Digital Commons Network^™

E Proteins Orchestrate Dynamic Transcriptional Cascades Implicated In The Suppression Of The Differentiation Of Group 2 Innate Lymphoid Cells, Vincent Peng, Constantin Georgescu, Anna Bakowska, Aneta Pankow, Liangyue Qian, Jonathan D. Wren, Xiao-Hong Sun

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 …

Assessment Of Plasma Amyloid-Β42/40 And Cognitive Decline Among Community-Dwelling Older Adults, Kelly Virecoulon Giudici, Philipe De Souto Barreto, Sophie Guyonnet, Yan Li, Randall J. Bateman, Bruno Vellas

Open Access Publications

Importance: Plasma measurement of amyloid-β (Aβ) peptides has been associated with cognitive function, but evidence of its ability to identify cognitive decline is still scarce.

Objective: To investigate the associations between plasma Aβ42/40 and cognitive decline over time among community-dwelling older adults with subjective memory concerns.

Design, Setting, and Participants: This multicenter cohort study used data from volunteers in the 5-year study Multidomain Alzheimer Preventive Trial (MAPT). Participants were aged 70 years or older and observed for a median (interquartile range) of 3.9 (2.0-4.0) years. Recruitment of participants started in May 2008 and ended in February 2011. Follow-up ended in …

The Genetic Architecture Of Sporadic And Multiple Consecutive Miscarriage, Triin Laisk, Avinash Ramu, Donald F. Conrad, Et Al.

Open Access Publications

No abstract provided.

The Landscape Of Novel Therapeutics And Challenges In Glioblastoma Multiforme: Contemporary State And Future Directions, Karam Khaddour, Tanner M Johanns, George Ansstas

Open Access Publications

BACKGROUND: Glioblastoma multiforme is a malignant intracranial neoplasm that constitutes a therapeutic challenge because of the associated high morbidity and mortality given the lack of effective approved medication and aggressive nature of the tumor. However, there has been extensive research recently to address the reasons implicated in the resistant nature of the tumor to pharmaceutical compounds, which have resulted in several clinical trials investigating promising treatment approaches.

METHODS: We reviewed literature published since 2010 from PUBMED and several annual meeting abstracts through 15 September 2020. Selected articles included those relevant to topics of glioblastoma tumor biology, original basic research, clinical …

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 …

Radiolabeled 6-(2, 3-Dichlorophenyl)-N4-Methylpyrimidine-2, 4-Diamine (Th287): A Potential Radiotracer For Measuring And Imaging Mth1, Huaping Chen, Sadia Afrin, Yingqiu Guo, Wenhua Chu, Tammie L S Benzinger, Buck E Rogers, Joel R Garbow, Joel S Perlmutter, Dong Zhou, Jinbin Xu

Open Access Publications

MTH1 (MutT homolog 1) or NUDT1 (Nudix Hydrolase 1), also known as oxidized purine nucleoside triphosphatase, has potential as a biomarker for monitoring cancer progression and quantifying target engagement for relevant therapies. In this study, we validate one MTH1 inhibitor TH287 as a PET MTH1 radiotracer. TH287 was radiolabeled with tritium and the binding of [

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). …

Chemical Mutagenesis Of A Gpcr Ligand: Detoxifying “Inflammo-Attraction” To Direct Therapeutic Stem Cell Migration, Jean-Pyo Lee, Edward B. Han, Et Al.

Open Access Publications

No abstract provided.

Social Jetlag And Prostate Cancer Incidence In Alberta's Tomorrow Project: A Prospective Cohort Study, Liang Hu, Andrew Harper, Emily Heer, Jessica Mcneil, Chao Cao, Yikyung Park, Kevin Martell, Geoffrey Gotto, Grace Shen-Tu, Cheryl Peters, Darren Brenner, Lin Yang

Open Access Publications

We investigated the association of social jetlag (misalignment between the internal clock and socially required timing of activities) and prostate cancer incidence in a prospective cohort in Alberta, Canada. Data were collected from 7455 cancer-free men aged 35-69 years enrolled in Alberta's Tomorrow Project (ATP) from 2001-2007. In the 2008 survey, participants reported usual bed- and wake-times on weekdays and weekend days. Social jetlag was defined as the absolute difference in waking time between weekday and weekend days, and was categorized into three groups: 0-<1 h (from 0 to anything smaller than 1), 1-<2 h (from 1 to anything smaller than 2), and 2+ h. ATP facilitated data linkage with the Alberta Cancer Registry in June 2018 to determine incident prostate cancer cases (

Tumor Microenvironment As A Regulator Of Radiation Therapy: New Insights Into Stromal-Mediated Radioresistance, Varintra E Krisnawan, Jennifer A Stanley, Julie K Schwarz, David G Denardo

Open Access Publications

No abstract provided.

Relations Between Sensory Responsiveness And Features Of Autism In Children, Jacob I Feldman, Margaret Cassidy, Yupeng Liu, Anne V Kirby, Mark T Wallace, Tiffany G Woynaroski

Open Access Publications

Autism is a neurodevelopmental condition defined by differences in social communication and by the presence of restricted and repetitive patterns of behavior, interests, and activities (RRBs). Individuals with autism also commonly present with atypical patterns of sensory responsiveness (i.e., hyporesponsiveness, hyperresponsiveness, and sensory seeking), which are theorized to produce cascading effects across other domains of development. The purpose of this study was to examine differences in sensory responsiveness in children with and without autism (ages 8-18 years), as well as relations between patterns of sensory responsiveness and core and related features of autism. Participants were 50 children with autism and …

Novel Multimodal Molecular Imaging Of Vitamin H (Biotin) Transporter Activity In The Murine Placenta, Ben Eliezer Noam, Lysenko Marina, Biton E. Inbal, Golani Ofra, Bartels L. Jennifer, Fernandez R. Solana, Aweda A. Tolulope, Clanton A. Nicholas, Beacham Rebecca, Lapi E. Suzanne, Garbow R. Joel, Neeman Michal

Open Access Publications

No abstract provided.

Histone H3.3 Beyond Cancer: Germline Mutations In Histone 3 Family 3a And 3b Cause A Previously Unidentified Neurodegenerative Disorder In 46 Patients, Laura Bryant, Marcia C Willing, Linda Manwaring, Et Al

Open Access Publications

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (

A Matricellular Protein Fibulin-4 Is Essential For The Activation Of Lysyl Oxidase, Kazuo Noda, Kaori Kitagawa, Takao Miki, Masahito Horiguchi, Tomoya O Akama, Takako Taniguchi, Hisaaki Taniguchi, Kazuaki Takahashi, Yasumitsu Ogra, Robert P Mecham, Masahiko Terajima, Mitsuo Yamauchi, Tomoyuki Nakamura

Open Access Publications

Fibulin-4 is a matricellular protein required for extracellular matrix (ECM) assembly. Mice deficient in fibulin-4 (

Distinct Inflammatory Profiles Distinguish Covid-19 From Influenza With Limited Contributions From Cytokine Storm, Philip A Mudd, Jackson S Turner, Daniel Reynolds, Diane Bender, Adrianus C M Boon, Stacey L House, Kenneth E Remy, Richard S Hotchkiss, Rachel M Presti, Jane A O'Halloran, William G Powderly, Ali H Ellebedy, Et Al

Open Access Publications

We pursued a study of immune responses in coronavirus disease 2019 (COVID-19) and influenza patients. Compared to patients with influenza, patients with COVID-19 exhibited largely equivalent lymphocyte counts, fewer monocytes, and lower surface human leukocyte antigen (HLA)-class II expression on selected monocyte populations. Furthermore, decreased HLA-DR on intermediate monocytes predicted severe COVID-19 disease. In contrast to prevailing assumptions, very few (7 of 168) patients with COVID-19 exhibited cytokine profiles indicative of cytokine storm syndrome. After controlling for multiple factors including age and sample time point, patients with COVID-19 exhibited lower cytokine levels than patients with influenza. Up-regulation of IL-6, G-CSF, …

Adolescent Alcohol, Nuts, And Fiber: Combined Effects On Benign Breast Disease Risk In Young Women, Catherine S. Berkey, Rulla M. Tamimi, Walter C. Willett, Bernard Rosner, Martha Hickey, Adetunji T. Toriola, A. Lindsay Frazier, Graham A. Colditz

Open Access Publications

No abstract provided.

Natural Bladder Flling Alters Resting Brain Function At Multiple Spatial Scales: A Proof‑Of‑Concept Mapp Network Neuroimaging Study, Ishtiaq Mawla, Henry Lai, Gerald Andriole, Et Al.

Open Access Publications

No abstract provided.

Termini Restraining Of Small Membrane Proteins Enables Structure Determination At Near-Atomic Resolution, Shixuan Liu, Shuang Li, Yihu Yang, Weikai Li

Open Access Publications

Small membrane proteins are difficult targets for structural characterization. Here, we stabilize their folding by restraining their amino and carboxyl termini with associable protein entities, exemplified by the two halves of a superfolder GFP. The termini-restrained proteins are functional and show improved stability during overexpression and purification. The reassembled GFP provides a versatile scaffold for membrane protein crystallization, enables diffraction to atomic resolution, and facilitates crystal identification, phase determination, and density modification. This strategy gives rise to 14 new structures of five vertebrate proteins from distinct functional families, bringing a substantial expansion to the structural database of small membrane proteins. …

Integration Of The Drug-Gene Interaction Database (Dgidb 4.0) With Open Crowdsource Efforts, Sharon L. Freshour, Susanna Kiwala, Kelsy C. Cotto, Adam C. Coffman, Joshua F. Mcmichael, Jonathan J. Song, Malachi Griffith, Obi L. Griffith, Alex H. Wagner

Open Access Publications

The Drug-Gene Interaction Database (DGIdb, www.dgidb.org) is a web resource that provides information on drug-gene interactions and druggable genes from publications, databases, and other web-based sources. Drug, gene, and interaction data are normalized and merged into conceptual groups. The information contained in this resource is available to users through a straightforward search interface, an application programming interface (API), and TSV data downloads. DGIdb 4.0 is the latest major version release of this database. A primary focus of this update was integration with crowdsourced efforts, leveraging the Drug Target Commons for community-contributed interaction data, Wikidata to facilitate term normalization, and export …

Decreased Adipose Tissue Oxygenation Associates With Insulin Resistance In Individuals With Obesity, Vincenza Cifarelli, Scott C Beeman, Gordon I Smith, Jun Yoshino, Darya Morozov, Joseph W Beals, Brandon D Kayser, Jeramie D Watrous, Mohit Jain, Bruce W Patterson, Samuel Klein

Open Access Publications

BACKGROUNDData from studies conducted in rodent models have shown that decreased adipose tissue (AT) oxygenation is involved in the pathogenesis of obesity-induced insulin resistance. Here, we evaluated the potential influence of AT oxygenation on AT biology and insulin sensitivity in people.METHODSWe evaluated subcutaneous AT oxygen partial pressure (pO2); liver and whole-body insulin sensitivity; AT expression of genes and pathways involved in inflammation, fibrosis, and branched-chain amino acid (BCAA) catabolism; systemic markers of inflammation; and plasma BCAA concentrations, in 3 groups of participants that were rigorously stratified by adiposity and insulin sensitivity: metabolically healthy lean (MHL; n = 11), metabolically healthy …

Astrocyte Deletion Of Α2-Na/K Atpase Triggers Episodic Motor Paralysis In Mice Via A Metabolic Pathway, Sarah A. Smith, Xiaoying Chen, Lindsey M. Brier, Jonathan R. Bumstead, Nicholas R. Rensing, Alison E. Ringel, Haewon Shin, Anna Oldenborg, Jan R. Crowley, Annie R. Bice, Krikor Dikranian, Joseph E. Ippolito, Marcia C. Haigis, Thomas Papouin, Guoyan Zhao, Michael Wong, Joseph P. Culver, Azad Bonni

Open Access Publications

No abstract provided.

Pathophysiological Consequences Of Katp Channel Overactivity And Pharmacological Response To Glibenclamide In Skeletal Muscle Of A Murine Model Of Cantù Syndrome, Rosa Scala, Fatima Maqoud, Nicola Zizzo, Antonietta Mele, Giulia Maria Camerino, Francesco Alfredo Zito, Girolamo Ranieri, Conor Mcclenaghan, Theresa M Harter, Colin G Nichols, Domenico Tricarico

Open Access Publications

Cantù syndrome (CS) arises from mutations in

Mycena Genomes Resolve The Evolution Of Fungal Bioluminescence, Huei-Mien Ke, Rita Jui-Hsien Lu, Et Al.

Open Access Publications

No abstract provided.

Pediatric Research Priorities In Healthcare-Associated Infections And Antimicrobial Stewardship, Susan E Coffin, Stephanie Fritz, Jason Newland, Et Al

Open Access Publications

OBJECTIVE: To develop a pediatric research agenda focused on pediatric healthcare-associated infections and antimicrobial stewardship topics that will yield the highest impact on child health.

PARTICIPANTS: The study included 26 geographically diverse adult and pediatric infectious diseases clinicians with expertise in healthcare-associated infection prevention and/or antimicrobial stewardship (topic identification and ranking of priorities), as well as members of the Division of Healthcare Quality and Promotion at the Centers for Disease Control and Prevention (topic identification).

METHODS: Using a modified Delphi approach, expert recommendations were generated through an iterative process for identifying pediatric research priorities in healthcare associated infection prevention and …

Cholesterol 25-Hydroxylase Suppresses Sars-Cov-2 Replication By Blocking Membrane Fusion, Ruochen Zang, James Brett Case, Xiucui Ma, Maria Florencia Gomez Castro, Zhuoming Liu, Qiru Zeng, Haiyan Zhao, Juhee Son, Paul W. Rothlauf, Gaopeng Hou, Michael D. Vahey, Kartik Mani, Daved H. Fremont, Abhinav Diwan, Michael S. Diamond, Sean P.J. Whelan, Siyuan Ding, Et Al.

Open Access Publications

No abstract provided.

A 2020 View Of Tension-Based Cortical Morphogenesis, David C. Van Essen

Open Access Publications

No abstract provided.

Endothelial Cell Cd36 Deficiency Prevents Normal Angiogenesis And Vascular Repair, Lara Bou Khzam, Ni-Huiping Son, Adam E Mullick, Nada A Abumrad, Ira J Goldberg

Open Access Publications

Endothelial cells (ECs) maintain vascular integrity and mediate vascular repair and angiogenesis, by which new blood vessels are formed from pre-existing blood vessels. Hyperglycemia has been shown to increase EC angiogenic potential. However, few studies have investigated effects of fatty acids (FAs) on EC angiogenesis. Cluster of differentiation 36 (CD36) is a FA transporter expressed by ECs, but its role in EC proliferation, migration, and angiogenesis is unknown. We sought to determine if circulating FAs regulate angiogenic function in a CD36-dependent manner. CD36-dependent effects of FAs on EC proliferation and migration of mouse heart ECs (MHECs) and lung ECs (MLECs) …

Food Addiction And Psychosocial Adversity: Biological Embedding, Contextual Factors, And Public Health Implications, David A Wiss, Nicole Avena, Mark Gold

Open Access Publications

The role of stress, trauma, and adversity particularly early in life has been identified as a contributing factor in both drug and food addictions. While links between traumatic stress and substance use disorders are well documented, the pathways to food addiction and obesity are less established. This review focuses on psychosocial and neurobiological factors that may increase risk for addiction-like behaviors and ultimately increase BMI over the lifespan. Early childhood and adolescent adversity can induce long-lasting alterations in the glucocorticoid and dopamine systems that lead to increased addiction vulnerability later in life. Allostatic load, the hypothalamic-pituitary-adrenal axis, and emerging data …

A Framework For Advancing Our Understanding Of Cancer-Associated Fibroblasts, Erik Sahai, David G. Denardo, Sheila Stewart, Et Al.

Open Access Publications

No abstract provided.