Digital Commons Network^™

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.

Global Proteomics Analysis Of Circulating Extracellular Vesicles Isolated From Lung Transplant Recipients, Sandhya Bansal, Marissa Mcgilvrey, Krystine Garcia-Mansfield, Ritin Sharma, Ross M. Bremner, Michael A. Smith, Ramsey Hachem, Patrick Pirrotte, Thalachallour Mohanakumar

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.

Depletion Interactions Modulate The Binding Between Disordered Proteins In Crowded Environments, Franziska Zosel, Andrea Soranno, Karin J. Buholzer, Daniel Nettels, Benjamin Schuler

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.

End Of An Era Of Administering Erythropoiesis Stimulating Agents Among Veterans Administration Cancer Patients With Chemotherapy-Induced Anemia, Shamia Hoque, Brian J. Chen, Martin W. Schoen, Kenneth R. Carson, Jesse Keller, Bartlett J. Witherspoon, Kevin B. Knopf, Y Tony Yang, Benjamin Schooley, Chadi Nabhan, Oliver Sartor, Paul R. Yarnold, Paul Ray, Laura Bobolts, William J. Hrushesky, Michael Dickson, Charles L. Bennett

Open Access Publications

Erythropoisis stimulating agent (ESA) use was addressed in Food and Drug Administration (FDA) Oncology Drug Advisory Committee (ODAC) meetings between 2004 and 2008. FDA safety-focused regulatory actions occurred in 2007 and 2008. In 2007, black box warnings advised of early death and venous thromboembolism (VTE) risks with ESAs in oncology. In 2010, a Risk Evaluation Strategies (REMS) was initiated, with cancer patient consent that mortality and VTE risks were noted with ESAs. We report warnings and REMS impacts on ESA utilization among Veterans Administration (VA) cancer patients with chemotherapy-induced anemia (CIA). Data were from Veterans Affairs database (2003-2012). Epoetin and …

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 …

Malaria Parasite Plasmepsins: More Than Just Plain Old Degradative Pepsins, Armiyaw S. Nasamu, Alexander J. Polino, Eva S. Istvan, Daniel E. Goldberg

Open Access Publications

No abstract provided.

19f Nmr Reveals The Conformational Properties Of Free Thrombin And Its Zymogen Precursor Prethrombin-2, Eliza A. Ruben, Prafull S. Gandhi, Zhiwei Chen, Sarah K. Koester, Gregory T. Dekoster, Carl Frieden, Enrico Di Cera

Open Access Publications

No abstract provided.

Domain-Centric Database To Uncover Structure Of Minimally Characterized Viral Genomes, John C. Bramley, Alex L. Yenkin, Mark A. Zaydman, Aaron Diantonio, Jeffrey D. Milbrandt, William J. Buchser

Open Access Publications

No abstract provided.

Using Polygenic Scores For Identifying Individuals At Increased Risk Of Substance Use Disorders In Clinical And Population Samples, Peter B. Barr, Emma C. Johnson, Andrey Anokhin, Arpana Agrawal, Et Al.

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.

Comparison Of Differential Accessibility Analysis Strategies For Atac-Seq Data, Paul Gontarz, Shuhua Fu, Xiaoyun Xing, Shaopeng Liu, Benpeng Miao, Viktoriia Bazylianska, Akhil Sharma, Pamela Madden, Kitra Cates, Andrew Yoo, Anna Moszczynska, Ting Wang, Bo Zhang

Open Access Publications

No abstract provided.

Combination Of Dasatinib With Chemotherapy In Previously Untreated Core Binding Factor Acute Myeloid Leukemia: Calgb 10801, Guido Marcucci, Geoffrey L. Uy, Et Al.

Open Access Publications

No abstract provided.

Kir B Donors Improve The Outcome For Aml Patients Given Reduced Intensity Conditioning And Unrelated Donor Transplantation, Daniel Weisdorf, Todd A. Fehniger, Et Al.

Open Access Publications

No abstract provided.

Atypical Cadherin Fat4 Orchestrates Lymphatic Endothelial Cell Polarity In Response To Flow, Kelly L Betterman, Drew L Sutton, Genevieve A Secker, Jan Kazenwadel, Anna Oszmiana, Lillian Lim, Naoyuki Miura, Lydia Sorokin, Benjamin M Hogan, Mark L Kahn, Helen Mcneill, Natasha L Harvey

Open Access Publications

The atypical cadherin FAT4 has established roles in the regulation of planar cell polarity and Hippo pathway signaling that are cell context dependent. The recent identification of FAT4 mutations in Hennekam syndrome, features of which include lymphedema, lymphangiectasia, and mental retardation, uncovered an important role for FAT4 in the lymphatic vasculature. Hennekam syndrome is also caused by mutations in collagen and calcium binding EGF domains 1 (CCBE1) and ADAM metallopeptidase with thrombospondin type 1 motif 3 (ADAMTS3), encoding a matrix protein and protease, respectively, that regulate activity of the key prolymphangiogenic VEGF-C/VEGFR3 signaling axis by facilitating the proteolytic cleavage and …

Influence Of Adiposity, Insulin Resistance, And Intrahepatic Triglyceride Content On Insulin Kinetics, Gordon I Smith, David C Polidori, Mihoko Yoshino, Monica L Kearney, Bruce W Patterson, Bettina Mittendorfer, Samuel Klein

Open Access Publications

BACKGROUNDInsulin is a key regulator of metabolic function. The effects of excess adiposity, insulin resistance, and hepatic steatosis on the complex integration of insulin secretion and hepatic and extrahepatic tissue extraction are not clear.METHODSA hyperinsulinemic-euglycemic clamp and a 3-hour oral glucose tolerance test were performed to evaluate insulin sensitivity and insulin kinetics after glucose ingestion in 3 groups: (a) lean subjects with normal intrahepatic triglyceride (IHTG) and glucose tolerance (lean-NL; n = 14), (b) obese subjects with normal IHTG and glucose tolerance (obese-NL; n = 24), and (c) obese subjects with nonalcoholic fatty liver disease (NAFLD) and prediabetes (obese-NAFLD; n …

Inhibition Of The Translesion Synthesis Polymerase Rev1 Exploits Replication Gaps As A Cancer Vulnerability, Sumeet Nayak, Jennifer A Calvo, Ke Cong, Min Peng, Emily Berthiaume, Jessica Jackson, Angela M Zaino, Alessandro Vindigni, M Kyle Hadden, Sharon B Cantor

Open Access Publications

The replication stress response, which serves as an anticancer barrier, is activated not only by DNA damage and replication obstacles but also oncogenes, thus obscuring how cancer evolves. Here, we identify that oncogene expression, similar to other replication stress-inducing agents, induces single-stranded DNA (ssDNA) gaps that reduce cell fitness. DNA fiber analysis and electron microscopy reveal that activation of translesion synthesis (TLS) polymerases restricts replication fork slowing, reversal, and fork degradation without inducing replication gaps despite the continuation of replication during stress. Consistent with gap suppression (GS) being fundamental to cancer, we demonstrate that a small-molecule inhibitor targeting the TLS …

Contacting Domains Segregate A Lipid Transporter From A Solute Transporter In The Malarial Host–Parasite Interface, Matthias Garten, Josh R. Beck, Robyn Roth, Tatyana Tenkova-Heuser, John Heuser, Eva S. Istvan, Christopher K.E. Bleck, Daniel E. Goldberg, Joshua Zimmerberg

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 …

The Clonal Evolution Of Metastatic Colorectal Cancer, Ha X Dang, Bradley A Krasnick, Julie G Grossman, Matthew S Strand, Jin Zhang, Christopher A Miller, Robert S Fulton, S Peter Goedegebuure, Catrina C Fronick, Malachi Griffith, David E Larson, Brian D Goetz, Jason R Walker, William G Hawkins, Steven M Strasberg, Kian H Lim, Timothy J Ley, Christopher A Maher, Ryan C Fields, Et Al

Open Access Publications

Tumor heterogeneity and evolution drive treatment resistance in metastatic colorectal cancer (mCRC). Patient-derived xenografts (PDXs) can model mCRC biology; however, their ability to accurately mimic human tumor heterogeneity is unclear. Current genomic studies in mCRC have limited scope and lack matched PDXs. Therefore, the landscape of tumor heterogeneity and its impact on the evolution of metastasis and PDXs remain undefined. We performed whole-genome, deep exome, and targeted validation sequencing of multiple primary regions, matched distant metastases, and PDXs from 11 patients with mCRC. We observed intricate clonal heterogeneity and evolution affecting metastasis dissemination and PDX clonal selection. Metastasis formation followed …

Mapping Of The Language Network With Deep Learning, Patrick Luckett, John J Lee, Ki Yun Park, Donna Dierker, Andy G S Daniel, Benjamin A Seitzman, Carl D Hacker, Beau M Ances, Eric C Leuthardt, Abraham Z Snyder, Joshua S Shimony

Open Access Publications

No abstract provided.

Site-1 Protease Ablation In The Osterix-Lineage In Mice Results In Bone Marrow Neutrophilia And Hematopoietic Stem Cell Alterations, Debabrata Patra, Joongho Kim, Qiang Zhang, Eric Tycksen, Linda J Sandell

Open Access Publications

Site-1 protease (S1P) ablation in the osterix-lineage in mice drastically reduces bone development and downregulates bone marrow-derived skeletal stem cells. Here we show that these mice also suffer from spina bifida occulta with a characteristic lack of bone fusion in the posterior neural arches. Molecular analysis of bone marrow-derived non-red blood cell cells, via single-cell RNA-Seq and protein mass spectrometry, demonstrate that these mice have a much-altered bone marrow with a significant increase in neutrophils and

Deep Learning Assessment Of Breast Terminal Duct Lobular Unit Involution: Towards Automated Prediction Of Breast Cancer Risk, Suzanne C. Wetstein, Ying Liu, Et Al.

Open Access Publications

Terminal duct lobular unit (TDLU) involution is the regression of milk-producing structures in the breast. Women with less TDLU involution are more likely to develop breast cancer. A major bottleneck in studying TDLU involution in large cohort studies is the need for labor-intensive manual assessment of TDLUs. We developed a computational pathology solution to automatically capture TDLU involution measures. Whole slide images (WSIs) of benign breast biopsies were obtained from the Nurses' Health Study. A set of 92 WSIs was annotated for acini, TDLUs and adipose tissue to train deep convolutional neural network (CNN) models for detection of acini, and …

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.