Digital Commons Network^™

Cardiovascular Assessment Tool For Breast Cancer Survivors And Oncology Providers: Usability Study, Kathryn E Weaver, Heidi D Klepin, Brian J Wells, Emily V Dressler, Karen M Winkfield, Zanetta S Lamar, Tiffany P Avery, Nicholas M Pajewski, W Gregory Hundley, Aimee Johnson, Eleanor C Davidson, Marcelo Lopetegui, Randi E Foraker

Open Access Publications

BACKGROUND: Cardiovascular health is of increasing concern to breast cancer survivors and their health care providers, as many survivors are more likely to die from cardiovascular disease than cancer. Implementing clinical decision support tools to address cardiovascular risk factor awareness in the oncology setting may enhance survivors' attainment or maintenance of cardiovascular health.

OBJECTIVE: We sought to evaluate survivors' awareness of cardiovascular risk factors and examine the usability of a novel electronic health record enabled cardiovascular health tool from the perspective of both breast cancer survivors and oncology providers.

METHODS: Breast cancer survivors (n=49) recruited from a survivorship clinic interacted …

A Priori Activation Of Apoptosis Pathways Of Tumor (Aaapt) Technology: Development Of Targeted Apoptosis Initiators For Cancer Treatment, Raghu S. Pandurangi, Marco Tomasetti, Sekar T. Verapazham, Ramasamy Paulmurugan, Cynthia Ma, Sandeep Rajput, Manjushree Anjanappa, Harikrishna Nakshatri

Open Access Publications

Cancer cells develop tactics to circumvent the interventions by desensitizing themselves to interventions. Amongst many, the principle routes of desensitization include a) activation of survival pathways (e.g. NF-kB, PARP) and b) downregulation of cell death pathways (e.g. CD95/CD95L). As a result, it requires high therapeutic dose to achieve tumor regression which, in turn damages normal cells through the collateral effects. Methods are needed to sensitize the low and non-responsive resistant tumor cells including cancer stem cells (CSCs) in order to evoke a better response from the current treatments. Current treatments including chemotherapy can induce cell death only in bulk cancer …

Multistage And Transmission-Blocking Targeted Antimalarials Discovered From The Open-Source Mmv Pandemic Response Box, Janette Reader, Natalie J. Spillman, Eva S. Istvan, Daniel E. Goldberg, Et Al.

Open Access Publications

No abstract provided.

Allosteric Effects Of Ssb C-Terminal Tail On Assembly Of E. Coli Recor Proteins, Min Kyung Shinn, Alexander G. Kozlov, Timothy M. Lohman

Open Access Publications

Escherichia coli RecO is a recombination mediator protein that functions in the RecF pathway of homologous recombination, in concert with RecR, and interacts with E. coli single stranded (ss) DNA binding (SSB) protein via the last 9 amino acids of the C-terminal tails (SSB-Ct). Structures of the E. coli RecR and RecOR complexes are unavailable; however, crystal structures from other organisms show differences in RecR oligomeric state and RecO stoichiometry. We report analytical ultracentrifugation studies of E. coli RecR assembly and its interaction with RecO for a range of solution conditions using both sedimentation velocity and equilibrium approaches. We find …

Proteomic And Functional Mapping Of Cardiac Nav1.5 Channel Phosphorylation Sites, Maxime Lorenzini, Emily Wagner, Kiersten M. Ruff, Rohit V. Pappu, Jeanne M. Nerbonne, Jonathan R. Silva, R. Reid Townsend, Et Al

Open Access Publications

Phosphorylation of the voltage-gated Na+ (NaV) channel NaV1.5 regulates cardiac excitability, yet the phosphorylation sites regulating its function and the underlying mechanisms remain largely unknown. Using a systematic, quantitative phosphoproteomic approach, we analyzed NaV1.5 channel complexes purified from nonfailing and failing mouse left ventricles, and we identified 42 phosphorylation sites on NaV1.5. Most sites are clustered, and three of these clusters are highly phosphorylated. Analyses of phosphosilent and phosphomimetic NaV1.5 mutants revealed the roles of three phosphosites in regulating NaV1.5 channel expression and gating. The phosphorylated serines S664 and S667 regulate the voltage dependence of channel activation in a cumulative …

Acupuncture And Oxytocinergic System: The Promising Treatment For Autism, Tangfeng Su, Lei Pei

Open Access Publications

No abstract provided.

Time Resolved Speckle Contrast Optical Spectroscopy At Quasi-Null Source-Detector Separation For Non-Invasive Measurement Of Microvascular Blood Flow, Marco Pagliazzi, Lorenzo Colombo, Ernesto E. Vidal-Rosas, Tanja Dragojević, Veronika Parfentyeva, Joseph P. Culver, Sanathana Konugolu Venkata Sekar, Laura Di Sieno, Davide Contini, Alessandro Torricelli, Antonio Pifferi, Alberto Dalla Mora, Turgut Durduran

Open Access Publications

No abstract provided.

Extended Amygdala-Parabrachial Circuits Alter Threat Assessment And Regulate Feeding, Andrew T Luskin, Dionnet L Bhatti, Bernard Mulvey, Christian E Pedersen, Kasey S Girven, Hannah Oden-Brunson, Kate Kimbell, Taylor Blackburn, Abbie Sawyer, Robert W Gereau, Joseph D Dougherty, Michael R Bruchas

Open Access Publications

An animal's evolutionary success depends on the ability to seek and consume foods while avoiding environmental threats. However, how evolutionarily conserved threat detection circuits modulate feeding is unknown. In mammals, feeding and threat assessment are strongly influenced by the parabrachial nucleus (PBN), a structure that responds to threats and inhibits feeding. Here, we report that the PBN receives dense inputs from two discrete neuronal populations in the bed nucleus of the stria terminalis (BNST), an extended amygdala structure that encodes affective information. Using a series of complementary approaches, we identify opposing BNST-PBN circuits that modulate neuropeptide-expressing PBN neurons to control …

Pore-Forming Transmembrane Domains Control Ion Selectivity And Selectivity Filter Conformation In The Kirbac1.1 Potassium Channel, Marcos Matamoros, Colin G. Nichols

Open Access Publications

Potassium (K+) channels are membrane proteins with the remarkable ability to very selectively conduct K+ ions across the membrane. High-resolution structures have revealed that dehydrated K+ ions permeate through the narrowest region of the pore, formed by the backbone carbonyls of the signature selectivity filter (SF) sequence TxGYG. However, the existence of nonselective channels with similar SF sequences, as well as effects of mutations in other regions on selectivity, suggest that the SF is not the sole determinant of selectivity. We changed the selectivity of the KirBac1.1 channel by introducing mutations at residue I131 in transmembrane helix 2 (TM2). These …

Genome-Wide Analysis Suggests The Importance Of Vascular Processes And Neuroinflammation In Late-Life Antidepressant Response, Victoria S. Marshe, Eric J. Lenze, Et Al.

Open Access Publications

No abstract provided.

Task-Generic And Task-Specific Connectivity Modulations In The Adhd Brain: An Integrated Analysis Across Multiple Tasks, Roselyne J. Chauvin, Jan K. Buitelaar, Emma Sprooten, Marianne Oldehinkel, Barbara Franke, Catharina Hartman, Dirk J. Heslenfeld, Pieter J. Hoekstra, Jaap Oosterlaan, Christian F. Beckmann, Maarten Mennes

Open Access Publications

No abstract provided.

A Chromosome-Level Genome Of Astyanax Mexicanus Surface Fish For Comparing Population-Specific Genetic Differences Contributing To Trait Evolution, Wesley C. Warren, Chad Tomlinson, Milinn Kremitzki, Tina Graves-Lindsay, Et Al.

Open Access Publications

No abstract provided.

Trem2 Sustains Macrophage-Hepatocyte Metabolic Coordination In Nonalcoholic Fatty Liver Disease And Sepsis, Jinchao Hou, Yingyue Zhou, Marco Colonna, Et Al

Open Access Publications

Sepsis is a leading cause of death in critical illness, and its pathophysiology varies depending on preexisting medical conditions. Here we identified nonalcoholic fatty liver disease (NAFLD) as an independent risk factor for sepsis in a large clinical cohort and showed a link between mortality in NAFLD-associated sepsis and hepatic mitochondrial and energetic metabolism dysfunction. Using in vivo and in vitro models of liver lipid overload, we discovered a metabolic coordination between hepatocyte mitochondria and liver macrophages that express triggering receptor expressed on myeloid cells-2 (TREM2). Trem2-deficient macrophages released exosomes that impaired hepatocytic mitochondrial structure and energy supply because of …

Autophagy Buffers Ras-Induced Genotoxic Stress Enabling Malignant Transformation In Keratinocytes Primed By Human Papillomavirus, Eduardo Cararo-Lopes, Matheus H. Dias, Marcelo S. Da Silva, Julianna D. Zeidler, Alexandre T. Vessoni, Marcelo S. Reis, Enrique Boccardo, Hugo A. Armelin

Open Access Publications

No abstract provided.

Atoh7-Independent Specification Of Retinal Ganglion Cell Identity, Justin Brodie-Kommit, Brian S Clark, Fion Shiau, Philip A Ruzycki, Et Al

Open Access Publications

Retinal ganglion cells (RGCs) relay visual information from the eye to the brain. RGCs are the first cell type generated during retinal neurogenesis. Loss of function of the transcription factor

Loss Of Quaking Rna Binding Protein Disrupts The Expression Of Genes Associated With Astrocyte Maturation In Mouse Brain, Kristina Sakers, Yating Liu, Lorida Llaci, Scott M. Lee, Michael J. Vasek, Michael A. Rieger, Sean Brophy, Eric Tycksen, Renate Lewis, Susan E. Maloney, Joseph D. Dougherty

Open Access Publications

No abstract provided.

Noninvasive Immuno-Pet Imaging Of Cd8 + T Cell Behavior In Influenza A Virus-Infected Mice, Paul W Rothlauf, Zeyang Li, Novalia Pishesha, Yushu Joy Xie, Andrew W Woodham, Djenet Bousbaine, Stephen C Kolifrath, Vincent L Verschoor, Hidde L Ploegh

Open Access Publications

Immuno-positron emission tomography (immuno-PET) is a noninvasive imaging method that enables tracking of immune cells in living animals. We used a nanobody that recognizes mouse CD8α and labeled it with

Continuous Renal Replacement Therapy For Two Neonates With Hyperammonemia, Christopher Markham, Caroline Williams, Cory Miller, Dorothy K Grange, T Keefe Davis, Kenneth E Remy

Open Access Publications

No abstract provided.

Resting-State Functional Magnetic Resonance Imaging Networks As A Quantitative Metric For Impact Of Neurosurgical Interventions, Peter H Yang, Carl D Hacker, Bhuvic Patel, Andy G S Daniel, Eric C Leuthardt

Open Access Publications

No abstract provided.

Evaluation Of Kratom Opioid Derivatives As Potential Treatment Option For Alcohol Use Disorder, Anna M Gutridge, Soumen Chakraborty, Balazs R Varga, Elizabeth S Rhoda, Alexander R French, Arryn T Blaine, Quinten H Royer, Haoyue Cui, Jinling Yuan, Robert J Cassell, Márk Szabó, Susruta Majumdar, Richard M Van Rijn

Open Access Publications

No abstract provided.

Endocannabinoid System Unlocks The Puzzle Of Autism Treatment, Tangfeng Su, Yu Yan, Qiang Li, Jiacai Ye, Lei Pei

Open Access Publications

Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder and characterized by early childhood-onset impairments in social interaction and communication, restricted and repetitive patterns of behavior or interests. So far there is no effective treatment for ASD, and the pathogenesis of ASD remains unclear. Genetic and epigenetic factors have been considered to be the main cause of ASD. It is known that endocannabinoid and its receptors are widely distributed in the central nervous system, and provide a positive and irreversible change toward a more physiological neurodevelopment. Recently, the endocannabinoid system (ECS) has been found to participate in the regulation of …

High Affinity Associations With Α-Snap Enable Calcium Entry Via Orai1 Channels, Ramanagouda Ramanagoudr-Bhojappa, Yong Miao, Monika Vig

Open Access Publications

Molecular steps that activate store-operated calcium entry (SOCE) via Orai channel supramolecular complex remain incompletely defined. We have earlier shown that α-SNAP regulates the on-site functional assembly and calcium selectivity of Orai1 channels. Here we investigate the molecular basis of its association with Orai, Stim and find that the affinity of α-SNAP for Orai and Stim is substantially higher than previously reported affinities between Stim and Orai sub-domains. α-SNAP binds the coiled-coil 3 (CC3) sub-domain of Stim1. Mutations of Tryptophan 430 in Stim1-CC3 disrupted α-SNAP association and SOCE, demonstrating a novel α-SNAP dependent function for this crucial subdomain. Further, α-SNAP …

Consensus Guidelines For Improving Quality Of Assessment And Training For Neuromuscular Diseases, Tina Duong, Kristin J Krosschell, Meredith K James, Leslie Nelson, Lindsay N Alfano, Katy Eichinger, Elena Mazzone, Kristy Rose, Linda P Lowes, Anna Mayhew, Julaine Florence, Wendy King, Claudia R Senesac, Michelle Eagle

Open Access Publications

Critical components of successful evaluation of clinical outcome assessments (COAs) in multisite clinical trials and clinical practice are standardized training, administration, and documented reliability of scoring. Experiences of evaluators, alongside patient differences from regional standards of care, may contribute to heterogeneity in clinical center's expertise. Achieving low variability and high reliability of COA is fundamental to clinical research and to give confidence in our ability to draw rational, interpretable conclusions from the data collected. The objective of this manuscript is to provide a framework to guide the learning process for COAs for use in clinics and clinical trials to maximize …

Pharmacological And Biophysical Characteristics Of Picrotoxin-Resistant, Δsubunit-Containing Gabaa Receptors, Hong-Jin Shu, Xinguo Lu, John Bracamontes, Joe Henry Steinbach, Charles F Zorumski, Steven Mennerick

Open Access Publications

GABA

Tms-Eeg Biomarkers Of Amnestic Mild Cognitive Impairment Due To Alzheimer's Disease: A Proof-Of-Concept Six Years Prospective Study, Florinda Ferreri, Andrea Guerra, Luca Vollero, David Ponzo, Sara Määtta, Mervi Könönen, Fabrizio Vecchio, Patrizio Pasqualetti, Francesca Miraglia, Ilaria Simonelli, Maurizio Corbetta, Paolo Maria Rossini

Open Access Publications

No abstract provided.

Bladder Exposure To Gardnerella Activates Host Pathways Necessary For Escherichia Coli Recurrent Uti, Valerie P O'Brien, Amanda L Lewis, Nicole M Gilbert

Open Access Publications

Recurrent urinary tract infections (rUTI) are a costly clinical problem affecting millions of women worldwide each year. The majority of rUTI cases are caused by uropathogenic

Antibiotic-Driven Intestinal Dysbiosis In Pediatric Short Bowel Syndrome Is Associated With Persistently Altered Microbiome Functions And Gut-Derived Bloodstream Infections, Robert Thänert, Anna Thänert, Jocelyn Ou, Adam Bajinting, Carey-Ann D Burnham, Holly J Engelstad, Maria E Tecos, I Malick Ndao, Carla Hall-Moore, Colleen Rouggly-Nickless, Mike A Carl, Deborah C Rubin, Nicholas O Davidson, Phillip I Tarr, Barbara B Warner, Gautam Dantas, Brad W Warner

Open Access Publications

Surgical removal of the intestine, lifesaving in catastrophic gastrointestinal disorders of infancy, can result in a form of intestinal failure known as short bowel syndrome (SBS). Bloodstream infections (BSIs) are a major challenge in pediatric SBS management. BSIs require frequent antibiotic therapy, with ill-defined consequences for the gut microbiome and childhood health. Here, we combine serial stool collection, shotgun metagenomic sequencing, multivariate statistics and genome-resolved strain-tracking in a cohort of 19 patients with surgically-induced SBS to show that antibiotic-driven intestinal dysbiosis in SBS enriches for persistent intestinal colonization with BSI causative pathogens in SBS. Comparing the gut microbiome composition of …

Discovery Of Novel Reductive Elimination Pathway For 10-Hydroxywarfarin, Dakota L Pouncey, Dustyn A Barnette, Riley W Sinnott, Sarah J Phillips, Noah R Flynn, Howard P Hendrickson, S Joshua Swamidass, Grover P Miller

Open Access Publications

Coumadin (R/S-warfarin) anticoagulant therapy is highly efficacious in preventing the formation of blood clots; however, significant inter-individual variations in response risks over or under dosing resulting in adverse bleeding events or ineffective therapy, respectively. Levels of pharmacologically active forms of the drug and metabolites depend on a diversity of metabolic pathways. Cytochromes P450 play a major role in oxidizing R- and S-warfarin to 6-, 7-, 8-, 10-, and 4'-hydroxywarfarin, and warfarin alcohols form through a minor metabolic pathway involving reduction at the C11 position. We hypothesized that due to structural similarities with warfarin, hydroxywarfarins undergo reduction, possibly impacting their pharmacological …

Perceptions Of Clinical Dental Students Toward Online Education During The Covid-19 Crisis: An Egyptian Multicenter Cross-Sectional Survey, Reham Hassan, Ayman R Khalifa, Tarek Elsewify, Mohamed G Hassan

Open Access Publications

No abstract provided.

Academic Performance Of Children With Sickle Cell Disease In The United States: A Meta-Analysis, Andrew M Heitzer, Latacha Hamilton, Claire Stafford, Jeffrey Gossett, Lara Ouellette, Ana Trpchevska, Allison A King, Guolian Kang, Jane S Hankins

Open Access Publications

No abstract provided.