Digital Commons Network^™

Genetic And Biochemical Characterization Of The Na+/H+ Antiporters Of Pseudomonas Aeruginosa, Sara Foreman, Kristina Ferrara, Teri N Hreha, Ana E Duran-Pinedo, Jorge Frias-Lopez, Blanca Barquera

Open Access Publications

Pseudomonas aeruginosa has four Na

Glial-Specific Deletion Of Med12 Results In Rapid Hearing Loss Via Degradation Of The Stria Vascularis, Teng-Wei Huang, Amrita A. Iyer, Jeanne M. Manalo, Junsung Woo, Navish A. Bosquez Huerta, Melissa M. Mcgovern, Heinrich Schrewe, Fredrick A. Pereira, Andrew K. Groves, Kevin K. Ohlemiller, Benjamin Deneen

Open Access Publications

Mediator protein complex subunit 12 (Med12) is a core component of the basal transcriptional apparatus and plays a critical role in the development of many tissues. Mutations in Med12 are associated with X-linked intellectual disability syndromes and hearing loss; however, its role in nervous system function remains undefined. Here, we show that temporal conditional deletion of Med12 in astrocytes in the adult CNS results in region-specific alterations in astrocyte morphology. Surprisingly, behavioral studies revealed rapid hearing loss after adult deletion of Med12 that was confirmed by a complete abrogation of auditory brainstem responses. Cellular analysis of the cochlea revealed degeneration …

Reweighting Of Molecular Simulations With Explicit-Solvent Saxs Restraints Elucidates Ion-Dependent Rna Ensembles, Mattia Bernetti, Kathleen B. Hall, Giovanni Bussi

Open Access Publications

Small-angle X-ray scattering (SAXS) experiments are increasingly used to probe RNA structure. A number of forward models that relate measured SAXS intensities and structural features, and that are suitable to model either explicit-solvent effects or solute dynamics, have been proposed in the past years. Here, we introduce an approach that integrates atomistic molecular dynamics simulations and SAXS experiments to reconstruct RNA structural ensembles while simultaneously accounting for both RNA conformational dynamics and explicit-solvent effects. Our protocol exploits SAXS pure-solute forward models and enhanced sampling methods to sample an heterogenous ensemble of structures, with no information towards the experiments provided on-the-fly. …

A Troponin T Variant Linked With Pediatric Dilated Cardiomyopathy Reduces The Coupling Of Thin Filament Activation To Myosin And Calcium Binding, Samantha K. Barrick, Lina Greenberg, Michael J. Greenberg

Open Access Publications

Dilated cardiomyopathy (DCM) is a significant cause of pediatric heart failure. Mutations in proteins that regulate cardiac muscle contraction can cause DCM; however, the mechanisms by which molecular-level mutations contribute to cellular dysfunction are not well understood. Better understanding of these mechanisms might enable the development of targeted therapeutics that benefit patient subpopulations with mutations that cause common biophysical defects. We examined the molecular- and cellular-level impacts of a troponin T variant associated with pediatric-onset DCM, R134G. The R134G variant decreased calcium sensitivity in an in vitro motility assay. Using stopped-flow and steady-state fluorescence measurements, we determined the molecular mechanism …

Diagnosis Of Mast Cell Activation Syndrome: A Global “Consensus-2”, Lawrence B. Afrin, Leonard B. Weinstock, Et Al

Open Access Publications

No abstract provided.

Hif1Α Is Required For Nk Cell Metabolic Adaptation During Virus Infection, Francisco Victorino, Tarin M. Bigley, Eugene Park, Cong-Hui Yao, Jeanne Benoit, Li-Ping Yang, Sytse J. Piersma, Elvin J. Lauron, Rebecca M. Davidson, Gary J. Patti, Wayne M. Yokoyama

Open Access Publications

Natural killer (NK) cells are essential for early protection against virus infection and must metabolically adapt to the energy demands of activation. Here, we found upregulation of the metabolic adaptor hypoxia-inducible factor-1α (HIF1α) is a feature of mouse NK cells during murine cytomegalovirus (MCMV) infection in vivo. HIF1α-deficient NK cells failed to control viral load, causing increased morbidity. No defects were found in effector functions of HIF1αKO NK cells; however, their numbers were significantly reduced. Loss of HIF1α did not affect NK cell proliferation during in vivo infection and in vitro cytokine stimulation. Instead, we found that HIF1α-deficient NK cells …

Dynamically Linking Influenza Virus Infection Kinetics, Lung Injury, Inflammation, And Disease Severity, Margaret A. Myers, Amanda P. Smith, Lindey C. Lane, David J. Moquin, Rosemary Aogo, Stacie Woolard, Paul Thomas, Peter Vogel, Amber M. Smith

Open Access Publications

Influenza viruses cause a significant amount of morbidity and mortality. Understanding host immune control efficacy and how different factors influence lung injury and disease severity are critical. We established and validated dynamical connections between viral loads, infected cells, CD8

Multicenter Analysis Of Geriatric Fitness And Real-World Outcomes In Older Patients With Classical Hodgkin Lymphoma, Victor M. Orellana-Noia, Mary-Kate Malecek, Nancy L. Bartlett, Et Al

Open Access Publications

No abstract provided.

Contemporary Clinical Isolates Of Staphylococcus Aureus From Pediatric Osteomyelitis Patients Display Unique Characteristics In A Mouse Model Of Hematogenous Osteomyelitis, Philip M. Roper, Kara R. Eichelberger, Linda Cox, Luke O'Connor, Christine Shao, Caleb A. Ford, Stephanie A. Fritz, James E. Cassat, Deborah J. Veis

Open Access Publications

No abstract provided.

Cognitive Dysfunction After Analgesia And Sedation: Out Of The Operating Room And Into The Pediatric Intensive Care Unit, Ashley D Turner, Travis Sullivan, Kurt Drury, Trevor A Hall, Cydni N Williams, Kristin P Guilliams, Sarah Murphy, A M Iqbal O'Meara

Open Access Publications

In the midst of concerns for potential neurodevelopmental effects after surgical anesthesia, there is a growing awareness that children who require sedation during critical illness are susceptible to neurologic dysfunctions collectively termed pediatric post-intensive care syndrome, or PICS-p. In contrast to healthy children undergoing elective surgery, critically ill children are subject to inordinate neurologic stress or injury and need to be considered separately. Despite recognition of PICS-p, inconsistency in techniques and timing of post-discharge assessments continues to be a significant barrier to understanding the specific role of sedation in later cognitive dysfunction. Nonetheless, available pediatric studies that account for analgesia …

Decoding Neural Activity In Sulcal And White Matter Areas Of The Brain To Accurately Predict Individual Finger Movement And Tactile Stimuli Of The Human Hand, Chad Bouton, Nikunj Bhagat, Santosh Chandrasekaran, Jose Herrero, Noah Markowitz, Elizabeth Espinal, Joo-Won Kim, Richard Ramdeo, Junqian Xu, Matthew F Glasser, Stephan Bickel, Ashesh Mehta

Open Access Publications

Millions of people worldwide suffer motor or sensory impairment due to stroke, spinal cord injury, multiple sclerosis, traumatic brain injury, diabetes, and motor neuron diseases such as ALS (amyotrophic lateral sclerosis). A brain-computer interface (BCI), which links the brain directly to a computer, offers a new way to study the brain and potentially restore impairments in patients living with these debilitating conditions. One of the challenges currently facing BCI technology, however, is to minimize surgical risk while maintaining efficacy. Minimally invasive techniques, such as stereoelectroencephalography (SEEG) have become more widely used in clinical applications in epilepsy patients since they can …

Using Optical Coherence Tomography And Intravascular Ultrasound Imaging To Quantify Coronary Plaque Cap Stress/Strain And Progression: A Follow-Up Study Using 3d Thin-Layer Models, Rui Lv, Akiko Maehara, Mitsuaki Matsumura, Liang Wang, Caining Zhang, Mengde Huang, Xiaoya Guo, Habib Samady, Don P Giddens, Jie Zheng, Gary S Mintz, Dalin Tang

Open Access Publications

Accurate plaque cap thickness quantification and cap stress/strain calculations are of fundamental importance for vulnerable plaque research. To overcome uncertainties due to intravascular ultrasound (IVUS) resolution limitation, IVUS and optical coherence tomography (OCT) coronary plaque image data were combined together to obtain accurate and reliable cap thickness data, stress/strain calculations, and reliable plaque progression predictions. IVUS, OCT, and angiography baseline and follow-up data were collected from nine patients (mean age: 69; m: 5) at Cardiovascular Research Foundation with informed consent obtained. IVUS and OCT slices were coregistered and merged to form IVUS + OCT (IO) slices. A total of 114 …

Centering Inclusivity In The Design Of Online Conferences-An Ohbm-Open Science Perspective, Elizabeth Levitis, Janine D. Bijsterbosch, Et Al

Open Access Publications

As the global health crisis unfolded, many academic conferences moved online in 2020. This move has been hailed as a positive step towards inclusivity in its attenuation of economic, physical, and legal barriers and effectively enabled many individuals from groups that have traditionally been underrepresented to join and participate. A number of studies have outlined how moving online made it possible to gather a more global community and has increased opportunities for individuals with various constraints, e.g., caregiving responsibilities. Yet, the mere existence of online conferences is no guarantee that everyone can attend and participate meaningfully. In fact, many elements …

Identification Of Genes Encoding Antimicrobial Proteins In Langerhans Cells, Aislyn Oulee, Feiyang Ma, Rosane M B Teles, Bruno J De Andrade Silva, Matteo Pellegrini, Eynav Klechevsky, Andrew N Harman, Jake W Rhodes, Robert L Modlin

Open Access Publications

Langerhans cells (LCs) reside in the epidermis where they are poised to mount an antimicrobial response against microbial pathogens invading from the outside environment. To elucidate potential pathways by which LCs contribute to host defense, we mined published LC transcriptomes deposited in GEO and the scientific literature for genes that participate in antimicrobial responses. Overall, we identified 31 genes in LCs that encode proteins that contribute to antimicrobial activity, ten of which were cross-validated in at least two separate experiments. Seven of these ten antimicrobial genes encode chemokines,

Genomic Characterization And Therapeutic Targeting Of Hpv Undetected Cervical Carcinomas, Fiona J Ruiz, Aishwarya Sundaresan, Jin Zhang, Chandra S Pedamallu, Mari K Halle, Vinodh Srinivasasainagendra, Jianqing Zhang, Naoshad Muhammad, Jennifer Stanley, Stephanie Markovina, Hemant K Tiwari, Perry W Grigsby, Camilla Krakstad, Julie K Schwarz, Akinyemi I Ojesina

Open Access Publications

Cervical cancer tumors with undetectable HPV (HPV

A Bone-Specific Adipogenesis Pathway In Fat-Free Mice Defines Key Origins And Adaptations Of Bone Marrow Adipocytes With Age And Disease, Xiao Zhang, Hero Robles, Kristann L. Magee, Madelyn R. Lorenz, Zhaohua Wang, Charles A. Harris, Clarissa S. Craft, Erica L. Scheller

Open Access Publications

Bone marrow adipocytes accumulate with age and in diverse disease states. However, their origins and adaptations in these conditions remain unclear, impairing our understanding of their context-specific endocrine functions and relationship with surrounding tissues. In this study, by analyzing bone and adipose tissues in the lipodystrophic 'fat-free' mouse, we define a novel, secondary adipogenesis pathway that relies on the recruitment of adiponectin-negative stromal progenitors. This pathway is unique to the bone marrow and is activated with age and in states of metabolic stress in the fat-free mouse model, resulting in the expansion of bone marrow adipocytes specialized for lipid storage …

Biological Resurfacing In A Canine Model Of Hip Osteoarthritis, Bradley T Estes, Masataka Enomoto, Franklin T Moutos, Megan A Carson, Jeffrey M Toth, Peter Eggert, Jonathan Stallrich, Vincent P Willard, Deborah J Veis, Dianne Little, Farshid Guilak, B Duncan X Lascelles

Open Access Publications

[Figure: see text].

Parrot Is A Flexible Recurrent Neural Network Framework For Analysis Of Large Protein Datasets, Daniel Griffith, Alex S. Holehouse

Open Access Publications

The rise of high-throughput experiments has transformed how scientists approach biological questions. The ubiquity of large-scale assays that can test thousands of samples in a day has necessitated the development of new computational approaches to interpret this data. Among these tools, machine learning approaches are increasingly being utilized due to their ability to infer complex nonlinear patterns from high-dimensional data. Despite their effectiveness, machine learning (and in particular deep learning) approaches are not always accessible or easy to implement for those with limited computational expertise. Here we present PARROT, a general framework for training and applying deep learning-based predictors on …

An Essential, Kinetoplastid-Specific Gdp-Fuc: Β-D-Gal Α-1,2-Fucosyltransferase Is Located In The Mitochondrion Of Trypanosoma Brucei, Giulia Bandini, Sebastian Damerow, Maria Lucia Sempaio Guther, Hongjie Guo, Angela Mehlert, Jose Carlos Paredes Franco, Stephen Beverley, Michael A.J. Ferguson

Open Access Publications

Fucose is a common component of eukaryotic cell-surface glycoconjugates, generally added by Golgi-resident fucosyltransferases. Whereas fucosylated glycoconjugates are rare in kinetoplastids, the biosynthesis of the nucleotide sugar GDP-Fuc has been shown to be essential in

Ip3r-Driven Increases In Mitochondrial Ca2+ Promote Neuronal Death In Npc Disease, Scott A. Tiscione, Maria Casas, Jonathan D. Horvath, Vincent Lam, Keiko Hino, Daniel S. Ory, L. Fernando Santana, Sergi Simó, Rose E. Dixon, Eamonn J. Dickson

Open Access Publications

No abstract provided.

Racial Comparison Of Patients Undergoing Minimally Invasive Partial Nephrectomy For Renal Masses At A Large Volume Tertiary Center, Kenneth G. Sands, Rohit Bhatt, Joel Vetter, Alethea Paradis, Alexander K. Chow, Sam Bhayani, Robert S. Figenshau, Ramakrishna Venkatesh

Open Access Publications

No abstract provided.

Predictors Of Annual Prostate-Specific Antigen (Psa) Screening Among Black Men: Results From An Urban Community-Based Prostate Cancer Screening Program, Marquita W. Lewis-Thames, Saira Khan, Veronica Hicks, Bettina F. Drake

Open Access Publications

No abstract provided.

Postdischarge Prophylactic Antibiotics Following Mastectomy With And Without Breast Reconstruction, David K Warren, Kate M Peacock, Katelin B Nickel, Victoria J Fraser, Margaret A Olsen, Cdc Prevention Epicenter Program

Open Access Publications

BACKGROUND: Prophylactic antibiotics are commonly prescribed at discharge for mastectomy, despite guidelines recommending against this practice. We investigated factors associated with postdischarge prophylactic antibiotic use after mastectomy with and without immediate reconstruction and the impact on surgical-site infection (SSI).

STUDY DESIGN: We studied a cohort of women aged 18-64 years undergoing mastectomy between January 1, 2010, and June 30, 2015, using the MarketScan commercial database. Patients with nonsurgical perioperative infections were excluded. Postdischarge oral antibiotics were identified from outpatient drug claims. SSI was defined using International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) diagnosis codes. Generalized linear models were …

Elac2/Rnasez-Linked Cardiac Hypertrophy In Drosophila Melanogaster, Ekaterina Migunova, Joanna Theophilopoulos, Marisa Mercadante, Jing Men, Chao Zhou, Edward B Dubrovsky

Open Access Publications

A severe form of infantile cardiomyopathy (CM) has been linked to mutations in ELAC2, a highly conserved human gene. It encodes Zinc phosphodiesterase ELAC protein 2 (ELAC2), which plays an essential role in the production of mature tRNAs. To establish a causal connection between ELAC2 variants and CM, here we used the Drosophila melanogaster model organism, which carries the ELAC2 homolog RNaseZ. Even though RNaseZ and ELAC2 have diverged in some of their biological functions, our study demonstrates the use of the fly model to study the mechanism of ELAC2-related pathology. We established transgenic lines harboring RNaseZ with CM-linked mutations …

Basal Epithelial Stem Cells Cross An Alarmin Checkpoint For Postviral Lung Disease, Kangyun Wu, Kenji Kamimoto, Yong Zhang, Kuangying Yang, Shamus P Keeler, Benjamin J Gerovac, Eugene V Agapov, Stephen P Austin, Jennifer Yantis, Kelly A Gissy, Derek E Byers, Jennifer Alexander-Brett, Christy M Hoffmann, Matthew Wallace, Michael E Hughes, Erika C Crouch, Samantha A Morris, Michael J Holtzman

Open Access Publications

Epithelial cells are charged with protection at barrier sites, but whether this normally beneficial response might sometimes become dysfunctional still needs definition. Here, we recognized a pattern of imbalance marked by basal epithelial cell growth and differentiation that replaced normal airspaces in a mouse model of progressive postviral lung disease due to the Sendai virus. Single-cell and lineage-tracing technologies identified a distinct subset of basal epithelial stem cells (basal ESCs) that extended into gas-exchange tissue to form long-term bronchiolar-alveolar remodeling regions. Moreover, this cell subset was selectively expanded by crossing a cell-growth and survival checkpoint linked to the nuclear-localized alarmin …

Determining Subpopulation Methylation Profiles From Bisulfite Sequencing Data Of Heterogeneous Samples Using Dxm, Jerry Fong, Jacob R. Gardner, Jared M. Andrews, Amanda F. Cashen, Jacqueline E. Payton, Kilian Q. Weinberger, John R. Edwards

Open Access Publications

Epigenetic changes, such as aberrant DNA methylation, contribute to cancer clonal expansion and disease progression. However, identifying subpopulation-level changes in a heterogeneous sample remains challenging. Thus, we have developed a computational approach, DXM, to deconvolve the methylation profiles of major allelic subpopulations from the bisulfite sequencing data of a heterogeneous sample. DXM does not require prior knowledge of the number of subpopulations or types of cells to expect. We benchmark DXM's performance and demonstrate improvement over existing methods. We further experimentally validate DXM predicted allelic subpopulation-methylation profiles in four Diffuse Large B-Cell Lymphomas (DLBCLs). Lastly, as proof-of-concept, we apply DXM …

Breast Cancer Derived Gm-Csf Regulates Arginase 1 In Myeloid Cells To Promote An Immunosuppressive Microenvironment, Xinming Su, Yalin Xu, Gregory C Fox, Jingyu Xiang, Kristin A Kwakwa, Jennifer L Davis, Jad I Belle, Wen-Chih Lee, Wing H Wong, Francesca Fontana, Leonel Hernandez-Aya, Takayuki Kobayashi, Helen M Tomasson, Junyi Su, Suzanne J Bakewell, Sheila A Stewart, Christopher Egbulefu, Partha Karmakar, Melissa A Meyer, Deborah J Veis, David G Denardo, Gregory M Lanza, Samuel Achilefu, Katherine N Weilbaecher

Open Access Publications

Tumor-infiltrating myeloid cells contribute to the development of the immunosuppressive tumor microenvironment. Myeloid cell expression of arginase 1 (Arg-1) promotes a protumor phenotype by inhibiting T cell function and depleting extracellular L-arginine, but the mechanism underlying this expression, especially in breast cancer, is poorly understood. In breast cancer clinical samples and in our mouse models, we identified tumor derived GM-CSF as the primary regulator of myeloid cell Arg-1 expression and local immune suppression through a gene knockout screen of breast tumor cell-produced factors. The induction of myeloid cell Arg-1 required GM-CSF and a low pH environment. GM-CSF signaling through STAT3, …

Insights Into The Expanding Phenotypic Spectrum Of Inherited Disorders Of Biogenic Amines, Oya Kuseyri Hübschmann, Toni S. Pearson, Et Al

Open Access Publications

No abstract provided.

A Pilot Study Of 3d Tissue‑Engineered Bone Marrow Culture As A Tool To Predict Patient Response To Therapy In Multiple Myeloma, Kinan Alhallak, Amanda Jeske, Pilar De La Puente, Jennifer Sun, Mark Fiala, Feda Azab, Barbara Muz, Ilyas Sahin, Ravi Vij, John F. Dipersio, Abdel Kareem Azab

Open Access Publications

No abstract provided.

Prevalence Of Elevated Serum Fatty Acid Synthase In Chronic Limb‑Threatening Ischemia, Shirli Tay, Gayan S. De Silva, Connor M. Engel, Nikolai Harroun, Amanda S. Penrose, Kshitij A. Desai, Yan Yan, Clay F. Semenkovich, Mohamed A. Zayed

Open Access Publications

No abstract provided.