Digital Commons Network^™

The Pathway To Secondary Prevention Of Alzheimer's Disease, Eric Mcdade, Martin M Bednar, H Robert Brashear, David S Miller, Paul Maruff, Christopher Randolph, Zahinoor Ismail, Maria C Carrillo, Christopher J Weber, Lisa J Bain, Ann Marie Hake

Open Access Publications

Alzheimer's disease (AD) is a continuum consisting of a preclinical stage that occurs decades before symptoms appear. As researchers make advances in investigating the continuum, the importance of developing drugs for secondary prevention is garnering increased discussion. For efficacious drug development for secondary prevention it is important to define what are the earliest biological stages of AD. The Alzheimer's Association Research Roundtable convened November 27 to 28, 2018 to focus on pre-clinical AD. This review will address the biological approach to defining pre-clinical AD, detection, identification of at-risk individuals, and lessons learned from trials such as A4 and TOMMORROW.

Lactate-Protechypoglycemia (Lph), Matthew L Goodwin, L Bruce Gladden, Maarten W N Nijsten

Open Access Publications

Here, we provide an overview of the concept of a lactate-protected hypoglycemia ("LPH"), originally proposed as lowering glucose while simultaneously increasing lactate concentration as a method by which tumors might be targeted. Central to this hypothesis is that lactate can act as a critical salvage fuel for the central nervous system, allowing for wide perturbations in whole body and central nervous system glucose concentrations. Further, many tumors exhibit "the Warburg" effect, consuming glucose and producing and exporting lactate despite adequate oxygenation. While some recent data have provided evidence for a "reverse-Warburg," where some tumors may preferentially consume lactate, many of …

Harnessing Real-World Data To Inform Decision-Making: Multiple Sclerosis Partners Advancing Technology And Health Solutions (Ms Paths), Ellen M Mowry, Tammie L S Benzinger, Robert T Naismith, Et Al

Open Access Publications

No abstract provided.

Inhibition Of Pikfyve Kinase Prevents Infection By Zaire Ebolavirus And Sars-Cov-2, Yuan-Lin Kang, Yi-Ying Chou, Paul W. Rothlauf, Zhuoming Liu, Timothy K. Soh, David Cureton, James Brett Case, Rita E. Chen, Michael S. Diamond, Sean P.J. Whelan, Tom Kirchhausen

Open Access Publications

No abstract provided.

The Membrane-Associated Form Of Cyclin D1 Enhances Cellular Invasion, Ke Chen, Xuanmao Jiao, Anthony Ashton, Agnese Di Rocco, Timothy G. Pestell, Yunguang Sun, Jun Zhao, Mathew C. Casimiro, Zhiping Li, Michael P. Lisanti, Peter A. Mccue, Duanwen Shen, Samuel Achilefu, Hallgeir Rui, Richard G. Pestell

Open Access Publications

No abstract provided.

Hypoxia Protects Rat Bone Marrow Mesenchymal Stem Cells Against Compression-Induced Apoptosis In The Degenerative Disc Microenvironment Through Activation Of The Hif-1a/Yap Signaling Pathway, Zhe Wang, Min Cui, Yanji Qu, Ruijun He, Wei Wu, Hui Lin, Zengwu Shao

Open Access Publications

No abstract provided.

Tert, A Promoter Of Cns Malignancies, Bhuvic Patel, Rukayat Taiwo, Albert H. Kim, Gavin P. Dunn

Open Access Publications

As cells replicate their DNA during mitosis, telomeres are shortened due to the inherent limitations of the DNA replication process. Maintenance of telomere length is critical for cancer cells to overcome cellular senescence induced by telomere shortening. Telomerase reverse transcriptase (TERT) is the rate-limiting catalytic subunit of telomerase, an RNA-dependent DNA polymerase that lengthens telomeric DNA to maintain telomere homeostasis.

Huntingtin-Interacting Protein Family Members Have A Conserved Pro-Viral Function From Caenorhabditis Elegans To Humans, Hongbing Jiang, Luis Enrique Sandoval Del Prado, Christian Leung, David Wang

Open Access Publications

No abstract provided.

Association Of Sex And Apoe Ε4 With Brain Tau Deposition And Atrophy In Older Adults With Alzheimer’S Disease, Shaozhen Yan, Chaojie Zheng, Manish D. Paranjpe, Jian Li, Tammie L.S. Benzinger, Jie Lu, Yun Zhou

Open Access Publications

No abstract provided.

Increased Aqueous Humor Gdf15 Is Associated With Worse Visual Field Loss In Pseudoexfoliative Glaucoma Patients, Jonathan B. Lin, Arsham Sheybani, Andrea Santeford, Alicia De Maria, Rajendra S. Apte

Open Access Publications

No abstract provided.

Functional Analysis Of Rare Genetic Variants In Complement Factor I (Cfi) Using A Serum-Based Assay In Advanced Age-Related Macular Degeneration, Anuja Java, Peter Baciu, Rafael Widjajahakim, Yun Ju Sung, Jae Yang, David Kavanagh, John Atkinson, Johanna Seddon

Open Access Publications

No abstract provided.

Discovery Of A Novel Simian Pegivirus In Common Marmosets (Callithrix Jacchus) With Lymphocytic Enterocolitis, Anna S. Heffron, Michael Lauck, Elizabeth D. Somsen, Elizabeth C. Townsend, Adam L. Bailey, Megan Sosa, Jens Eickhoff, Saverio Capuano Iii, Christina M. Newman, Jens H. Kuhn, Andres Mejia, Heather A. Simmons, David H. O'Connor

Open Access Publications

No abstract provided.

Human Ferroportin Mediates Proton-Coupled Active Transport Of Iron, Shuang Li, Yihu Yang, Weikai Li

Open Access Publications

No abstract provided.

Acvr1/Jak1/Jak2 Inhibitor Momelotinib Reverses Transfusion Dependency And Suppresses Hepcidin In Myelofibrosis Phase 2 Trial, Stephen T. Oh, Et Al.

Open Access Publications

No abstract provided.

Mitochondrial Calcium Uniporter (Mcu) Defciency Reveals An Alternate Path For ­Ca2+ Uptake In Photoreceptor Mitochondria, Celia M. Bisbach, Rachel A. Hutto, Deepak Poria, Whitney M. Cleghorn, Fatima Abbas, Frans Vinberg, Vladimir J. Kefalov, James B. Hurley, Susan E. Brockerhoff

Open Access Publications

No abstract provided.

Six-Year Follow-Up Of A Trial Of Antenatal Vitamin D For Asthma Reduction, Augusto A. Litonjua, Vincent J. Carey, Nancy Laranjo, Benjamin J. Stubbs, Hooman Mirzakhani, George T. O'Connor, Megan Sandel, Avraham Beigelman, Leonard B. Bacharier, Robert S. Zeiger, Michael Schatz, Bruce W. Hollis, Scott T. Weiss

Open Access Publications

No abstract provided.

Self-Reported Sleep Disturbance In Crohn’S Disease Is Not Confrmed By Objective Sleep Measures, Heba N. Iskandar, Emily E. Linan, Ami Patel, Renee Moore, Yi Lasanajak, C. Prakash Gyawali, Gregory S. Sayuk, Matthew A. Ciorba

Open Access Publications

No abstract provided.

Heavy Metals Contaminating The Environment Of A Progressive Supranuclear Palsy Cluster Induce Tau Accumulation And Cell Death In Cultured Neurons, Carolina Alquezar, Jessica B. Felix, Elizabeth Mccandlish, Brian T. Buckley, Dominique Caparros-Lefebvre, Celeste M. Karch, Lawrence I. Golbe, Aimee W. Kao

Open Access Publications

No abstract provided.

Generation Of Light-Producing Somatic-Transgenic Mice Using Adeno-Associated Virus Vectors, Rajvinder Karda, Jonathan D. Cooper, Et Al.

Open Access Publications

No abstract provided.

Improved Small Blob Detection In 3d Images Using Jointly Constrained Deep Learning And Hessian Analysis, Yanzhe Xu, Teresa Wu, Fei Gao, Jennifer R. Charlton, Kevin M. Bennett

Open Access Publications

No abstract provided.

Patient-Derived Small Intestinal Myofibroblasts Direct Perfused, Physiologically Responsive Capillary Development In A Microfluidic Gut-On-A-Chip Model, Kristen M. Seiler, Adam Bajinting, David M. Alvarado, Mahama A. Traore, Michael M. Binkley, William H. Goo, Wyatt E. Lanik, Jocelyn Ou, Usama Ismail, Micah Iticovici, Cristi R. King, Kelli L. Vandussen, Elzbieta A. Swietlicki, Vered Gazit, Jun Guo, Cliff J. Luke, Thaddeus Stappenbeck, Matthew A. Ciorba, Steven C. George, J. Mark Meacham, Deborah C. Rubin, Misty Good, Brad W. Warner

Open Access Publications

No abstract provided.

Inhibition Of Grb14, A Negative Modulator Of Insulin Signaling, Improves Glucose Homeostasis Without Causing Cardiac Dysfunction, Xunshan Ding, Rugmani Iyer, Christopher Novotny, Daniel Metzger, Heather H. Zhou, Gordon I. Smith, Mihoko Yoshino, Jun Yoshino, Samuel Klein, Gayathri Swaminath, Saswata Talukdar, Yingjiang Zhou

Open Access Publications

No abstract provided.

Live Neuron High-Content Screening Reveals Synaptotoxic Activity In Alzheimer Mouse Model Homogenates, Hao Jiang, Thomas J. Esparza, Terrance T. Kummer, Haining Zhong, Jens Rettig, David L. Brody

Open Access Publications

No abstract provided.

Remethylation Of Dnmt3a−/− Hematopoietic Cells Is Associated With Partial Correction Of Gene Dysregulation And Reduced Myeloid Skewing, Shamika Ketkar, Angela M. Verdoni, Amanda M. Smith, Celia V. Bangert, Elizabeth R. Leight, David Y. Chen, Meryl K. Brune, Nichole M. Helton, Mieke Hoock, Daniel R. George, Catrina Fronick, Robert S. Fulton, Sai Mukund Ramakrishnan, Gue Su Chang, Allegra A. Petti, David H. Spencer, Christopher A. Miller, Timothy J. Ley

Open Access Publications

No abstract provided.

Exercise Training Results In Lower Amyloid Plaque Load And Greater Cognitive Function In An Intensity Dependent Manner In The Tg2576 Mouse Model Of Alzheimer's Disease, Riya Thomas, Scott D Zimmerman, Kayla M Yuede, John R Cirrito, Leon M Tai, Benjamin F Timson, Carla M Yuede

Open Access Publications

Three months of exercise training (ET) decreases soluble Aβ

Sensitivity Analysis Of Monte Carlo Model Of A Gantry-Mounted Passively Scattered Proton System, Milad Baradaran-Ghahfarokhi, Francisco Reynoso, Michael T Prusator, Baozhou Sun, Tianyu Zhao

Open Access Publications

PURPOSE: This study aimed to present guidance on the correlation between treatment nozzle and proton source parameters, and dose distribution of a passive double scattering compact proton therapy unit, known as Mevion S250.

METHODS: All 24 beam options were modeled using the MCNPX MC code. The calculated physical dose for pristine peak, profiles, and spread out Bragg peak (SOBP) were benchmarked with the measured data. Track-averaged LET (LET

RESULTS: For the physical dose distribution, the MCNPX MC model matched measurements data for all the options to within 2 mm and 2% criterion. The Mevion S250 was found to have a …

Human Plasmacytoid Dendritic Cells And Cutaneous Melanoma, Matilde Monti, Francesca Consoli, Raffaella Vescovi, Mattia Bugatti, William Vermi

Open Access Publications

The prognosis of metastatic melanoma (MM) patients has remained poor for a long time. However, the recent introduction of effective target therapies (BRAF and MEK inhibitors for BRAFV600-mutated MM) and immunotherapies (anti-CTLA-4 and anti-PD-1) has significantly improved the survival of MM patients. Notably, all these responses are highly dependent on the fitness of the host immune system, including the innate compartment. Among immune cells involved in cancer immunity, properly activated plasmacytoid dendritic cells (pDCs) exert an important role, bridging the innate and adaptive immune responses and directly eliminating cancer cells. A distinctive feature of pDCs is the production of high …

A Single-Nucleotide Polymorphism In A Plasmodium Berghei Apiap2 Transcription Factor Alters The Development Of Host Immunity, Munir Akkaya, Patrick W Sheehan, Et Al

Open Access Publications

The acquisition of malaria immunity is both remarkably slow and unpredictable. At present, we know little about the malaria parasite genes that influence the host's ability to mount a protective immune response. Here, we show that a single-nucleotide polymorphism (SNP) resulting in a single amino acid change (S to F) in an ApiAP2 transcription factor in the rodent malaria parasite

Mirna-Based Rapid Differentiation Of Purified Neurons From Hpscs Advancestowards Quick Screening For Neuronal Disease Phenotypes In Vitro, Mitsuru Ishikawa, Takeshi Aoyama, Shoichiro Shibata, Takefumi Sone, Hiroyuki Miyoshi, Hirotaka Watanabe, Mari Nakamura, Saori Morota, Hiroyuki Uchino, Andrew S Yoo, Hideyuki Okano

Open Access Publications

Obtaining differentiated cells with high physiological functions by an efficient, but simple and rapid differentiation method is crucial for modeling neuronal diseases in vitro using human pluripotent stem cells (hPSCs). Currently, methods involving the transient expression of one or a couple of transcription factors have been established as techniques for inducing neuronal differentiation in a rapid, single step. It has also been reported that microRNAs can function as reprogramming effectors for directly reprogramming human dermal fibroblasts to neurons. In this study, we tested the effect of adding neuronal microRNAs, miRNA-9/9*, and miR-124 (miR-9/9*-124), for the neuronal induction method of hPSCs …

Radiation And Checkpoint Inhibitor Immunotherapy Lead To Long Term Disease Control In A Metastatic Rcc Patient With Brain Metastases, Maria Levitin, Joel Ofori, Woo Jae Shin, Jiayi Huang, Mackenzie Daly, Dengfeng Cao, Russell Pachynski

Open Access Publications

Renal cell carcinoma (RCC) comprises 4.2% of all new cancer cases in the United States and 30% of cases are metastatic (mRCC) at diagnosis. Brain metastatic RCC historically has poor prognosis, but the development of immune checkpoint inhibitors has revolutionized their care and may be successfully combined with SBRT to improve prognosis. Here, we present a case of a patient with mRCC who had brain metastases treated with concurrent immune checkpoint inhibitors and SBRT. He continues to survive with good functional status years following his initial diagnosis. We discuss the relevant history regarding treatment approach in patients with brain metastatic …