bluuebunny/crossref_metadata_2025_split huggingface dataset:
The utilization of a clinically relevant Immunological research case example within undergraduate biomedical sciences education
Authors: Sika-Paotonu Dianne 
Published: January 2023

Abstract
Mechanistic and cellular Immunology related teaching and learning content can be difficult to assimilate when being introduced for the first time even when appropriate scientific language communication is being utilized. To support the application of scientific Immunological content information and facilitate the in-depth understanding within the clinical context, integration of clinically relevant Immunological course elements and related research teaching examples into undergraduate biomedical sciences education are needed. Acute rheumatic fever (ARF) is an autoimmune condition caused by untreated Group A Streptococcal (GAS) infection of the upper respiratory tract (and possibly skin). Multiple or severe attacks of ARF can cause permanent cardiac damage known as rheumatic heart disease (RHD). Rates of ARF in New Zealand, Australia and the Pacific are among the highest in the world. Management for ARF requires painful monthly injections for at least 10 years of a type of Penicillin known as Benzathine Penicilin G (BPG). A less painful and longer acting BPG formulation is urgently needed would help prevent recurrence of ARF. Work being undertaken in New Zealand seeks to make a more appropriate form of Peniclilin for ARF and RHD. The purpose of this work was to successfully incorporate ARF as a clinically relevant case example within undergraduate Immunological course teaching. Students demonstrated improved improved in-class engagement and ability to answer in-class questions in addition to better understanding and recall of Immunological concepts. Student knowledge and understanding of Immunology was achieved using integration of a clinically relevant Immunological condition for undergraduate biomedical education.
The successful use of Immunology based Peer Teaching strategies within postgraduate clinical health sciences blended learning education frameworks
Authors: Sika-Paotonu Dianne 
Published: January 2023

Abstract
Immunology education remains a vital component for in-depth learning within clinical health sciences. The inclusion of undergraduate Immunology teaching content within nursing, midwifery and health related courses however remains inconsistent. The blended learning context provides avenues where active learning in-class activities that are learner centered can support and form synergies with more traditional learning forms. To support effective teaching and learning of Immunological related content at postgraduate level for classes with students with mixed experiences of Immunology education, integration of active learning and teaching strategies into postgraduate clinical sciences education are needed. The purpose of this work was to explore and assess the impact of Immunological based peer-teaching within a blended learning environment for postgraduate clinical health sciences students. Face-to-face Immunology teaching sessions for the postgraduate Pathophysiology course were delivered with the incorporation of short peer teaching sections allocated throughout the in-class session time. Instructions were carefully presented to ensure clarity and that communication was culturally appropriate for all students. Students demonstrated marked improvements in their understanding, memory recall of immunological concepts in addition to improved in-class engagement and when responding to in-class questions. In addition to enjoying the session time in class, improved confidence regarding immunological content covered in class was also noted. The integration of clinically active learning and teaching strategies such as Immunologically based peer teaching within postgraduate clinical sciences education.
Play your way to the finals: An immunology board game project to teach Immunology to undergraduate students.
Authors: Kucknoor Ashwini S. 
Published: January 2023

Abstract
It is a normal practice to use the last class day of class to review the course materials before the finals. Most of the time, all the students are seldom engaged and are not participating in these review sessions. It is important to engage the students and make the session more student-centered than the common instructor-centered ones. Here I describe the use of a semester long Immunology board game group project, as a tool to review the course material on the last day of the class. The board game project serves as a perfect learning tool to review the course material learnt during the semester in several ways. First of all, it helps all the students in the group to actively participate and be engaged in learning the concept assigned to each of the group. Secondly, since the students have to transform the board game of their choice to incorporate one specific concept of Immunology, they have to understand clearly and think deeply about the concept to come up with the details of the game, for example the board strategy, clues, game piece etc. Third and most importantly, to encourages creativity, teamwork and active participation of all students. I use this Board game group project for an upper division Immunology class with class size ranging from 24-28 students. On the day of the game, each group will play their game with their peers. Each group will design their board game to include a specific concept in detail. When all the groups (usually 4-5 groups for about 25 students) have played their games, most important concepts of the course material would be reviewed. More than 90% agreed that the Board game project helped them understand a given concept way better and that playing the board games before finals helped them tie up all the concepts well before the final exams.
Too Many B cells, When Food Fights Back, and Hacking T cells: The effective use of case studies to teach methods in an undergraduate Immunology course.
Authors: Dinkel Brittney A. , Walser-Kuntz Debby R. 
Published: January 2023

Abstract
The rapidly changing nature of immunology makes it a challenging course for both undergraduate students and faculty. A teaching approach that incorporates essential immunological techniques and an introduction to the primary literature helps undergraduates navigate the discipline and remain current. Case studies are an effective active learning approach that provide real world examples to engage undergraduates and an opportunity for hands on problem solving, data analysis, and critical thinking as students must consider outcomes and consequences. Although case studies that explore clinical connections already exist for undergraduates, they do not include key techniques or provide experience working with the primary literature. We have developed several case studies to help undergraduate immunology students understand and analyze data involving: flow cytometry, CRISPR/Cas, CAR T cells, and ELISAs. The case studies 1) introduce students to techniques and methods they may not have access to in their laboratory courses due to the lack of appropriate instruments or the cost of reagents, 2) build on difficult concepts covered in the course, and 3) incorporate figures from papers that challenge students to apply what they have learned. Assessment of student learning includes in-class quizzes and small group responses to data analysis questions, the use of “clickers”/personal response system, and related exam questions. Students self-report that the case studies are a highly effective teaching method that allow them to both reinforce their understanding of the course material and apply it to practical problems.
Role of Acinetobacter baumannii thioredoxin in pulmonary bacterial dissemination following LPS induced lung injury
Authors: May Holly , Yu Jieh-Juen , Guentzel M. Neal , Arulananadam Bernard P. 
Published: January 2023

Abstract
Despite medical advances, sepsis remains an increasing and major cause of death in hospitalized patients in the United States. Multiple-drug resistant Acinetobacter baumannii has emerged as an important hospital-acquired pathogen in both pulmonary infections and sepsis. Previously, our lab has shown the importance of bacterial thioredoxin during infection. A TrxA-null mutant (ΔTrxA) generated from A. baumannii Clinical isolate 79 (Ci79) showed a 100-fold decrease in virulence during systemic challenge. To further define the role of thioredoxin, our lab has created a pulmonary model of infection that leads to sepsis and death in C57BL/6 mice. This model is dependent on the induction of acute lung injury through E. coli lipopolysaccharide (LPS) injection. Lungs were analyzed for increased permeability using FITC-labeled dextran. Mice receiving the LPS showed significantly higher FITC-dextran particles in their serum compared to those that did not. Additionally, histopathology and cytokine production indicated limited immune response to the dose of LPS used. Using this model, mice showed significantly increased WT organ burdens in the lungs, liver, kidneys, cervical lymph nodes, and spleen compared to the mutant. Concurrently, mortality was significantly greater in the WT compared to ΔTrxA (~85%). Histopathological assessment showed increased cellular infiltrates and pulmonary inflammation during WT vs ΔTrxA infection. Finally, when the WT was treated with a thioredoxin blocker (PX-12) before challenge, mice survival improved from ~15% to ~75% with treatment. Together, this data demonstrates that thioredoxin plays a vital role in dissemination and virulence and could be a potential target to attenuate sepsis.
ALCOHOL ENHANCES TYPE 1 INTERFERON-α AND MORTALITY OF YOUNG MICE INFECTED WITH Mycobacterium tuberculosis
Authors: Tripathi Deepak , Welch Elwyn , Cheekatla Satyanarayana Swamy , Radhakrishnan Rajesh Kumar , Venkatasubramanian Sambasivan , Paidipally Padmaja , Van Abhinav , Tvinnereim Amy R. , Samten Buka , Devalraju Kamakshi P. , Neela Venkata Sanjeev Kumar , Valluri Vijaya Lakshmi , Mason Carol , Nelson Steve , Vankayalapati Ramakrishna 
Published: January 2023

Abstract
In the current study, we determined the effects of chronic alcohol consumption on the mortality of young and old mice and immune responses during Mycobacterium tuberculosis (Mtb) infection. Eighty percent of Mtb H37Rv infected alcohol-fed young mice died in five months compared to twenty-five percent in Mtb infected alcohol-fed old mice. There is no significant difference in lung bacterial burden of control and alcohol diet fed young and old mice. IFN-α levels were significantly higher in the lungs of Mtb infected alcohol-fed young mice and treatment with anti-IFNAR-1 antibody enhanced their survival. There are significantly higher numbers of CD11b+Ly6G+ neutrophils in the lungs of Mtb infected alcoholic young mice compared to Mtb infected alcohol-fed old mice and Mtb infected control diet-fed young mice. CD11b+Ly6G+ neutrophils are the major source of IFN-α in Mtb-infected alcohol-fed young mice and IFN-α enhanced the expression of RIP-1 and RIP-3 molecules, which are known to be involved in necroptosis. Alcohol-fed old Mtb infected mice and Mtb infected control diet-fed old and young mice expressed low level of IFN-α and RIP-1 and RIP-3 in their lungs. In response to Mtb stimulation, peripheral blood mononuclear cells (PBMC) from young healthy alcoholic individuals with latent tuberculosis infection (LTBI) produced significantly higher amounts of IFN-α compared to non-alcoholic young, alcoholic and non-alcoholic old healthy LTBI+ individuals. Our findings demonstrate that in Mtb infected young mice, alcohol enhances CD11b+Ly6G+ neutrophil infiltration in lungs and excess IFN-α production by neutrophils causes lung macrophage necroptosis and enhanced mortality.
Tissue Specific Overexpression of Human Heat Shock Protein 70 in Mouse Oviduct Epithelium Reduces Chlamydia Induced Immunopathology
Authors: Murthy Ashlesh K. , Keeler Kelly Rae , Do Jennifer , Seetharaman Aravind , Ramsey Kyle H. , Ciancio Mae , Li weidang 
Published: January 2023

Abstract
Chlamydia trachomatis genital infections lead to severe immunopathological consequences in the upper genital tract (UGT), including pelvic inflammatory disease and infertility, in a small subset of infected women. Heat shock protein 70 (Hsp70) is an evolutionarily conserved stress-induced protein and has been shown to exhibit significant cytoprotective and immunoregulatory activities. However, the role of Hsp70 in genital chlamydial pathologies had not been examined. Hsp70 transgenic (Hsp70 Tg) mice were created by injecting a villin promoter-driven human Hsp70 targeting vector into C57BL/6 oocytes. The villin promoter is active only in the epithelium of the mouse oviduct but not in other parts of the female mouse genital tract. Female, 6-8 week old, Hsp70 Tg and non-transgenic (NTG) littermates were infected intravaginally with 5×104 IFU of C. muridarum. Vaginal chlamydial shedding, bacterial burden in the upper genital tract including oviducts and uterine horns, Chlamydia-specific IFN-γ, TNF-α, and IL-17 production, and serum anti-Chlamydia antibody levels were comparable between NTG and Hsp70 Tg mice. However, at day 80 after inoculation, the incidence and severity of pathology in oviducts, not neighboring uterine horns, was significantly reduced in Hsp70 Tg mice compared to NTG mice. Given the highly polymorphic nature of hsp-70 gene and associated susceptibility to various inflammatory conditions, and the occurrence of immunopathology in only a subset of Chlamydia-infected women, these results also underscore the need to further evaluate the role of hsp-70 in chlamydial immunopathogenesis in the female upper reproductive tract.
Novel Pycard gene polymorphism impairs Nlpr3 inflammasome-induced IL-1β production in mice selected for low inflammatory response.
Authors: Ibañez Olga M. , Starobinas Nancy , Monteleone Leticia Figueiredo , Borrego Andrea , Icimoto Marcelo Yudi , Cabrera Wafa Koury , Ribeiro Orlando Garcia , De Franco Marcelo , Jensen José Ricardo , Dragani Tommaso Antonio 
Published: January 2023

Abstract
A SNP based linkage study in mouse lines phenotypically selected for maximal (AIRmax) or minimal (AIRmin) acute inflammatory response (AIR), mapped a major locus, Inflammatory response modulator 1 (Irm1) at 128Mb (3.5Mb interval) in chr 7 controlling AIR, measured by leukocyte and IL-6 levels in exudates and IL-1β production by circulating leukocytes after Nlpr3 inflammasome activation. Sequencing of this region in mice with extreme high or low IL-1β levels revealed 14 SNPs between the two groups, narrowing the locus interval to 420Kb. Candidate genes at Irm1 include Pycard with an undescribed exon 3 (C/T) mutation leading to E19K substitution at the pyrin domain, and Itgam, Rgs10 and BC017158 with intronic SNPs. In Pycard, the C allele was fixed in high responder AIRmax mice whereas the C and T alleles frequencies were 39% and 61%, respectively in AIRmin. We then investigated the effect of this novel Pycard SNP in inflammation phenotypes.

Methods
AIRmin mice bearing the 3 genotypes at Pycard: CC, CT, TT were produced by genotype-assisted mating. Inflammatory response was measured in AIRmax and in the 3 AIRmin sublines by the number of infiltrating cells and IL-6 concentration in the 24h exudate induced by sc Biogel P-100 bead injection and ex vivo IL-1β production by circulating leukocytes after E coli LPS (1 ug) and ATP (5mM) activation.

Results
IL-1β levels were similar in AIRmaxCC (4.5-±0.4 ng/ml) and AIRminCC (3.4±2.4 ng/ml) whereas AIRminCT produced 0.3±0.5 and AIRminTT &lt;0.05 ng/ml IL-1β. Leukocyte influx and IL-6 levels in inflammatory exudates were not affected.

Conclusion
The E19K substitution in Pycard causes a negative effect in inflammasome activation for IL-1β production, without interfering in other inflammation phenotypes.
Mitochondrial SLC25 proteins interact with NLRP3 to regulate inflammasome function
Authors: Shuvarikov Andrey A. , Davis Michael A. , Esser-Nobis Katharina , Gale Michael J. 
Published: January 2023

Abstract
The NLRP3 protein is a key initiator of inflammation in humans. NLRP3 becomes activated by a multitude of danger signals, including pathogens, markers of metabolic dysfunction, and internalized particulates. Upon activation, NLRP3 nucleates formation of a multiprotein complex called the inflammasome, in which caspase-1 activity mediates processing of the pro-inflammatory cytokines IL-1β and IL-18 and induces pyroptosis, a pro-inflammatory form of cell death that serves to release the mature cytokines along with other inflammatory mediators, thus initiating the inflammatory response. While multiple regulators of the NLRP3 inflammasome have been described, specific ligand(s) of NLRP3 and its mechanism of activation remain largely unknown. We performed a proteomics screen using co-immunoprecipitation (IP) and mass spectrometry to identify cellular proteins that bind NLRP3. Using this screen, we identified multiple NLRP3 interactors, including a family of solute carrier (SLC) proteins that localize to the inner mitochondrial membrane. Co-IP experiments verified that four of these proteins, namely SLC25A1, a citrate transporter, SLC25A6, an ADP/ATP translocase, SLC25A11, a 2-oxoglutarate/malate carrier, and SLC25A13, a calcium-dependent glutamate transporter, specifically interact with NLRP3. Because of its linkage with known metabolic disease, we further assessed the role of SCL25A13 in inflammasome function. When ectopically expressed, SLC25A13 enhanced IL-1β release from cells, while CRISPR/Cas9 knockout of SLC25A13 from THP-1 macrophages partially abrogated NLRP3-dependent pyroptosis. Our studies reveal a novel role for mitochondrial SLC25 proteins in regulation of the NLRP3 inflammasome.
Identification of age-related changes in gene expression and chromatin accessibility in T cells from thymus to periphery
Authors: achour achouak , Chen Guobing , Sharov Alexei , Nugyen Thomas , Peng Weiqun , Patrick Michael , Wood William lll , De Supriyo , Becker Kevin , Weng Nan-ping 
Published: January 2023

Abstract
Aging of immune system is characterized by progressive decline of physiological and cellular function of T cells. Recent studies of naïve T cells from young and old mice have identified age-related altered gene expressions but the mechanisms underlying age associated changes of naïve T cells remain poorly understood. Here we compared the transcriptome and chromatin accessibility in mature CD4 and CD8 thymocytes and in naïve CD4 and CD8 T cells of spleen between young (6–8 weeks) and old (95–110 weeks) C57Bl/6 mice. We used Agilent microarray method and identified the age-related altering gene expressions 1) only in mature CD4 and CD8 T cell from thymus, 2) shared by both thymus and spleen naïve T cells, and 3) only in naïve T cells from spleen. The shared changes include increased chemokine and chemokine receptor expressions and decreased cell cycle regulator expression. We further analyzed the chromatin basis of altered gene expression using ATAC seq between young and old mice. We have identified age-related changes of chromatin accessibility in T cells from thymus and spleen, and some correlated changes between gene expression and chromatin accessibility. Overall, we observed more age-related alterations of gene expression and chromatin accessibility in thymus than in spleen, suggesting some age-related changes of T cells in thymus did not retain in periphery. Together, our findings have identified tissue specific altered gene expressions and chromatin status in T cells during aging and further study of these altered genes will shed new insights into the mechanisms underlying these age-related changes.
This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging.
Kmt2d regulates naive CD8 T-cell development and activation-related survival
Authors: Kim Jaekwan , Ge Kai , Weng Nan-Ping 
Published: January 2023

Abstract
Lysine specific methyl-transferase 2D (Kmt2d) catalyzes the mono-methylation of histone 3 lysine 4 (H3K4me1) and play a critical role in enhancer-mediated gene expression regulation. However, its role in CD8 T cell development and differentiation has not been addressed. Here, we analyzed a T-cell specific KMT2D knockout mouse (KMT2Dfl/flCD4cre+) and found that the number of CD8 T cells in spleen and blood was greatly decreased compared to wild type (KMT2Dfl/flCD4cre-, WT) mice. The decrease in CD8 T cells is caused by defective production of T cells in the thymus based on the following observations. First, numbers of recent thymic emigrant (RTE) CD8 cells in blood and spleen of KMT2Dfl/flCD4cre+ mice were significantly less in KMT2Dfl/flCD4cre+RAG-GFP mice. Second, thymic development of T cells was compromised (CD4+/CD8+ population was less and immature CD8SP cells are increased in KMT2Dfl/flCD4cre+ mice). Third, naïve CD8 T cells (CD62Lhi/CD44lo) were more significantly reduced (WT:KO=7:1) than memory (CD62Llo/CD44hi, WT:KO=2:1) CD8 T cells. Furthermore, naïve CD8 T cells isolated from KMT2Dfl/flCD4cre+ mice with anti-CD3 and anti-CD28 in vitro showed increased apoptosis compared to that from WT mice. RNA-seq analysis of naïve CD8 T cells revealed increased expressions of genes related to apoptosis prior stimulation, suggesting Kmt2d regulates activation-induced apoptosis. Together, our findings reveal a role of Kmt2d in naïve CD8 T cell production and survival after activation.
This research was supported entirely by the Intramural Research Programs of the NIH, National Institute on Aging and National Institute of Diabetes, Digestive and Kidney Diseases.
Local and long-range transcriptional regulation of the Bcl6 locus by Ikaros zinc finger factors
Authors: Powell Michael Duane , Read Kaitlin A. , Sreekumar Bharath , Carrillo Gabriela L. , Ringel-Scaia Veronica , Bachus Holly , Allen Irving C. , Ballesteros-Tato Andre , Oestreich Kenneth J. 
Published: January 2023

Abstract
T follicular helper (TFH) cells play a pivotal role in the humoral immune response by providing help to B cells, resulting in germinal center formation and the subsequent generation of pathogen-neutralizing antibodies. The development of TFH cells requires the expression of the transcriptional repressor Bcl-6; however, the mechanisms underlying Bcl6 transcriptional regulation are incompletely understood. Here we identify the Ikaros Zinc Finger (IkZF) transcription factors Aiolos and Ikaros as novel regulators of Bcl6 expression. We demonstrate that the expression of Aiolos and Ikaros is upregulated in antigen-specific TFH cells generated in response to both Listeria monocytogenes and influenza infection. Mechanistically, we find that Aiolos and Ikaros directly associate with the Bcl6 promoter. This association corresponds with chromatin remodeling events consistent with gene activation including the recruitment of chromatin remodeling complexes, increased histone acetylation, and RNA polymerase II binding. Additionally, we find that Aiolos and Ikaros are enriched at a conserved noncoding sequence 273 kb (CNS273) upstream of the Bcl6 transcriptional start site. CNS273 exhibits a covalent histone modification profile indicative of an active enhancer and is capable of enhancing Bcl6 promoter activity in an Aiolos-dependent manner. Collectively, these data provide insight into the multifaceted mechanisms by which Aiolos and Ikaros regulate Bcl6 expression.