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Washington University School of Medicine

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Altered Capicua Expression Drives Regional Purkinje Neuron Vulnerability Through Ion Channel Gene Dysregulation In Spinocerebellar Ataxia Type 1, Ravi Chopra, David D Bushart, John P Cooper, Dhananjay Yellajoshyula, Logan M Morrison, Haoran Huang, Hillary P Handler, Luke J Man, Warunee Dansithong, Daniel R Scoles, Stefan M Pulst, Harry T Orr, Vikram G Shakkottai Nov 2020

Altered Capicua Expression Drives Regional Purkinje Neuron Vulnerability Through Ion Channel Gene Dysregulation In Spinocerebellar Ataxia Type 1, Ravi Chopra, David D Bushart, John P Cooper, Dhananjay Yellajoshyula, Logan M Morrison, Haoran Huang, Hillary P Handler, Luke J Man, Warunee Dansithong, Daniel R Scoles, Stefan M Pulst, Harry T Orr, Vikram G Shakkottai

2020-Current year OA Pubs

Selective neuronal vulnerability in neurodegenerative disease is poorly understood. Using the ATXN1[82Q] model of spinocerebellar ataxia type 1 (SCA1), we explored the hypothesis that regional differences in Purkinje neuron degeneration could provide novel insights into selective vulnerability. ATXN1[82Q] Purkinje neurons from the anterior cerebellum were found to degenerate earlier than those from the nodular zone, and this early degeneration was associated with selective dysregulation of ion channel transcripts and altered Purkinje neuron spiking. Efforts to understand the basis for selective dysregulation of channel transcripts revealed modestly increased expression of the ATXN1 co-repressor Capicua (Cic) in anterior cerebellar Purkinje neurons. Importantly, …


The Intriguing Interaction Of Escherichia Coli With The Host Environment And Innovative Strategies To Interfere With Colonization: A Summary Of The 2019 E. Coli And The Mucosal Immune System Meeting, Eric Cox, Meryem Aloulou, James M Fleckenstein, Christina Schäffer, Åsa Sjöling, Stephanie Schüller, Kurt Hanevik, Bert Devriendt, Weiping Zhang, Ann-Mari Svennerholm, Edward G Dudley Nov 2020

The Intriguing Interaction Of Escherichia Coli With The Host Environment And Innovative Strategies To Interfere With Colonization: A Summary Of The 2019 E. Coli And The Mucosal Immune System Meeting, Eric Cox, Meryem Aloulou, James M Fleckenstein, Christina Schäffer, Åsa Sjöling, Stephanie Schüller, Kurt Hanevik, Bert Devriendt, Weiping Zhang, Ann-Mari Svennerholm, Edward G Dudley

Open Access Publications

The third


Transcriptional Remodeling Patterns In Murine Dendritic Cells Infected With Paracoccidioides Brasiliensis: More Is Not Necessarily Better, Calliandra M De-Souza-Silva, Fabián Andrés Hurtado, Aldo Henrique Tavares, Getúlio P De Oliveira, Taina Raiol, Christiane Nishibe, Daniel Paiva Agustinho, Nalvo Franco Almeida, Maria Emília Machado Telles Walter, André Moraes Nicola, Anamélia Lorenzetti Bocca, Patrícia Albuquerque, Ildinete Silva-Pereira Nov 2020

Transcriptional Remodeling Patterns In Murine Dendritic Cells Infected With Paracoccidioides Brasiliensis: More Is Not Necessarily Better, Calliandra M De-Souza-Silva, Fabián Andrés Hurtado, Aldo Henrique Tavares, Getúlio P De Oliveira, Taina Raiol, Christiane Nishibe, Daniel Paiva Agustinho, Nalvo Franco Almeida, Maria Emília Machado Telles Walter, André Moraes Nicola, Anamélia Lorenzetti Bocca, Patrícia Albuquerque, Ildinete Silva-Pereira

Open Access Publications

Most people infected with the fungus


High-Resolution Transcriptional And Morphogenetic Profiling Of Cells From Micropatterned Human Esc Gastruloid Cultures, Kyaw Thu Minn, Yuheng C. Fu, Shenghua He, Sabine Dietmann, Steven C. George, Mark A. Anastasio, Samantha A. Morris, Lilianna Solnica-Krezel Nov 2020

High-Resolution Transcriptional And Morphogenetic Profiling Of Cells From Micropatterned Human Esc Gastruloid Cultures, Kyaw Thu Minn, Yuheng C. Fu, Shenghua He, Sabine Dietmann, Steven C. George, Mark A. Anastasio, Samantha A. Morris, Lilianna Solnica-Krezel

Open Access Publications

During mammalian gastrulation, germ layers arise and are shaped into the body plan while extraembryonic layers sustain the embryo. Human embryonic stem cells, cultured with BMP4 on extracellular matrix micro-discs, reproducibly differentiate into gastruloids, expressing markers of germ layers and extraembryonic cells in radial arrangement. Using single-cell RNA sequencing and cross-species comparisons with mouse, cynomolgus monkey gastrulae, and post-implantation human embryos, we reveal that gastruloids contain cells transcriptionally similar to epiblast, ectoderm, mesoderm, endoderm, primordial germ cells, trophectoderm, and amnion. Upon gastruloid dissociation, single cells reseeded onto micro-discs were motile and aggregated with the same but segregated from distinct cell …


Full-Length Trkb Variant In Nsclc Is Associated With Brain Metastasis, Mariangela Lombardi, Michela D'Ascanio, Stefania Scarpino, Davide Scozzi, Marco Giordano, Leopoldo Costarelli, Enrico Rathina Raj, Rita Mancini, Giuseppe Cardillo, Vittorio Cardaci, Marta Innammorato, Andrea Vecchione, Alberto Ricci Nov 2020

Full-Length Trkb Variant In Nsclc Is Associated With Brain Metastasis, Mariangela Lombardi, Michela D'Ascanio, Stefania Scarpino, Davide Scozzi, Marco Giordano, Leopoldo Costarelli, Enrico Rathina Raj, Rita Mancini, Giuseppe Cardillo, Vittorio Cardaci, Marta Innammorato, Andrea Vecchione, Alberto Ricci

Open Access Publications

Despite remarkable therapeutic advances have been made in the last few decades, non-small cell lung cancer (NSCLC) is still one of the leading causes of death worldwide. Brain metastases are a common complication of a wide range of human malignancies and in particular NSCLC. Brain-derived neurotrophic factor (BDNF), binding its high-affinity tyrosine kinase B receptor, has been shown to promote cancer progression and metastasis. We hereby investigated the expression of the BDNF and its TrkB receptor in its full-length and truncated isoform T1, in samples from primary adenocarcinomas (ADKs) of the lung and in their metastasis to evaluate if their …


Structure Of The Receptor Binding Domain Of Envp(B)1, An Endogenous Retroviral Envelope Protein Expressed In Human Tissues, Kevin R Mccarthy, Joseph L Timpona, Simon Jenni, Louis-Marie Bloyet, Vesna Brusic, Welkin E Johnson, Sean P J Whelan, Lindsey R Robinson-Mccarthy Nov 2020

Structure Of The Receptor Binding Domain Of Envp(B)1, An Endogenous Retroviral Envelope Protein Expressed In Human Tissues, Kevin R Mccarthy, Joseph L Timpona, Simon Jenni, Louis-Marie Bloyet, Vesna Brusic, Welkin E Johnson, Sean P J Whelan, Lindsey R Robinson-Mccarthy

Open Access Publications

EnvP(b)1 is an endogenous retroviral envelope gene found in human and other primate genomes. We report EnvP(b)1 sequences in primate genomes consistent with an integration event between 40 and 71 million years ago. Using a highly specific polyclonal antiserum raised against the putative receptor binding domain (RBD) of human EnvP(b)1, we detected expression in human placenta, ovaries, and thymus. We found that EnvP(b)1 is proteolytically processed, and using cell-cell fusion assays in multiple primate cell lines, we demonstrated that extant EnvP(b)1 proteins from a variety of primate genomes are fusogenic. This work supports the idea that EnvP(b)1 is under purifying …


A Praziquantel Treatment Study Of Immune And Transcriptome Profiles In Schistosoma Haematobium-Infected Gabonese Schoolchildren, Lucja A Labuda, Ayola A Adegnika, Bruce A Rosa, John Martin, Ulysse Ateba-Ngoa, Abena Serwaa Amoah, Honorine Mbenkep Lima, Lynn Meurs, Moustapha Mbow, Mikhael D Manurung, Jeannot F Zinsou, Hermelijn H Smits, Peter G Kremsner, Makedonka Mitreva, Maria Yazdanbakhsh Nov 2020

A Praziquantel Treatment Study Of Immune And Transcriptome Profiles In Schistosoma Haematobium-Infected Gabonese Schoolchildren, Lucja A Labuda, Ayola A Adegnika, Bruce A Rosa, John Martin, Ulysse Ateba-Ngoa, Abena Serwaa Amoah, Honorine Mbenkep Lima, Lynn Meurs, Moustapha Mbow, Mikhael D Manurung, Jeannot F Zinsou, Hermelijn H Smits, Peter G Kremsner, Makedonka Mitreva, Maria Yazdanbakhsh

2020-Current year OA Pubs

BACKGROUND: Although Schistosoma haematobium infection has been reported to be associated with alterations in immune function, in particular immune hyporesponsiveness, there have been only few studies that have used the approach of removing infection by drug treatment to establish this and to understand the underlying molecular mechanisms.

METHODS: Schistosoma haematobium-infected schoolchildren were studied before and after praziquantel treatment and compared with uninfected controls. Cellular responses were characterized by cytokine production and flow cytometry, and in a subset of children RNA sequencing (RNA-Seq) transcriptome profiling was performed.

RESULTS: Removal of S haematobium infection resulted in increased schistosome-specific cytokine responses that were …


Increased Mtor Activity And Metabolic Efficiency In Mouse And Human Cells Containing The African-Centric Tumor-Predisposing P53 Variant Pro47ser, Keerthana Gnanapradeepan, Julia I-Ju Leu, Subhasree Basu, Thibaut Barnoud, Madeline Good, Joyce V. Lee, William J. Quinn, Che-Pei Kung, Rexford Ahima, Joseph A. Baur, Kathryn E. Wellen, Qin Liu, Zachary T. Schug, Donna L. George, Maureen E. Murphy Nov 2020

Increased Mtor Activity And Metabolic Efficiency In Mouse And Human Cells Containing The African-Centric Tumor-Predisposing P53 Variant Pro47ser, Keerthana Gnanapradeepan, Julia I-Ju Leu, Subhasree Basu, Thibaut Barnoud, Madeline Good, Joyce V. Lee, William J. Quinn, Che-Pei Kung, Rexford Ahima, Joseph A. Baur, Kathryn E. Wellen, Qin Liu, Zachary T. Schug, Donna L. George, Maureen E. Murphy

Open Access Publications

The Pro47Ser variant of p53 (S47) exists in African-descent populations and is associated with increased cancer risk in humans and mice. Due to impaired repression of the cystine importer


Tfeb Transcriptional Responses Reveal Negative Feedback By Bhlhe40 And Bhlhe41, Kimberly L Carey, Geraldine L C Paulus, Lingfei Wang, Dale R Balce, Jessica W Luo, Phil Bergman, Ianina C Ferder, Lingjia Kong, Nicole Renaud, Shantanu Singh, Maria Kost-Alimova, Beat Nyfeler, Kara G Lassen, Herbert W Virgin, Ramnik J Xavier Nov 2020

Tfeb Transcriptional Responses Reveal Negative Feedback By Bhlhe40 And Bhlhe41, Kimberly L Carey, Geraldine L C Paulus, Lingfei Wang, Dale R Balce, Jessica W Luo, Phil Bergman, Ianina C Ferder, Lingjia Kong, Nicole Renaud, Shantanu Singh, Maria Kost-Alimova, Beat Nyfeler, Kara G Lassen, Herbert W Virgin, Ramnik J Xavier

Open Access Publications

Transcription factor EB (TFEB) activates lysosomal biogenesis genes in response to environmental cues. Given implications of impaired TFEB signaling and lysosomal dysfunction in metabolic, neurological, and infectious diseases, we aim to systematically identify TFEB-directed circuits by examining transcriptional responses to TFEB subcellular localization and stimulation. We reveal that steady-state nuclear TFEB is sufficient to activate transcription of lysosomal, autophagy, and innate immunity genes, whereas other targets require higher thresholds of stimulation. Furthermore, we identify shared and distinct transcriptional signatures between mTOR inhibition and bacterial autophagy. Using a genome-wide CRISPR library, we find TFEB targets that protect cells from or sensitize …


Kir6.1- And Sur2-Dependent Katp Over-Activity Disrupts Intestinal Motility In Murine Models Of Cantu Syndrome, Nathaniel W York, Helen Parker, Zili Xie, David Tyus, Maham A Waheed, Zihan Yan, Dorothy K Grange, Maria S Remedi, Sarah K England, Hongzhen Hu, Colin G Nichols Nov 2020

Kir6.1- And Sur2-Dependent Katp Over-Activity Disrupts Intestinal Motility In Murine Models Of Cantu Syndrome, Nathaniel W York, Helen Parker, Zili Xie, David Tyus, Maham A Waheed, Zihan Yan, Dorothy K Grange, Maria S Remedi, Sarah K England, Hongzhen Hu, Colin G Nichols

Open Access Publications

Cantύ Syndrome (CS), caused by gain-of-function (GOF) mutations in pore-forming (Kir6.1, KCNJ8) and accessory (SUR2, ABCC9) ATP-sensitive potassium (KATP) channel subunit genes, is frequently accompanied by gastrointestinal (GI) dysmotility, and we describe one CS patient who required an implanted intestinal irrigation system for successful stooling. We used gene-modified mice to assess the underlying KATP channel subunits in gut smooth muscle, and to model the consequences of altered KATP channels in CS gut. We show that Kir6.1/SUR2 subunits underlie smooth muscle KATP channels throughout the small intestine and colon. Knock-in mice, carrying human KCNJ8 and ABCC9 CS mutations in the endogenous …


Antimicrobial Resistance In Enteric Bacteria: Current State And Next-Generation Solutions, M J Wallace, S R S Fishbein, G Dantas Nov 2020

Antimicrobial Resistance In Enteric Bacteria: Current State And Next-Generation Solutions, M J Wallace, S R S Fishbein, G Dantas

2020-Current year OA Pubs

Antimicrobial resistance is one of the largest threats to global health and imposes substantial burdens in terms of morbidity, mortality, and economic costs. The gut is a key conduit for the genesis and spread of antimicrobial resistance in enteric bacterial pathogens. Distinct bacterial species that cause enteric disease can exist as invasive enteropathogens that immediately evoke gastrointestinal distress, or pathobionts that can arise from established bacterial commensals to inflict dysbiosis and disease. Furthermore, various environmental reservoirs and stressors facilitate the evolution and transmission of resistance. In this review, we present a comprehensive discussion on circulating resistance profiles and gene mobilization …


Phosphodiesterase 5 (Pde5) Restricts Intracellular Cgmp Accumulation During Enterotoxigenic Escherichia Coli Infection, Jennifer Foulke-Abel, Huimin Yu, Laxmi Sunuwar, Ruxian Lin, James M Fleckenstein, James B Kaper, Mark Donowitz Nov 2020

Phosphodiesterase 5 (Pde5) Restricts Intracellular Cgmp Accumulation During Enterotoxigenic Escherichia Coli Infection, Jennifer Foulke-Abel, Huimin Yu, Laxmi Sunuwar, Ruxian Lin, James M Fleckenstein, James B Kaper, Mark Donowitz

2020-Current year OA Pubs

Diarrhea caused by enterotoxigenic


Treatment Of Epithelial Ovarian Cancer, Lindsay Kuroki, Saketh R Guntupalli Nov 2020

Treatment Of Epithelial Ovarian Cancer, Lindsay Kuroki, Saketh R Guntupalli

Open Access Publications

Ovarian cancer is the third most common gynecologic malignancy worldwide but accounts for the highest mortality rate among these cancers. A stepwise approach to assessment, diagnosis, and treatment is vital to appropriate management of this disease process. An integrated approach with gynecologic oncologists as well as medical oncologists, pathologists, and radiologists is of paramount importance to improving outcomes. Surgical cytoreduction to R0 is the mainstay of treatment, followed by adjuvant chemotherapy. Genetic testing for gene mutations that affect treatment is the standard of care for all women with epithelial ovarian cancer. Nearly all women will have a recurrence, and the …


Myh3-Associated Distal Arthrogryposis Zebrafish Model Is Normalized With Para-Aminoblebbistatin, Julia Whittle, Lilian Antunes, Mya Harris, Zachary Upshaw, Diane S Sepich, Aaron N Johnson, Mayssa Mokalled, Lilianna Solnica-Krezel, Matthew B Dobbs, Christina A Gurnett Nov 2020

Myh3-Associated Distal Arthrogryposis Zebrafish Model Is Normalized With Para-Aminoblebbistatin, Julia Whittle, Lilian Antunes, Mya Harris, Zachary Upshaw, Diane S Sepich, Aaron N Johnson, Mayssa Mokalled, Lilianna Solnica-Krezel, Matthew B Dobbs, Christina A Gurnett

Open Access Publications

Distal arthrogryposis (DA) is group of syndromes characterized by congenital joint contractures. Treatment development is hindered by the lack of vertebrate models. Here, we describe a zebrafish model in which a common MYH3 missense mutation (R672H) was introduced into the orthologous zebrafish gene smyhc1 (slow myosin heavy chain 1) (R673H). We simultaneously created a smyhc1 null allele (smyhc1


Genetics And Geography Of Leukocyte Telomere Length In Sub-Saharan Africans, Steven C Hunt, Michael A Province, Et Al. Nov 2020

Genetics And Geography Of Leukocyte Telomere Length In Sub-Saharan Africans, Steven C Hunt, Michael A Province, Et Al.

2020-Current year OA Pubs

Leukocyte telomere length (LTL) might be causal in cardiovascular disease and major cancers. To elucidate the roles of genetics and geography in LTL variability across humans, we compared LTL measured in 1295 sub-Saharan Africans (SSAs) with 559 African-Americans (AAms) and 2464 European-Americans (EAms). LTL differed significantly across SSAs (P = 0.003), with the San from Botswana (with the oldest genomic ancestry) having the longest LTL and populations from Ethiopia having the shortest LTL. SSAs had significantly longer LTL than AAms [P = 6.5(e-16)] whose LTL was significantly longer than EAms [P = 2.5(e-7)]. Genetic variation in SSAs explained 52% of …


Moonshots For Aging, Sandeep Kumar, Timothy R Peterson Nov 2020

Moonshots For Aging, Sandeep Kumar, Timothy R Peterson

Open Access Publications

As the global population ages, there is increased interest in living longer and improving one's quality of life in later years. However, studying aging - the decline in body function - is expensive and time-consuming. And despite research success to make model organisms live longer, there still aren't really any feasible solutions for delaying aging in humans. With space travel, scientists and engineers couldn't know what it would take to get to the moon. They had to extrapolate from theory and shorter-range tests. Perhaps with aging, we need a similar moonshot philosophy. And though "shot" might imply medicine, perhaps we …


Blood Plasma Phosphorylated-Tau Isoforms Track Cns Change In Alzheimer's Disease, Nicolas R. Barthélemy, Kanta Horie, Chihiro Sato, Randall J. Bateman Nov 2020

Blood Plasma Phosphorylated-Tau Isoforms Track Cns Change In Alzheimer's Disease, Nicolas R. Barthélemy, Kanta Horie, Chihiro Sato, Randall J. Bateman

Open Access Publications

Highly sensitive and specific plasma biomarkers for Alzheimer's disease (AD) have the potential to improve diagnostic accuracy in the clinic and facilitate research studies including enrollment in prevention and treatment trials. We recently reported CSF tau hyperphosphorylation, especially on T217, is an accurate predictor of β-amyloidosis at asymptomatic and symptomatic stages. In the current study, we determine by mass spectrometry the potential utility of plasma p-tau isoforms to detect AD pathology and investigate CSF and plasma tau isoforms' profile relationships. Plasma tau was truncated as previously described in CSF. CSF and plasma measures of p-tau-217 and p-tau-181 were correlated. No …


Prospective, Randomized, Double-Blind, Placebo-Controlled Evaluation Of The Pharmacokinetics, Safety And Efficacy Of Recombinant Antithrombin Versus Placebo In Preterm Preeclampsia, Michael J Paidas, George A Macones, Et Al Nov 2020

Prospective, Randomized, Double-Blind, Placebo-Controlled Evaluation Of The Pharmacokinetics, Safety And Efficacy Of Recombinant Antithrombin Versus Placebo In Preterm Preeclampsia, Michael J Paidas, George A Macones, Et Al

Open Access Publications

BACKGROUND: Despite expectant management, preeclampsia remote from term usually results in preterm delivery. Antithrombin, which displays antiinflammatory and anticoagulant properties, may have a therapeutic role in treating preterm preeclampsia, a disorder characterized by endothelial dysfunction, inflammation, and activation of the coagulation system.

OBJECTIVE: This randomized, placebo-controlled clinical trial aimed to evaluate whether intravenous recombinant human antithrombin could prolong gestation and therefore improve maternal and fetal outcomes.

STUDY DESIGN: We performed a double-blind, placebo-controlled trial at 23 hospitals. Women were eligible if they had a singleton pregnancy, early-onset or superimposed preeclampsia at 23 0/7 to 30 0/7 weeks' gestation, and planned …


Maternal Altitude And Risk Of Low Birthweight: A Systematic Review And Meta-Analyses, Lin Yang, Veronika Helbich-Poschacher, Chao Cao, Katrin Klebermass-Schrehof, Thomas Waldhoer Nov 2020

Maternal Altitude And Risk Of Low Birthweight: A Systematic Review And Meta-Analyses, Lin Yang, Veronika Helbich-Poschacher, Chao Cao, Katrin Klebermass-Schrehof, Thomas Waldhoer

2020-Current year OA Pubs

BACKGROUND: Previous studies conducted in high altitude regions showed that maternal altitude was associated with low birth weight. The effect size of birth weight reduction is inclusive with unknown effects due to preterm birth. We systematically reviewed the literature and synthesize evidence on associations between altitude elevation from sea level and birth weight.

METHOD: We searched MEDLINE/PubMed, Embase, Scopus, Web of Science, and Cochrane database, from inception to May 5, 2020 for studies that reported maternal altitude and birth weight. Bayesian multilevel effect models were employed to estimate the effect size on birth weight (and gestational age) associated with altitude. …


Implications Of Pneumonitis After Chemoradiation And Durvalumab For Locally Advanced Non-Small Cell Lung Cancer, Comron Hassanzadeh, Timothy Sita, Rohan Savoor, Pamela P Samson, Jeffrey Bradley, Michelle Gentile, Michael Roach, Nisha Mohindra, Saiama Waqar, Timothy J Kruser, Clifford Robinson Nov 2020

Implications Of Pneumonitis After Chemoradiation And Durvalumab For Locally Advanced Non-Small Cell Lung Cancer, Comron Hassanzadeh, Timothy Sita, Rohan Savoor, Pamela P Samson, Jeffrey Bradley, Michelle Gentile, Michael Roach, Nisha Mohindra, Saiama Waqar, Timothy J Kruser, Clifford Robinson

Open Access Publications

Background: Consolidation durvalumab improved overall survival (OS) in locally advanced non-small cell lung cancer (LA-NSCLC) treated with chemoradiotherapy (CRT) in the PACIFIC trial; however, pneumonitis was increased with durvalumab. We sought to examine real-world outcomes with the PACIFIC paradigm, especially factors associated with pneumonitis, using a multi-institutional review.

Methods: Patients with LA-NSCLC treated with CRT followed by durvalumab from January 2017-February 2019 were identified at 2 institutions. We characterized demographics, tumor factors, radiotherapy, and duration of durvalumab. We examined pneumonitis outcomes including re-challenge success, with secondary endpoints of progression-free survival (PFS) and OS.

Results: Thirty-four patients were included with median …


Characterization Of Glycan Determinants That Mediate Recognition Of The Major Wuchereria Bancrofti Circulating Antigen By Diagnostic Antibodies, Marla I Hertz, Amy Rush, Thomas B Nutman, Gary J Weil, Sasisekhar Bennuru, Philip J Budge Nov 2020

Characterization Of Glycan Determinants That Mediate Recognition Of The Major Wuchereria Bancrofti Circulating Antigen By Diagnostic Antibodies, Marla I Hertz, Amy Rush, Thomas B Nutman, Gary J Weil, Sasisekhar Bennuru, Philip J Budge

2020-Current year OA Pubs

The Global Program to Eliminate Lymphatic Filariasis (GPELF) relies heavily on a rapid diagnostic test (RDT) to a Wuchereria bancrofti circulating filarial antigen (Wb-CFA) to identify endemic areas and for determining when mass drug administration can stop. The antigen contains a carbohydrate epitope that is recognized by monoclonal antibody AD12. Og4C3, a monoclonal antibody that is used in a commercial ELISA for Wb-CFA recognizes the same moiety. Despite its diagnostic importance, little is known about the structure and function of this "AD12 epitope". It is also present on other W. bancrofti glycoproteins and on glycoproteins of other filarial worms, but …


Comparing Intervention Strategies For Reducing Clostridioides Difficile Transmission In Acute Healthcare Settings: An Agent-Based Modeling Study, Brittany Stephenson, Cristina Lanzas, Suzanne Lenhart, Eduardo Ponce, Jason Bintz, Erik R Dubberke, Judy Day Oct 2020

Comparing Intervention Strategies For Reducing Clostridioides Difficile Transmission In Acute Healthcare Settings: An Agent-Based Modeling Study, Brittany Stephenson, Cristina Lanzas, Suzanne Lenhart, Eduardo Ponce, Jason Bintz, Erik R Dubberke, Judy Day

2020-Current year OA Pubs

BACKGROUND: Clostridioides difficile infection (CDI) is one of the most common healthcare infections. Common strategies aiming at controlling CDI include antibiotic stewardship, environmental decontamination, and improved hand hygiene and contact precautions. Mathematical models provide a framework to evaluate control strategies. Our objective is to evaluate the effectiveness of control strategies in decreasing C. difficile colonization and infection using an agent-based model in an acute healthcare setting.

METHODS: We developed an agent-based model that simulates the transmission of C. difficile in medical wards. This model explicitly incorporates healthcare workers (HCWs) as vectors of transmission, tracks individual patient antibiotic histories, incorporates varying …


Sarm1 Depletion Rescues Nmnat1-Dependent Photoreceptor Cell Death And Retinal Degeneration, Yo Sasaki, Hiroki Kakita, Shunsuke Kubota, Abdoulaye Sene, Tae Jun Lee, Norimitsu Ban, Zhenyu Dong, Joseph B. Lin, Sanford L. Boye, Aaron Diantonio, Shannon E. Boye, Rajendra S. Apte, Jeffrey Milbrandt Oct 2020

Sarm1 Depletion Rescues Nmnat1-Dependent Photoreceptor Cell Death And Retinal Degeneration, Yo Sasaki, Hiroki Kakita, Shunsuke Kubota, Abdoulaye Sene, Tae Jun Lee, Norimitsu Ban, Zhenyu Dong, Joseph B. Lin, Sanford L. Boye, Aaron Diantonio, Shannon E. Boye, Rajendra S. Apte, Jeffrey Milbrandt

Open Access Publications

Leber congenital amaurosis type nine is an autosomal recessive retinopathy caused by mutations of the NAD


Brain Function Distinguishes Female Carriers And Non-Carriers Of Familial Risk For Autism, Adam T Eggebrecht, Ally Dworetsky, Zoë Hawks, Rebecca Coalson, Babatunde Adeyemo, Savannah Davis, Daniel Gray, Alana Mcmichael, Steven E Petersen, John N Constantino, John R Pruett Oct 2020

Brain Function Distinguishes Female Carriers And Non-Carriers Of Familial Risk For Autism, Adam T Eggebrecht, Ally Dworetsky, Zoë Hawks, Rebecca Coalson, Babatunde Adeyemo, Savannah Davis, Daniel Gray, Alana Mcmichael, Steven E Petersen, John N Constantino, John R Pruett

2020-Current year OA Pubs

BACKGROUND: Autism spectrum disorder (ASD) is characterized by high population-level heritability and a three-to-one male-to-female ratio that occurs independent of sex linkage. Prior research in a mixed-sex pediatric sample identified neural signatures of familial risk elicited by passive viewing of point light motion displays, suggesting the possibility that both resilience and risk of autism might be associated with brain responses to biological motion. To confirm a relationship between these signatures and inherited risk of autism, we tested them in families enriched for genetic loading through undiagnosed ("carrier") females.

METHODS: Using functional magnetic resonance imaging, we examined brain responses to passive …


Role Of Endothelial Nitric Oxide Synthase In Isoflurane Conditioning-Induced Neurovascular Protection In Subarachnoid Hemorrhage, Umeshkumar Athiraman, Keshav Jayaraman, Meizi Liu, Tusar Giri, Jane Yuan, Gregory J Zipfel Oct 2020

Role Of Endothelial Nitric Oxide Synthase In Isoflurane Conditioning-Induced Neurovascular Protection In Subarachnoid Hemorrhage, Umeshkumar Athiraman, Keshav Jayaraman, Meizi Liu, Tusar Giri, Jane Yuan, Gregory J Zipfel

Open Access Publications

Background Delayed cerebral ischemia remains a common and profound risk factor for poor outcome after subarachnoid hemorrhage (SAH). The aim of our current study is to define the role of endothelial nitric oxide synthase (eNOS) in isoflurane conditioning-induced neurovascular protection after SAH. Methods and Results Ten- to 14-week-old male wild-type mice (C57BL/6) as controls and eNOS knockout male mice (strain # 002684) were obtained for the study. Animals underwent either sham surgery, SAH surgery, or SAH with isoflurane conditioning. Anesthetic post conditioning was performed with isoflurane 2% for 1 hour, 1 hour after SAH. Normothermia was maintained with the homeothermic …


Burst Mitofusin Activation Reverses Neuromuscular Dysfunction In Murine Cmt2a, Antonietta Franco, Xiawei Dang, Emily K. Walton, Joshua N. Ho, Barbara Zablocka, Cindy Ly, Timothy M. Miller, Robert H. Baloh, Michael E. Shy, Andrew S. Yoo, Gerald W. Dorn Oct 2020

Burst Mitofusin Activation Reverses Neuromuscular Dysfunction In Murine Cmt2a, Antonietta Franco, Xiawei Dang, Emily K. Walton, Joshua N. Ho, Barbara Zablocka, Cindy Ly, Timothy M. Miller, Robert H. Baloh, Michael E. Shy, Andrew S. Yoo, Gerald W. Dorn

Open Access Publications

Charcot-Marie-Tooth disease type 2A (CMT2A) is an untreatable childhood peripheral neuropathy caused by mutations of the mitochondrial fusion protein, mitofusin (MFN) 2. Here, pharmacological activation of endogenous normal mitofusins overcame dominant inhibitory effects of CMT2A mutants in reprogrammed human patient motor neurons, reversing hallmark mitochondrial stasis and fragmentation independent of causal


The Fgf8 Subfamily (Fgf8, Fgf17 And Fgf18) Is Required For Closure Of The Embryonic Ventral Body Wall, Michael Boylan, Matthew J Anderson, David M Ornitz, Mark Lewandoski Oct 2020

The Fgf8 Subfamily (Fgf8, Fgf17 And Fgf18) Is Required For Closure Of The Embryonic Ventral Body Wall, Michael Boylan, Matthew J Anderson, David M Ornitz, Mark Lewandoski

Open Access Publications

The closure of the embryonic ventral body wall in amniotes is an important morphogenetic event and is essential for life. Defects in human ventral wall closure are a major class of birth defect and a significant health burden. Despite this, very little is understood about how the ventral body wall is formed. Here, we show that fibroblast growth factor (FGF) ligands FGF8, FGF17 and FGF18 are essential for this process. Conditional mouse mutants for these genes display subtle migratory defects in the abdominal muscles of the ventral body wall and an enlarged umbilical ring, through which the internal organs are …


Macrophage-Associated Lipin-1 Promotes Β-Oxidation In Response To Proresolving Stimuli, Robert M Schilke, Cassidy M R Blackburn, Shashanka Rao, David M Krzywanski, Brian N Finck, Matthew D Woolard Oct 2020

Macrophage-Associated Lipin-1 Promotes Β-Oxidation In Response To Proresolving Stimuli, Robert M Schilke, Cassidy M R Blackburn, Shashanka Rao, David M Krzywanski, Brian N Finck, Matthew D Woolard

2020-Current year OA Pubs

Macrophages reprogram their metabolism to promote appropriate responses. Proresolving macrophages primarily use fatty acid oxidation as an energy source. Metabolites generated during the catabolism of fatty acids aid in the resolution of inflammation and tissue repair, but the regulatory mechanisms that control lipid metabolism in macrophages are not fully elucidated. Lipin-1, a phosphatidic acid phosphatase that has transcriptional coregulator activity, regulates lipid metabolism in a variety of cells. In this current study, we show that lipin-1 is required for increased oxidative phosphorylation in IL-4 stimulated mouse (


Splicing Factor Sf3b1 Promotes Endometrial Cancer Progression Via Regulating Ksr2 Rna Maturation, Pooja Popli, Megan M Richters, Sangappa B Chadchan, Tae Hoon Kim, Eric Tycksen, Obi Griffith, Premal H Thaker, Malachi Griffith, Ramakrishna Kommagani Oct 2020

Splicing Factor Sf3b1 Promotes Endometrial Cancer Progression Via Regulating Ksr2 Rna Maturation, Pooja Popli, Megan M Richters, Sangappa B Chadchan, Tae Hoon Kim, Eric Tycksen, Obi Griffith, Premal H Thaker, Malachi Griffith, Ramakrishna Kommagani

2020-Current year OA Pubs

Although endometrial cancer is the most common cancer of the female reproductive tract, we have little understanding of what controls endometrial cancer beyond the transcriptional effects of steroid hormones such as estrogen. As a result, we have limited therapeutic options for the ~62,000 women diagnosed with endometrial cancer each year in the United States. Here, in an attempt to identify new prognostic and therapeutic targets, we focused on a new area for this cancer-alternative mRNA splicing-and investigated whether splicing factor, SF3B1, plays an important role in endometrial cancer pathogenesis. Using a tissue microarray, we found that human endometrial tumors expressed …


Acute Kidney Injury Pathology And Pathophysiology: A Retrospective Review, Joseph P. Gaut, Helen Liapis Oct 2020

Acute Kidney Injury Pathology And Pathophysiology: A Retrospective Review, Joseph P. Gaut, Helen Liapis

Open Access Publications

Acute kidney injury (AKI) is the clinical term used for decline or loss of renal function. It is associated with chronic kidney disease (CKD) and high morbidity and mortality. However, not all causes of AKI lead to severe consequences and some are reversible. The underlying pathology can be a guide for treatment and assessment of prognosis. The Kidney Disease: Improving Global Outcomes guidelines recommend that the cause of AKI should be identified if possible. Renal biopsy can distinguish specific AKI entities and assist in patient management. This review aims to show the pathology of AKI, including glomerular and tubular diseases.