Digital Commons Network^™

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.

Electroporation Safety Factor Of 300 Nanosecond And 10 Millisecond Defibrillation In Langendorff-Perfused Rabbit Hearts, Johanna U. Neuber, Andrei G. Pakhomov, Christian W. Zemlin

Open Access Publications

AIMS: Recently, a new defibrillation modality using nanosecond pulses was shown to be effective at much lower energies than conventional 10 millisecond monophasic shocks in ex vivo experiments. Here we compare the safety factors of 300 nanosecond and 10 millisecond shocks to assess the safety of nanosecond defibrillation.

METHODS AND RESULTS: The safety factor, i.e. the ratio of median effective doses (ED50) for electroporative damage and defibrillation, was assessed for nanosecond and conventional (millisecond) defibrillation shocks in Langendorff-perfused New Zealand white rabbit hearts. In order to allow for multiple shock applications in a single heart, a pair of needle electrodes …

Accelerated Functional Brain Aging In Pre-Clinical Familial Alzheimer’S Disease, Julie Gonneaud, Brian A. Gordon, Carlos Cruchaga, Tammie L. S. Benzinger, John C. Morris, Randall J. Bateman, Susan Brandon, Virginia Buckles, Tamara Donahue, Anne Fagan, Gigi Flynn, Erin Franklin, Cortaiga Gant, Julia Gray, Alexander Groves, Jason Hassenstab, Laura Hoechst-Swisher, David Holtzman, Russ Hornbeck, Gina Jerome, Celeste Karch, Denise Maue-Dreyfus, Eric Mcdade, Joanne Norton, Richard Perrin, Marc Raichle, Wendy Sigurdson, Peter Wang, Chengjie Xiong, Xiong Xu, Nigel J. Cairns, Erin Householder, Lisa Taylor Reinwald, Beau Ances, Maria Carroll, Sue Leon, Mark A. Mintun, Stacy Schneider, Et Al

Open Access Publications

No abstract provided.

Application Of A Time-Series Deep Learning Model To Predict Cardiac Dysrhythmias In Electronic Health Records, Aixia Guo, Sakima Smith, Yosef M. Khan, James R. Langabeer Ii, Randi E. Foraker

Open Access Publications

BACKGROUND: Cardiac dysrhythmias (CD) affect millions of Americans in the United States (US), and are associated with considerable morbidity and mortality. New strategies to combat this growing problem are urgently needed.

OBJECTIVES: Predicting CD using electronic health record (EHR) data would allow for earlier diagnosis and treatment of the condition, thus improving overall cardiovascular outcomes. The Guideline Advantage (TGA) is an American Heart Association ambulatory quality clinical data registry of EHR data representing 70 clinics distributed throughout the US, and has been used to monitor outpatient prevention and disease management outcome measures across populations and for longitudinal research on the …

Tracheal Aspirate Rna Sequencing Identifies Distinct Immunological Features Of Covid-19 Ards, Aartik Sarma, Pratik Sinha, Et Al

Open Access Publications

No abstract provided.

Isolation Of Reconstructed Functional Ribonucleoprotein Complexes Of Machupo Virus, Jesse D. Pyle, Sean P.J. Whelan

Open Access Publications

Arenaviruses initiate infection by delivering a transcriptionally competent ribonucleoprotein (RNP) complex into the cytosol of host cells. The arenavirus RNP consists of the large (L) RNA-dependent RNA polymerase (RdRP) bound to a nucleoprotein (NP)-encapsidated genomic RNA (viral RNA [vRNA]) template. During transcription and replication, L must transiently displace RNA-bound NP to allow for template access into the RdRP active site. Concomitant with RNA replication, new subunits of NP must be added to the nascent complementary RNAs (cRNA) as they emerge from the product exit channel of L. Interactions between L and NP thus play a central role in arenavirus gene …

Comprehensive Characterization Of 536 Patient-Derived Xenograft Models Prioritizes Candidates For Targeted Treatment, Hua Sun, Song Cao, R. Jay Mashl, Chia-Kuei Mo, Sherri R. Davies, Tina M. Primeau, Jeremy Hoog, Jacqueline L. Mudd, Matthew A. Wyczalkowski, Reyka G. Jayasinghe, Fernanda Martins Rodrigues, Nadezhda V. Terekhanova, Yize Li, Kian-Huat Lim, Andrea Wang-Gillam, Brian A. Van Tine, Cynthia X. Ma, Katherine C. Fuh, John F. Dipersio, Julie Belmar, Jason Held, Rose Tipton, Yige Wu, Lijun Yao, Daniel Cui Zhou, Feng Chen, Shunqiang Li, Ramaswamy Govindan, Li Ding, Michael C. Wendl, Rebecca Aft, Julie K. Schwarz, Jose P. Zevallos, Sidharth V. Puram, Jingqin Luo, Ryan C. Fields, Et Al

Open Access Publications

No abstract provided.

Zika Virus Infection Of Pregnant Ifnar1-/- Mice Triggers Strain-Specific Differences In Fetal Outcomes, Ellie K. Bohm, Jennifer T. Vangorder-Braid, Anna S. Jaeger, Ryan V. Moriarty, John J. Baczenas, Natalie C. Bennett, Shelby L. O'Connor, Michael K. Fritsch, Nicole A. Fuhler, Kevin K. Noguchi, Matthew T. Aliota

Open Access Publications

Zika virus (ZIKV) is a flavivirus that causes a constellation of adverse fetal outcomes collectively termed congenital Zika syndrome (CZS). However, not all pregnancies exposed to ZIKV result in an infant with apparent defects. During the 2015 to 2016 American outbreak of ZIKV, CZS rates varied by geographic location. The underlying mechanisms responsible for this heterogeneity in outcomes have not been well defined. Therefore, we sought to characterize and compare the pathogenic potential of multiple Asian-/American-lineage ZIKV strains in an established

Charge Syndrome Protein Chd7 Regulates Epigenomic Activation Of Enhancers In Granule Cell Precursors And Gyrification Of The Cerebellum, Naveen C. Reddy, Shahriyar P. Majidi, Lingchun Kong, Mati Nemera, Cole J. Ferguson, Michael Moore, Tassia M. Goncalves, Hai-Kun Liu, James A. J. Fitzpatrick, Guoyan Zhao, Tomoko Yamada, Azad Bonni, Harrison W. Gabel

Open Access Publications

No abstract provided.

Circulating Cd5l Is Associated With Cardiovascular Events And All-Cause Mortality In Individuals With Chronic Kidney Disease, Esmeralda Castelblanco, Maria R. Sarrias, Àngels Betriu, Berta Soldevila, Maria Barranco-Altirriba, Josep Franch-Nadal, Jose M. Valdivielso, Marcelino Bermudez-Lopez, Per-Henrik Groop, Elvira Fernández, Núria Alonso, Didac Mauricio

Open Access Publications

This study assessed the association of CD5L and soluble CD36 (sCD36) with the risk of a cardiovascular event (CVE), including CV death and all-cause mortality in CKD. We evaluated the association of CD5L and sCD36 with a predefined composite CV endpoint (unstable angina, myocardial infarction, transient ischemic attack, cerebrovascular accident, congestive heart failure, arrhythmia, peripheral arterial disease [PAD] or amputation by PAD, aortic aneurysm, or death from CV causes) and all-cause mortality using Cox proportional hazards regression, adjusted for CV risk factors. The analysis included 1,516 participants free from pre-existing CV disease followed up for 4 years. The median age …

Lyve1+ Macrophages Of Murine Peritoneal Mesothelium Promote Omentum-Independent Ovarian Tumor Growth, Nan Zhang, Anastasiia Gainullina, Emma C. Erlich, Emily J. Onufer, Rafael S. Czepielewski, Beth A. Helmink, Brian T. Saunders, Jesse W. Williams, Bernd H. Zinselmeyer, Gwendalyn J. Randolph, Ki-Wook Kim, Et Al

Open Access Publications

Two resident macrophage subsets reside in peritoneal fluid. Macrophages also reside within mesothelial membranes lining the peritoneal cavity, but they remain poorly characterized. Here, we identified two macrophage populations (LYVE1hi MHC IIlo-hi CX3CR1gfplo/- and LYVE1lo/- MHC IIhi CX3CR1gfphi subsets) in the mesenteric and parietal mesothelial linings of the peritoneum. These macrophages resembled LYVE1+ macrophages within surface membranes of numerous organs. Fate-mapping approaches and analysis of newborn mice showed that LYVE1hi macrophages predominantly originated from embryonic-derived progenitors and were controlled by CSF1 made by Wt1+ stromal cells. Their gene expression profile closely overlapped with ovarian tumor-associated macrophages previously described in the …

Modeling Spinal Locomotor Circuits For Movements In Developing Zebrafish, Yann Roussel, Stephanie F. Gaudreau, Emily R. Kacer, Mohini Sengupta, Tuan V. Bui

Open Access Publications

Many spinal circuits dedicated to locomotor control have been identified in the developing zebrafish. How these circuits operate together to generate the various swimming movements during development remains to be clarified. In this study, we iteratively built models of developing zebrafish spinal circuits coupled to simplified musculoskeletal models that reproduce coiling and swimming movements. The neurons of the models were based upon morphologically or genetically identified populations in the developing zebrafish spinal cord. We simulated intact spinal circuits as well as circuits with silenced neurons or altered synaptic transmission to better understand the role of specific spinal neurons. Analysis of …

Is Left-Behind A Real Reason For Children's Social Cognition Deficit? An Fnirs Study On The Effect Of Social Interaction On Left-Behind Preschooler's Prefrontal Activation, Keya Ding, Chuanjiang Li, Huibin Jia, Mingming Zhang, Dongchuan Yu

Open Access Publications

The left-behind phenomenon, caused by parent out-migration, has become a common social issue and might lead to long-term and potential risks for children in rural areas of China. It is important to investigate the effect of social interaction on prefrontal activation of left-behind children in China because of possible effects of parent out-migration on children's social cognition. We recruited 81 rural Chinese preschoolers aged 52-76 months (mean = 64.98 ± 6.321 months) preschoolers with three different statuses of parental out-migration (including non-, partially, and completely left-behind children). Using functional Near-Infrared Spectroscopy (fNIRS), we compared behavior and brain activation and in …

Neuronal Activity In Dorsal Anterior Cingulate Cortex During Economic Choices Under Variable Action Costs, Xinying Cai, Camillo Padoa-Schioppa

Open Access Publications

The role of the dorsal anterior cingulate cortex (ACCd) in decision making has often been discussed but remains somewhat unclear. On the one hand, numerous studies implicated this area in decisions driven by effort or action cost. On the other hand, work on economic choices between goods (under fixed action costs) found that neurons in ACCd encoded only post-decision variables. To advance our understanding of the role played by this area in decision making, we trained monkeys to choose between different goods (juice types) offered in variable amounts and with different action costs. Importantly, the task design dissociated computation of …

Development And Assessment Of A Clinical Calculator For Estimating The Likelihood Of Recurrence And Survival Among Patients With Locally Advanced Rectal Cancer Treated With Chemotherapy, Radiotherapy, And Surgery, Martin R Weiser, William C. Chapman, Philip S. Bauer, Matthew G. Mutch, Parag J. Parikh, Et Al

Open Access Publications

Importance: Predicting outcomes in patients receiving neoadjuvant therapy for rectal cancer is challenging because of tumor downstaging. Validated clinical calculators that can estimate recurrence-free survival (RFS) and overall survival (OS) among patients with rectal cancer who have received multimodal therapy are needed.

Objective: To develop and validate clinical calculators providing estimates of rectal cancer recurrence and survival that are better for individualized decision-making than the American Joint Committee on Cancer (AJCC) staging system or the neoadjuvant rectal (NAR) score.

Design, Setting, and Participants: This prognostic study developed risk models, graphically represented as nomograms, for patients with incomplete pathological response using …

Acaricidal Activity Of Foeniculum Vulgare Against Rhipicephalus Annulatus Is Mainly Dependent On Its Constituent From Trans-Anethone, Shawky M. Aboelhadid, Waleed M. Arafa, Abdel-Azeem S. Abdel-Baki, Atalay Sokmen, Saleh Al-Quraishy, Ahmed O. Hassan, Asmaa A. Kamel

Open Access Publications

Globally, the economic losses due to hard ticks infestation and the control of the associated diseases have been calculated at USD $13.9-18.7 billion per year. The economic impact is related to its direct damage to the skins, blood loss, anemia, severe immunological reactions and indirect losses that related to the effects of hemoparasites, cost of treatment for clinical cases and expenses incurred in the control of ticks. The current study evaluated the acaricidal activities of fennel Foeniculum vulgare essential oil and its main components; trans-anethole and fenchone; against R. annulatus. GC-MS analysis revealed that this oil contained 16 components representing …

The Kanyakla Study: Randomized Controlled Trial Of A Microclinic Social Network Intervention For Promoting Engagement And Retention In Hiv Care In Rural Western Kenya, Matthew D. Hickey, Elvin H. Geng, Et Al

Open Access Publications

BACKGROUND: Existing social relationships are a potential source of "social capital" that can enhance support for sustained retention in HIV care. A previous pilot study of a social network-based 'microclinic' intervention, including group health education and facilitated HIV status disclosure, reduced disengagement from HIV care. We conducted a pragmatic randomized trial to evaluate microclinic effectiveness.

METHODS: In nine rural health facilities in western Kenya, we randomized HIV-positive adults with a recent missed clinic visit to either participation in a microclinic or usual care (NCT02474992). We collected visit data at all clinics where participants accessed care and evaluated intervention effect on …

Live Imaging Reveals The Cellular Events Downstream Of Sarm1 Activation, Kwang Woo Ko, Laura Devault, Yo Sasaki, Jeffrey Milbrandt, Aaron Diantonio

Open Access Publications

SARM1 is an inducible NAD

Intestinal Goblet Cells Sample And Deliver Lumenal Antigens By Regulated Endocytic Uptake And Transcytosis, Jenny K. Gustafsson, Jazmyne E. Davis, Tracy Rappai, Keely G. Mcdonald, Devesha H. Kulkarni, Kathryn A. Knoop, Simon P. Hogan, James A.J. Fitzpatrick, Wayne I. Lencer, Rodney D. Newberry

Open Access Publications

Intestinal goblet cells maintain the protective epithelial barrier through mucus secretion and yet sample lumenal substances for immune processing through formation of goblet cell associated antigen passages (GAPs). The cellular biology of GAPs and how these divergent processes are balanced and regulated by goblet cells remains unknown. Using high-resolution light and electron microscopy, we found that in mice, GAPs were formed by an acetylcholine (ACh)-dependent endocytic event remarkable for delivery of fluid-phase cargo retrograde into the trans-golgi network and across the cell by transcytosis - in addition to the expected transport of fluid-phase cargo by endosomes to multi-vesicular bodies and …