faculty, Staff and Student Publications

Peripheral arterial disease (PAD) is a prevalent cardiovascular complication of limb vascular insufficiency, causing ischemic injury, mitochondrial metabolic damage and functional impairment in the skeletal muscle, and ultimately leading to immobility and mortality. While potential therapies have been mostly focussed on revascularization, none of the currently available pharmacological treatments are fully effective in PAD, often leading to amputations, particularly in chronic metabolic diseases. One major limitation of focussed angiogenesis and revascularization as a therapeutic strategy is a limited effect on metabolic restoration and muscle regeneration in the affected limb. Therefore, additional preclinical investigations are needed to discover novel treatment options …


Kunitz-Type Protease Inhibitor Tfpi2 Remodels Stemness And Immunosuppressive Tumor Microenvironment In Glioblastoma, Lizhi Pang, Madeline Dunterman, Songlin Guo, Fatima Khan, Yang Liu, Erfan Taefi, Atousa Bahrami, Changiz Geula, Wen-Hao Hsu, Craig Horbinski, Charles David James, Peiwen Chen Oct 2023

Kunitz-Type Protease Inhibitor Tfpi2 Remodels Stemness And Immunosuppressive Tumor Microenvironment In Glioblastoma, Lizhi Pang, Madeline Dunterman, Songlin Guo, Fatima Khan, Yang Liu, Erfan Taefi, Atousa Bahrami, Changiz Geula, Wen-Hao Hsu, Craig Horbinski, Charles David James, Peiwen Chen

Faculty, Staff and Student Publications

Glioblastoma (GBM) tumors consist of multiple cell populations, including self-renewing glioblastoma stem cells (GSCs) and immunosuppressive microglia. Here we identified Kunitz-type protease inhibitor TFPI2 as a critical factor connecting these cell populations and their associated GBM hallmarks of stemness and immunosuppression. TFPI2 promotes GSC self-renewal and tumor growth via activation of the c-Jun N-terminal kinase-signal transducer and activator of transcription (STAT)3 pathway. Secreted TFPI2 interacts with its functional receptor CD51 on microglia to trigger the infiltration and immunosuppressive polarization of microglia through activation of STAT6 signaling. Inhibition of the TFPI2-CD51-STAT6 signaling axis activates T cells and synergizes with anti-PD1 therapy …


Advances In Vaccine Development For Cancer Prevention And Treatment In Lynch Syndrome, Ana M Bolivar, Fahriye Duzagac, Krishna M Sinha, Eduardo Vilar Oct 2023

Advances In Vaccine Development For Cancer Prevention And Treatment In Lynch Syndrome, Ana M Bolivar, Fahriye Duzagac, Krishna M Sinha, Eduardo Vilar

Faculty, Staff and Student Publications

Lynch Syndrome (LS) is one of the most common hereditary cancer syndromes, and is caused by mutations in one of the four DNA mismatch repair (MMR) genes, namely MLH1, MSH2, MSH6 and PMS2. Tumors developed by LS carriers display high levels of microsatellite instability, which leads to the accumulation of large numbers of mutations, among which frameshift insertion/deletions (indels) within microsatellite (MS) loci are the most common. As a result, MMR-deficient (MMRd) cells generate increased rates of tumor-specific neoantigens (neoAgs) that can be recognized by the immune system to activate cancer cell killing. In this context, LS is an ideal …


Emerging Therapeutics And Evolving Assessment Criteria For Intracranial Metastases In Patients With Oncogene-Driven Non-Small-Cell Lung Cancer, Kelsey Pan, Kyle Concannon, Jing Li, Jianjun Zhang, John V Heymach, Xiuning Le Oct 2023

Emerging Therapeutics And Evolving Assessment Criteria For Intracranial Metastases In Patients With Oncogene-Driven Non-Small-Cell Lung Cancer, Kelsey Pan, Kyle Concannon, Jing Li, Jianjun Zhang, John V Heymach, Xiuning Le

Faculty, Staff and Student Publications

The improved survival outcomes of patients with non-small-cell lung cancer (NSCLC), largely owing to the improved control of systemic disease provided by immune-checkpoint inhibitors and novel targeted therapies, have highlighted the challenges posed by central nervous system (CNS) metastases as a devastating yet common complication, with up to 50% of patients developing such lesions during the course of the disease. Early-generation tyrosine-kinase inhibitors (TKIs) often provide robust systemic disease control in patients with oncogene-driven NSCLCs, although these agents are usually unable to accumulate to therapeutically relevant concentrations in the CNS owing to an inability to cross the blood-brain barrier. However, …


Renal Cell Carcinoma Of Variant Histology: Biology And Therapies, Pavlos Msaouel, Giannicola Genovese, Nizar M Tannir Oct 2023

Renal Cell Carcinoma Of Variant Histology: Biology And Therapies, Pavlos Msaouel, Giannicola Genovese, Nizar M Tannir

Faculty, Staff and Student Publications

The term variant histology renal cell carcinomas (vhRCCs), also known as non-clear cell RCCs, refers to a diverse group of malignancies with distinct biologic and therapeutic considerations. The management of vhRCC subtypes is often based on extrapolating results from the more common clear cell RCC studies or basket trials that are not specific to each histology. The unique management of each vhRCC subtype necessitates accurate pathologic diagnosis and dedicated research efforts. Herein, we discuss tailored recommendations for each vhRCC histology informed by ongoing research and clinical experience.


Bayesian Approach For Design And Analysis Of Medical Device Trials In The Era Of Modern Clinical Studies, Han Cao, Chen Yao, Ying Yuan Oct 2023

Bayesian Approach For Design And Analysis Of Medical Device Trials In The Era Of Modern Clinical Studies, Han Cao, Chen Yao, Ying Yuan

Faculty, Staff and Student Publications

Medical device technology develops rapidly, and the life cycle of a medical device is much shorter than drugs. It is necessary to evaluate the safety and effectiveness of a medical device in a timely manner to keep up with technology flux. Bayesian methods provides an efficient approach to addressing this challenge. In this article, we review the characteristics of the Bayesian approach and some Bayesian designs that were commonly used in medical device regulatory setting, including Bayesian adaptive design, Bayesian diagnostic design, Bayesian multiregional design, and Bayesian label expansion study. We illustrate these designs with medical devices approved by the …


Cytosolic Dna Accumulation Promotes Breast Cancer Immunogenicity Via A Sting-Independent Pathway, Jing Zhang, Hui Dai, Lei Huo, Jared K Burks, Daniel J Mcgrail, Shiaw-Yih Lin Oct 2023

Cytosolic Dna Accumulation Promotes Breast Cancer Immunogenicity Via A Sting-Independent Pathway, Jing Zhang, Hui Dai, Lei Huo, Jared K Burks, Daniel J Mcgrail, Shiaw-Yih Lin

Faculty, Staff and Student Publications

BACKGROUND: Immune checkpoint blockade (ICB) has revolutionized cancer treatment. However, ICB alone has demonstrated only benefit in a small subset of patients with breast cancer. Recent studies have shown that agents targeting DNA damage response improve the efficacy of ICB and promote cytosolic DNA accumulation. However, recent clinical trials have shown that these agents are associated with hematological toxicities. More effective therapeutic strategies are urgently needed.

METHODS: Primary triple negative breast cancer tumors were stained for cytosolic single-stranded DNA (ssDNA) using multiplex immunohistochemical staining. To increase cytosolic ssDNA, we genetically silenced TREX1. The role of tumor cytosolic ssDNA in promoting …


Anchors: A Way For Ftsz Filaments To Stay Membrane Bound, Arindam Naha, Daniel P Haeusser, William Margolin Oct 2023

Anchors: A Way For Ftsz Filaments To Stay Membrane Bound, Arindam Naha, Daniel P Haeusser, William Margolin

Faculty, Staff and Student Publications

Most bacteria use the tubulin homolog FtsZ to organize their cell division. FtsZ polymers initially assemble into mobile complexes that circle around a ring-like structure at the cell midpoint, followed by the recruitment of other proteins that will constrict the cytoplasmic membrane and synthesize septal peptidoglycan to divide the cell. Despite the need for FtsZ polymers to associate with the membrane, FtsZ lacks intrinsic membrane binding ability. Consequently, FtsZ polymers have evolved to interact with the membrane through adaptor proteins that both bind FtsZ and the membrane. Here, we discuss recent progress in understanding the functions of these FtsZ membrane …


A Translational Blueprint For Developing Intraoperative Imaging Agents Via Radiopharmaceutical-Guided Drug Design, Teresa E Sullivan, Servando Hernandez Vargas, Sukhen C Ghosh, Solmaz Aghaamiri, Naruhiko Ikoma, Ali Azhdarinia Oct 2023

A Translational Blueprint For Developing Intraoperative Imaging Agents Via Radiopharmaceutical-Guided Drug Design, Teresa E Sullivan, Servando Hernandez Vargas, Sukhen C Ghosh, Solmaz Aghaamiri, Naruhiko Ikoma, Ali Azhdarinia

Faculty, Staff and Student Publications

Cancer imaging is a rapidly evolving field due to the discovery of novel molecular targets and the availability of corresponding techniques to detect them with high precision, accuracy, and sensitivity. Nuclear medicine is the most widely used molecular imaging modality and has a growing toolkit of clinically used radiopharmaceuticals that enable whole-body tumor visualization, staging, and treatment monitoring for a variety of tumors in a non-invasive manner. The need for similar imaging capabilities in the operating room has led to the emergence of fluorescence-guided surgery (FGS) as a powerful technique that gives surgeons unprecedented ability to distinguish tumors from healthy …


Pd-1 Blockade In Combination With Dasatinib Potentiates Induction Of Anti-Acute Lymphocytic Leukemia Immunity, Paul Koller, Natalia Baran, Karine Harutyunyan, Antonio Cavazos, Saradhi Mallampati, Renee L Chin, Zhou Jiang, Xian Sun, Heng-Huan Lee, Jennifer L Hsu, Patrick Williams, Xuelin Huang, Michael A Curran, Mien-Chie Hung, Marina Konopleva Oct 2023

Pd-1 Blockade In Combination With Dasatinib Potentiates Induction Of Anti-Acute Lymphocytic Leukemia Immunity, Paul Koller, Natalia Baran, Karine Harutyunyan, Antonio Cavazos, Saradhi Mallampati, Renee L Chin, Zhou Jiang, Xian Sun, Heng-Huan Lee, Jennifer L Hsu, Patrick Williams, Xuelin Huang, Michael A Curran, Mien-Chie Hung, Marina Konopleva

Faculty, Staff and Student Publications

Immunotherapy, in the form of hematopoietic stem cell transplantation (HSCT), has been part of the standard of care in the treatment of acute leukemia for over 40 years. Trials evaluating novel immunotherapeutic approaches, such as targeting the programmed death-1 (PD-1) pathway, have unfortunately not yielded comparable results to those seen in solid tumors. Major histocompatibility complex (MHC) proteins are cell surface proteins essential for the adaptive immune system to recognize self versus non-self. MHC typing is used to determine donor compatibility when evaluating patients for HSCT. Recently, loss of MHC class II (MHC II) was shown to be a mechanism …


Sepsis Exacerbates Alzheimer’S Disease Pathophysiology, Modulates The Gut Microbiome, Increases Neuroinflammation And Amyloid Burden, Vijayasree V Giridharan, Celso S G Catumbela, Carlos Henrique R Catalão, Juneyoung Lee, Bhanu P Ganesh, Fabricia Petronilho, Felipe Dal-Pizzol, Rodrigo Morales, Tatiana Barichello Oct 2023

Sepsis Exacerbates Alzheimer’S Disease Pathophysiology, Modulates The Gut Microbiome, Increases Neuroinflammation And Amyloid Burden, Vijayasree V Giridharan, Celso S G Catumbela, Carlos Henrique R Catalão, Juneyoung Lee, Bhanu P Ganesh, Fabricia Petronilho, Felipe Dal-Pizzol, Rodrigo Morales, Tatiana Barichello

Faculty, Staff and Student Publications

While our understanding of the molecular biology of Alzheimer's disease (AD) has grown, the etiology of the disease, especially the involvement of peripheral infection, remains a challenge. In this study, we hypothesize that peripheral infection represents a risk factor for AD pathology. To test our hypothesis, APP/PS1 mice underwent cecal ligation and puncture (CLP) surgery to develop a polymicrobial infection or non-CLP surgery. Mice were euthanized at 3, 30, and 120 days after surgery to evaluate the inflammatory mediators, glial cell markers, amyloid burden, gut microbiome, gut morphology, and short-chain fatty acids (SCFAs) levels. The novel object recognition (NOR) task …


A Review Of Magnetic Resonance (Mr) Safety: The Essentials To Patient Safety, Aren Shah, Shima Aran Oct 2023

A Review Of Magnetic Resonance (Mr) Safety: The Essentials To Patient Safety, Aren Shah, Shima Aran

Faculty, Staff and Student Publications

Nearly 40 million magnetic resonance imaging (MRI) scans are performed each year in the United States. MRI has become a relatively safe non-invasive diagnostic tool. To maintain a safe magnetic resonance (MR) environment, specific policies and safety procedures are required. The four zones of an MR site allow MR personnel to closely monitor and restrict the area. Screening patients with a questionnaire asking about implants, allergies to contrast agents, and other relevant medical information is important to safely perform an MRI scan. Providers may need to consider anesthesia for patients with claustrophobia who are unable to remain motionless. Radiologists and …


Electrophysiological Responses To Emotional And Cocaine Cues Reveal Individual Neuroaffective Profiles In Cocaine Users, Heather E Webber, Constanza De Dios, Margaret C Wardle, Robert Suchting, Charles E Green, Joy M Schmitz, Scott D Lane, Francesco Versace Oct 2023

Electrophysiological Responses To Emotional And Cocaine Cues Reveal Individual Neuroaffective Profiles In Cocaine Users, Heather E Webber, Constanza De Dios, Margaret C Wardle, Robert Suchting, Charles E Green, Joy M Schmitz, Scott D Lane, Francesco Versace

Faculty, Staff and Student Publications

Smokers with stronger neuroaffective responses to drug-related cues compared to non-drug-related pleasant images (C>P) are more vulnerable to compulsive smoking than individuals with the opposite brain reactivity profile (P>C). However, it is unknown if these neurobehavioral profiles exist in individuals abusing other drugs. We tested whether individuals with cocaine use disorder (CUD) show similar neuroaffective profiles to smokers. We also monitored eye movements to assess attentional bias toward cues and we further performed exploratory analyses on demographics, personality, and drug use between profiles. Participants with CUD (n=43) viewed pleasant, unpleasant, cocaine, and neutral images while we recorded electroencephalogram. …


The Microtubule Quartet Protein Snap1 In Trypanosoma Brucei Facilitates Flagellum And Cell Division Plane Positioning By Promoting Basal Body Segregation, Martin Carbo-Tano, Mathilde Lapoix, Xinyu Jia, Olivier Thouvenin, Marco Pascucci, François Auclair, Feng B Quan, Shahad Albadri, Vernie Aguda, Younes Farouj, Elizabeth M C Hillman, Ruben Portugues, Filippo Del Bene, Tod R Thiele, Réjean Dubuc, Claire Wyart Oct 2023

The Microtubule Quartet Protein Snap1 In Trypanosoma Brucei Facilitates Flagellum And Cell Division Plane Positioning By Promoting Basal Body Segregation, Martin Carbo-Tano, Mathilde Lapoix, Xinyu Jia, Olivier Thouvenin, Marco Pascucci, François Auclair, Feng B Quan, Shahad Albadri, Vernie Aguda, Younes Farouj, Elizabeth M C Hillman, Ruben Portugues, Filippo Del Bene, Tod R Thiele, Réjean Dubuc, Claire Wyart

Faculty, Staff and Student Publications

The mesencephalic locomotor region (MLR) is a brain stem area whose stimulation triggers graded forward locomotion. How MLR neurons recruit downstream vsx2+ (V2a) reticulospinal neurons (RSNs) is poorly understood. Here, to overcome this challenge, we uncovered the locus of MLR in transparent larval zebrafish and show that the MLR locus is distinct from the nucleus of the medial longitudinal fasciculus. MLR stimulations reliably elicit forward locomotion of controlled duration and frequency. MLR neurons recruit V2a RSNs via projections onto somata in pontine and retropontine areas, and onto dendrites in the medulla. High-speed volumetric imaging of neuronal activity reveals that …


Erythrocyte Ent1-Ampd3 Axis Is An Essential Purinergic Hypoxia Sensor And Energy Regulator Combating Ckd In A Mouse Model, Changhan Chen, Tingting Xie, Yujin Zhang, Yiyan Wang, Fang Yu, Lizhen Lin, Weiru Zhang, Benjamin C Brown, Xin Zhang, Rodney E Kellems, Angelo D'Alessandro, Yang Xia Oct 2023

Erythrocyte Ent1-Ampd3 Axis Is An Essential Purinergic Hypoxia Sensor And Energy Regulator Combating Ckd In A Mouse Model, Changhan Chen, Tingting Xie, Yujin Zhang, Yiyan Wang, Fang Yu, Lizhen Lin, Weiru Zhang, Benjamin C Brown, Xin Zhang, Rodney E Kellems, Angelo D'Alessandro, Yang Xia

Faculty, Staff and Student Publications

Significance statement: Hypoxia drives kidney damage and progression of CKD. Although erythrocytes respond rapidly to hypoxia, their role and the specific molecules sensing and responding to hypoxia in CKD remain unclear. In this study, we demonstrated in a mouse model that erythrocyte ENT1-AMPD3 is a master energy regulator of the intracellular purinergic hypoxic compensatory response that promotes rapid energy supply from extracellular adenosine, eAMPK-dependent metabolic reprogramming, and O 2 delivery, which combat renal hypoxia and progression of CKD. ENT1-AMPD3-AMPK-BPGM comprise a group of circulating erythroid-specific biomarkers, providing early diagnostic and novel therapeutic targets for CKD.

Background: Hypoxia drives kidney damage …


Evaluation Of Inactivated Avian Influenza Virus And Newcastle Disease Virus Bivalent Vaccination Program Against Newly Circulated H5n8 And Ndv Strains, Ahmed A Azab, Nahed Yehia, Mohamed Makhareta, Mahmoud Samir, Abdelrahman Shoukry, Ahmed Abd Elhalem Mohamed, Sadeq K Alhag, Afaf S Alwabli, Mohamed T El-Saadony, Khaled A El-Tarabily, Mohamed A Soliman Oct 2023

Evaluation Of Inactivated Avian Influenza Virus And Newcastle Disease Virus Bivalent Vaccination Program Against Newly Circulated H5n8 And Ndv Strains, Ahmed A Azab, Nahed Yehia, Mohamed Makhareta, Mahmoud Samir, Abdelrahman Shoukry, Ahmed Abd Elhalem Mohamed, Sadeq K Alhag, Afaf S Alwabli, Mohamed T El-Saadony, Khaled A El-Tarabily, Mohamed A Soliman

Faculty, Staff and Student Publications

Avian influenza virus (AIV) and Newcastle disease virus (NDV) are respiratory illness syndromes that have recently been detected in vaccinated flocks and are causing major financial losses in the chicken farming industry. The objective was to evaluate the efficacy of Valley Vac H5Plus NDVg7 vaccine in protecting chickens against the H5N8 and NDV strains that have recently been circulating in comparison with the efficacy of the commercially available bivalent H5+ND7 vaccine. In contrast to the H5+ND7 vaccine, which was made of genetically distinct H5N8/2018 clade 2.3.4.4b genotype group (G5), H9N2/2016, H5N1/2017, and genetically comparable NDV genotype VII 1.1/2019 of the …


X, But Not Y, Chromosomal Complement Contributes To Stroke Sensitivity In Aged Animals, Shaohua Qi, Conelius Ngwa, Abdullah Al Mamun, Sharmeen Romana, Ting Wu, Sean P Marrelli, Arthur P Arnold, Louise D Mccullough, Fudong Liu Oct 2023

X, But Not Y, Chromosomal Complement Contributes To Stroke Sensitivity In Aged Animals, Shaohua Qi, Conelius Ngwa, Abdullah Al Mamun, Sharmeen Romana, Ting Wu, Sean P Marrelli, Arthur P Arnold, Louise D Mccullough, Fudong Liu

Faculty, Staff and Student Publications

Post-menopausal women become vulnerable to stroke and have poorer outcomes and higher mortality than age-matched men, and previous studies suggested that sex chromosomes play a vital role in mediating stroke sensitivity in the aged. It is unknown if this is due to effects of the X or Y chromosome. The present study used the XY* mouse model (with four genotypes: XX and XO gonadal females and XY and XXY gonadal males) to compare the effect of the X vs. Y chromosome compliment in stroke. Aged (18-20 months) and gonadectomized young (8-12 weeks) mice were subjected to a 60-min middle cerebral …


Clinical And Biological Significance Of Circulating Mirnas In Chronic Pancreatitis Patients Undergoing Total Pancreatectomy With Islet Autotransplantation, Srividya Vasu, Giovanna Saracino, Carly M Darden, Kenjiro Kumano, Yang Liu, Michael C Lawrence, Bashoo Naziruddin Oct 2023

Clinical And Biological Significance Of Circulating Mirnas In Chronic Pancreatitis Patients Undergoing Total Pancreatectomy With Islet Autotransplantation, Srividya Vasu, Giovanna Saracino, Carly M Darden, Kenjiro Kumano, Yang Liu, Michael C Lawrence, Bashoo Naziruddin

Faculty, Staff and Student Publications

Background: Specific microRNAs (miRNAs) were elevated in chronic pancreatitis (CP) patients during islet infusion after total pancreatectomy (TPIAT). We aimed to identify circulating miRNA signatures of pancreatic damage, predict miRNA-mRNA networks to identify potential links to CP pathogenesis and identify islet isolation and transplantation functional outcomes.

Methods: Small RNA sequencing was performed to identify distinct circulating miRNA signatures in CP. Plasma miRNAs were measured using miRCURY LNA SYBR green quantitative real-time polymerase chain reaction assays. Correlation analyses were performed using R software. The miRNA target and disease interactions were determined using miRNet and the miRNA enrichment and annotation tool.

Results: …


Diagnosis Of Chronic Pancreatitis Using Semi-Quantitative Mri Features Of The Pancreatic Parenchyma: Results From The Multi-Institutional Minimap Study, Temel Tirkes, Dhiraj Yadav, Darwin L Conwell, Paul R Territo, Xuandong Zhao, Scott A Persohn, Anil K Dasyam, Zarine K Shah, Sudhakar K Venkatesh, Naoki Takahashi, Ashley Wachsman, Liang Li, Yan Li, Stephen J Pandol, Walter G Park, Santhi Swaroop Vege, Phil A Hart, Mark Topazian, Dana K Andersen, Evan L Fogel, Consortium For The Study Of Chronic Pancreatitis, Diabetes, Pancreatic Cancer (Cpdpc) Oct 2023

Diagnosis Of Chronic Pancreatitis Using Semi-Quantitative Mri Features Of The Pancreatic Parenchyma: Results From The Multi-Institutional Minimap Study, Temel Tirkes, Dhiraj Yadav, Darwin L Conwell, Paul R Territo, Xuandong Zhao, Scott A Persohn, Anil K Dasyam, Zarine K Shah, Sudhakar K Venkatesh, Naoki Takahashi, Ashley Wachsman, Liang Li, Yan Li, Stephen J Pandol, Walter G Park, Santhi Swaroop Vege, Phil A Hart, Mark Topazian, Dana K Andersen, Evan L Fogel, Consortium For The Study Of Chronic Pancreatitis, Diabetes, Pancreatic Cancer (Cpdpc)

Faculty, Staff and Student Publications

Purpose: To determine the diagnostic performance of parenchymal MRI features differentiating CP from controls.

Methods: This prospective study performed abdominal MRI scans at seven institutions, using 1.5 T Siemens and GE scanners, in 50 control and 51 definite CP participants, from February 2019 to May 2021. MRI parameters included the T1-weighted signal intensity ratio of the pancreas (T1 score), arterial-to-venous enhancement ratio (AVR) during venous and delayed phases, pancreas volume, and diameter. We evaluated the diagnostic performance of these parameters individually and two semi-quantitative MRI scores derived using logistic regression: SQ-MRI Model A (T1 score, AVR venous, and tail diameter) …


Toward Standardization In Reporting Data On Basic Human Semen Examination: A Crucial Step In Advancing The Field Of Andrology And Reproductive Medicine, Marie-Claude Hofmann, Aleksander Giwercman Oct 2023

Toward Standardization In Reporting Data On Basic Human Semen Examination: A Crucial Step In Advancing The Field Of Andrology And Reproductive Medicine, Marie-Claude Hofmann, Aleksander Giwercman

Faculty, Staff and Student Publications

No abstract provided.