bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magnolol attenuates the cisplatin-induced muscle wasting via M2c macrophage activation
Authors: Lee Chanju , Park Seon-young , Min Daeun , Bae Hyunsu 
Published: January 2023

Abstract
Cancer chemotherapy induces malnutrition and rapid loss of muscle mass which directly restricts the daily activities leading to poor quality of life and increased mortality. Although the hormone-related therapies have been used to improve appetite and nutritional status, but current treatments are considered palliative. Thus, the maintenance of skeletal muscle mass without side effects is essential in sarcopenia. Magnolol from Magnolia officianlis has been reported to have several pharmacological effects including anti-cancer and anti-inflammatory effects, but the correlations of immune cell infiltrations and muscle protection in muscle atrophy are not well understood. In the present study, we investigated the effects of magnolol on muscle wasting and macrophage subtypes in cisplatin-induced sarcopenia mice model. We showed that magnolol significantly attenuated the body weight loss and muscle loss induced by cisplatin injection. The diameter of tiabialis anterior (TA) muscle was markedly increased by magnolol treatement compared with cisplatin group. Importantly, magnolol increased the percentages of total macrophages without affecting the percentages of T cells. Furthermore, magnolol reduced the CD206−CD163− M1 inflammatory macrophages whereas the CD206+CD163+ M2c tissue reparative macrophages were increased in CD45+CD11b+F4/80+ macrophages. We also showed that cisplatin increased the M1/M2 ratio and magnolol significantly lowered the M1/M2 ratio in TA muscle. Taken together, magnolol may be a promising chemoprotective agent for preventing muscle atrophy by upregulating M2c macrophages.
Knockdown of circular RNA FSCN1 impairs dendritic cell immune function through regulating the NFKB and Foxo3 signaling pathways
Authors: Zheng Xiufen , Zhu Cuilin , Su Yale , Wang Bowen , O’Brien Dana 
Published: January 2023

Abstract
Circular RNAs (circRNAs) that are a new class of endogenously expressed non-coding RNAs produced from back splicing with a covalently closed loop structure have been emerging as an important gene regulator in the physiological and pathological development of cells. It remains unknown about roles of circRNAs in DCs. The objective of the study is to investigate the impact of circular RNA FSCN1 (circFSCN1) on dendritic cell immune function. Bone marrow derived dendritic cells were cultured in vitro and circRNA expression was detected by circRNA microarrays and qRT-PCR. The effect of circFSCN1 on DCs was studied. We found that the expression profiles of circRNAs were significantly different in mature immunogenic DCs v.s immature immunosuppressive DCs. circFSCN1 was the most significantly highly expressed in mature DCs compared with immature DCs. Treatment with immunosuppressive cytokines TGF β and GDF15 reduced circFSCN1 expression in DCs. Knockdown of circFSCN1 using siRNA reduced the phosphorylation of Rel Ap65, but increased phosphorylated Foxo3. Silencing of circFSCN1 impaired DCs to activate T cells, changed inflammatory cytokine production and enhanced Treg generation whereas circFSCN1 siRNA did not affect DC maturation. In conclusion, it is a first report to demonstrate that circFSCN1 is essential for DC immune response.
Student Outcomes in a CURE Course Using Simple Model Organisms to Characterize Host-Pathogen Interactions
Authors: Snyder Michelle , Trauth Amy 
Published: January 2023

Abstract
Course-based undergraduate research experiences (CUREs) can increase the inclusivity of scientific research by breaking down both barriers associated with student awareness and confidence in seeking research experiences, as well as faculty biases in selection of student researchers. We developed a CURE using the social amoeba Dictyostelium discoideum and its bacterial prey Escherichia coli as a model for host-pathogen interactions. D. discoideum phagocytize bacteria and can be used as a simple model to characterize innate immune processes. Our CURE course focuses on characterization of genes potentially associated with resistance to phagocytic killing, which were identified in a screen for mutant E. coli strains with enhanced survival upon D. discoideum phagocytosis. These mutant E. coli strains were sequenced, and students in the course use bioinformatics tools to identify mutated genes. From there, students work with E. coli strains deficient for the mutated genes, performing assays to characterize both bacterial phenotypes as well as D. discoideum phagocytic and signaling responses to these mutant strains. Using various tools, including pre- and post-tests, interviews and the SURE survey to assess student outcomes, we found significant gains in student knowledge and skills, as well as student-reported gains in knowledge of the research process, confidence in working in a research team, and ability to interpret results. Our CURE course was used as a model for implementation of the TU-Research Enhancement Program (TU-REP), which is funded by the HHMI Inclusive Excellence initiative, and seeks to transform the scientific curriculum at TU by offering opportunities for students to engage early and often in authentic research.
Using IF AT strategy in the Dental Immunology curriculum has a beneficial impact on the performance of second year dental students
Authors: Alard Pascale 
Published: January 2023

Abstract
When considering health professions education, providing tools that allow students to become life-long learners is critical. Acquisition of knowledge is more effective in the form of practice activities where learners can think critically and solve problems. Learning Immunology not only requires memorization of new terminology, but also learning concepts. The Immunology program for dental students is very intensive as they learn a tremendous amount of information in a very compressed period of time. In this study, students were divided into groups of 4 – 6 who worked on several questions about the material covered that week using the Immediate Feedback Assessment Technique (IF AT). Students in each group discussed the possible answers before selecting the final answer. If the answer was incorrect, they could choose another answer until they were successful. At the end of each session, the answers and concepts behind the questions and answers were thoroughly discussed. Students appeared to be engaged, and in response to a survey, most found the exercise helpful in achieving a deeper understanding of the concepts as well as good practice for the exam. Their performance on the exam was better than the previous year, with a 50% decrease in students scoring &lt;70, and a 40% increase in students scoring &gt;87. Since the same group of students did not perform better on the following exam on Microbiology, where the instructors did not include this learning strategy, we ruled out the possibility that this group was stronger overall. In addition, the order of the questions and the time spent on the exam had no impact on overall performance. In conclusion, holding IF AT sessions before the exam is highly beneficial and improves the performance of the students.
An Immunological basis for improving interest and participation of underrepresented student groups in High school science classes
Authors: Sika-Paotonu Dianne , Anderson Jane , Cashin Philippa , Cockburn Alana 
Published: January 2023

Abstract
In New Zealand (NZ) children and young people of Māori and Pacific Peoples heritage are underrepresented in high school science and higher education science, medical and health courses. To help support improved engagement and interest in laboratory science learning that was clinically relevant amongst high school students from underrepresented groups that included Māori and Pacific students, a laboratory workshop session was arranged to incorporate a visit from a Pacific Biomedical Scientist teaching laboratory content with an Immunological focus. This visit was organised during the workshop session to support the Immunologically based teaching and also to field questions from the students directly. Amongst other discussion points, the implications of Penicillin as an antibiotic of choice to prevent the autoimmune response to Group A Streptococcal bacteria known as Acute Rheumatic Fever (ARF) was also discussed. It is recognised that Indigenous Māori and Pacific population groups remain disproportionately affected by Acute Rheumatic Fever (ARF) and Rheumatic Heart Disease (RHD) in NZ and in the Pacific Region. Feedback from the high school students indicated that a key source of interest remained the clinical relevance of the scientific discussion emphasised with the Pacific Biomedical Scientist. This work demonstrated the value of Immunology incorporation within the laboratory focus for this wider context and also the role modelling concept for the Pacific students in particular, both as important factors to support heightened interest and engagement levels of underrepresented high school students in science.
Manipulating peripheral blood cell populations to mimic immune disease states: a novel approach to teach flow cytometry to undergraduate immunology students
Authors: Costabile Maurizio , Nguyen Hong , Kenyon Amanda 
Published: January 2023

Abstract
Flow cytometry (FC) allows for the quantification of individual cell populations whose levels are known to change in disease states, such as, the reduction in CD4+ T cells in AIDS. While FC is a powerful technique, it can be difficult to teach its principles and applications to undergraduate students. Assessing changes in cell populations is an excellent approach to teach FC, however obtaining real patient samples is not often possible. In addition, hands on use of a flow cytometer by students is difficult or impossible to achieve when class sizes are large. To address these challenges, we taught the principles of FC, sample preparation (Week 1) and data analysis (Week 2) of mock “control” and “patient” samples. In Week 1, the theory of FC was covered and the students labelled “control” and “patient” blood with anti-CD3, 4, 8, 14, 19 and 66 mAbs. In Wk 2, students were provided with data files where the levels of major cell populations had been manipulated using magnetic beads to mimic immune diseases states. Using written and video instructions for the software and supplied reference ranges, and using a PC, were asked to identify the disease status of their patient sample. Student perceived understanding of FC was found to significantly increase after the practical session, and student feedback was also overwhelmingly positive. The manipulation of cell populations in whole blood to mimic disease states is an excellent way to teach undergraduate students the major principles of FC. These include labelling of cells, learning to use the software, interpreting the data and disease diagnosis. We will continue to expand our list of disease conditions. All data files are freely available to any teaching staff who may wish to use them as part of their teaching.
Novel role of zinc homeostasis in IL-23 regulation and host defense following bacterial infection
Authors: Hall Sannette C , Smith Deandra R. , Katafiasz Dawn M. , Bailey Kristina L. , Knoell Daren L. 
Published: January 2023

Abstract
Zinc homeostasis is crucial for immune cell activation and intracellular zinc is tightly regulated by zinc transporters. Zinc deficiency is associated with increased prevalence of respiratory bacterial infections. Although the association between zinc and immunity is well established, the mechanisms by which zinc protects against bacteria remain to be elucidated. In human monocytes the zinc transporter Zip8 regulates inflammation in a zinc-dependent manner after LPS exposure. Given the critical role of APCs (macrophages and dendritic cells) in guiding the immune response against bacteria, we sought to determine the role of Zip8 in coordinating the immune response after bacterial exposure.
In a novel myeloid-specific Zip8KO mouse model we observed that intranasal instillation of S. pneumoniae resulted in a significant increase of infiltrating neutrophils in the airways of Zip8KO mice when compared to WT counterparts. Analysis of BAL fluid revealed elevated levels of CXCL1 and IL-23 in the Zip8KO mice. To determine whether dendritic cells potentially play a role in the observed response, BMDCs were generated from Zip8KO and WT mice. LPS stimulation produced mature BMDCs with high CD11c and MHC-II expression in both groups. No significant changes were observed in the production of most cytokines examined (TNF-α, CXCL1, IL-6, IL-12), except for IL-23 which was consistently increased in the stimulated Zip8KO cells in comparison to WT control DCs. These results potentially reveal a vital axis that couples zinc homeostasis to IL-23 production in myeloid cells and ultimately host defense against invasive bacterial pathogens. To what extent this alters pathogen clearance and host recovery is the focus of future studies.
Alarmin(g) outcomes of intracellular LPS sensing
Authors: Rathinam Vijay , Russo Ashley , Menoret Antoine , Rabinovich Gabriel , Duduskar Shivalee , Deshmukh Sachin , Vella Anthony T 
Published: January 2023

Abstract
Intracellular sensing of LPS by inflammatory caspases such as caspase-11 has emerged as a key mechanism of innate immune activation during Gram-negative bacterial infections. Cytosolic recognition of LPS by caspase-11 leads to inflammatory cell death or pyroptosis and maturation of IL-1 cytokines. Remarkably, the activation of inflammatory caspases also results in the extracellular release of alarmins and damage associated molecular patterns (DAMPs). These alarmins and DAMPs lack leader signals for classical secretion and are therefore released via a caspase-11 mediated unconventional secretory mechanism. Alarmins and DAMPs—structurally diverse molecules participating in various cellular processes under steady state conditions—are released rapidly upon infections and tissue damage. In the extracellular milieu, these proteins elicit inflammatory reactions by regulating pattern recognition receptor signaling and recruiting innate cells. Despite their potential roles in sepsis, the identity of alarmins and DAMPs released as a result of cytosolic LPS sensing and their contribution to sepsis are poorly understood. Addressing this knowledge gap, we employed an unbiased proteomic approach involving two-dimensional liquid phase fractionation system and mass spectrometry and identified alarmins released in response to caspase-11 activation by cytosolic LPS. In this presentation, the molecular basis of secretion of a candidate alarmin in vitro and in vivo as well as its function in murine models of host defense will be discussed.
Redefining the TIR domain: From Axon Degeneration to Innate Immunity and Beyond
Authors: Essuman Kow , Wan Li , Summers Daniel W. , Anderson Ryan G. , Sasaki Yo , Mao Xianrong , Yim Aldrin Kay Yuen , Monteiro Freddy , Chung Eui-Hwan , Osborne-Nishimura Erin , Dangl Jeffery , Nishimura Marc , DiAntonio Aaron , Milbrandt Jeffrey 
Published: January 2023

Abstract
The Toll/Interleukin-1 Receptor (TIR) domain is an evolutionary ancient protein domain, present in numerous receptors and adaptor proteins, and is the signature-signaling domain of Toll-Like Receptors (TLRs). In animals, these TIR domains generally serve as scaffolds that promote the assembly of signaling complexes to trigger activation of pro-inflammatory cytokines and other defense-related products. In plants, TIR domain proteins are known to mediate disease resistance against pathogens, and trigger hypersensitive cell death. However, their mechanism of action has remained elusive. In bacteria, TIR domains have been associated with virulence and defense against some viruses. Here, we redefine the canonical scaffolding function of the TIR domain by showing that TIR domains can possess intrinsic enzymatic activity, and constitute a family of enzymes that cleave the essential metabolic cofactor Nicotinamide Adenine Dinucleotide (NAD+). We identify the TIR domain of SARM1 as the founding member of the TIR NADase family that triggers axon self-destruction upon axonal injury. We show that the TIR enzymatic activity in conserved in bacteria, and archaea, where in bacteria this NADase activity has recently been linked to defense against viruses. Finally, we extend our findings to plant innate immunity, and show that plant TIR-domain Immune Receptors trigger cell death and transduce recognition of pathogens into an immune response via this conserved enzymatic activity. Altogether, our findings establish TIR domain proteins as a new family of metabolic enzymes, and we posit that the scaffolding function in TLR signaling likely represents a repurposing of this evolutionary ancient enzymatic function.
TRAF3IP3 negatively regulates type I interferon signaling by suppressing TBK1
Authors: Deng Meng , Tam Jason W. , Guo Haitao , Zhang Lu , Davis Beckley K , Brickey June , Sun Shaocong , Ting Jenny P 
Published: January 2023

Abstract
Type I interferon (IFN) signaling is important for antiviral and autoimmune response, and it is subjected to tight control, however molecular mechanisms to tune down these pathways is incompletely understood. Upon sensing cytosolic viral RNA, retinoic acid-induced gene I (RIG-I) and melanoma-differentiation-associated gene 5 (MDA5) interact with mitochondrial antiviral signaling protein (MAVS) and activate TANK binding kinase 1 (TBK1) to induce IFNs. A golgi-associated factor, TRAF3-interacting protein 3 (TRAF3IP3), has been found to be crucial for thymocyte development and T regulatory cell functions. However its role in myeloid cells has not been explored. We find that the overexpression of TRAF3IP3 suppressed cytosolic poly(I:C), 5’ ppp-dsRNA, and vesicular stomatitis virus (VSV) triggered IFN production, whereas deficiency of Traf3ip3 potentiated viral RNA triggered IFN production. In support of the in vitro data, Traf3ip3-deficient mice were infected with VSV and found to exhibit enhanced susceptibility to VSV challenge. Mechanistically, TRAF3IP3 interacted with TBK1 and targeted TBK1 for ubiquitination and degradation. These results uncovered a previously unrecognized role of TRAF3IP3 in the regulation of RNA induced IFN pathway.
Single cell sequencing reveals mouse MAIT cell diversity
Authors: Chandra Shilpi , Seumois Gregory , Ramirez Ciro , Seo Gooyoung , Vijayanand Pandurangan , Kronenberg Mitchell 
Published: January 2023

Abstract
Mucosal-associated invariant T (MAIT) cells are a novel subpopulation of innate-like T lymphocytes that recognize vitamin B metabolites and express an invariant T cell receptor (TCR) α chain. MAIT cells are less abundant in mouse blood (~0.1% of T cells) as compared to human blood (~5%). MAIT cells play an important role in various infectious non-infectious diseases. Given their small number in mouse, these cells have been not been fully characterized. To unravel MAIT cell heterogeneity in thymus and peripheral tissues, we have performed single-cell sequencing of MAIT cells from various organs using 10× single-cell genomics, where we sequenced more than 7,000 cells and identified 10 clusters of MAIT cells by unbiased clustering. Cells from different organs mostly are represented in the different clusters, except one cluster was lung MAIT cell specific and another cluster consisted of cells exclusively from thymus. The lung specific cluster also reveals a tissue residency gene signature. We compared the gene expression profile of MAIT cells with iNKT cells, another T lymphocyte population that recognizes non-peptide antigens with invariant α chains. Our data reveal that most mouse MAIT cells have a Th17/NKT17–like gene signature, although there are some with Th1/NKT1 like transcriptomes, particularly in liver and spleen. A Th2/NKT2 gene expression profile was not observed. The thymus specific cluster showed a gene expression profile similar to the most immature or progenitor iNKT cells (NKT0), consistent with other data suggesting a unique thymus differentiation pathway. Therefore, our study reveals that although MAIT cells are predominantly Th17 and Th1 cells, there is an unexpected degree of heterogeneity.
Supported by R01 AI71922
Effects of TNFα signaling on iNKT cell development, activation and maturation
Authors: Zhang Hui , Modrak Samantha , Zhang Faya , Little Alexander Armstrong 
Published: January 2023

Abstract
iNKT cells are CD1d-restricted T cells that recognize lipid antigens. Upon activation these cells rapidly produce large amount and a broad spectrum of cytokines. They are important immunoregulatory cells involved in autoimmune disease, liver injury and antitumor immunity. The mechanisms regarding iNKT cell development, activation and maturation have been studied extensively. It is well known that many cytokines and transcription factors are involved in these processes. TNFα, an inflammatory cytokine that can be produced by iNKT cells, co-occurs with iNKT cells in steady state and many disease conditions. How TNFα affects iNKT cell development, activation and maturation is not known. Herein we used a TNFα KO mouse model to address this issue. We found that depletion of TNFα did not affect the frequency of iNKT cells in thymus and spleen, but decreased iNKT cells in liver, and increased iNKT cell apoptosis in liver. The portion of stage-2 (NK1.1loCD44hi) iNKT cells increased, stage-3 (NK1.1hiCD44hi) iNKT cells decreased in the thymus of TNFα KO mice, suggesting that depletion of TNFα impairs iNKT cell development and maturation. The percentage of CD69+ iNKT cells was significantly lower in the thymus, spleen and liver of TNFα KO mice compared to their wild-type littermates, suggesting that depletion of TNFα inhibits iNKT cell activation. Moreover, upon activation, the percentage of splenic IL-4- and IFN-g-producing iNKT cells was significantly lower in TNFα KO mice than in their wild-type littermates. Depletion of TNFα increased PLZF+ iNKT cells in thymus and downregulated the expression of CD122 on iNKT cells. Taken together, TNFα signaling plays important roles in regulation of iNKT cell development, activation and maturation.