bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fam49b-deficient lymphocytes modulate whole body energy metabolism.
Authors: Park Chansu , Guan Jian , Rhee Peter , Sadegh-Nasseri Scheherazade , Shastri Nilabh 
Published: February 2023

Abstract
TCR signal strength is determined by the balance of positively regulating, and negatively regulating proteins. Fam49b is identified as new negative regulator of TCR signaling that functions by binding to active rac-1 GTPase. In the absence of Fam49b, thymocytes receive higher TCR signaling and are defective in development of conventional T cell as well as agonist selected T cells such as CD8αα+ αβ T cells. Obesity is characterized by chronic inflammation and immune dysregulation, but the link between obesity and T cells has remains unclear. We show that Fam49b-deficient mice have a high level of energy expenditure and are resistant to high fat diet induced obesity. Furthermore, the higher energy expenditure characteristic was also observed in Fam49b-deficient chimera mice. The study reveals that Fam49b deficient lymphocytes play an important role in whole body energy metabolism. [This research was supported by NIH grants R01 AI130210 and R37 AI060040]
Myeloid Mayhem: How sleep alters the myeloid compartment and promotes plaque rupture in atherosclerosis
Authors: Moriarty Alina K , Keeter W. Coles , Waseem Tayab , Ma Shelby , Butcher Matthew J , Mussbacher Marion , Wellman Laurie , Sanford Larry , Galkina Elena 
Published: February 2023

Abstract
Adequate sleep is vital for overall health; however, today’s fast-paced society often neglects the importance of sleep. Poor sleep quality is tightly correlated with atherosclerosis and increased risk of mortality due to a cardiovascular event. Evidence demonstrates neutrophilia and monocytosis following chronic sleep fragmentation, but their effects on aortic inflammation and atherosclerotic plaque stability are not well understood. We found that chronic sleep fragmentation accelerated atherogenesis and decreased plaque stability in plaques of high fat diet (HFD) fed female apoliportein E-deficient (Apoe−/−) mice. Sleep fragmentation increased populations of pro-inflammatory monocytes and neutrophils in the bone marrow, blood, spleen, and small intestines of HFD fed female Apoe−/− mice. Additionally, sleep fragmentation increased gut permeability and circulating LPS in HFD fed female Apoe−/− mice. We also observed increased percentage of neutrophils in carotid arteries of sleep fragmented Apoe−/− mice. Importantly, these plaques exhibited increased necrotic areas, altered composition of extracellular matrix, and reduced production of stabilizing collagen. Taken together, our data indicates that sleep fragmentation accelerates plaque formation, and destabilizes atherosclerotic plaques by altering the local and systemic immune landscape. Sleep fragmentation contributes to systemic inflammation and likely activates the innate immune response at least partially, through the increase in circulating LPS mediated by inflammation in small intestines.
Autoimmunity against Cardiac Self-Antigen Drives Immune Checkpoint Inhibitor-Associated Myocarditis Development
Authors: Won Taejoon , Kalinoski Hannah M , Wood Megan K , Hughes David M , Talor Monica V , Reddy Jay , Cihakova Daniela 
Published: February 2023

Abstract
Immune checkpoint inhibitor (ICI) blocking PD-1 has been approved by the Food and Drug Administration for treatment of several types of cancers. However, fulminant myocarditis has occurred in the ICI-treated cancer patients, with low incidence but with 50 percent mortality. In this study, we investigated if PD-1 blockade can induce myocarditis in the mouse mimicking ICI-associated myocarditis in the human. We found that anti-PD-1 mAb treatment caused myocarditis development in A/J mice exhibiting enlarged heart and increased cardiac infiltration. In the cardiac infiltration, CD8+ T cells, CD4+ T cells, monocytes and macrophages were increased in the PD-1 blockade group compared to isotype control. Cardiac damage was confirmed by elevated serum level of cardiac troponin I and anti-myosin IgG. In addition, PD-1 blockade caused arrhythmia, right bundle branch block, while controls showed a normal ECG trace. The A/J mice with PD-1 blockade also developed systemic autoimmune responses such as colitis, sialadenitis, pneumonitis and myositis like immune-related adverse events in the human, supporting the immunotoxicity of PD-1 blockade. Next, using myosin-MHC tetramer staining, we found the increase of autoreactive T cells specific for cardiac myosin in the mouse heart with ICI-associated myocarditis compared to control. In the naïve heart, we were able to detect myosin-specific T cells, which number was very few but expressed a high level of PD-1. Collectively, we have developed the mouse model for human ICI-associated myocarditis and showed that the pathogenesis of this disease is an autoimmune reaction against heart-specific antigens.
Enhanced suppressive phenotype of Tim-3+ Treg during chronic infection
Authors: Nieves-Rosado Hector M , Banerjee Hridesh , Kane Lawrence P 
Published: February 2023

Abstract
T cell (or transmembrane) immunoglobulin and mucin-domain containing protein-3 (Tim-3) is a cell-surface protein expressed during T cell exhaustion, a process that leads to a progressive loss of effector function due to chronic T cell receptor (TCR) stimulation. In humans, Tim-3 expression has also been found to be increased on Treg isolated from tumors and during chronic viral infection. However, the role of Tim-3 on Treg during chronic viral infection remains largely unknown. Our main hypothesis is that Tim-3 expression on Treg will increase their proliferation and suppressive capacity during LCMV infection. To test this, we infected C57/BL6 mice for 30 days with LCMV clone-13, a well-established model for chronic infection. We found that at 16 days post-infection there is an increase in the frequency and number of Tim-3+Foxp3+ Treg in the spleen. By flow cytometry we found that Tim3+ Treg have increased expression of CD44, Ki67, Helios, ICOS, KLRG-1, CD39 and CD25, compared with Tim-3− Treg. Therefore, our data suggest that Tim-3+ Treg have a phenotype associated with higher activation, proliferation and suppression during chronic infection. Understanding the contributions of Tim-3 to Treg activation and function may provide new insights into the role of Tim-3 during disease progression and response to therapy.
MHCII-mediated antigen presentation by thymic stromal cells is required to enforce central T-cell tolerance
Authors: Proekt Irina , Miller Corey N , Chan Jackie Y , Hsieh Chyi-Song , Anderson Mark S 
Published: February 2023

Abstract
Central T-cell tolerance relies on elimination of self-reactive CD4+ T-cell clones in the thymus by either deletion or conversion to regulatory T cells (tTregs). Developing thymocytes are selected by exposure to tissue-specific antigens (TSAs) expressed by thymic medullary epithelial cells (mTECs) under the control of Autoimmune Regulator (Aire). TSA-derived peptides-MHCII complexes can be presented either directly by mTECs or indirectly by thymic DCs. Dissecting the contributions of these antigen presenting cell (APC) subsets to thymic tolerance has been hindered by the lack of appropriate genetic tools to selectively target presentation by mTECs. To address this, we created a mouse model in which MHCII can be inducibly ablated in Aire-expressing mTECs (iAire-CreERT2;MHCIIfl/fl). We show that treatment of these mice with tamoxifen leads to a complete loss of MHCII expression by Aire+ and post-Aire mTECs without affecting other thymic APCs or perturbing thymic homeostasis. In a TCR-restricted mouse model of negative selection, ablation of MHCII on mTECs led to a failure to delete self-reactive T cells, allowing escape and activation in the periphery. Surprisingly, we also found a defect in conversion of self-reactive CD4+ T cells to FoxP3+ tTregs. Similarly, in the diverse repertoire, loss of direct antigen presentation by mTECs resulted in tTreg reduction. In contrast, using CD11c-Cre;MHCIIfl/fl mice, in which MHCII is absent on thymic DCs but not mTECs, we found no disruption to negative selection or Treg generation. In sum, our data support a distinct and non-redundant role for direct antigen presentation by mTECs in shaping thymic T cell selection.
Integrative profiling of chromatin accessibility and gene expression elucidate specific transcriptional network in porcine neutrophils
Authors: Herrera-Uribe Juber , Daharsh Lance , Byrne Kristen A , Liu Haibo , Loving Crystal , Tuggle Christopher K 
Published: February 2023

Abstract
Pigs are an important component of global food security, and serve as a human biomedical model. Infectious diseases impact pig and human health and global food productivity. Components of the pig innate immune system, such as neutrophils, have not been fully described, and epigenetic mechanisms controlling gene expression remain unclear in pigs. We performed RNA- and assay for transposase-accessible chromatin (ATAC)-sequencing on two porcine neutrophil samples to characterize epigenetic regulation of gene expression in these differentiated cells. A deep neutrophil transcriptome detected expression of 10,974 genes. In comparison to previously reported RNA-seq data on eight sorted immune cell types from the same animals, we predicted 833 enriched (significantly higher and 2-fold higher than average across all other cell types) genes in neutrophils. The 833 gene list was significantly enriched for biological processes related to typical neutrophil functions using Gene Ontology and in comparison to human neutrophil RNA-seq data. ATAC-seq detected open chromatin (OP) regions from ~227 million total reads that identified on average 151,789 peaks located in intergenic (67%), intron (24%), promoter-TSS (6%), exon (3%) or TTS (1%) regions. OP regions whose signal is correlated with, and nearby to, genes with enriched neutrophil expression are being analyzed for sites predicted to be bound by transcription factors that could explain neutrophil-enriched expression patterns. The data reported here is the first integrative study of the epigenetics of porcine neutrophil gene expression and provide a valuable resource to elucidate neutrophil transcriptional regulatory networks.
Rapid cell cycling of both circulating and resident memory CD8+ T cells driven by common gamma chain-dependent cytokines
Authors: Jarjour Nicholas N , Wanhainen Kelsey M , Silva Henrique Borges da , Peng Changwei , Martinez Ryan J , Huggins Matthew A , Urban Joseph F , Hamilton Sara E , Jameson Stephen C 
Published: February 2023

Abstract
Diverse populations of resident leukocytes live and self-renew within the tissues of the body, but the mechanisms controlling their proliferation are poorly understood. Among these populations are many memory CD8+ T cells, which are found throughout the body and can locally control reinfection. A poor ability of vaccines to elicit stable and appropriate tissue-resident CD8+ T cell populations has likely contributed to long-standing challenges in vaccinating against several important pathogens. The factors required to support TRM proliferation in homeostasis are not well understood. We propose that proliferating TRMs flexibly use the available members of the common gamma chain-(γC)-dependent cytokine family to persist as bystanders during other immune responses. We have found that many γC-dependent cytokines can mediate cell-intrinsic signaling to drive proliferation of both circulating and resident memory CD8+ T cells of known antigen specificities without cognate antigen. Via transcriptional analysis of resting and in vivo cytokine-stimulated TRMs, we are elucidating downstream signaling and the gene expression signature of cytokine-driven TRM proliferation. We have also found that memory CD8+ T cells proliferate similarly in response to exogenous cytokines or unrelated pathogens, consistent with pathogen-elicited γC-dependent cytokine signals driving memory CD8+ T cell proliferation. These data support the concept that TRMs use γC-dependent cytokines produced during infections to support enhanced proliferation, likely to promote their maintenance. Our findings may lead to novel methods to therapeutically enhance TRM immunity.
Dietary fish oil directly impact viral immunity by modifying CD8 T cell membrane flexibility and bond lifetime under force
Authors: Kolawole Elizabeth Motunrayo , Evavold Brian D 
Published: February 2023

Abstract
Fish oil supplements enriched in omega-3s are increasingly consumed for their health benefits and exhibit immunosuppressive effects on both innate and adaptive immunity. While omega-3s have been shown to reduced inflammatory metabolites, we focused on the direct effects of a high omega-3 diet on T cell activation during viral infection. Using lymphocytic choriomeningitis (LCMV) infection we analyzed CD8 T cells response to antigen. The omega-3 based diet manipulated structural lipid content in plasma membranes leading to stiffer T cells which subsequently resulted in reduced frequency and activation of the prevalence immunodominant epitopes. We further found that a high omega-3 diet decreased 2D affinity and number of tetramer positive polyclonal as well as CD8 T cell receptor transgenic cells at peak anti-viral immunity. In addition to affinity, the bond lifetime under force of antigen recognition was also decreased. This resulted in decreased numbers of SLEC and effector cytokines without impeding viral clearance. Our work indicates that a major effect of dietary omega-3 fatty acids on T cells is the modification of the cell membrane to dampen the initial recognition of antigen leading to decreased but effective immunity.
Lung microbiome influences Coccidioides colonization and invasiveness
Authors: Tejeda-Garibay Susana , Diep Anh L. , Delgadillo Nadia Miranda , Hoyer Katrina K. 
Published: February 2023

Abstract
It has long been thought that the lung is a sterile environment; however, recent studies revealed that healthy lungs are colonized by bacteria, fungi, and viruses. Coccidioidomycosis, also known as Valley fever, is a lung infection caused by the fungal species Coccidioides. Because of poor testing strategies 60–80% of patients are treated with antibiotics prior to accurate diagnosis of coccidioidomycosis. This potentially depletes bacteria with symbiotic relationships within the lung microenvironment and promotes susceptibility to invasion by Coccidioides. Coccidioides immitis is a dimorphic fungal pathogens whose fungal life cycle alternates between the saprophytic phase (soil mycelia) and parasitic phase (tissue infecting spherules). Natural microbial antagonists that inhibit soil Coccidioides immitis have been identified; Bacillus subtilis displays antifungal activity against Coccidioides growth through a clear zone of inhibition between fungi and bacteria. Whether these findings hold true in the host phase of the Coccidioides life cycle is unknown but have major implications for patient treatment. Our preliminary data suggest that host microbiome inhibits Coccidioides growth, and antibiotic treatment shifts or depletes the lung microbiome allowing a niche for Coccidioides growth. We are also exploring how this interface between the lung, Coccidioides, and the microbiome influences host innate and adaptive immune responses. Furthermore, these findings could shape the way physicians assess prescription of antibiotics prior to fungal diagnosis.
Single-Nucleotide Polymorphisms in Glucose-6-Phosphate Dehydrogenase and their Relevance for the Deployment of Primaquine as a Radical Cure for Malaria
Authors: Nain Minu , Gill Jasmita , Mohan Mradul , Sharma Amit 
Published: February 2023

ABSTRACT.
Malaria remains an important public health problem despite efforts to control it. Besides active transmission, relapsing malaria caused by dormant liver stages of Plasmodium vivax and Plasmodium ovale hypnozoites is a major hurdle in malaria control and elimination programs. Primaquine (PQ) is the most widely used drug for radical cure of malaria. Due to its anti-hypnozoite and gametocidal activity, PQ plays a key role in malaria relapse and transmission. The human enzyme glucose-6-phosphate dehydrogenase (G6PD) is crucial in determining the safety of PQ because G6PD-deficient individuals are prone to hemolysis if treated with PQ. Therefore, there is a need to study the prevalence of G6PD-deficient genetic variants in endemic populations to assess the risk of PQ treatment and the necessity to develop alternative treatments. In this work, we discuss the common G6PD variants, their varying enzymatic activity, and their distribution on the three-dimensional structure of G6PD. Our work highlights the important G6PD variants and the need for large-scale G6PD gene polymorphism studies to predict populations at risk of PQ-induced toxicity.
“Our Friend Wang”
Authors: Kamenskikh Mikhail S. , Avdashkin Andrey A. 
Published: February 2023

The article is devoted to the visualization of the image of a Chinese in the periodical press of the Urals in the 1950s. Using the methodology of critical discourse analysis, the authors identify several target groups that form the image, describe their characteristic features and highlight the general and the special characteristics. The source base was made up of materials from the Ural periodical press. During “Great friendship” the Chinese who took part in labor training at enterprises and universities in the USSR became an object of attention of the Ural periodical press from the moment of their appearance in the region in 1954 and up to the almost complete return to their homeland. Periodical publications formed and broadcast to readers a positive image of the Chinese, using some lasting methods of description: putting in an industrial environment, displaying a certain hierarchy in the relationship “diligent” student – “wise” mentor, ‘humanizing’ the character, describing a “typical” and “correct” biography showing positive changes in China after its transition to the socialist path of development.
Recent Advancements in Gremlin-1: Breast cancer
Authors: Nimrah Inam  , Ayesha Hameed  , Lubna Vohra  , Sana Zeeshan  
Published: February 2023

One of the bone’s morphogenic protein (BMP) antagonists, Gremlin-1 or GREM-1, can bind directly to BMPs. GREM-1 can act in either BMP-dependent or -independent pathways, according to research. It reinforces organogenesis, tissue differentiation, and organ fibrosis. Recent research from numerous studies has demonstrated the significance of GREM-1 in the initiation, progression, and even metastasis of different cancers, including breast, cervical, gastric, and colorectal cancers. This review highlights the function of GREM-1 in the development of breast cancer and its effect on the cellular procedures and signalling pathways involved in carcinogenesis.
Keywords: Bone Morphogenetic, Carcinogenesis, Organogenesis, Colorectal Neoplasms, breast cancers, stem cells
Aquifer Vulnerability Assessment by DRASTIC and SI methods: The case study of Guelma Plain, Northeast Algeria
Authors: Baazi Houria 
Published: February 2023

Guelma plain, located in northern Algeria, contains an alluvial nappe that provides economic opportunities such as industrial and agricultural employment. In Guelma, the pressure of anthropogenic origin is combined with unfavorable climatological conditions that expose it to environmental and social risks. The current study aims to assess the level of groundwater vulnerability to pollution using two methods, DRASTIC and SI. These are coupled with the Arc Gis software in order to carry out the mapping. From south to north, several levels of vulnerability have been identified, from low to high. The result comparison allows us to conclude that the SI method is the most appropriate for assessing the vulnerability to pollution of the study region's wetlands. The result of this study can be used as a decision-support tool for the management and protection of the quality of water resources in the Guelma plain.
Demonstration of chewing-related areas in the brain via functional magnetic resonance imaging
Authors: Algin Oktay , Kocak Orhan Murat , Gokcekuyu Yasemin , Turker Kemal S. 
Published: February 2023

IntroductionTo localize and identify chewing-related areas and their connections with other centres in the human brain using functional magnetic resonance imaging (fMRI).Material and methodsThe paradigm of the present study was block designed. Spontaneous and controlled chewing with sugar-free gum was used as the main task in a 3-Tesla fMRI unit with a 32-channel birdcage coil. Our study popu­lation comprised 32 healthy volunteers. To determine possible intersections, we also put the rosary pulling (silent tell one’s beads) movement in the fMRI protocol. The data analyses were performed with the Statistical Parametric Mapping (SPM) toolbox integrated into the Matlab platform.ResultsThe superomedial part of the right cerebellum was activated during either pulling rosary beads or spontaneous chewing. This region, however, was not activated during controlled chewing. We did not find statistically significant activation or connection related to the brain stem.ConclusionsWe have confirmed that the cerebellum plays an important role in chewing. However, we could not find a definite central pattern generator (CPG) in the brain stem, which has been hypothesized to underlie spontaneous chewing.
Dupilumab (Dupixent)
Authors: CADTH  
Published: February 2023

CADTH recommends that Dupixent be reimbursed by public drug plans for the treatment of patients aged 12 years and older with moderate-to-severe atopic dermatitis (AD) whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable, if certain conditions are met.
This recommendation supersedes the CADTH Canadian Drug Expert Committee rec­om­men­dation for this drug and indication on April 24, 2020. A Request for Advice was filed in 2022 by public drug programs to address an inquiry regarding the 2020 reimbursement conditions.
Dupixent should only be covered for patients who previously tried and did not experience improvement with or are unable to use other treatments. These treatments include the highest dose of topically applied drugs combined with phototherapy (where available), and the highest dose of topically applied drugs and at least 1 of the following: methotrexate, cyclosporine, mycophenolate mofetil, or azathioprine.
Dupixent should only be reimbursed if prescribed by a dermatologist, allergist, clinical immunologist, or pediatrician, and if the cost of Dupixent is reduced.