Digital Commons Network^™

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

Open Access Publications

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

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

Open Access Publications

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

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

Open Access Publications

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

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

Open Access Publications

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

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

Open Access Publications

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

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

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

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

Open Access Publications

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

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

Open Access Publications

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

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

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

Open Access Publications

SARM1 is an inducible NAD

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

Open Access Publications

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

Practical Considerations For Quantitative Clinical Spect/Ct Imaging Of Alpha Particle Emitting Radioisotopes, Nadia Benabdallah, William Scheve, Nicholas Dunn, Delynn Silvestros, Paul Schelker, Diane Abou, Uday Jammalamadaka, Richard Laforest, Zekun Li, Jonathan Liu, David Ballard, Nichole Maughan, Hiram Gay, Brian Baumann, Robert Hobbs, Buck Rogers, Amir Iravani, Abhinav Jha, Farrokh Dehdashti, Daniel Thorek

Open Access Publications

No abstract provided.

Assessment Of Antibiotic De-Escalation By Spectrum Score In Patients With Nosocomial Pneumonia: A Single-Center, Retrospective Cohort Study, Dan Ilges, David J. Ritchie, Tamara Krekel, Elizabeth A. Neuner, Nicholas Hampton, Marin H. Kollef, Scott Micek

Open Access Publications

Background: Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) cause significant mortality. Guidelines recommend empiric broad-spectrum antibiotics followed by de-escalation (DE). This study sought to assess the impact of DE on treatment failure.

Methods: This single-center retrospective cohort study screened all adult patients with a discharge diagnosis code for pneumonia from 2016 to 2019. Patients were enrolled if they met predefined criteria for HAP/VAP ≥48 hours after admission. Date of pneumonia diagnosis was defined as day 0. Spectrum scores were calculated, and DE was defined as a score reduction on day 3 versus day 1. Patients with DE were compared to patients with …

Pet Study Of Sphingosine-1-Phosphate Receptor 1 Expression In Response To S. Aureus Infection, Hao Jiang, Jiwei Gu, Haiyang Zhao, Sumit Joshi, Joel Perlmutter, Robert Gropler, Robyn Klein, Tammie Benzinger, Zhude Tu

Open Access Publications

Sphingosine-1-phosphate receptor 1 (S1PR1) plays a crucial role in infectious diseases. Targeting S1PR1 provides protection against pathogens, such as influenza viruses. This study is aimed at investigating S1PR1 in response to bacterial infection by assessing S1PR1 expression in

Infectious Disease Providers’ Knowledge Of And Engagement In Quality Improvement, Kathleen R. Sheridan, Michael A. Lane, Thomas J. Kim, Joshua C. Eby

Open Access Publications

No abstract provided.

Comparison Of Response To Definitive Radiotherapy For Localized Prostate Cancer In Black And White Men: A Meta-Analysis, Ting Martin Ma, Jeff M. Michalski, Et Al

Open Access Publications

Importance: Black men have a 2-fold increased risk of dying from prostate cancer compared with White men. However, race-specific differences in response to initial treatment remain unknown.

Objective: To compare overall and treatment-specific outcomes of Black and White men with localized prostate cancer receiving definitive radiotherapy (RT).

Data Sources: A systematic search was performed of relevant published randomized clinical trials conducted by the NRG Oncology/Radiation Therapy Oncology Group between January 1, 1990, and December 31, 2010. This meta-analysis was performed from July 1, 2019, to July 1, 2021.

Study Selection: Randomized clinical trials of definitive RT for patients with localized …

A Proinflammatory Stimulus Disrupts Hippocampal Plasticity And Learning Via Microglial Activation And 25-Hydroxycholesterol, Yukitoshi Izumi, Anil G. Cashikar, Kathiresan Krishnan, Steven M. Paul, Douglas F. Covey, Steven J. Mennerick, Charles F. Zorumski

Open Access Publications

Inflammatory cells, including macrophages and microglia, synthesize and release the oxysterol 25-hydroxycholesterol (25HC), which has antiviral and immunomodulatory properties. Here, we examined the effects of lipopolysaccharide (LPS), an activator of innate immunity, on 25HC production in microglia, and the effects of LPS and 25HC on CA1 hippocampal synaptic plasticity and learning. In primary microglia, LPS markedly increases the expression of cholesterol 25-hydroxylase (Ch25h), the key enzyme involved in 25HC synthesis, and increases the levels of secreted 25HC. Wild-type microglia produced higher levels of 25HC than

A Randomized, Placebo-Controlled Trial Assessing The Effect Of Visbiome Es Probiotic In People With Hiv On Antiretroviral Therapy, Rachel M. Presti, Et Al

Open Access Publications

Background: A5350, a phase II, randomized, double-blind study, evaluated the safety and tolerability of the probiotic Visbiome Extra Strength (ES) over 24 weeks and measured effects on inflammation and intestinal barrier function.

Methods: The primary outcome was change in soluble CD14 (sCD14) levels; secondary outcomes included safety and tolerability, markers of inflammation and cellular activation, and microbiome. In a substudy, gut permeability was assessed by paired colonic biopsies measuring the area of lamina propria occupied by CD4+ cells, interleukin (IL)-17+ cells, and myeloperoxidase (MPO). Changes between arms were compared with the 2-sample

Results: Overall, 93 participants enrolled: 86% male, median …

Inhibitor Of Growth Protein 3 Epigenetically Silences Endogenous Retroviral Elements And Prevents Innate Immune Activation, Yanhua Song, Gaopeng Hou, Jonathan Diep, Yaw Shin Ooi, Natalia S. Akopyants, Stephen M. Beverley, Jan E. Carette, Harry B. Greenberg, Siyuan Ding

Open Access Publications

Endogenous retroviruses (ERVs) are subject to transcriptional repression in adult tissues, in part to prevent autoimmune responses. However, little is known about the epigenetic silencing of ERV expression. Here, we describe a new role for inhibitor of growth family member 3 (ING3), to add to an emerging group of ERV transcriptional regulators. Our results show that ING3 binds to several ERV promoters (for instance MER21C) and establishes an EZH2-mediated H3K27 trimethylation modification. Loss of ING3 leads to decreases of H3K27 trimethylation enrichment at ERVs, induction of MDA5-MAVS-interferon signaling, and functional inhibition of several virus infections. These data demonstrate an important …

The Genetic Architecture Of A Congenital Heart Defect Is Related To Its Fitness Cost, Ehiole Akhirome, Suk D Regmi, Rachel A Magnan, Nelson Ugwu, Yidan Qin, Claire E Schulkey, James M Cheverud, Patrick Y Jay

Open Access Publications

In newborns, severe congenital heart defects are rarer than mild ones. This epidemiological relationship between heart defect severity and incidence lacks explanation. Here, an analysis of ~10,000

Human B Cell Lineages Associated With Germinal Centers Following Influenza Vaccination Are Measurably Evolving, Kenneth B. Hoehn, Jackson S. Turner, Frederick I. Miller, Ruoyi Jiang, Oliver G. Pybus, Ali H. Ellebedy, Steven H. Kleinstein

Open Access Publications

The poor efficacy of seasonal influenza virus vaccines is often attributed to pre-existing immunity interfering with the persistence and maturation of vaccine-induced B cell responses. We previously showed that a subset of vaccine-induced B cell lineages are recruited into germinal centers (GCs) following vaccination, suggesting that affinity maturation of these lineages against vaccine antigens can occur. However, it remains to be determined whether seasonal influenza vaccination stimulates additional evolution of vaccine-specific lineages, and previous work has found no significant increase in somatic hypermutation among influenza-binding lineages sampled from the blood following seasonal vaccination in humans. Here, we investigate this issue …

The Shu Complex Prevents Mutagenesis And Cytotoxicity Of Single-Strand Specific Alkylation Lesions, Braulio Bonilla, Hani S. Zaher, Nima Mosammaparast, Et Al

Open Access Publications

Three-methyl cytosine (3meC) are toxic DNA lesions, blocking base pairing. Bacteria and humans express members of the AlkB enzymes family, which directly remove 3meC. However, other organisms, including budding yeast, lack this class of enzymes. It remains an unanswered evolutionary question as to how yeast repairs 3meC, particularly in single-stranded DNA. The yeast Shu complex, a conserved homologous recombination factor, aids in preventing replication-associated mutagenesis from DNA base damaging agents such as methyl methanesulfonate (MMS). We found that MMS-treated Shu complex-deficient cells exhibit a genome-wide increase in A:T and G:C substitutions mutations. The G:C substitutions displayed transcriptional and replicational asymmetries …

Toxoplasma Bradyzoites Exhibit Physiological Plasticity Of Calcium And Energy Stores Controlling Motility And Egress, Yong Fu, Kevin M. Brown, Nathaniel G. Jones, Silvia N.J. Moreno, L. David Sibley

Open Access Publications

No abstract provided.

Functional Implications Of The Dynamic Regulation Of Epcam During Epithelial-To-Mesenchymal Transition, Taylor C Brown, Narendra V Sankpal, William E Gillanders

Open Access Publications

Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein expressed in epithelial tissues. EpCAM forms intercellular, homophilic adhesions, modulates epithelial junctional protein complex formation, and promotes epithelial tissue homeostasis. EpCAM is a target of molecular therapies and plays a prominent role in tumor biology. In this review, we focus on the dynamic regulation of EpCAM expression during epithelial-to-mesenchymal transition (EMT) and the functional implications of EpCAM expression on the regulation of EMT. EpCAM is frequently and highly expressed in epithelial cancers, while silenced in mesenchymal cancers. During EMT, EpCAM expression is downregulated by extracellular signal-regulated kinases (ERK) and EMT transcription …

Cell Death And Transcriptional Responses Induced In Larvae Of The Nematode Haemonchus Contortus By Toxins/Toxicants With Broad Phylogenetic Efficacy, Douglas P Jasmer, Bruce A Rosa, Makedonka Mitreva

Open Access Publications

Establishing methods to investigate treatments that induce cell death in parasitic nematodes will promote experimental approaches to elucidate mechanisms and to identify prospective anthelmintics capable of inducing this outcome. Here, we extended recent progress on a method to monitor cell death and to identify small molecule inhibitors in

A Comprehensive Review Of Tic Disorders In Children, Keisuke Ueda, Kevin J. Black

Open Access Publications

Tics are characterized by sudden, rapid, recurrent, nonrhythmic movement or vocalization, and are the most common movement disorders in children. Their onset is usually in childhood and tics often will diminish within one year. However, some of the tics can persist and cause various problems such as social embarrassment, physical discomfort, or emotional impairments, which could interfere with daily activities and school performance. Furthermore, tic disorders are frequently associated with comorbid neuropsychiatric symptoms, which can become more problematic than tic symptoms. Unfortunately, misunderstanding and misconceptions of tic disorders still exist among the general population. Understanding tic disorders and their comorbidities …

Vaccines For Protecting Infants From Bacterial Causes Of Diarrheal Disease, Richard Walker, Robert W Kaminski, Chad Porter, Robert K M Choy, Jessica A White, James M Fleckenstein, Fred Cassels, Louis Bourgeois

Open Access Publications

The global diarrheal disease burden for

Toll-Like Receptor Signaling In The Establishment And Function Of The Immune System, Jahnavi Aluri, Megan A Cooper, Laura G Schuettpelz

Open Access Publications

Toll-like receptors (TLRs) are pattern recognition receptors that play a central role in the development and function of the immune system. TLR signaling promotes the earliest emergence of hematopoietic cells during development, and thereafter influences the fate and function of both primitive and effector immune cell types. Aberrant TLR signaling is associated with hematopoietic and immune system dysfunction, and both loss- and gain-of- function variants in TLR signaling-associated genes have been linked to specific infection susceptibilities and immune defects. Herein, we will review the role of TLR signaling in immune system development and the growing number of heritable defects in …

Flexor Tendon Injury And Repair: The Influence Of Synovial Environment On The Early Healing Response In A Canine Mode, Hua Shen, Susumu Yoneda, Shelly E Sakiyama-Elbert, Qiang Zhang, Stavros Thomopoulos, Richard H Gelberman

Open Access Publications

BACKGROUND: Environmental conditions strongly influence the healing capacity of connective tissues. Well-vascularized extrasynovial tendons typically undergo a robust wound-healing process following transection and repair. In contrast, avascular intrasynovial tendons do not mount an effective repair response. The current study tests the hypothesis that flexor tendons, as a function of their synovial environment, exhibit unique inflammatory, angiogenic, and metabolic responses to injury and repair.

METHODS: Flexor tendons present a distinct opportunity to test the study hypothesis, as they have proximal regions that are extrasynovial and distal regions that are intrasynovial. In an internally controlled study design, the second and fifth forepaw …

Eruptive Xanthoma Model Reveals Endothelial Cells Internalize And Metabolize Chylomicrons, Leading To Extravascular Triglyceride Accumulation, Ainara G Cabodevilla, Songtao Tang, Sungwoon Lee, Adam E Mullick, Jose O Aleman, M Mahmood Hussain, William C Sessa, Nada A Abumrad, Ira J Goldberg

Open Access Publications

Although tissue uptake of fatty acids from chylomicrons is primarily via lipoprotein lipase (LpL) hydrolysis of triglycerides (TGs), studies of patients with genetic LpL deficiency suggest additional pathways deliver dietary lipids to tissues. Despite an intact endothelial cell (EC) barrier, hyperchylomicronemic patients accumulate chylomicron-derived lipids within skin macrophages, leading to the clinical finding eruptive xanthomas. We explored whether an LpL-independent pathway exists for transfer of circulating lipids across the EC barrier. We found that LpL-deficient mice had a marked increase in aortic EC lipid droplets before and after a fat gavage. Cultured ECs internalized chylomicrons, which were hydrolyzed within lysosomes. …

Isolation And Characterization Of A Novel Bacteriophage Wo From Allonemobius Socius Crickets In Missouri, Jonah Kupritz, John Martin, Kerstin Fischer, Kurt C. Curtis, Joseph R. Fauver, Yuefang Huang, Young-Jun Choi, Wandy L. Beatty, Makedonka Mitreva, Peter U. Fischer

Open Access Publications

Wolbachia are endosymbionts of numerous arthropod and some nematode species, are important for their development and if present can cause distinct phenotypes of their hosts. Prophage DNA has been frequently detected in Wolbachia, but particles of Wolbachia bacteriophages (phage WO) have been only occasionally isolated. Here, we report the characterization and isolation of a phage WO of the southern ground cricket, Allonemobius socius, and provided the first whole-genome sequence of phage WO from this arthropod family outside of Asia. We screened A. socius abdomen DNA extracts from a cricket population in eastern Missouri by quantitative PCR for Wolbachia surface protein …

Prognostic And Pathophysiologic Significance Of Il-8 (Cxcl8) In Biliary Atresia, Nimish Godbole, Iiris Nyholm, Maria Hukkinen, Joseph R Davidson, Athanasios Tyraskis, Katja Eloranta, Noora Andersson, Jouko Lohi, Päivi Heikkilä, Antti Kyrönlahti, Marjut Pihlajoki, Mark Davenport, Markku Heikinheimo, Mikko P Pakarinen

Open Access Publications

Interleukin (IL)-8 (CXCL8), a chemokine involved in neutrophil recruitment, has been implicated in ductular reaction and liver fibrogenesis. We studied liver and serum IL-8 expression in a large biliary atresia (BA) cohort and explored its prognostic and pathophysiological potential. IL-8 expression was assessed in liver utilizing quantitative polymerase chain reaction (qPCR), immunohistochemistry and in situ hybridization and in serum using an enzyme-linked immunosorbent assay, among 115 BA patients, 10 disease controls and 68 normal controls. Results were correlated to portoenterostomy (PE) outcomes, biochemical and histological liver injury, transcriptional markers of fibrosis and cholangiocytes, and expression of other related cytokines. IL-8 …