bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation-Specific Metabolic Requirements for NK Cell IFN-γ Production
Authors: Keppel Molly P. , Saucier Nermina , Mah Annelise Y. , Vogel Tiphanie P. , Cooper Megan A. 
Published: January 2015

Abstract
There has been increasing recognition of the importance of cellular metabolism and metabolic substrates for the function and differentiation of immune cells. In this study, for the first time to our knowledge, we investigate the metabolic requirements for production of IFN-γ by freshly isolated NK cells. Primary murine NK cells mainly use mitochondrial oxidative phosphorylation at rest and with short-term activation. Remarkably, we discovered significant differences in the metabolic requirements of murine NK cell IFN-γ production depending upon the activation signal. Stimulation of NK cell IFN-γ production was independent of glycolysis or mitochondrial oxidative phosphorylation when cells were activated with IL-12 plus IL-18. By contrast, stimulation via activating NK receptors required glucose-driven oxidative phosphorylation. Prolonged treatment with high-dose, but not low-dose, IL-15 eliminated the metabolic requirement for receptor stimulation. In summary, this study demonstrates that metabolism provides an essential second signal for induction of IFN-γ production by activating NK cell receptors that can be reversed with prolonged high-dose IL-15 treatment.
CX3CR1 Reduces Kidney Fibrosis by Inhibiting Local Proliferation of Profibrotic Macrophages
Authors: Engel Daniel R. , Krause Torsten A. , Snelgrove Sarah L. , Thiebes Stephanie , Hickey Michael J. , Boor Peter , Kitching A. Richard , Kurts Christian 
Published: January 2015

Abstract
A dense network of macrophages and dendritic cells (DC) expressing the chemokine receptor CX3CR1 populates most tissues. We recently reported that CX3CR1 regulates the abundance of CD11c+ DC in the kidney and thereby promotes renal inflammation in glomerulonephritis. Given that chronic inflammation usually causes fibrosis, we hypothesized that CX3CR1 deficiency should attenuate renal fibrosis. However, when we tested this hypothesis using the DC-independent murine fibrosis model of unilateral ureteral obstruction, kidney fibrosis was unexpectedly more severe, despite less intrarenal inflammation. Two-photon imaging and flow cytometry revealed in kidneys of CX3CR1-deficient mice more motile Ly6C/Gr-1+ macrophages. Flow cytometry verified that renal macrophages were more abundant in the absence of CX3CR1 and produced more of the key profibrotic mediator, TGF-β. Macrophages accumulated because of higher intrarenal proliferation, despite reduced monocyte recruitment and higher signs of apoptosis within the kidney. These findings support the theory that tissue macrophage numbers are regulated through local proliferation and identify CX3CR1 as a regulator of such proliferation. Thus, CX3CR1 inhibition should be avoided in DC-independent inflammatory diseases because it may promote fibrosis.
IRAK-M Promotes Alternative Macrophage Activation and Fibroproliferation in Bleomycin-Induced Lung Injury
Authors: Ballinger Megan N. , Newstead Michael W. , Zeng Xianying , Bhan Urvashi , Mo Xiaokui M. , Kunkel Steven L. , Moore Bethany B. , Flavell Richard , Christman John W. , Standiford Theodore J. 
Published: January 2015

Abstract
Idiopathic pulmonary fibrosis is a devastating lung disease characterized by inflammation and the development of excessive extracellular matrix deposition. Currently, there are only limited therapeutic intervenes to offer patients diagnosed with pulmonary fibrosis. Although previous studies focused on structural cells in promoting fibrosis, our study assessed the contribution of macrophages. Recently, TLR signaling has been identified as a regulator of pulmonary fibrosis. IL-1R–associated kinase-M (IRAK-M), a MyD88-dependent inhibitor of TLR signaling, suppresses deleterious inflammation, but may paradoxically promote fibrogenesis. Mice deficient in IRAK-M (IRAK-M−/−) were protected against bleomycin-induced fibrosis and displayed diminished collagen deposition in association with reduced production of IL-13 compared with wild-type (WT) control mice. Bone marrow chimera experiments indicated that IRAK-M expression by bone marrow–derived cells, rather than structural cells, promoted fibrosis. After bleomycin, WT macrophages displayed an alternatively activated phenotype, whereas IRAK-M−/− macrophages displayed higher expression of classically activated macrophage markers. Using an in vitro coculture system, macrophages isolated from in vivo bleomycin-challenged WT, but not IRAK-M−/−, mice promoted increased collagen and α-smooth muscle actin expression from lung fibroblasts in an IL-13–dependent fashion. Finally, IRAK-M expression is upregulated in peripheral blood cells from idiopathic pulmonary fibrosis patients and correlated with markers of alternative macrophage activation. These data indicate expression of IRAK-M skews lung macrophages toward an alternatively activated profibrotic phenotype, which promotes collagen production, leading to the progression of experimental pulmonary fibrosis.
Elevation of c-MYC Disrupts HLA Class II–Mediated Immune Recognition of Human B Cell Tumors
Authors: God Jason M. , Cameron Christine , Figueroa Janette , Amria Shereen , Hossain Azim , Kempkes Bettina , Bornkamm Georg W. , Stuart Robert K. , Blum Janice S. , Haque Azizul 
Published: January 2015

Abstract
Elevated levels of the transcription factor c-myc are strongly associated with various cancers, and in particular B cell lymphomas. Although many of c-MYC’s functions have been elucidated, its effect on the presentation of Ag through the HLA class II pathway has not been reported previously. This is an issue of considerable importance, given the low immunogenicity of many c-MYC–positive tumors. We report in this paper that increased c-MYC expression has a negative effect on the ability of B cell lymphomas to functionally present Ags/peptides to CD4+ T cells. This defect was associated with alterations in the expression of distinct cofactors as well as interactions of antigenic peptides with class II molecules required for the presentation of class II–peptide complexes and T cell engagement. Using early passage Burkitt’s lymphoma (BL) tumors and transformed cells, we show that compared with B lymphoblasts, BL cells express decreased levels of the class II editor HLA-DM, lysosomal thiol-reductase GILT, and a 47-kDa enolase-like protein. Functional Ag presentation was partially restored in BL cells treated with a c-MYC inhibitor, demonstrating the impact of this oncogene on Ag recognition. This restoration of HLA class II–mediated Ag presentation in early passage BL tumors/cells was linked to enhanced HLA-DM expression and a concurrent decrease in HLA-DO in BL cells. Taken together, these results reveal c-MYC exerts suppressive effects at several critical checkpoints in Ag presentation, which contribute to the immunoevasive properties of BL tumors.
Neurturin Influences Inflammatory Responses and Airway Remodeling in Different Mouse Asthma Models
Authors: Mauffray Marion , Domingues Olivia , Hentges François , Zimmer Jacques , Hanau Daniel , Michel Tatiana 
Published: January 2015

Abstract
Neurturin (NTN) was previously described for its neuronal activities, but recently, we have shown that this factor is also involved in asthma physiopathology. However, the underlying mechanisms of NTN are unclear. The aim of this study was to investigate NTN involvement in acute bronchial Th2 responses, to analyze its interaction with airway structural cells, and to study its implication in remodeling during acute and chronic bronchial inflammation in C57BL/6 mice. We analyzed the features of allergic airway inflammation in wild-type and NTN−/− mice after sensitization with two different allergens, OVA and house dust mite. We showed that NTN−/− dendritic cells and T cells had a stronger tendency to activate the Th2 pathway in vitro than similar wild-type cells. Furthermore, NTN−/− mice had significantly increased markers of airway remodeling like collagen deposition. NTN−/− lung tissues showed higher levels of neutrophils, cytokine-induced neutrophil chemoattractant, matrix metalloproteinase 9, TNF-α, and IL-6. Finally, NTN had the capacity to decrease IL-6 and TNF-α production by immune and epithelial cells, showing a direct anti-inflammatory activity on these cells. Our findings support the hypothesis that NTN could modulate the allergic inflammation in different mouse asthma models.
Cancer-Associated Oxidoreductase ERO1-α Drives the Production of Tumor-Promoting Myeloid-Derived Suppressor Cells via Oxidative Protein Folding
Authors: Tanaka Tsutomu , Kajiwara Toshimitsu , Torigoe Toshihiko , Okamoto Yoshiharu , Sato Noriyuki , Tamura Yasuaki 
Published: January 2015

Abstract
Endoplasmic reticulum disulfide oxidase ERO1-α plays a role in the formation of disulfide bonds in collaboration with protein disulfide isomerase. Disulfide bond formation is required for the proper conformation and function of secreted and cell surface proteins. We found that ERO1-α was overexpressed in a variety of tumor types; therefore, we examined its role in tumor growth. In BALB/c mice, knockdown of ERO1-α within 4T1 mouse mammary gland cancer (KD) cells caused retardation of in vivo tumor growth compared with tumor growth of scrambled control (SCR) cells. In contrast, when ERO1-α–overexpressed 4T1 (OE) cells were compared with mock control cells, OE cells showed augmented tumor growth. However, differences in tumor growth were not observed among four groups of nude mice, suggesting that expression of ERO1-α diminished antitumor immunity. We observed dense peritumoral granulocytic infiltrates in tumors of wild-type 4T1 and SCR cells but not KD cells, and these cells were identified as polymorphonuclear myeloid-derived suppressor cells (MDSCs). In addition, production of G-CSF and CXCL1/2, which have intramolecular disulfide bonds, from KD cells was significantly decreased compared with that from SCR cells. In contrast, OE cells produced a larger amount of these molecules than did mock cells. These changes were regulated at the posttranscriptional level. These results suggest that overexpression of ERO1-α in the tumor inhibits the T cell response by recruiting polymorphonuclear MDSCs via regulation of MDSC-prone cytokines and chemokines.
Expansion of an Atypical NK Cell Subset in Mouse Models of Systemic Lupus Erythematosus
Authors: Voynova Elisaveta N. , Skinner Jeffrey , Bolland Silvia 
Published: January 2015

Abstract
Chronic inflammatory conditions, such as in autoimmune disease, can disturb immune cell homeostasis and induce the expansion of normally rare cell populations. In our analysis of various murine models of lupus, we detect increased frequency of an uncommon subset identified as NK1.1+CD11c+CD122+MHC class II+. These cells share characteristics with the NK cell lineage and with cells previously described as IFN-producing killer dendritic cells: 1) they depend on IL-15 and express E4BP4; 2) they are cytotoxic and produce type I and type II IFN upon activation; and 3) they are efficient APCs both through MHC class II expression and in cross-presentation to CD8s. These atypical NK cells are responsive to TLR stimulation and thus are most abundant in mice with high copy number of the Tlr7 gene. They are highly proliferative as assessed by in vivo BrdU incorporation. In adoptive transfer experiments they persist in high numbers for months and maintain their surface marker profile, indicating that this population is developmentally stable. Gene expression analyses on both mRNA and microRNAs show a modified cell cycle program in which various miR-15/16 family members are upregulated, presumably as a consequence of the proliferative signal mediated by the increased level of growth factors, Ras and E2F activity. Alternatively, low expression of miR-150, miR-181, and miR-744 in these cells implies a reduction in their differentiation capacity. These results suggest that cells of the NK lineage that undergo TLR stimulation might turn on a proliferative program in detriment of their full differentiation into mature NK cells.
Memory T Cells Specific for Murine Cytomegalovirus Re-Emerge after Multiple Challenges and Recapitulate Immunity in Various Adoptive Transfer Scenarios
Authors: Quinn Michael , Turula Holly , Tandon Mayank , Deslouches Berthony , Moghbeli Toktam , Snyder Christopher M. 
Published: January 2015

Abstract
Reconstitution of CMV-specific immunity after transplant remains a primary clinical objective to prevent CMV disease, and adoptive immunotherapy of CMV-specific T cells can be an effective therapeutic approach. Because of viral persistence, most CMV-specific CD8+ T cells become terminally differentiated effector phenotype CD8+ T cells (TEFF). A minor subset retains a memory-like phenotype (memory phenotype CD8+ T cells [TM]), but it is unknown whether these cells retain memory function or persist over time. Interestingly, recent studies suggest that CMV-specific CD8+ T cells with different phenotypes have different abilities to reconstitute sustained immunity after transfer. The immunology of human CMV infections is reflected in the murine CMV (MCMV) model. We found that human CMV– and MCMV-specific T cells displayed shared genetic programs, validating the MCMV model for studies of CMV-specific T cells in vivo. The MCMV-specific TM population was stable over time and retained a proliferative capacity that was vastly superior to TEFF. Strikingly, after transfer, TM established sustained and diverse T cell populations even after multiple challenges. Although both TEFF and TM could protect Rag−/− mice, only TM persisted after transfer into immune replete, latently infected recipients and responded if recipient immunity was lost. Interestingly, transferred TM did not expand until recipient immunity was lost, supporting that competition limits the Ag stimulation of TM. Ultimately, these data show that CMV-specific TM retain memory function during MCMV infection and can re-establish CMV immunity when necessary. Thus, TM may be a critical component for consistent, long-term adoptive immunotherapy success.
IRF5 Deficiency Ameliorates Lupus but Promotes Atherosclerosis and Metabolic Dysfunction in a Mouse Model of Lupus-Associated Atherosclerosis
Authors: Watkins Amanda A. , Yasuda Kei , Wilson Gabriella E. , Aprahamian Tamar , Xie Yao , Maganto-Garcia Elena , Shukla Prachi , Oberlander Lillian , Laskow Bari , Menn-Josephy Hanni , Wu Yuanyuan , Duffau Pierre , Fried Susan K. , Lichtman Andrew H. , Bonegio Ramon G. , Rifkin Ian R. 
Published: January 2015

Abstract
Premature atherosclerosis is a severe complication of lupus and other systemic autoimmune disorders. Gain-of-function polymorphisms in IFN regulatory factor 5 (IRF5) are associated with an increased risk of developing lupus, and IRF5 deficiency in lupus mouse models ameliorates disease. However, whether IRF5 deficiency also protects against atherosclerosis development in lupus is not known. In this study, we addressed this question using the gld.apoE−/− mouse model. IRF5 deficiency markedly reduced lupus disease severity. Unexpectedly, despite the reduction in systemic immune activation, IRF5-deficient mice developed increased atherosclerosis and also exhibited metabolic dysregulation characterized by hyperlipidemia, increased adiposity, and insulin resistance. Levels of the atheroprotective cytokine IL-10 were reduced in aortae of IRF5-deficient mice, and in vitro studies demonstrated that IRF5 is required for IL-10 production downstream of TLR7 and TLR9 signaling in multiple immune cell types. Chimera studies showed that IRF5 deficiency in bone marrow–derived cells prevents lupus development and contributes in part to the increased atherosclerosis. Notably, IRF5 deficiency in non–bone marrow–derived cells also contributes to the increased atherosclerosis through the generation of hyperlipidemia and increased adiposity. Together, our results reveal a protective role for IRF5 in lupus-associated atherosclerosis that is mediated through the effects of IRF5 in both immune and nonimmune cells. These findings have implications for the proposed targeting of IRF5 in the treatment of autoimmune disease as global IRF5 inhibition may exacerbate cardiovascular disease in these patients.
The Place of Idealism in Scientific –Technological Advancement in Nigeria
Authors: Ehigie JO , Osaigbovo JE 
Published: January 2015

Idealism, a School of Thought which emphasizes a kind of philosophy that described ultimate reality as ‘thought’ or ‘mind’ has fallen under the sledge hammer of some philosophers, especially the empiricists because, the empiricists believe that Idealism has no practical or empirical basis. Due to the current emphasis on the acquisition of scientific and technological knowledge in Nigeria, there has been the coming together of the wits on how best to achieve the said objective. This paper is aimed at contributing its quota by daring to propose Idealism as inevitability in the acquisition of scientific and technological knowledge. Against this backdrop, this paper examines the role of Idealism in Scientific Technological Advancement in Nigeria. While trying to do this, this writer critically examined the epistemological position of the Idealists, bringing out the inadequacies. Then proceeded to bring out the plausible roles Idealism would probably play in the acquisition of scientific and technological knowledge.
Incidence of Gummosis and Its Effect on Growth Attributes of Terminalia ivorensis A. Chev. and Taminalia mantaly H. Perrier in Port Harcourt, Nigeria
Authors: Omokhua GE , Chima UD 
Published: January 2015

Fifteen years old trees of Terminalia ivorensis and Taminalia mantaly established as landscape plants were studied for gummosis incidence and its effects on the species growth attributes. The study was conducted at the University of Port Harcourt, Port Harcourt, Nigeria in January to December, 2011. The result showed that Phytophlthora palmivora is the causal pathogen of gummosis in Terminalia ivorensis and T. mantaly at the University of Port Harcourt. The disease incidence was 76% and 29.5% in T. mantaly and T. ivorensis respectively. There were significant differences in disease incidence between the two species at 5% level of probability. The disease also had significant impact on the growth attributes of the two species. There were significant differences between healthy and infested trees of the species at 5% level of probability. An integrated management approach should be developed to curb the incidence of the diseases and reduce its effects on growth and development of the Terminalia species. The strategies should involve: appropriate cultural practices to mitigate disease spread, application of environmental friendly practices and breeding for resistant varieties.Keywords: incidence, Gummosis, growth, Terminalia ivorensis, T.mantaly, Phytophthora palmivora
Assessment of Water Supply Quality in Awka, Anambra State, Nigeria
Authors: Ezeabasili ACC , Okoro BU , Okonkwo AU 
Published: January 2015

The patronage of water of questionable qualities in the study area due to the failure of the Anambra State Water Corporation to provide potable water supply in Awka and environs prompted this research work. Various water sources patronized in the study area were collected and subjected to physical, chemical and microbial analysis to determine their pollution/contamination status. The work revealed that the surface and borehole/well Water sources are microbiologically polluted. Ca+2 and Mg+2 levels in water samples were high, this results to hard water. Fe+2 concentrations in the water samples ranged from 1.20-5.00 mg/l. 100% of samples exceeded the MPL of 0.3mg/l, low pH favours oxidation of ferrous iron to ferric iron, giving an objectionable reddish-brown colour to the water. Iron also promotes the growth of “iron bacteria”. Aggressive public awareness of the pollution status, routine check of the water quality and increased sanitary conditions in the study area in order to ameliorate this problem were recommended.Keywords: Patronage, Contamination, Aggressive, Water Quality
The Din of Malcolm
Authors: Ambar Saladin 
Published: January 2015

Abstract
This article addresses the purpose and question of Malcolm X's (El-Hajj Malik El-Shabazz's) articulation of Islam during his travels to Europe in the last months of his life and its implications for Africana religions fifty years after his assassination. While there has been growing scholarly attention to the international dimension of Malcolm X's politics, there has been far less attention paid to the projections of his religious identity abroad; this is especially true for his time in Europe. By focusing on three speeches he delivered in Paris, Oxford, and London in context, I hope to illuminate how and why Malcolm X's Muslim identity in Europe has significance for both contemporary scholars and laypersons alike—inasmuch as his personal presentation of Islam reflected, at times, both a reluctance to make his faith central to his arguments, as well as an acceptance of sorts of the idea that religion had a place in the broader anticolonial and antiracist movements of his era.
El-Hajj Malik El-Shabazz or Malcolm X
Authors: Burrows Cedric Dewayne 
Published: January 2015

Abstract
During the revival of El-Hajj Malik El-Shabazz's image in the late 1980s and early 1990s, composition anthologies known as readers began to heavily anthologize sections from The Autobiography of Malcolm X. This article analyzes how Shabazz has been constructed in readers by examining three popular examples—The Conscious Reader, Rereading America, and The Prose Reader. I argue that readers tend to focus on Shabazz's political image as a civil rights leader while ignoring how his evolving religious viewpoints influenced his political views.
Between the Secular and the Sectarian
Authors: Lubin Alex 
Published: January 2015

Abstract
This article explores the combined spiritual and political transformations Malcolm X's thought underwent during his two tours of the Middle East and North Africa in 1964. Drawing on personal communications with figures who met with Malcolm X in the region, I uncover the religious and political influences on Malcolm X while he was there. I pay special attention to Malcolm X's two visits to Beirut, where I argue he encountered a particular form of cosmopolitan sectarianism that both challenged and perhaps influenced his evolving worldview.
X Marks the Spot
Authors: O'Dell Emily Jane 
Published: January 2015

Abstract
Though Malik El-Shabazz's travels in the Middle East and Africa put him in touch with the most progressive revolutionary movements of his time, it was his ongoing contacts with students, scholars, and religious leaders from Sudan that had a truly transformative effect on his beliefs about religion and race. This article explores how Malcolm X was influenced by friends and contacts who lived in Sudan and the Sudanese diaspora. It pays special attention to the role of Sheikh Ahmed Hassoun, a religious scholar who became spiritual adviser to Shabazz and the Muslim Mosque, Inc., in 1964.
Christ, Creature, and Reader:
Authors: Barbara Zimbalist 
Published: January 2015

ABSTRACT
This article reads The Book of Margery Kempe as a rhetorically innovative visionary text that offered late medieval readers a powerful new method of accessing the vernacular Word of God. Through the textual representation of Christ's visionary speech and Margery's spoken responses, the Book establishes a devotional mode within which Margery's imitative prayer and public instruction exemplify effective verbal engagement with Christ. This departure from traditional critical views of the Book as the quintessential expression of medieval women's affective corporeality shows the Book in a new light: as the textual exemplar of a literary mode of engagement with the divine through vernacular reading and participatory speech.