Digital Commons Network^™

Structural Mechanism For Gating Of A Eukaryotic Mechanosensitive Channel Of Small Conductance, Zengqin Deng, Grigory Maksaev, Angela M. Schlegel, Jingying Zhang, Michael Rau, James A. J. Fitzpatrick, Elizabeth S. Haswell, Peng Yuan

Open Access Publications

No abstract provided.

Orbitofrontal-Striatal Potentiation Underlies Cocaine-Induced Hyperactivity, Sebastiano Bariselli, Nanami L. Miyazaki, Meaghan C. Creed, Alexxai V. Kravitz

Open Access Publications

No abstract provided.

Nanotherapy Delivery Of C-Myc Inhibitor Targets Protumor Macrophages And Preserves Antitumor Macrophages In Breast Cancer, Alison K. Esser, Michael H. Ross, Francesca Fontana, Xinming Su, Ariel Gabay, Gregory C. Fox, Yalin Xu, Jingyu Xiang, Anne H. Schmieder, Xiaoxia Yang, Grace Cui, Michael Scott, Samuel Achilefu, Jay Chauhan, Steven Fletcher, Gregory M. Lanza, Katherine N. Weilbaecher

Open Access Publications

No abstract provided.

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.

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 …

Canonical Signaling By Tgf Family Members In Mesenchymal Stromal Cells Is Dispensable For Hematopoietic Niche Maintenance Under Basal And Stress Conditions, Joseph Ryan Krambs, Grazia Abou Ezzi, Juo-Chin Yao, Daniel C. Link

Open Access Publications

Mesenchymal stromal cells are an important component of the bone marrow hematopoietic niche. Prior studies showed that signaling from members of the transforming growth factor (TGF) superfamily in mesenchymal stromal cells is required for normal niche development. Here, we assessed the impact of TGF family signaling on niche maintenance and stress responses by deleting Smad4 in mesenchymal stromal cells at birth, thereby abrogating canonical TGF signaling. No alteration in the number or spatial organization of CXCL12-abundant reticular (CAR) cells, osteoblasts, or adipocytes was observed in Osx-Cre, Smad4fl/fl mice, and expression of key niche factors was normal. Basal hematopoiesis and stress …

Diet-Induced Metabolic Dysregulation In Female Mice Causes Osteopenia In Adult Offspring, Yu Shi, Jessica L. Saben, Guangxu He, Kelle H. Moley, Fanxin Long

Open Access Publications

Bone mass and quality in humans are controlled by numerous genetic and environmental factors that are not fully understood. Increasing evidence has indicated that maternal metabolic dysregulation impairs multiple physiological processes in the adult offspring, but a similar effect on bone health is yet to be established. Here, we have analyzed the bones of first-generation offspring from murine dams that present metabolic syndrome due to a high-fat and high-sugar (HF/HS) diet. Micro-CT analyses show that the long bones of HF/HS offspring possess lower cortical bone mass and weaker mechanical strength than normal, even though the trabecular bone is not affected. …

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 …

Quantitative Definition Of Neurobehavior, Vision, Hearing And Brain Volumes In Macaques Congenitally Exposed To Zika Virus, Michelle R. Koenig, Kevin Noguchi, Et Al.

Open Access Publications

Congenital Zika virus (ZIKV) exposure results in a spectrum of disease ranging from severe birth defects to delayed onset neurodevelopmental deficits. ZIKV-related neuropathogenesis, predictors of birth defects, and neurodevelopmental deficits are not well defined in people. Here we assess the methodological and statistical feasibility of a congenital ZIKV exposure macaque model for identifying infant neurobehavior and brain abnormalities that may underlie neurodevelopmental deficits. We inoculated five pregnant macaques with ZIKV and mock-inoculated one macaque in the first trimester. Following birth, growth, ocular structure/function, brain structure, hearing, histopathology, and neurobehavior were quantitatively assessed during the first week of life. We identified …

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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Considerations In Preparative Regimen Selection To Minimize Rejection In Pediatric Hematopoietic Transplantation In Non-Malignant Diseases, Robert J Hayashi

Open Access Publications

The variables that influence the selection of a preparative regimen for a pediatric hematopoietic stem cell transplant procedure encompasses many issues. When one considers this procedure for non-malignant diseases, components in a preparative regimen that were historically developed to reduce malignant tumor burden may be unnecessary. The primary goal of the procedure in this instance becomes engraftment with the establishment of normal hematopoiesis and a normal immune system. Overcoming rejection becomes the primary priority, but pursuit of this goal cannot neglect organ toxicity, or post-transplant morbidity such as graft-versus-host disease or life threatening infections. With the improvements in supportive care, …

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.

Hla‑A Alleles Including Hla‑A29 Affect The Composition Of The Gut Microbiome: A Potential Clue To The Pathogenesis Of Birdshot Retinochoroidopathy, Peter R. Sternes, Tammy M. Martin, Michael Paley, Sarah Diamond, Mark J. Asquith, Matthew A. Brown, James T. Rosenbaum

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.

Immunotherapy And Radiation Therapy For Gastrointestinal Malignancies: Hope Or Hype?, Shahed Badiyan, Adeel Kaiser, Bory Eastman, Matthew Forsthoefel, Jing Zeng, Keith Unger, Michael Chuong

Open Access Publications

Immunotherapy represents the newest pillar in cancer care. Although there are increasing data showing the efficacy of immunotherapy there is a spectrum of response across unselected populations of cancer patients. In fact, response rates can be poor even among patients with immunogenic tumors for reasons that remain poorly understood. A promising clinical strategy to improve outcomes, which is supported by an abundance of preclinical data, is combining immunotherapy with radiation therapy. Here we review the existing evidence and future directions for combining immunotherapy and radiation therapy for patients with gastrointestinal cancers.

Tumor Microenvironment-Targeted Nanoparticles Loaded With Bortezomib And Rock Inhibitor Improve Efficacy In Multiple Myeloma, Cinzia Federico, Kinan Alhallak, Jennifer Sun, Kathleen Duncan, Feda Azab, Gail P. Sudlow, Pilar De La Puente, Barbara Muz, Vaishali Kapoor, Luna Zhang, Fangzheng Yuan, Matea Markovic, Joseph Kotsybar, Katherine Wasden, Nicole Guenthner, Shannon Gurley, Justin King, Daniel Kohnen, Noha N. Salama, Dinesh Thotala, Dennis E. Hallahan, Ravi Vij, John F. Dipersio, Samuel Achilefu, Abdel Kareem Azab

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.

A Feasibility Study To Evaluate Early Treatment Response Of Brain Metastases One Week After Stereotactic Radiosurgery Using Perfusion Weighted Imaging, Jiayi Huang, Mikhail Milchenko, Yuan J. Rao, Pamela Lamontagne, Christopher Abraham, Clifford G. Robinson, Yi Huang, Joshua S. Shimony, Keith M. Rich, Tammie Benzinger

Open Access Publications

BACKGROUND: To explore if early perfusion-weighted magnetic resonance imaging (PWI) may be a promising imaging biomarker to predict local recurrence (LR) of brain metastases after stereotactic radiosurgery (SRS).

METHODS: This is a prospective pilot study of adult brain metastasis patients who were treated with SRS and imaged with PWI before and 1 week later. Relative cerebral blood volume (rCBV) parameter maps were calculated by normalizing to the mean value of the contralateral white matter on PWI. Cox regression was conducted to explore factors associated with time to LR, with Bonferroni adjusted p<0.0006 for multiple testing correction. LR rates were estimated with the Kaplan-Meier method and compared using the log-rank test.

RESULTS: Twenty-three patients were enrolled from 2013 through …

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.

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) …

New Imaging Tools To Measure Nephron Number In Vivo: Opportunities For Developmental Nephrology, K M Bennett, E J Baldelomar, D Morozov, R L Chevalier, J R Charlton

Open Access Publications

The mammalian kidney is a complex organ, requiring the concerted function of up to millions of nephrons. The number of nephrons is constant after nephrogenesis during development, and nephron loss over a life span can lead to susceptibility to acute or chronic kidney disease. New technologies are under development to count individual nephrons in the kidney in vivo. This review outlines these technologies and highlights their relevance to studies of human renal development and disease.

Human Recombinant Apyrase Therapy Protects Against Myocardial Ischemia/Reperfusion Injury And Preserves Left Ventricular Systolic Function In Rats, As Evaluated By 7t Cardiovascular Magnetic Resonance Imaging, Ziqian Xu, Wei Chen, Ruzhi Zhang, Lei Wang, Ridong Chen, Jie Zheng, Fabao Gao

Open Access Publications

No abstract provided.

On Complement, Memory, And Microglia, Robyn S. Klein

Open Access Publications

No abstract provided.

Cathepsin S And Protease-Activated Receptor-2 Drive Alloimmunity And Immune Regulation In Kidney Allograft Rejection, Yutian Lei, Benjamin Ehle, Santhosh V Kumar, Susanne Müller, Solange Moll, Andrew F Malone, Benjamin D Humphreys, Joachim Andrassy, Hans-Joachim Anders

Open Access Publications

Alloantigen presentation is an essential process in acute allorejection. In this context, we speculated on a pathogenic role of cathepsin S (Cat-S), a cysteine protease known to promote antigenic peptide loading into MHC class II and to activate protease-activated receptor (PAR)-2 on intrarenal microvascular endothelial and tubular epithelial cells. Single-cell RNA sequencing and immunostaining of human kidney allografts confirmed Cat-S expression in intrarenal mononuclear phagocytes.

Come Together: Protein Assemblies, Aggregates And The Sarcostat At The Heart Of Cardiac Myocyte Homeostasis, Moydul Islam, Abhinav Diwan, Kartik Mani

Open Access Publications

Homeostasis in vertebrate systems is contingent on normal cardiac function. This, in turn, depends on intricate protein-based cellular machinery, both for contractile function, as well as, durability of cardiac myocytes. The cardiac small heat shock protein (csHsp) chaperone system, highlighted by αB-crystallin (CRYAB), a small heat shock protein (sHsp) that forms ∼3-5% of total cardiac mass, plays critical roles in maintaining proteostatic function via formation of self-assembled multimeric chaperones. In this work, we review these ancient proteins, from the evolutionarily preserved role of homologs in protists, fungi and invertebrate systems, as well as, the role of sHsps and chaperones in …