Digital Commons Network^™

Phase 1–2 Trial Of Antisense Oligonucleotide Tofersen For Sod1 Als, Timothy Miller, Robert C. Bucelli, Alan Pestronk, Et Al.

Open Access Publications

No abstract provided.

Androgen-Influenced Polarization Of Activin A-Producing Macrophages Accompanies Post-Pyelonephritic Renal Scarring, Teri N. Hreha, Christina A. Collins, Allyssa L. Daugherty, Jessie M. Griffith, Keith A. Hruska, David A. Hunstad

Open Access Publications

No abstract provided.

Targeting Unconventional Host Components For Vaccination-Induced Protection Against Tb, Elisa Nemes, Shabaana A Khader, Rosemary V Swanson, Willem A Hanekom

Open Access Publications

The current tuberculosis (TB) vaccine, Bacille Calmette-Guerin (BCG), is effective in preventing TB in young children but was developed without a basic understanding of human immunology. Most modern TB vaccine candidates have targeted CD4

Mitofusin 2 Dysfunction And Disease In Mice And Men, Gerald W Dorn Ii

Open Access Publications

A causal relationship between Mitofusin (MFN) 2 gene mutations and the hereditary axonal neuropathy Charcot-Marie-Tooth disease type 2A (CMT2A) was described over 15 years ago. During the intervening period much has been learned about MFN2 functioning in mitochondrial fusion, calcium signaling, and quality control, and the consequences of these MFN2 activities on cell metabolism, fitness, and development. Nevertheless, the challenge of defining the central underlying mechanism(s) linking mitochondrial abnormalities to progressive dying-back of peripheral arm and leg nerves in CMT2A is largely unmet. Here, a different perspective of why, in humans, MFN2 dysfunction preferentially impacts peripheral nerves is provided based …

Evaluating Circadian Dysfunction In Mouse Models Of Alzheimer's Disease: Where Do We Stand?, Patrick W Sheehan, Erik S Musiek

Open Access Publications

Circadian dysfunction has been described in patients with symptomatic Alzheimer's disease (AD), as well as in presymptomatic phases of the disease. Modeling this circadian dysfunction in mouse models would provide an optimal platform for understanding mechanisms and developing therapies. While numerous studies have examined behavioral circadian function, and in some cases clock gene oscillation, in mouse models of AD, the results are variable and inconsistent across models, ages, and conditions. Ultimately, circadian changes observed in APP/PS1 models are inconsistent across studies and do not always replicate circadian phenotypes observed in human AD. Other models, including the 3xTG mouse, tau transgenic …

Outcome Of Everolimus-Based Therapy In Hormone-Receptor-Positive Metastatic Breast Cancer Patients After Progression On Palbociclib, Ajay Dhakal, Roby Antony Thomas, Ellis G. Levine, Adam Brufsky, Kazuaki Takabe, Matthew G. Hanna, Kristopher Attwood, Austin Miller, Thaer Khoury, Amy P. Early, Saif Soniwala, Tracy O'Connor, Matuesz Opyrchal

Open Access Publications

No abstract provided.

Cryptococcus Neoformans Evades Pulmonary Immunity By Modulating Xylose Precursor Transport, Lucy X. Li, Camaron R. Hole, Javier Rangel-Moreno, Shabaana A. Khader, Tamara L. Doering

Open Access Publications

No abstract provided.

Dna Double-Strand Breaks Induce H2ax Phosphorylation Domains In A Contact-Dependent Manner, Patrick L. Collins, Caitlin Purman, Sofia I. Porter, Vincent Nganga, Ankita Saini, Katharina E. Hayer, Greer L. Gurewitz, Barry P. Sleckman, Jeffrey J. Bednarski, Craig H. Bassing, Eugene M. Oltz

Open Access Publications

No abstract provided.

A Comparative Study Of Sleep And Diurnal Patterns In House Mouse (Mus Musculus) And Spiny Mouse (Acomys Cahirinus), Chanung Wang, Lauren E. Guerriero, Dillon M. Huffman, Asmaa A. Ajwad, Trae C. Brooks, Sridhar Sunderam, Ashley W. Seifert, Bruce F. O'Hara

Open Access Publications

No abstract provided.

Enhancing The Anti-Tumour Activity Of 177lu-Dota-Octreotate Radionuclide Therapy In Somatostatin Receptor-2 Expressing Tumour Models By Targeting Parp, Carleen Cullinane, Kelly Waldeck, Laura Kirby, Buck E. Rogers, Peter Eu, Richard W. Tothill, Rodney J. Hicks

Open Access Publications

No abstract provided.

Bone Marrow Adipose Tissue Is A Unique Adipose Subtype With Distinct Roles In Glucose Homeostasis, Karla J. Suchacki, Erica L. Scheller, Et Al.

Open Access Publications

No abstract provided.

Combined Abdominal Heterotopic Heart And Aorta Transplant Model In Mice, Hao Dun, Li Ye, Yuehui Zhu, Brian W Wong

Open Access Publications

BACKGROUND: Allograft vasculopathy (AV) remains a major obstacle to long-term allograft survival. While the mouse aortic transplantation model has been proven as a useful tool for study of the pathogenesis of AV, simultaneous transplantation of the aorta alongside the transplantation of another organ may reveal more clinically relevant mechanisms that contribute to the pathogenesis of chronic allograft rejection. Therefore, we developed a combined abdominal heart and aorta transplantation model in mice which benefits from reducing animal and drug utilization, while providing an improved model to study the progressive nature of AV.

METHODS: The middle of the infrarenal aorta of the …

Unmasking Intra-Tumoral Heterogeneity And Clonal Evolution In Nf1-Mpnst, Chang-In Moon, William Tompkins, Yuxi Wang, Abigail Godec, Xiaochun Zhang, Patrik Pipkorn, Christopher A Miller, Carina Dehner, Sonika Dahiya, Angela C Hirbe

Open Access Publications

Sarcomas are highly aggressive cancers that have a high propensity for metastasis, fail to respond to conventional therapies, and carry a poor 5-year survival rate. This is particularly true for patients with neurofibromatosis type 1 (NF1), in which 8%-13% of affected individuals will develop a malignant peripheral nerve sheath tumor (MPNST). Despite continued research, no effective therapies have emerged from recent clinical trials based on preclinical work. One explanation for these failures could be the lack of attention to intra-tumoral heterogeneity. Prior studies have relied on a single sample from these tumors, which may not be representative of all subclones …

The Transcription Factor Eb Reduces The Intraneuronal Accumulation Of The Beta-Secretase-Derived App Fragment C99 In Cellular And Mouse Alzheimer’S Disease Models, Anaïs Bécot, Raphaëlle Pardossi-Piquard, Alexandre Bourgeois, Eric Duplan, Qingli Xiao, Abhinav Diwan, Jin-Moo Lee, Inger Lauritzen, Frédéric Checler

Open Access Publications

No abstract provided.

The Chromatin Remodeling Enzyme Chd4 Regulates Genome Architecture In The Mouse Brain, Jared V. Goodman, Tomoko Yamada, Yue Yang, Lingchun Kong, Dennis Y. Wu, Guoyan Zhao, Harrison W. Gabel, Azad Bonni

Open Access Publications

No abstract provided.

Single-Cell Rna-Seq Analysis Of Human Csf Microglia And Myeloid Cells In Neuroinflammation, Ekaterina Esaulova, Claudia Cantoni, Irina Shchukina, Konstantin Zaitsev, Robert C. Bucelli, Gregory F. Wu, Maxim N. Artyomov, Anne H. Cross, Brian T. Edelson

Open Access Publications

No abstract provided.

Deployment Of Convalescent Plasma For The Prevention And Treatment Of Covid-19, Evan M Bloch, Brenda J Grossman, Jeffrey P Henderson, Et Al

Open Access Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has spurred a global health crisis. To date, there are no proven options for prophylaxis for those who have been exposed to SARS-CoV-2, nor therapy for those who develop COVID-19. Immune (i.e., "convalescent") plasma refers to plasma that is collected from individuals following resolution of infection and development of antibodies. Passive antibody administration through transfusion of convalescent plasma may offer the only short-term strategy for conferring immediate immunity to susceptible individuals. There are numerous examples in which convalescent plasma has been used successfully as postexposure prophylaxis …

Prevention And Management Of Dermatologic Adverse Events Associated With Tumor Treating Fields In Patients With Glioblastoma, Mario E Lacouture, Milan J Anadkat, Matthew T Ballo, Fabio Iwamoto, Suriya A Jeyapalan, Renato V La Rocca, Margaret Schwartz, Jennifer N Serventi, Martin Glas

Open Access Publications

No abstract provided.

Identification And Characterization Of Novel Trpm1 Autoantibodies From Serum Of Patients With Melanoma-Associated Retinopathy, Juliette Varin, Margaret M. Reynolds, Nassima Bouzidi, Sarah Tick, Juliette Wohlschlegel, Ondine Becquart, Christelle Michiels, Olivier Dereure, Robert M. Duvoisin, Catherine W. Morgans, José-Alain Sahel, Quentin Samaran, Bernard Guillot, José S. Pulido, Isabelle Audo, Christina Zeitz

Open Access Publications

Melanoma-associated retinopathy (MAR) is a rare paraneoplastic retinal disorder usually occurring in the context of metastatic melanoma. Patients present with night blindness, photopsias and a constriction of the visual field. MAR is an auto-immune disorder characterized by the production of autoantibodies targeting retinal proteins, especially autoantibodies reacting to the cation channel TRPM1 produced in melanocytes and ON-bipolar cells. TRPM1 has at least three different isoforms which vary in the N-terminal region of the protein. In this study, we report the case of three new MAR patients presenting different anti-TRPM1 autoantibodies reacting to the three isoforms of TRPM1 with variable binding …

12-Lox Catalyzes The Oxidation Of 2-Arachidonoyl-Lysolipids In Platelets Generating Eicosanoid-Lysolipids That Are Attenuated By Ipla2Γ Knockout, Xinping Liu, Harold F. Sims, Christopher M. Jenkins, Shaoping Guan, Beverly G. Dilthey, Richard W. Gross

Open Access Publications

No abstract provided.

Ly6clo Non-Classical Monocytes Promote Resolution Of Rhesus Rotavirus-Mediated Perinatal Hepatic Infammation, Anas Alkhani, Claire S. Levy, Margaret Tsui, Katherine A. Rosenberg, Katya Polovina, Aras N. Mattis, Matthias Mack, Steven Van Dyken, Bruce M. Wang, Jacquelyn J. Maher, Amar Nijagal

Open Access Publications

No abstract provided.

Impact Of Trem2r47h Variant On Tau Pathology-Induced Gliosis And Neurodegeneration, Maud Gratuze, Cheryl Eg Leyns, Andrew D Sauerbeck, Marie-Kim St-Pierre, Monica Xiong, Nayeon Kim, Javier Remolina Serrano, Marie-Ève Tremblay, Terrance T Kummer, Marco Colonna, Jason D Ulrich, David M Holtzman

Open Access Publications

Alzheimer's disease (AD) is characterized by plaques containing amyloid-β (Aβ) and neurofibrillary tangles composed of aggregated, hyperphosphorylated tau. Beyond tau and Aβ, evidence suggests that microglia play an important role in AD pathogenesis. Rare variants in the microglia-expressed triggering receptor expressed on myeloid cells 2 (TREM2) gene increase AD risk 2- to 4-fold. It is likely that these TREM2 variants increase AD risk by decreasing the response of microglia to Aβ and its local toxicity. However, neocortical Aβ pathology occurs many years before neocortical tau pathology in AD. Thus, it will be important to understand the role of TREM2 in …

Modeling Biological And Genetic Diversity In Upper Tract Urothelial Carcinoma With Patient Derived Xenografts, Kwanghee Kim, James J. Hsieh, Et Al.

Open Access Publications

No abstract provided.

Core Warming Of Coronavirus Disease 2019 (Covid-19) Patients Undergoing Mechanical Ventilation-A Protocol For A Randomized Controlled Pilot Study, Nathaniel Bonfanti, Emily Gundert, Anne M. Drewry, Kristina Goff, Roger Bedimo, Erik Kulstad

Open Access Publications

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, is spreading rapidly across the globe, with little proven effective therapy. Fever is seen in most cases of COVID-19, at least at the initial stages of illness. Although fever is typically treated (with antipyretics or directly with ice or other mechanical means), increasing data suggest that fever is a protective adaptive response that facilitates recovery from infectious illness.

OBJECTIVE: To describe a randomized controlled pilot study of core warming patients with COVID-19 undergoing mechanical ventilation.

METHODS: This prospective single-site randomized controlled pilot study will enroll 20 patients undergoing mechanical ventilation …

Pain Relief After Surgical Decompression Of The Distal Brachial Plexus, Richard Morgan, Iain Elliot, Vibhu Banala, Christopher Dy, Briana Harris, Elizabeth Anne Ouellette

Open Access Publications

No abstract provided.

Assaying Three-Dimensional Cellular Architecture Using X-Ray Tomographic And Correlated Imaging Approaches, Peter O. Bayguinov, Max R. Fisher, James A. J. Fitzpatrick

Open Access Publications

No abstract provided.

Tetracycline-Inactivating Enzymes From Environmental, Human Commensal, And Pathogenic Bacteria Cause Broad-Spectrum Tetracycline Resistance, Andrew J. Gasparrini, Jana L. Markley, Hirdesh Kumar, Bin Wang, Luting Fang, Sidra Irum, Chanez T. Symister, Meghan Wallace, Carey-Ann D. Burnham, Saadia Andleeb, Niraj H. Tolia, Timothy A. Wencewicz, Gautam Dantas

Open Access Publications

No abstract provided.

Cockayne Syndrome: The Many Challenges And Approaches To Understand A Multifaceted Disease, Alexandre Teixeira Vessoni, Camila Chaves Coelho Guerra, Gustavo Satoru Kajitani, Livia Luz Souza Nascimento, Camila Carrião Machado Garcia

Open Access Publications

The striking and complex phenotype of Cockayne syndrome (CS) patients combines progeria-like features with developmental deficits. Since the establishment of the in vitro culture of skin fibroblasts derived from patients with CS in the 1970s, significant progress has been made in the understanding of the genetic alterations associated with the disease and their impact on molecular, cellular, and organismal functions. In this review, we provide a historic perspective on the research into CS by revisiting seminal papers in this field. We highlighted the great contributions of several researchers in the last decades, ranging from the cloning and characterization of CS …

Association Between Intake Of Energy And Macronutrients And Memory Impairment Severity In Us Older Adults, National Health And Nutrition Examination Survey 2011-2014, Qinran Liu, Jianjun Guo, Liang Hu, Nicola Veronese, Lee Smith, Lin Yang, Chao Cao

Open Access Publications

Without a cure, dementia affects about 50 million people worldwide. Understanding the effects of dietary habits, a key lifestyle behavior, on memory impairment is critical to inform early behavioral modification to delay further memory loss and progression to dementia. We examined the associations of total energy intake and energy intake from macronutrients with memory impairment among older US adults using data from the nationally representative National Health and Nutrition Examination Survey study 2011-2014. A total of 3623 participants aged ≥60 years were analyzed. Comparing to those with low total energy intake, individuals with high intake were more likely to have …

Cd46 And Oncologic Interactions: Friendly Fire Against Cancer, Michelle Elvington, M Kathryn Liszewski, John P Atkinson

Open Access Publications

One of the most challenging aspects of cancer therapeutics is target selection. Recently, CD46 (membrane cofactor protein; MCP) has emerged as a key player in both malignant transformation as well as in cancer treatments. Normally a regulator of complement activation, CD46 is co-expressed as four predominant isoforms on almost all cell types. CD46 is highly overexpressed on a variety of human tumor cells. Clinical and experimental data support an association between increased CD46 expression and malignant transformation and metastasizing potential. Further, CD46 is a newly discovered driver of metabolic processes and plays a role in the intracellular complement system (complosome). …