Digital Commons Network^™

Maternal Activation Of The Egfr Prevents Translocation Of Gut-Residing Pathogenic Escherichia Coli In A Model Of Late-Onset Neonatal Sepsis, Kathryn A. Knoop, Paige E. Coughlin, Alexandria N. Floyd, I. Malick Ndao, Carla Hall-Moore, Nurmohammad Shaikh, Andrew J. Gasparrini, Brigida Rusconi, Marilyn Escobedo, Misty Good, Barbara B. Warner, Phillip I. Tarr, Rodney D. Newberry

Open Access Publications

No abstract provided.

Tumor Burden, Inflammation, And Product Attributes Determine Outcomes Of Axicabtagene Ciloleucel In Large B-Cell Lymphoma, Frederick L. Locke, Armin Ghobadi, Et Al.

Open Access Publications

No abstract provided.

The Gut Microbiome Defines Social Group Membership In Honey Bee Colonies, Cassondra L Vernier, Iris M Chin, Boahemaa Adu-Oppong, Joshua J Krupp, Joel Levine, Gautam Dantas, Yehuda Ben-Shahar

Open Access Publications

In the honey bee, genetically related colony members innately develop colony-specific cuticular hydrocarbon profiles, which serve as pheromonal nestmate recognition cues. Yet, despite high intracolony relatedness, the innate development of colony-specific chemical signatures by individual colony members is largely determined by the colony environment, rather than solely relying on genetic variants shared by nestmates. Therefore, it is puzzling how a nongenic factor could drive the innate development of a quantitative trait that is shared by members of the same colony. Here, we provide one solution to this conundrum by showing that nestmate recognition cues in honey bees are defined, at …

Leukocyte Telomere Length Is Unrelated To Cognitive Performance Among Non-Demented And Demented Persons: An Examination Of Long Life Family Study Participants, Adiba Ashrafi, Stephanie Cosentino, Min S Kang, Joseph H Lee, Nicole Schupf, Stacy L Andersen, Kaare Christensen, Michael A Province, Bharat Thyagarajan, Joseph M Zmuda, Lawrence S Honig

Open Access Publications

OBJECTIVE: Leukocyte telomere length (LTL) is a widely hypothesized biomarker of biological aging. Persons with shorter LTL may have a greater likelihood of developing dementia. We investigate whether LTL is associated with cognitive function, differently for individuals without cognitive impairment versus individuals with dementia or incipient dementia.

METHOD: Enrolled subjects belong to the Long Life Family Study (LLFS), a multi-generational cohort study, where enrollment was predicated upon exceptional family longevity. Included subjects had valid cognitive and telomere data at baseline. Exclusion criteria were age ≤ 60 years, outlying LTL, and missing sociodemographic/clinical information. Analyses were performed using linear regression with …

Chemical Effects Of Dicect Staining Protocols On Fluid-Preserved Avian Specimens, Catherine M. Early, Ashley C. Morhardt, Timothy P. Cleland, Christopher M. Milensky, Gwénaëlle M. Kavich, Helen F. James

Open Access Publications

Diffusible iodine-based contrast-enhanced computed tomography (diceCT) techniques allow visualization of soft tissues of fluid-preserved specimens in three dimensions without dissection or histology. Two popular diceCT stains, iodine-potassium iodide (I2KI) dissolved in water and elemental iodine (I2) dissolved in 100% ethanol (EtOH), yield striking results. Despite the widespread use of these stains in clinical and biological fields, the molecular mechanisms that result in color change and radiopacity attributed to iodine staining are poorly understood. Requests to apply these stains to anatomical specimens preserved in natural history museums are increasing, yet curators have little information about the potential for degradation of treated …

Rev-Erb Agonism Improves Liver Pathology In A Mouse Model Of Nash, Kristine Griffett, Gonzalo Bedia-Diaz, Bahaa Elgendy, Thomas P. Burris

Open Access Publications

Non-alcoholic fatty liver disease (NAFLD) affects a significant number of people worldwide and currently there are no pharmacological treatments. NAFLD often presents with obesity, insulin resistance, and in some cases cardiovascular diseases. There is a clear need for treatment options to alleviate this disease since it often progresses to much more the much more severe non-alcoholic steatohepatitis (NASH). The REV-ERB nuclear receptor is a transcriptional repressor that regulates physiological processes involved in the development of NAFLD including lipogenesis and inflammation. We hypothesized that pharmacologically activating REV-ERB would suppress the progression of fatty liver in a mouse model of NASH. Using …

Functional Profiling Of Fsh And Estradiol In Ovarian Granulosa Cell Tumors, Ulla-Maija Haltia, Marjut Pihlajoki, Noora Andersson, Lotta Mäkinen, Johanna Tapper, Alejandra Cervera, Hugo M. Horlings, Ursula Turpeinen, Mikko Anttonen, Ralf Bützow, Leila Unkila-Kallio, Olli Carpén, David B. Wilson, Markku Heikinheimo, Anniina Färkkilä

Open Access Publications

Adult-type granulosa cell tumors (AGCTs) are sex-cord derived neoplasms with a propensity for late relapse. Hormonal modulators have been used empirically in the treatment of recurrent AGCT, albeit with limited success. To provide a more rigorous foundation for hormonal therapy in AGCT, we used a multimodal approach to characterize the expressions of key hormone biomarkers in 175 tumor specimens and 51 serum samples using RNA sequencing, immunohistochemistry, RNA

Effects Of Personality On The Developmental Trajectories Of Academic Burnout Among Korean Medical Students, Han Chae, C. Robert Cloninger, Soon Jin Lee

Open Access Publications

No abstract provided.

Evaluation Of Naturalistic Driving Behavior Using In-Vehicle Monitoring Technology In Preclinical And Early Alzheimer's Disease, Jennifer D Davis, Ganesh M Babulal, George D Papandonatos, Erin M Burke, Christopher B Rosnick, Brian R Ott, Catherine M Roe

Open Access Publications

Cognitive impairment is a significant risk factor for hazardous driving among older drivers with Alzheimer's dementia, but little is known about how the driving behavior of mildly symptomatic compares with those in the preclinical, asymptomatic phase of Alzheimer's disease (AD). This study utilized two in-car technologies to characterize driving behavior in symptomatic and preclinical AD. The goals of this pilot study were to (1) describe unsafe driving behaviors in individuals with symptomatic early AD using G-force triggered video capture and (2) compare the driving habits of these symptomatic AD drivers to two groups of cognitively normal drivers, those with and …

High-Throughput Analysis Of Adaptation Using Barcoded Strains Of Saccharomyces Cerevisiae, Vincent J Fasanello, Ping Liu, Carlos A Botero, Justin C Fay

Open Access Publications

Background: Experimental evolution of microbes can be used to empirically address a wide range of questions about evolution and is increasingly employed to study complex phenomena ranging from genetic evolution to evolutionary rescue. Regardless of experimental aims, fitness assays are a central component of this type of research, and low-throughput often limits the scope and complexity of experimental evolution studies. We created an experimental evolution system in

Results: We first confirm that barcode insertions do not alter fitness and that barcode sequencing can be used to efficiently detect fitness differences via pooled competition-based fitness assays. Next, we examine the effects …

Human Ipsc-Derived Neuronal Cells From Ctbp1-Mutated Patients Reveal Altered Expression Of Neurodevelopmental Gene Networks, S Vijayalingam, Eric Tycksen, Christina A Gurnett, Et Al

Open Access Publications

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Meningioma: A Review Of Clinicopathological And Molecular Aspects, Kristin Huntoon, Angus Martin Shaw Toland, Sonika Dahiya

Open Access Publications

Meningiomas are the most the common primary brain tumors in adults, representing approximately a third of all intracranial neoplasms. They classically are found to be more common in females, with the exception of higher grades that have a predilection for males, and patients of older age. Meningiomas can also be seen as a spectrum of inherited syndromes such as neurofibromatosis 2 as well as ionizing radiation. In general, the 5-year survival for a WHO grade I meningioma exceeds 80%; however, survival is greatly reduced in anaplastic meningiomas. The standard of care for meningiomas in a surgically-accessible location is gross total …

Coronavirus Proteins As Ion Channels: Current And Potential Research, Conor Mcclenaghan, Alex Hanson, Sun-Joo Lee, Colin G Nichols

Open Access Publications

Coronavirus (CoV) outbreaks have recently emerged as a global public health threat due to their exceptional zoonotic potential - a feature arising from their ability to infect a diverse range of potential hosts combined with their high capacity for mutation and recombination. After Severe Acute Respiratory Syndrome (SARS) CoV-1 in 2003 and Middle East Respiratory Syndrome (MERS) CoV in 2012, with the current SARS-CoV-2 pandemic we are now in the midst of the third deadly international CoV outbreak in less than 20 years. Coronavirus outbreaks present a critical threat to global public health and an urgent necessity for therapeutic options. …

Fenofibrate Prevents Iron Induced Activation Of Canonical Wnt/Β-Catenin And Oxidative Stress Signaling In The Retina, Ashok Mandala, Austin Armstrong, Becky Girresch, Jiyao Zhu, Aruna Chilakala, Sanmathi Chavalmane, Kapil Chaudhary, Pratim Biswas, Judith Ogilvie, Jaya P. Gnana-Prakasam

Open Access Publications

No abstract provided.

Comprehensive Profiling Of Extracellular Rna In Hpv‑Induced Cancers Using An Improved Pipeline For Small Rna‑Seq Analysis, Fangjia Tong, Arlise Andress, Gongyu Tang, Ping Liu, Xiaowei Wang

Open Access Publications

No abstract provided.

Protocol For A Proof-Of-Concept Observational Study Evaluating The Potential Utility And Acceptability Of A Telemedicine Solution For The Post-Anesthesia Care Unit, Thaddeus P Budelier, Christopher Ryan King, Shreya Goswami, Anchal Bansal, Stephen H Gregory, Troy S Wildes, Joanna Abraham, Sherry L Mckinnon, Amy Cooper, Ivan Kangrga, Jackie L Martin Jr., Melissa Milbrandt, Alex S Evers, Michael S Avidan

Open Access Publications

No abstract provided.

Primary Cilia As The Nexus Of Biophysical And Hedgehog Signaling At The Tendon Enthesis, Fei Fang, Andrea G Schwartz, Emily R Moore, Mckenzie E Sup, Stavros Thomopoulos

Open Access Publications

The tendon enthesis is a fibrocartilaginous tissue critical for transfer of muscle forces to bone. Enthesis pathologies are common, and surgical repair of tendon to bone is plagued by high failure rates. At the root of these failures is a gap in knowledge of how the tendon enthesis is formed and maintained. We tested the hypothesis that the primary cilium is a hub for transducing biophysical and hedgehog (Hh) signals to regulate tendon enthesis formation and adaptation to loading. Primary cilia were necessary for enthesis development, and cilia assembly was coincident with Hh signaling and enthesis mineralization. Cilia responded inversely …

A Harmonized Meta-Knowledgebase Of Clinical Interpretations Of Somatic Genomic Variants In Cancer, Alex H. Wagner, Kilannin Krysiak, Malachi Griffith, Obi L. Griffith, Et Al.

Open Access Publications

No abstract provided.

Diet Modifies Pioglitazone’S Influence On Hepatic Pparγ-Regulated Mitochondrial Gene Expression, Sakil Kulkarni, Jiansheng Huang, Eric Tycksen, Paul F. Cliften, David A. Rudnick

Open Access Publications

No abstract provided.

Expanding The Genetic Architecture Of Nicotine Dependence And Its Shared Genetics With Multiple Traits, Bryan C. Quach, Michael J. Bray, Pamela Madden, Laura J. Bierut, Nancy L. Saccone, Et Al.

Open Access Publications

No abstract provided.

Stretchable, Dynamic Covalent Polymers For Soft, Long-Lived Bioresorbable Electronic Stimulators Designed To Facilitate Neuromuscular Regeneration, Yeon Sik Choi, Ying Yan, Matthew R. Macewan, Wilson Z. Ray, Et Al.

Open Access Publications

No abstract provided.

Determining The Recommended Dose Of Pacritinib: Results From The Pac203 Dose-Finding Trial In Advanced Myelofibrosis, Aaron T. Gerds, Stephen T. Oh, Et Al.

Open Access Publications

No abstract provided.

Tp53 Abnormalities Correlate With Immune Infiltration And Associate With Response To Flotetuzumab Immunotherapy In Aml, Jayakumar Vadakekolathu, Michael P. Rettig, John F. Dipersio, Et Al.

Open Access Publications

No abstract provided.

Structural Basis Of Chikungunya Virus Inhibition By Monoclonal Antibodies, Qun Fei Zhou, Julie M. Fox, James T. Earnest, Thiam-Seng Ng, Arthur S. Kim, Guntur Fibriansah, Victor A. Kostyuchenko, Jian Shi, Bo Shu, Michael S. Diamond, Shee-Mei Lok

Open Access Publications

No abstract provided.

Tpl2 Enforces Ras-Induced Inflammatory Signaling And Is Activated By Point Mutations, Paarth B Dodhiawala, Namrata Khurana, Daoxiang Zhang, Yi Cheng, Lin Li, Qing Wei, Kuljeet Seehra, Hongmei Jiang, Patrick M Grierson, Andrea Wang-Gillam, Kian-Huat Lim

Open Access Publications

NF-κB transcription factors, driven by the IRAK/IKK cascade, confer treatment resistance in pancreatic ductal adenocarcinoma (PDAC), a cancer characterized by near-universal KRAS mutation. Through reverse-phase protein array and RNA sequencing we discovered that IRAK4 also contributes substantially to MAPK activation in KRAS-mutant PDAC. IRAK4 ablation completely blocked RAS-induced transformation of human and murine cells. Mechanistically, expression of mutant KRAS stimulated an inflammatory, autocrine IL-1β signaling loop that activated IRAK4 and the MAPK pathway. Downstream of IRAK4, we uncovered TPL2 (also known as MAP3K8 or COT) as the essential kinase that propels both MAPK and NF-κB cascades. Inhibition of TPL2 blocked …

Accuracy Of Electromyometrial Imaging Of Uterine Contractions In Clinical Environment, Hui Wang, Wenjie Wu, Michael Talcott, Robert C Mckinstry, Pamela K Woodard, George A Macones, Alan L Schwartz, Phillip Cuculich, Alison G Cahill, Yong Wang

Open Access Publications

Clinically, uterine contractions are monitored with tocodynamometers or intrauterine pressure catheters. In the research setting, electromyography (EMG), which detects electrical activity of the uterus from a few electrodes on the abdomen, is feasible, can provide more accurate data than these other methods, and may be useful for predicting preterm birth. However, EMG lacks sufficient spatial resolution and coverage to reveal where uterine contractions originate, how they propagate, and whether preterm contractions differ between women who do and do not progress to preterm delivery. To address those limitations, electromyometrial imaging (EMMI) was recently developed and validated to non-invasively assess three-dimensional (3D) …

Development Of A New Macrophage-Specifc Trap Mouse (Mactrap) And Definition Of The Renal Macrophage Translational Signature, Andreas Hofmeister, Maximilian C. Thomaßen, Sabrina Markert, André Marquardt, Mathieu Preußner, Martin Rußwurm, Ralph T. Schermuly, Ulrich Steinhoff, Hermann-Josef Gröne, Joachim Hoyer, Benjamin D. Humphreys, Ivica Grgic

Open Access Publications

No abstract provided.

Plasmacytoid Dendritic Cell Impairment In Metastatic Melanoma By Lactic Acidosis, Matilde Monti, Raffaella Vescovi, Francesca Consoli, Davide Farina, Daniele Moratto, Alfredo Berruti, Claudia Specchia, William Vermi

Open Access Publications

The introduction of targeted therapies and immunotherapies has significantly improved the outcome of metastatic melanoma (MM) patients. These approaches rely on immune functions for their anti-melanoma response. Plasmacytoid dendritic cells (pDCs) exhibit anti-tumor function by production of effector molecules, type I interferons (I-IFNs), and cytokines. Tissue and blood pDCs result compromised in MM, although these findings are still partially conflicting. This study reports that blood pDCs were dramatically depleted in MM, particularly in patients with high lactate dehydrogenase (LDH) and high tumor burden; the reduced pDC frequency was associated with poor overall survival. Circulating pDCs resulted also in significant impairment …

Distinct Neural Networks Associated With Obsession And Delusion: A Connectome-Wide Association Study, Tae Young Lee, Wi Hoon Jung, Yoo Bin Kwak, Youngwoo B Yoon, Junhee Lee, Minah Kim, Euitae Kim, Jun Soo Kwon

Open Access Publications

BACKGROUND: Obsession and delusion are theoretically distinct from each other in terms of reality testing. Despite such phenomenological distinction, no extant studies have examined the identification of common and distinct neural correlates of obsession and delusion by employing biologically grounded methods. Here, we investigated dimensional effects of obsession and delusion spanning across the traditional diagnostic boundaries reflected upon the resting-state functional connectivity (RSFC) using connectome-wide association studies (CWAS).

METHODS: Our study sample comprised of 96 patients with obsessive-compulsive disorder, 75 patients with schizophrenia, and 65 healthy controls. A connectome-wide analysis was conducted to examine the relationship between obsession and delusion …

Individualization Of Attention-Deficit/Hyperactivity Disorder Treatment: Pharmacotherapy Considerations By Age And Co-Occurring Conditions, Greg W Mattingly, Joshua Wilson, Leticia Ugarte, Paul Glaser

Open Access Publications

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that manifests in childhood and can persist into adolescence and adulthood. Impairments associated with ADHD can impact quality of life, social interactions, and increase the risk of morbidity and mortality; however, for many patients, effective treatment can lessen these effects. Pharmacotherapy with stimulants or nonstimulants is recommended in conjunction with psychosocial therapy for most patients. Determining the optimal pharmacotherapy can be complex, and the clinician needs to consider many factors such as the patient's age, comorbidities, and lifestyle. Furthermore, the needs of the patient with ADHD will change over time, with specific challenges …