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Articles 3631 - 3660 of 11062
Full-Text Articles in Entire DC Network
Growth, Detection, Quantification, And Inactivation Of Sars-Cov-2, James Brett Case, Adam L. Bailey, Arthur S. Kim, Rita E. Chen, Michael S. Diamond
Growth, Detection, Quantification, And Inactivation Of Sars-Cov-2, James Brett Case, Adam L. Bailey, Arthur S. Kim, Rita E. Chen, Michael S. Diamond
2020-Current year OA Pubs
Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is the agent responsible for the coronavirus disease 2019 (COVID-19) global pandemic. SARS-CoV-2 is closely related to SARS-CoV, which caused the 2003 SARS outbreak. Although numerous reagents were developed to study SARS-CoV infections, few have been applicable to evaluating SARS-CoV-2 infection and immunity. Current limitations in studying SARS-CoV-2 include few validated assays with fully replication-competent wild-type virus. We have developed protocols to propagate, quantify, and work with infectious SARS-CoV-2. Here, we describe: (1) virus stock generation, (2) RT-qPCR quantification of SARS-CoV-2 RNA; (3) detection of SARS-CoV-2 antigen by flow cytometry, (4) quantification of infectious …
Adrenal Insufficiency Is A Contraindication For Omalizumab Therapy In Mast Cell Activation Disease: Risk For Serum Sickness, G J Molderings, L B Weinstock, Et Al.
Adrenal Insufficiency Is A Contraindication For Omalizumab Therapy In Mast Cell Activation Disease: Risk For Serum Sickness, G J Molderings, L B Weinstock, Et Al.
2020-Current year OA Pubs
Omalizumab is an effective therapeutic humanized murine IgE antibody in many cases of primary systemic mast cell activation disease (MCAD). The present study should enable the clinician to recognize when treatment of MCAD with omalizumab is contraindicated because of the potential risk of severe serum sickness and to report our successful therapeutic strategy for such adverse event (AE). Our clinical observations, a review of the literature including the event reports in the FDA AE Reporting System, the European Medicines Agency Eudra-Vigilance databases (preferred search terms: omalizumab, Xolair®, and serum sickness) and information from the manufacturer's Novartis database were used. Omalizumab …
Optimal Co-Clinical Radiomics: Sensitivity Of Radiomic Features To Tumour Volume, Image Noise And Resolution In Co-Clinical T1-Weighted And T2-Weighted Magnetic Resonance Imaging, Sudipta Roy, Timothy D Whitehead, James D Quirk, Amber Salter, Foluso O Ademuyiwa, Shunqiang Li, Hongyu An, Kooresh I Shoghi
Optimal Co-Clinical Radiomics: Sensitivity Of Radiomic Features To Tumour Volume, Image Noise And Resolution In Co-Clinical T1-Weighted And T2-Weighted Magnetic Resonance Imaging, Sudipta Roy, Timothy D Whitehead, James D Quirk, Amber Salter, Foluso O Ademuyiwa, Shunqiang Li, Hongyu An, Kooresh I Shoghi
Open Access Publications
BACKGROUND: Radiomics analyses has been proposed to interrogate the biology of tumour as well as to predict/assess response to therapy in vivo. The objective of this work was to assess the sensitivity of radiomics features to noise, resolution, and tumour volume in the context of a co-clinical trial.
METHODS: Triple negative breast cancer (TNBC) patients were recruited into an ongoing co-clinical imaging trial. Sub-typed matched TNBC patient-derived tumour xenografts (PDX) were generated to investigate optimal co-clinical MR radiomic features. The MR imaging protocol included T1-weighed and T2-weighted imaging. To test the sensitivity of radiomics to resolution, PDX were imaged at …
Parietal Epithelial Cell Differentiation To A Podocyte Fate In The Aged Mouse Kidney, Natalya V. Kaverina, Diana G. Eng, Jeffrey H. Miner, Jeffrey W. Pippin, Stuart J. Shankland
Parietal Epithelial Cell Differentiation To A Podocyte Fate In The Aged Mouse Kidney, Natalya V. Kaverina, Diana G. Eng, Jeffrey H. Miner, Jeffrey W. Pippin, Stuart J. Shankland
Open Access Publications
Healthy aging is typified by a progressive and absolute loss of podocytes over the lifespan of animals and humans. To test the hypothesis that a subset of glomerular parietal epithelial cell (PEC) progenitors transition to a podocyte fate with aging, dual reporter
Genetic Variants And Functional Pathways Associated With Resilience To Alzheimer's Disease, Logan Dumitrescu, Carlos Cruchaga, Et Al
Genetic Variants And Functional Pathways Associated With Resilience To Alzheimer's Disease, Logan Dumitrescu, Carlos Cruchaga, Et Al
Open Access Publications
Approximately 30% of older adults exhibit the neuropathological features of Alzheimer's disease without signs of cognitive impairment. Yet, little is known about the genetic factors that allow these potentially resilient individuals to remain cognitively unimpaired in the face of substantial neuropathology. We performed a large, genome-wide association study (GWAS) of two previously validated metrics of cognitive resilience quantified using a latent variable modelling approach and representing better-than-predicted cognitive performance for a given level of neuropathology. Data were harmonized across 5108 participants from a clinical trial of Alzheimer's disease and three longitudinal cohort studies of cognitive ageing. All analyses were run …
Developmental Changes In Myocardial B Cells Mirror Changes In B Cells Associated With Different Organs, Cibele Rocha-Resende, Wei Yang, Wenjun Li, Daniel Kreisel, Luigi Adamo, Douglas L Mann
Developmental Changes In Myocardial B Cells Mirror Changes In B Cells Associated With Different Organs, Cibele Rocha-Resende, Wei Yang, Wenjun Li, Daniel Kreisel, Luigi Adamo, Douglas L Mann
Open Access Publications
The naive heart harbors a population of intravascular B cells that make close contact with the cardiac microvasculature. However, the timing of their appearance and their organ specificity remain unknown. To address this knowledge gap, we performed a systematic analysis of B cells isolated from the myocardium and other organs, from embryonic life to adulthood. We found that the phenotype of myocardial B cells changed dynamically during development. While neonatal heart B cells were mostly CD11b+ and CD11b- CD21-CD23-, adult B cells were predominantly CD11b-CD21+CD23+. Histological analysis and intravital microscopy of lung and liver showed that organ-associated B cells in …
Cd300lf Polymorphisms Of Inbred Mouse Strains Confer Resistance To Murine Norovirus Infection In A Cell Type-Dependent Manner, Kevin Furlong, Scott B. Biering, Jayoung Choi, Craig B. Wilen, Robert C. Orchard, Christiane E. Wobus, Christopher A. Nelson, Daved H. Fremont, Megan T. Baldridge, Glenn Randall, Seungmin Hwang
Cd300lf Polymorphisms Of Inbred Mouse Strains Confer Resistance To Murine Norovirus Infection In A Cell Type-Dependent Manner, Kevin Furlong, Scott B. Biering, Jayoung Choi, Craig B. Wilen, Robert C. Orchard, Christiane E. Wobus, Christopher A. Nelson, Daved H. Fremont, Megan T. Baldridge, Glenn Randall, Seungmin Hwang
Open Access Publications
Human norovirus is the leading cause of gastroenteritis worldwide, yet basic questions about its life cycle remain unanswered due to an historical lack of robust experimental systems. Recent studies on the closely related murine norovirus (MNV) have identified CD300LF as an indispensable entry factor for MNV. We compared the MNV susceptibilities of cells from different mouse strains and identified polymorphisms in murine CD300LF which are critical for its function as an MNV receptor. Bone marrow-derived macrophages (BMDMs) from I/LnJ mice were resistant to infection from multiple MNV strains which readily infect BMDMs from C57BL/6J mice. The resistance of I/LnJ BMDMs …
Diarrhea As A Potential Cause And Consequence Of Reduced Gut Microbial Diversity Among Undernourished Children In Peru, Saba Rouhani, Nicholas W Griffin, Pablo Peñataro Yori, Jeanette L Gehrig, Maribel Paredes Olortegui, Mery Siguas Salas, Dixner Rengifo Trigoso, Lawrence H Moulton, Eric R Houpt, Michael J Barratt, Margaret N Kosek, Jeffrey I Gordon
Diarrhea As A Potential Cause And Consequence Of Reduced Gut Microbial Diversity Among Undernourished Children In Peru, Saba Rouhani, Nicholas W Griffin, Pablo Peñataro Yori, Jeanette L Gehrig, Maribel Paredes Olortegui, Mery Siguas Salas, Dixner Rengifo Trigoso, Lawrence H Moulton, Eric R Houpt, Michael J Barratt, Margaret N Kosek, Jeffrey I Gordon
2020-Current year OA Pubs
BACKGROUND: Detrimental effects of diarrhea on child growth and survival are well documented, but details of the underlying mechanisms remain poorly understood. Recent evidence demonstrates that perturbations to normal development of the gut microbiota in early life may contribute to growth faltering and susceptibility to related childhood diseases. We assessed associations between diarrhea, gut microbiota configuration, and childhood growth in the Peruvian Amazon.
METHODS: Growth, diarrhea incidence, illness, pathogen infection, and antibiotic exposure were assessed monthly in a birth cohort of 271 children aged 0-24 months. Gut bacterial diversity and abundances of specific bacterial taxa were quantified by sequencing 16S …
Gut Microbiota Features Associated With Campylobacter Burden And Postnatal Linear Growth Deficits In A Peruvian Birth Cohort, Saba Rouhani, Nicholas W Griffin, Pablo Peñataro Yori, Maribel Paredes Olortegui, Mery Siguas Salas, Dixner Rengifo Trigoso, Lawrence H Moulton, Eric R Houpt, Michael J Barratt, Margaret N Kosek, Jeffrey I Gordon
Gut Microbiota Features Associated With Campylobacter Burden And Postnatal Linear Growth Deficits In A Peruvian Birth Cohort, Saba Rouhani, Nicholas W Griffin, Pablo Peñataro Yori, Maribel Paredes Olortegui, Mery Siguas Salas, Dixner Rengifo Trigoso, Lawrence H Moulton, Eric R Houpt, Michael J Barratt, Margaret N Kosek, Jeffrey I Gordon
2020-Current year OA Pubs
BACKGROUND: Campylobacter infection is associated with impaired growth of children, even in the absence of symptoms. To examine the underlying mechanisms, we evaluated associations between Campylobacter infection, linear growth, and fecal microbial community features in a prospective birth cohort of 271 children with a high burden of diarrhea and stunting in the Amazonian lowlands of Peru.
METHODS: Campylobacter was identified using a broadly reactive, genus-specific enzyme-linked immunosorbent assay. 16S rRNA-based analyses were used to identify bacterial taxa in fecal samples at ages 6, 12, 18, and 24 months (N = 928). Associations between infection, growth, and gut microbial community composition …
Testing The Impact Of A Single Nucleotide Polymorphism In A Plasmodium Berghei Apiap2 Transcription Factor On Experimental Cerebral Malaria In Mice, Munir Akkaya, Abhisheka Bansal, Patrick W Sheehan, Mirna Pena, Clare K Cimperman, Chen Feng Qi, Takele Yazew, Thomas D Otto, Oliver Billker, Louis H Miller, Susan K Pierce
Testing The Impact Of A Single Nucleotide Polymorphism In A Plasmodium Berghei Apiap2 Transcription Factor On Experimental Cerebral Malaria In Mice, Munir Akkaya, Abhisheka Bansal, Patrick W Sheehan, Mirna Pena, Clare K Cimperman, Chen Feng Qi, Takele Yazew, Thomas D Otto, Oliver Billker, Louis H Miller, Susan K Pierce
Open Access Publications
Cerebral malaria (CM) is the deadliest form of severe Plasmodium infections. Currently, we have limited understanding of the mechanisms by which Plasmodium parasites induce CM. The mouse model of CM, experimental CM (ECM), induced by infection with the rodent parasite, Plasmodium berghei ANKA (PbANKA) has been extensively used to study the pathophysiology of CM. Recent genomic analyses revealed that the coding regions of PbANKA and the closely related Plasmodium berghei NK65 (PbNK65), that does not cause ECM, differ in only 21 single nucleotide polymorphysims (SNPs). Thus, the SNP-containing genes might contribute to the pathogenesis of ECM. Although the majority of …
Tonic Tcr Signaling Inversely Regulates The Basal Metabolism Of Cd4+ T Cells, Ashley A Viehmann Milam, Juliet M Bartleson, Michael D Buck, Chih-Hao Chang, Alexey Sergushichev, David L Donermeyer, Wing Y Lam, Erika L Pearce, Maxim N Artyomov, Paul M Allen
Tonic Tcr Signaling Inversely Regulates The Basal Metabolism Of Cd4+ T Cells, Ashley A Viehmann Milam, Juliet M Bartleson, Michael D Buck, Chih-Hao Chang, Alexey Sergushichev, David L Donermeyer, Wing Y Lam, Erika L Pearce, Maxim N Artyomov, Paul M Allen
2020-Current year OA Pubs
The contribution of self-peptide-MHC signaling in CD4
Selective Inhibition Of Mtorc1 In Tumor Vessels Increases Antitumor Immunity, Shan Wang, Ariel Raybuck, Eileen Shiuan, Sung Hoon Cho, Qingfei Wang, Dana M Brantley-Sieders, Deanna Edwards, Margaret M Allaman, James Nathan, Keith T Wilson, David Denardo, Siyuan Zhang, Rebecca Cook, Mark Boothby, Jin Chen
Selective Inhibition Of Mtorc1 In Tumor Vessels Increases Antitumor Immunity, Shan Wang, Ariel Raybuck, Eileen Shiuan, Sung Hoon Cho, Qingfei Wang, Dana M Brantley-Sieders, Deanna Edwards, Margaret M Allaman, James Nathan, Keith T Wilson, David Denardo, Siyuan Zhang, Rebecca Cook, Mark Boothby, Jin Chen
Open Access Publications
A tumor blood vessel is a key regulator of tissue perfusion, immune cell trafficking, cancer metastasis, and therapeutic responsiveness. mTORC1 is a signaling node downstream of multiple angiogenic factors in the endothelium. However, mTORC1 inhibitors have limited efficacy in most solid tumors, in part due to inhibition of immune function at high doses used in oncology patients and compensatory PI3K signaling triggered by mTORC1 inhibition in tumor cells. Here we show that low-dose RAD001/everolimus, an mTORC1 inhibitor, selectively targets mTORC1 signaling in endothelial cells (ECs) without affecting tumor cells or immune cells, resulting in tumor vessel normalization and increased antitumor …
Synchronization Of Mothers And Offspring Promotes Tolerance And Limits Allergy, Kathryn A Knoop, Keely G Mcdonald, Paige E Coughlin, Devesha H Kulkarni, Jenny K Gustafsson, Brigida Rusconi, Vini John, I Malick Ndao, Avraham Beigelman, Misty Good, Barbara B Warner, Charles O Elson, Chyi-Song Hsieh, Simon P Hogan, Phillip I Tarr, Rodney D Newberry
Synchronization Of Mothers And Offspring Promotes Tolerance And Limits Allergy, Kathryn A Knoop, Keely G Mcdonald, Paige E Coughlin, Devesha H Kulkarni, Jenny K Gustafsson, Brigida Rusconi, Vini John, I Malick Ndao, Avraham Beigelman, Misty Good, Barbara B Warner, Charles O Elson, Chyi-Song Hsieh, Simon P Hogan, Phillip I Tarr, Rodney D Newberry
Open Access Publications
Allergic disorders, characterized by Th2 immune responses to environmental substances, are increasingly common in children in Western societies. Multiple studies indicate that breastfeeding, early complementary introduction of food allergens, and antibiotic avoidance in the first year of life reduces allergic outcomes in at-risk children. Why the benefit of these practices is restricted to early life is largely unknown. We identified a preweaning interval during which dietary antigens are assimilated by the colonic immune system. This interval is under maternal control via temporal changes in breast milk, coincides with an influx of naive T cells into the colon, and is followed …
The Complement System In Covid-19: Friend And Foe?, Anuja Java, Anthony J Apicelli, M Kathryn Liszewski, Ariella Coler-Reilly, John P Atkinson, Alfred Hj Kim, Hrishikesh S Kulkarni
The Complement System In Covid-19: Friend And Foe?, Anuja Java, Anthony J Apicelli, M Kathryn Liszewski, Ariella Coler-Reilly, John P Atkinson, Alfred Hj Kim, Hrishikesh S Kulkarni
Open Access Publications
Coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in a global pandemic and a disruptive health crisis. COVID-19-related morbidity and mortality have been attributed to an exaggerated immune response. The role of complement activation and its contribution to illness severity is being increasingly recognized. Here, we summarize current knowledge about the interaction of coronaviruses with the complement system. We posit that (a) coronaviruses activate multiple complement pathways; (b) severe COVID-19 clinical features often resemble complementopathies; (c) the combined effects of complement activation, dysregulated neutrophilia, endothelial injury, and hypercoagulability appear to be intertwined …
Enantiomerically Pure Quinoline-Based Κ-Opioid Receptor Agonists: Chemoenzymatic Synthesis And Pharmacological Evaluation, Benedikt Martin, Dirk Schepmann, Freddy A Bernal, Thomas J Schmidt, Tao Che, Karin Loser, Bernhard Wünsch
Enantiomerically Pure Quinoline-Based Κ-Opioid Receptor Agonists: Chemoenzymatic Synthesis And Pharmacological Evaluation, Benedikt Martin, Dirk Schepmann, Freddy A Bernal, Thomas J Schmidt, Tao Che, Karin Loser, Bernhard Wünsch
2020-Current year OA Pubs
Racemic
Osterix-Cre Marks Distinct Subsets Of Cd45- And Cd45+ Stromal Populations In Extra-Skeletal Tumors With Pro-Tumorigenic Characteristics, Biancamaria Ricci, Eric Tycksen, Hamza Celik, Jad I. Belle, Francesca Fontana, Roberto Civitelli, Roberta Faccio
Osterix-Cre Marks Distinct Subsets Of Cd45- And Cd45+ Stromal Populations In Extra-Skeletal Tumors With Pro-Tumorigenic Characteristics, Biancamaria Ricci, Eric Tycksen, Hamza Celik, Jad I. Belle, Francesca Fontana, Roberto Civitelli, Roberta Faccio
Open Access Publications
Cancer-associated fibroblasts (CAFs) are a heterogeneous population of mesenchymal cells supporting tumor progression, whose origin remains to be fully elucidated. Osterix (Osx) is a marker of osteogenic differentiation, expressed in skeletal progenitor stem cells and bone-forming osteoblasts. We report
Sarm1 Acts Downstream Of Neuroinflammatory And Necroptotic Signaling To Induce Axon Degeneration, Kwang Woo Ko, Jeffrey Milbrandt, Aaron Diantonio
Sarm1 Acts Downstream Of Neuroinflammatory And Necroptotic Signaling To Induce Axon Degeneration, Kwang Woo Ko, Jeffrey Milbrandt, Aaron Diantonio
Open Access Publications
Neuroinflammation and necroptosis are major contributors to neurodegenerative disease, and axon dysfunction and degeneration is often an initiating event. SARM1 is the central executioner of pathological axon degeneration. Here, we demonstrate functional and mechanistic links among these three pro-degenerative processes. In a neuroinflammatory model of glaucoma, TNF-α induces SARM1-dependent axon degeneration, oligodendrocyte loss, and subsequent retinal ganglion cell death. TNF-α also triggers SARM1-dependent axon degeneration in sensory neurons via a noncanonical necroptotic signaling mechanism. MLKL is the final executioner of canonical necroptosis; however, in axonal necroptosis, MLKL does not directly trigger degeneration. Instead, MLKL induces loss of the axon survival …
Basement Membrane Ligands Initiate Distinct Signalling Networks To Direct Cell Shape, Michael J Randles, Franziska Lausecker, Jonathan D Humphries, Adam Byron, Simon J Clark, Jeffrey H Miner, Roy Zent, Martin J Humphries, Rachel Lennon
Basement Membrane Ligands Initiate Distinct Signalling Networks To Direct Cell Shape, Michael J Randles, Franziska Lausecker, Jonathan D Humphries, Adam Byron, Simon J Clark, Jeffrey H Miner, Roy Zent, Martin J Humphries, Rachel Lennon
Open Access Publications
Cells have evolved mechanisms to sense the composition of their adhesive microenvironment. Although much is known about general mechanisms employed by adhesion receptors to relay signals between the extracellular environment and the cytoskeleton, the nuances of ligand-specific signalling remain undefined. Here, we investigated how glomerular podocytes, and four other basement membrane-associated cell types, respond morphologically to different basement membrane ligands. We defined the composition of the respective adhesion complexes using mass spectrometry-based proteomics. On type IV collagen, all epithelial cell types adopted a round morphology, with a single lamellipodium and large adhesion complexes rich in actin-binding proteins. On laminin (511 …
Tlr2/6 Signaling Promotes The Expansion Of Premalignant Hematopoietic Stem And Progenitor Cells In The Nup98-Hoxd13 Mouse Model Of Mds, Darlene A Monlish, Zev J Greenberg, Sima T Bhatt, Kathryn M Leonard, Molly P Romine, Qian Dong, Lauren Bendesky, Eric J Duncavage, Jeffrey A Magee, Laura G Schuettpelz
Tlr2/6 Signaling Promotes The Expansion Of Premalignant Hematopoietic Stem And Progenitor Cells In The Nup98-Hoxd13 Mouse Model Of Mds, Darlene A Monlish, Zev J Greenberg, Sima T Bhatt, Kathryn M Leonard, Molly P Romine, Qian Dong, Lauren Bendesky, Eric J Duncavage, Jeffrey A Magee, Laura G Schuettpelz
Open Access Publications
Toll-like receptor 2 (TLR2) expression is increased on hematopoietic stem and progenitor cells (HSPCs) of patients with myelodysplastic syndromes (MDS), and enhanced TLR2 signaling is thought to contribute to MDS pathogenesis. Notably, TLR2 heterodimerizes with TLR1 or TLR6, and while high TLR2 is associated with lower-risk disease, high TLR6, but not TLR1, correlates with higher-risk disease. This raises the possibility of heterodimer-specific effects of TLR2 signaling in MDS, and in the work described here, we tested the effects of specific modulation of TLR1/2 versus TLR2/6 signaling on premalignant HSPCs. Indeed, chronic stimulation of TLR2/6, but not TLR1/2, accelerates leukemic transformation …
De Novo Variants Of Nr4a2 Are Associated With Neurodevelopmental Disorder And Epilepsy, Sakshi Singh, Rachel Slaugh, Jorge Granadillo, Et Al.
De Novo Variants Of Nr4a2 Are Associated With Neurodevelopmental Disorder And Epilepsy, Sakshi Singh, Rachel Slaugh, Jorge Granadillo, Et Al.
2020-Current year OA Pubs
PURPOSE: This study characterizes the clinical and genetic features of nine unrelated patients with de novo variants in the NR4A2 gene.
METHODS: Variants were identified and de novo origins were confirmed through trio exome sequencing in all but one patient. Targeted RNA sequencing was performed for one variant to confirm its splicing effect. Independent discoveries were shared through GeneMatcher.
RESULTS: Missense and loss-of-function variants in NR4A2 were identified in patients from eight unrelated families. One patient carried a larger deletion including adjacent genes. The cases presented with developmental delay, hypotonia (six cases), and epilepsy (six cases). De novo status was …
Tumor Organoids To Study Gastroesophageal Cancer: A Primer, Ramon U Jin, Jason C Mills
Tumor Organoids To Study Gastroesophageal Cancer: A Primer, Ramon U Jin, Jason C Mills
2020-Current year OA Pubs
Gastroesophageal cancers are leading causes of cancer death. Our attempts at adopting molecularly based treatment approaches have been slow and ineffective even though we begin to identify specific targetable gene mutations and pathways. It is clear that we should no longer treat all gastroesophageal cancers as a homogeneous disease, which is what we do when we use non-specific chemotherapy. However, we currently cannot monitor successful gene/pathway targeting, nor understand how/when tumors develop resistance, nor predict which patients will derive maximal benefit. To improve outcomes, we must precisely detail the heterogeneity of these tumors to then individualize cancer therapy as well …
Parkes Weber Syndrome Associated With Two Somatic Pathogenic Variants In Rasa1, Josue A. Flores Daboub, Johanes F. Grimmer, Alice Frigerio, Whitney Wooderchak-Donahue, Ryan Arnold, Jeff Szymanski, Nicola Longo, Pinar Bayrak-Toydemir
Parkes Weber Syndrome Associated With Two Somatic Pathogenic Variants In Rasa1, Josue A. Flores Daboub, Johanes F. Grimmer, Alice Frigerio, Whitney Wooderchak-Donahue, Ryan Arnold, Jeff Szymanski, Nicola Longo, Pinar Bayrak-Toydemir
Open Access Publications
Parkes Weber syndrome is associated with autosomal dominant inheritance, caused by germline heterozygous inactivating changes in the
Deconvolving The Contributions Of Cell-Type Heterogeneity On Cortical Gene Expression, Ellis Patrick, Mariko Taga, Ayla Ergun, Bernard Ng, William Casazza, Maria Cimpean, Christina Yung, Julie A. Schneider, David A. Bennett, Chris Gaiteri, Philip L. De Jager, Elizabeth M. Bradshaw, Sara Mostafavi
Deconvolving The Contributions Of Cell-Type Heterogeneity On Cortical Gene Expression, Ellis Patrick, Mariko Taga, Ayla Ergun, Bernard Ng, William Casazza, Maria Cimpean, Christina Yung, Julie A. Schneider, David A. Bennett, Chris Gaiteri, Philip L. De Jager, Elizabeth M. Bradshaw, Sara Mostafavi
Open Access Publications
Complexity of cell-type composition has created much skepticism surrounding the interpretation of bulk tissue transcriptomic studies. Recent studies have shown that deconvolution algorithms can be applied to computationally estimate cell-type proportions from gene expression data of bulk blood samples, but their performance when applied to brain tissue is unclear. Here, we have generated an immunohistochemistry (IHC) dataset for five major cell-types from brain tissue of 70 individuals, who also have bulk cortical gene expression data. With the IHC data as the benchmark, this resource enables quantitative assessment of deconvolution algorithms for brain tissue. We apply existing deconvolution algorithms to brain …
Glycan Cross-Feeding Supports Mutualism Between Fusobacterium And The Vaginal Microbiota, Kavita Agarwal, Lloyd S. Robinson, Somya Aggarwal, Lynne R. Foster, Ariel Hernandez-Leyva, Hueylie Lin, Brett A. Tortelli, Valerie P. O'Brien, Liza Miller, Andrew L. Kau, Hilary Reno, Nicole M. Gilbert, Warren G. Lewis, Amanda L. Lewis
Glycan Cross-Feeding Supports Mutualism Between Fusobacterium And The Vaginal Microbiota, Kavita Agarwal, Lloyd S. Robinson, Somya Aggarwal, Lynne R. Foster, Ariel Hernandez-Leyva, Hueylie Lin, Brett A. Tortelli, Valerie P. O'Brien, Liza Miller, Andrew L. Kau, Hilary Reno, Nicole M. Gilbert, Warren G. Lewis, Amanda L. Lewis
Open Access Publications
Women with bacterial vaginosis (BV), an imbalance of the vaginal microbiome, are more likely to be colonized by potential pathogens such as Fusobacterium nucleatum, a bacterium linked with intrauterine infection and preterm birth. However, the conditions and mechanisms supporting pathogen colonization during vaginal dysbiosis remain obscure. We demonstrate that sialidase activity, a diagnostic feature of BV, promoted F. nucleatum foraging and growth on mammalian sialoglycans, a nutrient resource that was otherwise inaccessible because of the lack of endogenous F. nucleatum sialidase. In mice with sialidase-producing vaginal microbiotas, mutant F. nucleatum unable to consume sialic acids was impaired in vaginal colonization. …
Radiation Causes Tissue Damage By Dysregulating Inflammasome-Gasdermin D Signaling In Both Host And Transplanted Cells, Jianqiu Xiao, Chun Wang, Juo-Chin Yao, Yael Alippe, Tong Yang, Dustin Kress, Kai Sun, Kourtney L. Kostecki, Joseph B. Monahan, Deborah J. Veis, Yousef Abu-Amer, Daniel C. Link, Gabriel Mbalaviele
Radiation Causes Tissue Damage By Dysregulating Inflammasome-Gasdermin D Signaling In Both Host And Transplanted Cells, Jianqiu Xiao, Chun Wang, Juo-Chin Yao, Yael Alippe, Tong Yang, Dustin Kress, Kai Sun, Kourtney L. Kostecki, Joseph B. Monahan, Deborah J. Veis, Yousef Abu-Amer, Daniel C. Link, Gabriel Mbalaviele
Open Access Publications
Radiotherapy is a commonly used conditioning regimen for bone marrow transplantation (BMT). Cytotoxicity limits the use of this life-saving therapy, but the underlying mechanisms remain poorly defined. Here, we use the syngeneic mouse BMT model to test the hypothesis that lethal radiation damages tissues, thereby unleashing signals that indiscriminately activate the inflammasome pathways in host and transplanted cells. We find that a clinically relevant high dose of radiation causes severe damage to bones and the spleen through mechanisms involving the NLRP3 and AIM2 inflammasomes but not the NLRC4 inflammasome. Downstream, we demonstrate that gasdermin D (GSDMD), the common effector of …
Postmenopausal Hormone Therapy And Colorectal Cancer Risk By Molecularly Defined Subtypes And Tumor Location, Julia D. Labadie, Yin Cao, Et Al
Postmenopausal Hormone Therapy And Colorectal Cancer Risk By Molecularly Defined Subtypes And Tumor Location, Julia D. Labadie, Yin Cao, Et Al
Open Access Publications
Background: Postmenopausal hormone therapy (HT) is associated with a decreased colorectal cancer (CRC) risk. As CRC is a heterogeneous disease, we evaluated whether the association of HT and CRC differs across etiologically relevant, molecularly defined tumor subtypes and tumor location.
Methods: We pooled data on tumor subtypes (microsatellite instability status, CpG island methylator phenotype status,
Results: Among postmenopausal women, ever HT use was associated with a 38% reduction in overall CRC risk (OR =0.62, 95% CI = 0.56 to 0.69). This association was similar according to microsatellite instability, CpG island methylator phenotype and
Conclusions: We observed a strong inverse association …
The Personality Profile Of Chronic Alcohol Dependent Patients With Comorbid Gambling Disorder Symptoms, Ildikó Kovács, Ildikó Katalin Pribék, Ildikó Demeter, Sándor Rózsa, Zoltán Janka, Zsolt Demetrovics, Bálint Andó
The Personality Profile Of Chronic Alcohol Dependent Patients With Comorbid Gambling Disorder Symptoms, Ildikó Kovács, Ildikó Katalin Pribék, Ildikó Demeter, Sándor Rózsa, Zoltán Janka, Zsolt Demetrovics, Bálint Andó
Open Access Publications
BACKGROUND AND AIMS: The importance of personality characteristics in the diagnosis and treatment of gambling disorder (GD) and alcohol use disorder (AUD) is often highlighted in scientific literature. This study aimed to test predictions about the associations of temperament and character in chronic AUD patients with comorbid GD symptoms and without them.
METHODS: Chronic AUD patients enrolled from an inpatient clinic were divided in two groups based on cluster analysis, AUD patients with (AUD + GD group: n = 30) and without (AUD group: n = 68) GD symptoms. Severity of GD symptoms and personality dimensions (Cloninger's Temperament and Character …
Whole Exome Sequencing In Patients With Williams-Beuren Syndrome Followed By Disease Modeling In Mice Points To Four Novel Pathways That May Modify Stenosis Risk, Phoebe C R Parrish, Delong Liu, Russell H Knutsen, Charles J Billington, Robert P Mecham, Yi-Ping Fu, Beth A Kozel
Whole Exome Sequencing In Patients With Williams-Beuren Syndrome Followed By Disease Modeling In Mice Points To Four Novel Pathways That May Modify Stenosis Risk, Phoebe C R Parrish, Delong Liu, Russell H Knutsen, Charles J Billington, Robert P Mecham, Yi-Ping Fu, Beth A Kozel
2020-Current year OA Pubs
Supravalvular aortic stenosis (SVAS) is a narrowing of the aorta caused by elastin (ELN) haploinsufficiency. SVAS severity varies among patients with Williams-Beuren syndrome (WBS), a rare disorder that removes one copy of ELN and 25-27 other genes. Twenty percent of children with WBS require one or more invasive and often risky procedures to correct the defect while 30% have no appreciable stenosis, despite sharing the same basic genetic lesion. There is no known medical therapy. Consequently, identifying genes that modify SVAS offers the potential for novel modifier-based therapeutics. To improve statistical power in our rare-disease cohort (N = 104 exomes), …
Virus Infection Is Controlled By Hematopoietic And Stromal Cell Sensing Of Murine Cytomegalovirus Through Sting, Sytse J. Piersma, Jennifer Poursine-Laurent, Liping Yang, Glen N. Barber, Bijal A. Parikh, Wayne M. Yokoyama
Virus Infection Is Controlled By Hematopoietic And Stromal Cell Sensing Of Murine Cytomegalovirus Through Sting, Sytse J. Piersma, Jennifer Poursine-Laurent, Liping Yang, Glen N. Barber, Bijal A. Parikh, Wayne M. Yokoyama
Open Access Publications
Recognition of DNA viruses, such as cytomegaloviruses (CMVs), through pattern-recognition receptor (PRR) pathways involving MyD88 or STING constitute a first-line defense against infections mainly through production of type I interferon (IFN-I). However, the role of these pathways in different tissues is incompletely understood, an issue particularly relevant to the CMVs which have broad tissue tropisms. Herein, we contrasted anti-viral effects of MyD88 versus STING in distinct cell types that are infected with murine CMV (MCMV). Bone marrow chimeras revealed STING-mediated MCMV control in hematological cells, similar to MyD88. However, unlike MyD88, STING also contributed to viral control in non-hematological, stromal …
Transcriptional Profiling Reveals Altered Biological Characteristics Of Chorionic Stem Cells From Women With Gestational Diabetes, Liyun Chen, Chung-Teng Wang, Nicholas R Forsyth, Pensee Wu
Transcriptional Profiling Reveals Altered Biological Characteristics Of Chorionic Stem Cells From Women With Gestational Diabetes, Liyun Chen, Chung-Teng Wang, Nicholas R Forsyth, Pensee Wu
Open Access Publications
BACKGROUND: Gestational diabetes (GDM) is a common complication of pregnancy. The impact of pregnancy complications on placental function suggests that extraembryonic stem cells in the placenta may also be affected during pregnancy. Neonatal tissue-derived stem cells, with the advantages of their differentiation capacity and non-invasive isolation processes, have been proposed as a promising therapeutic avenue for GDM management through potential cell therapy approaches. However, the influence of GDM on autologous stem cells remains unclear. Thus, studies that provide comprehensive understanding of stem cells isolated from women with GDM are essential to guide future clinical applications.
METHODS: Human chorionic membrane-derived stem …