Digital Commons Network^™

Chamber-Specific Transcriptional Responses In Atrial Fibrillation, Catherine E Lipovsky, Jesus Jimenez, Qiusha Guo, Gang Li, Tiankai Yin, Stephanie C Hicks, Somya Bhatnagar, Kentaro Takahashi, David M Zhang, Brittany D Brumback, Uri Goldsztejn, Rangarajan D Nadadur, Carlos Perez-Cervantez, Ivan P Moskowitz, Shaopeng Liu, Bo Zhang, Stacey L Rentschler

Open Access Publications

Atrial fibrillation (AF) is the most common cardiac arrhythmia, yet the molecular signature of the vulnerable atrial substrate is not well understood. Here, we delineated a distinct transcriptional signature in right versus left atrial cardiomyocytes (CMs) at baseline and identified chamber-specific gene expression changes in patients with a history of AF in the setting of end-stage heart failure (AF+HF) that are not present in heart failure alone (HF). We observed that human left atrial (LA) CMs exhibited Notch pathway activation and increased ploidy in AF+HF but not in HF alone. Transient activation of Notch signaling within adult CMs in a …

Etv6 Germline Mutations Cause Hdac3/Ncor2 Mislocalization And Upregulation Of Interferon Response Genes, Marlie H Fisher, Gregory D Kirkpatrick, Brett Stevens, Courtney Jones, Michael Callaghan, Madhvi Rajpurkar, Joy Fulbright, Megan A Cooper, Jesse Rowley, Christopher C Porter, Arthur Gutierrez-Hartmann, Kenneth Jones, Craig Jordan, Eric M Pietras, Jorge Di Paola

Open Access Publications

ETV6 is an ETS family transcription factor that plays a key role in hematopoiesis and megakaryocyte development. Our group and others have identified germline mutations in ETV6 resulting in autosomal dominant thrombocytopenia and predisposition to malignancy; however, molecular mechanisms defining the role of ETV6 in megakaryocyte development have not been well established. Using a combination of molecular, biochemical, and sequencing approaches in patient-derived PBMCs, we demonstrate abnormal cytoplasmic localization of ETV6 and the HDAC3/NCOR2 repressor complex that led to overexpression of HDAC3-regulated interferon response genes. This transcriptional dysregulation was also reflected in patient-derived platelet transcripts and drove aberrant proplatelet formation …

Anti-Human Trem2 Induces Microglia Proliferation And Reduces Pathology In An Alzheimer's Disease Model, Shoutang Wang, Carla M. Yuede, Susan Gilfillan, Marco Colonna, Et Al

Open Access Publications

TREM2 is a receptor for lipids expressed in microglia. The R47H variant of human TREM2 impairs ligand binding and increases Alzheimer's disease (AD) risk. In mouse models of amyloid β (Aβ) accumulation, defective TREM2 function affects microglial response to Aβ plaques, exacerbating tissue damage, whereas TREM2 overexpression attenuates pathology. Thus, AD may benefit from TREM2 activation. Here, we examined the impact of an anti-human TREM2 agonistic mAb, AL002c, in a mouse AD model expressing either the common variant (CV) or the R47H variant of TREM2. Single-cell RNA-seq of microglia after acute systemic administration of AL002c showed induction of proliferation in …

Higher Csf Strem2 And Microglia Activation Are Associated With Slower Rates Of Beta-Amyloid Accumulation, Michael Ewers, Laura Piccio, Carlos Cruchaga, Et Al

Open Access Publications

Microglia activation is the brain's major immune response to amyloid plaques in Alzheimer's disease (AD). Both cerebrospinal fluid (CSF) levels of soluble TREM2 (sTREM2), a biomarker of microglia activation, and microglia PET are increased in AD; however, whether an increase in these biomarkers is associated with reduced amyloid-beta (Aβ) accumulation remains unclear. To address this question, we pursued a two-pronged translational approach. Firstly, in non-demented and demented individuals, we tested CSF sTREM2 at baseline to predict (i) amyloid PET changes over ∼2 years and (ii) tau PET cross-sectionally assessed in a subset of patients. We found higher CSF sTREM2 associated …

Amygdalin Promotes Fracture Healing Through Tgf- Β/Smad Signaling In Mesenchymal Stem Cells, Jun Ying, Jie Shen, Et Al

Open Access Publications

No abstract provided.

Bypass Of Dna Interstrand Crosslinks By A Rev1-Dna Polymerase Ζ Complex, Rachel Bezalel-Buch, Young K. Cheun, Upasana Roy, Orlando D. Schärer, Peter M. Burgers

Open Access Publications

DNA polymerase ζ (Pol ζ) and Rev1 are essential for the repair of DNA interstrand crosslink (ICL) damage. We have used yeast DNA polymerases η, ζ and Rev1 to study translesion synthesis (TLS) past a nitrogen mustard-based interstrand crosslink (ICL) with an 8-atom linker between the crosslinked bases. The Rev1-Pol ζ complex was most efficient in complete bypass synthesis, by 2-3 fold, compared to Pol ζ alone or Pol η. Rev1 protein, but not its catalytic activity, was required for efficient TLS. A dCMP residue was faithfully inserted across the ICL-G by Pol η, Pol ζ, and Rev1-Pol ζ. Rev1-Pol …

Severe Immunosuppression And Not A Cytokine Storm Characterizes Covid-19 Infections, Kenneth E Remy, Monty Mazer, David A Striker, Ali H Ellebedy, Andrew H Walton, Jacqueline Unsinger, Teresa M Blood, Philip A Mudd, Daehan J Yi, Daniel A Mannion, Dale F Osborne, R Scott Martin, Nitin J Anand, James P Bosanquet, Jane Blood, Anne M Drewry, Charles C Caldwell, Isaiah R Turnbull, Scott C Brakenridge, Lyle L Moldwawer, Richard S Hotchkiss

Open Access Publications

COVID-19-associated morbidity and mortality have been attributed to a pathologic host response. Two divergent hypotheses have been proposed: hyperinflammatory cytokine storm; and failure of host protective immunity that results in unrestrained viral dissemination and organ injury. A key explanation for the inability to address this controversy has been the lack of diagnostic tools to evaluate immune function in COVID-19 infections. ELISpot, a highly sensitive, functional immunoassay, was employed in 27 patients with COVID-19, 51 patients with sepsis, 18 critically ill nonseptic (CINS) patients, and 27 healthy control volunteers to evaluate adaptive and innate immune status by quantitating T cell IFN-ɣ …

A Simplified Quantitative Real-Time Pcr Assay For Monitoring Sars-Cov-2 Growth In Cell Culture, Christian Shema Mugisha, Hung R Vuong, Maritza Puray-Chavez, Adam L Bailey, Julie M Fox, Rita E Chen, Alex W Wessel, Jason M Scott, Houda H Harastani, Adrianus C M Boon, Haina Shin, Sebla B Kutluay

Open Access Publications

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions within just a few months, causing severe respiratory disease and mortality. Assays to monitor SARS-CoV-2 growth

Malignant Cell-Specific Cxcl14 Promotes Tumor Lymphocyte Infiltration In Oral Cavity Squamous Cell Carcinoma, Anuraag Parikh, Juneho Shin, William Faquin, Derrick T Lin, Itay Tirosh, John B Sunwoo, Sidharth V Puram

Open Access Publications

OBJECTIVES: To explore lymphocyte infiltration as a potential mechanism behind CXCL14-mediated tumor growth suppression in oral cavity squamous cell carcinoma (OSCC).

METHODS: We analyzed single cell RNA-sequencing (scRNA-seq) data from OSCC to identify expression changes among malignant cells in lymph nodes (LN) versus primary tumors. CXCL14 expression in murine OSCC cell lines was quantified using qRT-PCR. Short hairpin RNA knockdown of CXCL14 was performed in mouse oral cavity (MOC)1 cells, and CXCL14 overexpression was performed in MOC2 cells. Cells in each condition were injected into C57BL/6 mice with and without T cell depletion, and tumor volume was measured. At 30 …

Co-Clinical Imaging Resource Program (Cirp): Bridging The Translational Divide To Advance Precision Medicine, Kooresh I. Shoghi, Richard Laforest, Daniel S. Marcus, Et Al

Open Access Publications

The National Institutes of Health's (National Cancer Institute) precision medicine initiative emphasizes the biological and molecular bases for cancer prevention and treatment. Importantly, it addresses the need for consistency in preclinical and clinical research. To overcome the translational gap in cancer treatment and prevention, the cancer research community has been transitioning toward using animal models that more fatefully recapitulate human tumor biology. There is a growing need to develop best practices in translational research, including imaging research, to better inform therapeutic choices and decision-making. Therefore, the National Cancer Institute has recently launched the Co-Clinical Imaging Research Resource Program (CIRP). Its …

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

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

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

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

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 …

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 …

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

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

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 …

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

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

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

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 …

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

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

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

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

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

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 …

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 …