Digital Commons Network^™

Direct N-Glycosylation Profiling Of Urine And Prostatic Fluid Glycoproteins And Extracellular Vesicles, Calvin R K Blaschke, Jordan P Hartig, Grace Grimsley, Liping Liu, O John Semmes, Jennifer D Wu, Joseph E Ippolito, Chanita Hughes-Halbert, Julius O Nyalwidhe, Richard R Drake

Open Access Publications

Expressed prostatic secretions (EPS), also called post digital rectal exam urines, are proximal fluids of the prostate that are widely used for diagnostic and prognostic assays for prostate cancer. These fluids contain an abundant number of glycoproteins and extracellular vesicles secreted by the prostate gland, and the ability to detect changes in their N-glycans composition as a reflection of disease state represents potential new biomarker candidates. Methods to characterize these N-glycan constituents directly from clinical samples in a timely manner and with minimal sample processing requirements are not currently available. In this report, an approach is described to directly profile …

The Crossroads Of Glycoscience, Infection, And Immunology, Tanya R Mckitrick, Margaret E Ackerman, Robert M Anthony, Clay S Bennett, Michael Demetriou, Gregory A Hudalla, Katharina Ribbeck, Stefan Ruhl, Christina M Woo, Loretta Yang, Seth J Zost, Ronald L Schnaar, Tamara L Doering

Open Access Publications

Advances in experimental capabilities in the glycosciences offer expanding opportunities for discovery in the broad areas of immunology and microbiology. These two disciplines overlap when microbial infection stimulates host immune responses and glycan structures are central in the processes that occur during all such encounters. Microbial glycans mediate host-pathogen interactions by acting as surface receptors or ligands, functioning as virulence factors, impeding host immune responses, or playing other roles in the struggle between host and microbe. In the context of the host, glycosylation drives cell-cell interactions that initiate and regulate the host response and modulates the effects of antibodies and …

Antidiabetic Dpp-4 Inhibitors Reprogram Tumor Microenvironment That Facilitates Murine Breast Cancer Metastasis Through Interaction With Cancer Cells Via A Ros-Nf-Кb-Nlrp3 Axis, Rui Li, Xin Zeng, Meihua Yang, Jinmei Feng, Xiaohui Xu, Liming Bao, Tingbo Ye, Xin Wang, Bingqian Xue, Yi Huang

Open Access Publications

Improvement of understanding of the safety profile and biological significance of antidiabetic agents in breast cancer (BC) progression may shed new light on minimizing the unexpected side effect of antidiabetic reagents in diabetic patients with BC. Our recent finding showed that Saxagliptin (Sax) and Sitagliptin (Sit), two common antidiabetic dipeptidyl peptidase-4 inhibitors (DPP-4i) compounds, promoted murine BC 4T1 metastasis

Conserved Mechanism Of Bicarbonate-Induced Sensitization Of Catsper Channels In Human And Mouse Sperm, Juan J Ferreira, Pascale Lybaert, Lis C Puga-Molina, Celia M Santi

Open Access Publications

To fertilize an egg, mammalian sperm must undergo capacitation in the female genital tract. A key contributor to capacitation is the calcium (Ca

Phylum-Spanning Neuropeptide Gpcr Identification And Prioritization: Shaping Drug Target Discovery Pipelines For Nematode Parasite Control, Louise E Atkinson, Ciaran J Mccoy, Bethany A Crooks, Fiona M Mckay, Paul Mcveigh, Darrin Mckenzie, Allister Irvine, John Harrington, Bruce A Rosa, Makedonka Mitreva, Nikki J Marks, Aaron G Maule, Angela Mousley

Open Access Publications

Nematode parasites undermine human health and global food security. The frontline anthelmintic portfolio used to treat parasitic nematodes is threatened by the escalation of anthelmintic resistance, resulting in a demand for new drug targets for parasite control. Nematode neuropeptide signalling pathways represent an attractive source of novel drug targets which currently remain unexploited. The complexity of the nematode neuropeptidergic system challenges the discovery of new targets for parasite control, however recent advances in parasite 'omics' offers an opportunity for the

Sensory Percepts Elicited By Chronic Macro-Sieve Electrode Stimulation Of The Rat Sciatic Nerve, Nikhil S Chandra, Weston M Mccarron, Ying Yan, Luis C Ruiz, Eric G Sallinger, Nathan K Birenbaum, Harold Burton, Leonard Green, Daniel W Moran, Wilson Z Ray, Matthew R Macewan

Open Access Publications

No abstract provided.

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

[Figure: see text].

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. …