Digital Commons Network^™

Rotavirus Susceptibility Of Antibiotic-Treated Mice Ascribed To Diminished Expression Of Interleukin-22, Daniel Schnepf, Pedro Hernandez, Tanel Mahlakõiv, Stefania Crotta, Meagan E. Sullender, Stefan T. Peterson, Annette Ohnemus, Camille Michiels, Ian Gentle, Laure Dumoutier, Celso A. Reis, Andreas Diefenbach, Andreas Wack, Megan T. Baldridge, Peter Staeheli

Open Access Publications

The commensal microbiota regulates susceptibility to enteric pathogens by fine-tuning mucosal innate immune responses, but how susceptibility to enteric viruses is shaped by the microbiota remains incompletely understood. Past reports have indicated that commensal bacteria may either promote or repress rotavirus replication in the small intestine of mice. We now report that rotavirus replicated more efficiently in the intestines of germ-free and antibiotic-treated mice compared to animals with an unmodified microbiota. Antibiotic treatment also facilitated rotavirus replication in type I and type III interferon (IFN) receptor-deficient mice, revealing IFN-independent proviral effects. Expression of interleukin-22 (IL-22) was strongly diminished in the …

Clinical Characteristics And Outcomes Of Colorectal Cancer In The Colocare Study: Differences By Age Of Onset, Caroline Himbert, Matthew Mutch, Cory Bernadt, Deyali Chatterjee, Adetunji T Toriola, Et Al

Open Access Publications

Early-onset colorectal cancer has been on the rise in Western populations. Here, we compare patient characteristics between those with early- (<50 years) vs. late-onset (≥50 years) disease in a large multinational cohort of colorectal cancer patients (

Analysis Of Ureteral Diameter And Peristalsis In Response To Irrigant Fluid Temperature Changes In An In Vivo Porcine Model, Roshan M. Patel, Pengbo Jiang, Rajiv Karani, Tarik Phillips, Raphael B. Arada, Lillian Xie, Hyder Said, Shlomi Tapiero, Jaime Landman, Ted Farzaneh, Ramakrishna Venkatesh, Ralph V. Clayman

Open Access Publications

No abstract provided.

Formation Of Osteochondral Organoids From Murine Induced Pluripotent Stem Cells, Shannon K. O'Connor, Dakota B. Katz, Sara J. Oswald, Logan Groneck, Farshid Guilak

Open Access Publications

No abstract provided.

Interleukin 33 Triggers Early Eosinophil-Dependent Events Leading To Metaplasia In A Chronic Model Of Gastritis-Prone Mice, Carlo De Salvo, Jason C. Mills, Et Al

Open Access Publications

No abstract provided.

Fluvoxamine: A Review Of Its Mechanism Of Action And Its Role In Covid-19, Vikas P Sukhatme, Angela M Reiersen, Sharat J Vayttaden, Vidula V Sukhatme

Open Access Publications

Fluvoxamine is a well-tolerated, widely available, inexpensive selective serotonin reuptake inhibitor that has been shown in a small, double-blind, placebo-controlled, randomized study to prevent clinical deterioration of patients with mild coronavirus disease 2019 (COVID-19). Fluvoxamine is also an agonist for the sigma-1 receptor, through which it controls inflammation. We review here a body of literature that shows important mechanisms of action of fluvoxamine and other SSRIs that could play a role in COVID-19 treatment. These effects include: reduction in platelet aggregation, decreased mast cell degranulation, interference with endolysosomal viral trafficking, regulation of inositol-requiring enzyme 1α-driven inflammation and increased melatonin levels, …

Identify. Quantify. Predict. Why Immunologists Should Widely Use Molecular Imaging For Coronavirus Disease 2019, Freimut D Juengling, Antonio Maldonado, Frank Wuest, Thomas H Schindler

Open Access Publications

Molecular imaging using PET/CT or PET/MRI has evolved from an experimental imaging modality at its inception in 1972 to an integral component of diagnostic procedures in oncology, and, to lesser extent, in cardiology and neurology, by successfully offering

Label-Free Macroscopic Fluorescence Lifetime Imaging Of Brain Tumors, Maria Lukina, Konstantin Yashin, Elena E Kiseleva, Anna Alekseeva, Varvara Dudenkova, Elena V Zagaynova, Evgenia Bederina, Igor Medyanic, Wolfgang Becker, Deependra Mishra, Mikhail Berezin, Vladislav I Shcheslavskiy, Marina Shirmanova

Open Access Publications

Advanced stage glioma is the most aggressive form of malignant brain tumors with a short survival time. Real-time pathology assisted, or image guided surgical procedures that eliminate tumors promise to improve the clinical outcome and prolong the lives of patients. Our work is focused on the development of a rapid and sensitive assay for intraoperative diagnostics of glioma and identification of optical markers essential for differentiation between tumors and healthy brain tissues. We utilized fluorescence lifetime imaging (FLIM) of endogenous fluorophores related to metabolism of the glioma from freshly excised brains tissues. Macroscopic time-resolved fluorescence images of three intracranial animal …

Scalable Bio Marker Combinations For Early Stroke Diagnosis: A Systematic Review, Saiyet De La C Baez, Diana García Del Barco, Anette Hardy-Sosa, Gerardo Guillen Nieto, Maria Luisa Bringas-Vega, Jorge J Llibre-Guerra, Pedro Valdes-Sosa

Open Access Publications

No abstract provided.

Fractal Motor Activity Regulation And Sex Differences In Preclinical Alzheimer's Disease Pathology, Lei Gao, Peng Li, Arlen Gaba, Erik Musiek, Yo-El S Ju, Kun Hu

Open Access Publications

Introduction: Degradation in fractal motor activity regulation (FMAR), a measure of multiscale self-similarity of motor control, occurs in aging and accelerates with clinical progression to Alzheimer's disease (AD). Whether FMAR changes occur during the pre-symptomatic phase of the disease in women and men remains unknown.

Methods: FMAR was assessed in cognitively normal participants (n = 178) who underwent 7 to 14 days of home actigraphy. Preclinical AD pathology was determined by amyloid imaging-Pittsburgh compound B (PiB) and cerebrospinal fluid (CSF) phosphorylated-tau181 (p-tau) to amyloid beta 42 (Aβ42) ratio.

Results: Degradation in daytime FMAR was overall significantly associated with preclinical amyloid …

Societal Issues And Policy Implications Related To The Use Of Cannabinoids, Cannabis, And Cannabis-Based Medicines For Pain Management, Simon Haroutounian, Ian Gilron, Joletta Belton, Louisa Degenhardt, Marta Di Forti, David P. Finn, Alexandra Fogarty, Eija Kalso, Elliot Krane, R. Andrew Moore, Michael Rowbotham, Mark Wallace, Andrew S.C. Rice

Open Access Publications

No abstract provided.

Pleiotropic Effects Between Cardiovascular Disease Risk Factors And Measures Of Cognitive And Physical Function In Long‑Lived Adults, Julia J. Yudkovicz, Ryan L. Minster, Emma Barinas-Mitchell, Kaare Christensen, Mary Feitosa, Megan S. Barker, Anne B. Newman, Allison L. Kuipers

Open Access Publications

No abstract provided.

Boosting And Lassoing New Prostate Cancer Snp Risk Factors And Their Connection To Selenium, David E. Booth, Venugopal Gopalakrishna-Remani, Matthew L. Cooper, Fiona R. Green, Margaret P. Rayman

Open Access Publications

No abstract provided.

Loss Of Snora73 Reprograms Cellular Metabolism And Protects Against Steatohepatitis, Arthur C. Sletten, Jessica W. Davidson, Busra Yagabasan, Samantha Moores, Michaela Schwaiger-Haber, Hideji Fujiwara, Sarah Gale, Xuntian Jiang, Rohini Sidhu, Susan Gelman, Shuang Zhao, Gary Patti, Daniel S. Ory, Jean E. Schaffer

Open Access Publications

No abstract provided.

Striatal Oxidative Damages And Neuroinflammation Correlate With Progression And Survival Of Lewy Body And Alzheimer Diseases, Huifangjie Li, William C. Knight, Jinbin Xu

Open Access Publications

No abstract provided.

Brown Adipose Tissue Monocytes Support Tissue Expansion, Alexandre Gallerand, Hannah P. Luehmann, Deborah H. Sultan, Yongjian Liu, Et Al

Open Access Publications

No abstract provided.

A Machine Learning Approach For The Factorization Of Psychometric Data With Application To The Delis Kaplan Executive Function System, J.A. Camilleri, S.B. Eickhoff, S. Weis, J. Chen, J. Amunts, A. Sotiras, S. Genon

Open Access Publications

No abstract provided.

Joint Degeneration In A Mouse Model Of Pseudoachondroplasia: Er Stress, Inflammation, And Block Of Autophagy, Jacqueline T Hecht, Alka C Veerisetty, Mohammad G Hossain, Debabrata Patra, Frankie Chiu, Francoise Coustry, Karen L Posey

Open Access Publications

Pseudoachondroplasia (PSACH), a short limb skeletal dysplasia associated with premature joint degeneration, is caused by misfolding mutations in cartilage oligomeric matrix protein (COMP). Here, we define mutant-COMP-induced stress mechanisms that occur in articular chondrocytes of MT-COMP mice, a murine model of PSACH. The accumulation of mutant-COMP in the ER occurred early in MT-COMP articular chondrocytes and stimulated inflammation (TNFα) at 4 weeks, and articular chondrocyte death increased at 8 weeks while ER stress through CHOP was elevated by 12 weeks. Importantly, blockage of autophagy (pS6), the major mechanism that clears the ER, sustained cellular stress in MT-COMP articular chondrocytes. Degeneration …

Machine Learning Model With Physical Constraints For Diffuse Optical Tomography, Yun Zou, Yifeng Zeng, Shuying Li, Quing Zhu

Open Access Publications

No abstract provided.

A Genome-Engineered Bioartificial Implant For Autoregulated Anticytokine Drug Delivery, Yun-Rak Choi, Kelsey H Collins, Luke E Springer, Lara Pferdehirt, Alison K Ross, Chia-Lung Wu, Franklin T Moutos, Natalia S Harasymowicz, Jonathan M Brunger, Christine T N Pham, Farshid Guilak

Open Access Publications

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Sustained Oxygenation Accelerates Diabetic Wound Healing By Promoting Epithelialization And Angiogenesis And Decreasing Inflammation, Ya Guan, Hong Niu, Zhongting Liu, Yu Dang, Jie Shen, Mohamed Zayed, Liang Ma, Jianjun Guan

Open Access Publications

Nonhealing diabetic wounds are common complications for diabetic patients. Because chronic hypoxia prominently delays wound healing, sustained oxygenation to alleviate hypoxia is hypothesized to promote diabetic wound healing. However, sustained oxygenation cannot be achieved by current clinical approaches, including hyperbaric oxygen therapy. Here, we present a sustained oxygenation system consisting of oxygen-release microspheres and a reactive oxygen species (ROS)-scavenging hydrogel. The hydrogel captures the naturally elevated ROS in diabetic wounds, which may be further elevated by the oxygen released from the administered microspheres. The sustained release of oxygen augmented the survival and migration of keratinocytes and dermal fibroblasts, promoted angiogenic …

Genetic And Biochemical Characterization Of The Na+/H+ Antiporters Of Pseudomonas Aeruginosa, Sara Foreman, Kristina Ferrara, Teri N Hreha, Ana E Duran-Pinedo, Jorge Frias-Lopez, Blanca Barquera

Open Access Publications

Pseudomonas aeruginosa has four Na

Glial-Specific Deletion Of Med12 Results In Rapid Hearing Loss Via Degradation Of The Stria Vascularis, Teng-Wei Huang, Amrita A. Iyer, Jeanne M. Manalo, Junsung Woo, Navish A. Bosquez Huerta, Melissa M. Mcgovern, Heinrich Schrewe, Fredrick A. Pereira, Andrew K. Groves, Kevin K. Ohlemiller, Benjamin Deneen

Open Access Publications

Mediator protein complex subunit 12 (Med12) is a core component of the basal transcriptional apparatus and plays a critical role in the development of many tissues. Mutations in Med12 are associated with X-linked intellectual disability syndromes and hearing loss; however, its role in nervous system function remains undefined. Here, we show that temporal conditional deletion of Med12 in astrocytes in the adult CNS results in region-specific alterations in astrocyte morphology. Surprisingly, behavioral studies revealed rapid hearing loss after adult deletion of Med12 that was confirmed by a complete abrogation of auditory brainstem responses. Cellular analysis of the cochlea revealed degeneration …

Reweighting Of Molecular Simulations With Explicit-Solvent Saxs Restraints Elucidates Ion-Dependent Rna Ensembles, Mattia Bernetti, Kathleen B. Hall, Giovanni Bussi

Open Access Publications

Small-angle X-ray scattering (SAXS) experiments are increasingly used to probe RNA structure. A number of forward models that relate measured SAXS intensities and structural features, and that are suitable to model either explicit-solvent effects or solute dynamics, have been proposed in the past years. Here, we introduce an approach that integrates atomistic molecular dynamics simulations and SAXS experiments to reconstruct RNA structural ensembles while simultaneously accounting for both RNA conformational dynamics and explicit-solvent effects. Our protocol exploits SAXS pure-solute forward models and enhanced sampling methods to sample an heterogenous ensemble of structures, with no information towards the experiments provided on-the-fly. …

A Troponin T Variant Linked With Pediatric Dilated Cardiomyopathy Reduces The Coupling Of Thin Filament Activation To Myosin And Calcium Binding, Samantha K. Barrick, Lina Greenberg, Michael J. Greenberg

Open Access Publications

Dilated cardiomyopathy (DCM) is a significant cause of pediatric heart failure. Mutations in proteins that regulate cardiac muscle contraction can cause DCM; however, the mechanisms by which molecular-level mutations contribute to cellular dysfunction are not well understood. Better understanding of these mechanisms might enable the development of targeted therapeutics that benefit patient subpopulations with mutations that cause common biophysical defects. We examined the molecular- and cellular-level impacts of a troponin T variant associated with pediatric-onset DCM, R134G. The R134G variant decreased calcium sensitivity in an in vitro motility assay. Using stopped-flow and steady-state fluorescence measurements, we determined the molecular mechanism …

Diagnosis Of Mast Cell Activation Syndrome: A Global “Consensus-2”, Lawrence B. Afrin, Leonard B. Weinstock, Et Al

Open Access Publications

No abstract provided.

Hif1Α Is Required For Nk Cell Metabolic Adaptation During Virus Infection, Francisco Victorino, Tarin M. Bigley, Eugene Park, Cong-Hui Yao, Jeanne Benoit, Li-Ping Yang, Sytse J. Piersma, Elvin J. Lauron, Rebecca M. Davidson, Gary J. Patti, Wayne M. Yokoyama

Open Access Publications

Natural killer (NK) cells are essential for early protection against virus infection and must metabolically adapt to the energy demands of activation. Here, we found upregulation of the metabolic adaptor hypoxia-inducible factor-1α (HIF1α) is a feature of mouse NK cells during murine cytomegalovirus (MCMV) infection in vivo. HIF1α-deficient NK cells failed to control viral load, causing increased morbidity. No defects were found in effector functions of HIF1αKO NK cells; however, their numbers were significantly reduced. Loss of HIF1α did not affect NK cell proliferation during in vivo infection and in vitro cytokine stimulation. Instead, we found that HIF1α-deficient NK cells …

Dynamically Linking Influenza Virus Infection Kinetics, Lung Injury, Inflammation, And Disease Severity, Margaret A. Myers, Amanda P. Smith, Lindey C. Lane, David J. Moquin, Rosemary Aogo, Stacie Woolard, Paul Thomas, Peter Vogel, Amber M. Smith

Open Access Publications

Influenza viruses cause a significant amount of morbidity and mortality. Understanding host immune control efficacy and how different factors influence lung injury and disease severity are critical. We established and validated dynamical connections between viral loads, infected cells, CD8

Multicenter Analysis Of Geriatric Fitness And Real-World Outcomes In Older Patients With Classical Hodgkin Lymphoma, Victor M. Orellana-Noia, Mary-Kate Malecek, Nancy L. Bartlett, Et Al

Open Access Publications

No abstract provided.

Contemporary Clinical Isolates Of Staphylococcus Aureus From Pediatric Osteomyelitis Patients Display Unique Characteristics In A Mouse Model Of Hematogenous Osteomyelitis, Philip M. Roper, Kara R. Eichelberger, Linda Cox, Luke O'Connor, Christine Shao, Caleb A. Ford, Stephanie A. Fritz, James E. Cassat, Deborah J. Veis

Open Access Publications

No abstract provided.