Digital Commons Network^™

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 …

Youth Participatory Research Evidence To Inform Health Policy: A Systematic Review Protocol, Janet Njelesani, Jean Hunleth

Open Access Publications

INTRODUCTION: Young people's participation in health research produces knowledge that is indispensable for creating appropriate and effective policies. However, how best to disseminate youth participatory research evidence to impact health policy is not known. Therefore, the objectives of this systematic review are to describe the evidence produced through youth participatory research, including the strategies used to disseminate youth participatory research evidence to health policymakers. These are necessary to improve policymakers' use of youth participatory research evidence and, thereby, make programmes more impactful for young people.

METHODS AND ANALYSIS: The meta-narrative methodology will guide the systematic review to highlight the contrasting …

Thalidomide For Refractory Gastrointestinal Bleeding From Vascular Malformations In Patients With Significant Comorbidities, Alexis Mae Bayudan, Chien-Huan Chen

Open Access Publications

BACKGROUND: Refractory gastrointestinal bleeding (GIB) secondary to gastrointestinal vascular malformations (GIVM) such as gastrointestinal angiodysplasia (GIAD) and gastric antral vascular ectasia (GAVE) remains challenging to treat when endoscopic therapy fails. Recently thalidomide has been suggested as a treatment option for refractory GIB.

AIM: To determine the outcome of patients treated with thalidomide for refractory GIB due to GIVM.

METHODS: IRB approved, single center, retrospective review of electronic medical records from January 2012 to November 2018. Patients age > 18 years old, who had > 3 episodes of GIB refractory to medical or endoscopic therapy, and who had been treated with thalidomide for …

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 …

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 …

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 …

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

Protocol For Economic Evaluation Alongside The Shine (Supporting Healthy Image, Nutrition And Exercise) Cluster Randomised Controlled Trial, Victoria Brown, Joanne Williams, Lisa Mcgivern, Susan Sawyer, Liliana Orellana, Wei Luo, Kylie D Hesketh, Denise E Wilfley, Marj Moodie

Open Access Publications

INTRODUCTION: Limited evidence exists on the cost-effectiveness of interventions to prevent obesity and promote healthy body image in adolescents. The SHINE (Supporting Healthy Image, Nutrition and Exercise) study is a cluster randomised control trial (cRCT) aiming to deliver universal education about healthy nutrition and physical activity to adolescents, as well as targeted advice to young people with body image concerns who are at risk of developing disordered eating behaviours. This paper describes the methods for the economic evaluation of the SHINE cRCT, to determine whether the intervention is cost-effective as an obesity prevention measure.

METHODS AND ANALYSIS: A public payer …

Effectiveness Of A Digital Cognitive Behavior Therapy-Guided Self-Help Intervention For Eating Disorders In College Women: A Cluster Randomized Clinical Trial, Ellen E. Fitzsimmons-Craft, C. Barr Taylor, Andrea K. Graham, Shiri Sadeh-Sharvit, Katherine N. Balantekin, Dawn M. Eichen, Grace E. Monterubio, Neha J. Goel, Rachael E. Flatt, Anna M. Karam, Marie-Laure Firebaugh, Corinna Jacobi, Booil Jo, Mickey T. Trockel, Denise E. Wilfley

Open Access Publications

Importance: Eating disorders (EDs) are common, serious psychiatric disorders on college campuses, yet most affected individuals do not receive treatment. Digital interventions have the potential to bridge this gap.

Objective: To determine whether a coached, digital, cognitive behavior therapy (CBT) intervention improves outcomes for college women with EDs compared with referral to usual care.

Design, Setting, and Participants: This cluster randomized trial was conducted from 2014 to 2018 at 27 US universities. Women with binge-purge EDs (with both threshold and subthreshold presentations) were recruited from enrolled universities. The 690 participants were followed up for up to 2 years after the …

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 …

Fragment Screening Targeting Ebola Virus Nucleoprotein C-Terminal Domain Identifies Lead Candidates, David J Aceti, Hamza Ahmed, William M Westler, Chao Wu, Hesam Dashti, Marco Tonelli, Hamid Eghbalnia, Gaya K Amarasinghe, John L Markley

Open Access Publications

The Ebola Virus is a causative agent of viral hemorrhagic fever outbreaks and a potential global health risk. The outbreak in West Africa (2013-2016) led to 11,000+ deaths and 30,000+ Ebola infected individuals. The current outbreak in the Democratic Republic of Congo (DRC) with 3000+ confirmed cases and 2000+ deaths attributed to Ebola virus infections provides a reminder that innovative countermeasures are still needed. Ebola virus encodes 7 open reading frames (ORFs). Of these, the nucleocapsid protein (eNP) encoded by the first ORF plays many significant roles, including a role in viral RNA synthesis. Here we describe efforts to target …

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 …

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 …

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 …

Which Metrics Are Being Used To Evaluate Children And Adolescents After Acl Reconstruction? A Systematic Review, Peter D Fabricant, Christopher M Brusalis, Jonathan M Schachne, Pluto Study Group, Matthew J Matava

Open Access Publications

PURPOSE: To identify a comprehensive list of outcome measures previously used in the literature to evaluate clinical outcomes after reconstruction of the anterior cruciate ligament (ACL) in patients 18 years of age or younger.

METHODS: A literature search was performed by querying MEDLINE, Embase and Cochrane computerized databases for relevant articles that reported clinical outcomes in pediatric patients undergoing ACL reconstruction. Studies that were nonclinical, that reported on patients older than 19 years, that were not available in English, or that included fewer than 10 patients were excluded. Outcome measures of all eligible studies were recorded.

RESULTS: We identified 77 …

Dopamine D2 Receptor Signaling On Imsns Is Required For Initiation And Vigor Of Learned Actions, Shana M Augustin, Gabriel C Loewinger, Timothy J O'Neal, Alexxai V Kravitz, David M Lovinger

Open Access Publications

Striatal dopamine D2 receptors (D2Rs) are important for motor output. Selective deletion of D2Rs from indirect pathway-projecting medium spiny neurons (iMSNs) impairs locomotor activities in a task-specific manner. However, the role of D2Rs in the initiation of motor actions in reward seeking and taking is not fully understood, and there is little information about how receptors contribute under different task demands and with different outcome types. The iMSN-D2Rs modulate neuronal activity and synaptic transmission, exerting control on circuit functions that may play distinct roles in action learning and performance. Selective deletion of D2Rs on iMSNs resulted in slower action initiation …

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 …

Thoracolaparoscopic Management Of A Traumatic Subacute Transdiaphragmatic Intercostal Hernia. Second Case Reported, Eduardo Smith-Singares

Open Access Publications

BACKGROUND: Transdiaphragmatic intercostal hernias are extremely rare. Their physiopathology is different from traumatic diaphragmatic ruptures, and their clinical presentation and management strategies place them in a different category than abdominal intercostal hernias.

CASE PRESENTATION: A 56 yo female presented to the outpatient trauma clinic with a symptomatic, subacute left sided transdiaphragmatic intercostal hernia secondary to a motor vehicle crash almost 3 months prior to presentation. The injury was managed with a combined thoracoscopic and laparoscopic approach, only the second time ever this has been reported. She was discharged on POD#3, and after 6 months of follow up continues to do …

Identification Of Challenges And A Framework For Implementation Of The Amp/Asco/Cap Classification Guidelines For Reporting Somatic Variants, Bijal A Parikh, Latisha Love-Gregory, Eric J Duncavage, Jonathan W Heusel

Open Access Publications

OBJECTIVES: In 2017, AMP, ASCO and CAP jointly published the first formalized classification system for the interpretation and reporting of sequence variants in cancer. The challenges of incorporating new variant interpretation guidelines into existing, validated workflows have likely hampered adoption and implementation in labs with classification methods in place. Ambiguity in assigning clinical significance across guidelines is grounded in differential weighting of evidence used in variant assessment. Therefore, we undertook an internal process-improvement exercise to correlate the two classification schemes using historical laboratory data.

DESIGN AND METHODS: Existing clinical variant assignments from 40 consecutive oncology cases comprising 150 somatic variants …

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 …

Mutation Of Cfap57, A Protein Required For The Asymmetric Targeting Of A Subset Of Inner Dynein Arms In Chlamydomonas, Causes Primary Ciliary Dyskinesia, Ximena M. Bustamante-Marin, Amjad Horani, Mihaela Stoyanova, Wu-Lin Charng, Mathieu Bottier, Patrick R. Sears, Wei-Ning Yin, Leigh Anne Daniels, Hailey Bowen, Donald F. Conrad, Michael R. Knowles, Lawrence E. Ostrowski, Maimoona A. Zariwala, Susan K. Dutcher

Open Access Publications

Primary ciliary dyskinesia (PCD) is characterized by chronic airway disease, reduced fertility, and randomization of the left/right body axis. It is caused by defects of motile cilia and sperm flagella. We screened a cohort of affected individuals that lack an obvious axonemal defect for pathogenic variants using whole exome capture, next generation sequencing, and bioinformatic analysis assuming an autosomal recessive trait. We identified one subject with an apparently homozygous nonsense variant [(c.1762C>T), p.(Arg588*)] in the uncharacterized CFAP57 gene. Interestingly, the variant results in the skipping of exon 11 (58 amino acids), which may be due to disruption of an …

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 …

Mapping Geographical Inequalities In Oral Rehydration Therapy Coverage In Low-Income And Middle-Income Countries, 2000-17, Local Burden Of Disease Diarrhoea Collaborators, Ziyad Al-Aly, Et Al

Open Access Publications

BACKGROUND: Oral rehydration solution (ORS) is a form of oral rehydration therapy (ORT) for diarrhoea that has the potential to drastically reduce child mortality; yet, according to UNICEF estimates, less than half of children younger than 5 years with diarrhoea in low-income and middle-income countries (LMICs) received ORS in 2016. A variety of recommended home fluids (RHF) exist as alternative forms of ORT; however, it is unclear whether RHF prevent child mortality. Previous studies have shown considerable variation between countries in ORS and RHF use, but subnational variation is unknown. This study aims to produce high-resolution geospatial estimates of relative …

A Cross-Reactive Antibody Protects Against Ross River Virus Musculoskeletal Disease Despite Rapid Neutralization Escape In Mice, Julie M. Fox, Ling Huang, Stephen Tahan, Laura A. Powell, James E. Crowe, David Wang, Michael S. Diamond

Open Access Publications

Arthritogenic alphaviruses cause debilitating musculoskeletal disease and historically have circulated in distinct regions. With the global spread of chikungunya virus (CHIKV), there now is more geographic overlap, which could result in heterologous immunity affecting natural infection or vaccination. Here, we evaluated the capacity of a cross-reactive anti-CHIKV monoclonal antibody (CHK-265) to protect against disease caused by the distantly related alphavirus, Ross River virus (RRV). Although CHK-265 only moderately neutralizes RRV infection in cell culture, it limited clinical disease in mice independently of Fc effector function activity. Despite this protective phenotype, RRV escaped from CHK-265 neutralization in vivo, with resistant variants …

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. …

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 …

The "Secret Sauce" For A Mentored Training Program: Qualitative Perspectives Of Trainees In Implementation Research For Cancer Control, Rebekah R Jacob, Angeline Gacad, Christine Pfund, Margaret Padek, David A Chambers, Jon F Kerner, Anne Sales, Maureen Dobbins, Shiriki Kumanyika, Ross C Brownson

Open Access Publications

BACKGROUND: Mentored training approaches help build capacity for research through mentoring networks and skill building activities. Capacity for dissemination and implementation (D&I) research in cancer is needed and mentored training programs have been developed. Evaluation of mentored training programs through quantitative approaches often provides us with information on "what" improved for participants. Qualitative approaches provide a deeper understanding of "how" programs work best.

METHODS: Qualitative interviews were conducted with 21 fellows of the National Cancer Institute-funded Mentored Training for Dissemination and Implementation in Cancer to gain understanding of their experiences with mentoring received during the program. Fellows were selected from …

Control Of Viral Infection By Natural Killer Cell Inhibitory Receptors, Bijal A Parikh, Michael D Bern, Sytse J Piersma, Liping Yang, Diana L Beckman, Jennifer Poursine-Laurent, Béatrice Plougastel-Douglas, Wayne M Yokoyama

Open Access Publications

Major histocompatibility complex class I (MHC-I)-restricted immune responses are largely attributed to cytotoxic T lymphocytes (CTLs). However, natural killer (NK) cells, as predicted by the missing-self hypothesis, have opposing requirements for MHC-I, suggesting that they may also demonstrate MHC-I-restricted effects. In mice, the Ly49 inhibitory receptors prevent NK cell killing of missing-self targets in effector responses, and they have a proposed second function in licensing or educating NK cells via self-MHC-I in vivo. Here we show MHC-I-restricted control of murine cytomegalovirus (MCMV) infection in vivo that is NK cell dependent. Using mice lacking specific Ly49 receptors, we show that control …