bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancer of Zeste Homolog 2 Is a Negative Regulator of Mitochondria-Mediated Innate Immune Responses
Authors: Chen Shuai , Sheng Chunjie , Liu Dong , Yao Chen , Gao Shijuan , Song Liping , Jiang Wei , Li Jiandong , Huang Wenlin 
Published: August 2013

Abstract
The intracellular RIG-I–like receptors recognize 5′-triphosphate viral genomic RNA and initiate the production of cytokines through mitochondria adaptor VISA. The regulation of this signal pathway is largely unknown. In this study, we report that the histone methyltransferase enhancer of zeste homolog 2 (EZH2) inhibits RIG-I signal pathway in an methyltransferase-independent manner. Knockdown EZH2 expression enhances VISA-induced activation of IFN-β promoter and NF-κB signaling. Cytosolic distributed EZH2 colocalizes with VISA and binds to its caspase recruitment domain (CARD), thus blocking its association with RIG-I. During the infection of influenza A virus (IAV) strain A/WSN/33 (WSN), EZH2 translocates to RIG-I and continuously interferes the interaction between RIG-I and VISA. Both N and C termini of EZH2 interact with VISA and attenuate its downstream signaling. WSN virus infection–induced expression of TNF-α, IFN-β, and IL-8 is inhibited by EZH2 and its catalytic dead form ΔSET. EZH2 overexpression facilitates the replications of IAV strains WSN and A/Puerto Rico/8/34 influenza virus. Knockdown EZH2 expression activates infection-induced IFN-β transcription and inhibits virus replication. We further provided evidence to show that pharmacological disruption of EZH2 expression by its inhibitor 3-deazaneplanocin A activates innate immune responses and attenuates the replication of WSN virus in HeLa, MDCK, and mouse primary bone marrow–derived macrophages, but not in IFN-deficient Vero cells. Collectively, these results revealed that EZH2 binds to VISA and interferes with the interaction between VISA and RIG-I. Targeting EZH2 activates mitochondria-mediated antiviral innate immune responses, and thus represses the replication of IAV in cells.
Two Phases of Inflammatory Mediator Production Defined by the Study of IRAK2 and IRAK1 Knock-in Mice
Authors: Pauls Eduardo , Nanda Sambit K. , Smith Hilary , Toth Rachel , Arthur J. Simon C. , Cohen Philip 
Published: August 2013

Abstract
The roles of IL-1R–associated kinase (IRAK)2 and IRAK1 in cytokine production were investigated using immune cells from knock-in mice expressing the TNFR-associated factor 6 (TRAF6) binding-defective mutant IRAK2[E525A] or the catalytically inactive IRAK1[D359A] mutant. In bone marrow–derived macrophages (BMDMs), the IRAK2–TRAF6 interaction was required for the late (2–8 h) but not the early phase (0–2 h) of il6 and tnfa mRNA production, and hence for IL-6 and TNF-α secretion by TLR agonists that signal via MyD88. Loss of the IRAK2–TRAF6 interaction had little effect on the MyD88-dependent production of anti-inflammatory molecules produced during the early phase, such as Dual Specificity Phosphatase 1, and a modest effect on IL-10 secretion. The LPS/TLR4-stimulated production of il6 and tnfa mRNA and IL-6 and TNF-α secretion was hardly affected, because the Toll/IL-1R domain–containing adapter-inducing IFN-β (TRIF) signaling pathway was used instead of the IRAK2–TRAF6 interaction to sustain late-phase mRNA production. IRAK1 catalytic activity was not rate limiting for il6, tnfa, or il10 mRNA production or the secretion of these cytokines by BMDMs, but IFN-β mRNA induction by TLR7 and TLR9 agonists was greatly delayed in plasmacytoid dendritic cells (pDCs) from IRAK1[D359A] mice. In contrast, IFN-β mRNA production was little affected in pDCs from IRAK2[E525A] mice, but subsequent IFN-α mRNA production and IFN-α secretion were reduced. IFN-β and IFN-α production were abolished in pDCs from IRAK1[D359A] × IRAK2[E525A] double knock-in mice. Our results establish that the IRAK2–TRAF6 interaction is rate limiting for the late, but not the early phase of cytokine production in BMDM and pDCs, and that the IRAK2–TRAF6 interaction is needed to sustain IκB-inducing kinase β activity during prolonged activation of the MyD88 signaling.
The C-Type Lectin Receptor DCIR Is Crucial for the Development of Experimental Cerebral Malaria
Authors: Maglinao Maha , Klopfleisch Robert , Seeberger Peter H. , Lepenies Bernd 
Published: August 2013

AbstractCerebral malaria (CM) is the most severe complication of malaria. The murine Plasmodium berghei ANKA (PbA) infection model has helped to identify crucial players in the pathogenesis of CM. However, the role of pattern recognition receptors in innate immunity to CM induction is still poorly understood. C-type lectin receptors (CLRs) represent a family of pattern recognition receptors that recognize carbohydrate structures on pathogens and self-Ags often in a Ca2+-dependent manner. In this study, we investigated the role of the CLR dendritic cell immunoreceptor (DCIR) in the genesis of CM. Using the murine PbA infection, we show in this article that DCIR is essential for the development of CM. Although PbA infection led to 80% CM in wild-type C57BL/6 mice, DCIR-deficient mice were highly protected with only 15% CM development. In accordance with the reduced CM incidence in DCIR−/− mice, CD8+ T cell sequestration was markedly reduced in brains of PbA-infected DCIR−/− mice, which was accompanied by reduced brain inflammation. Reduced T cell sequestration in the brain was caused by decreased TNF-α levels in sera, as well as a modulated activation of CD4+ and CD8+ T cells in spleen of PbA-infected DCIR−/− mice. This study indicates that DCIR is critically involved in CM induction, thus highlighting the importance of this CLR in innate immunity during malaria infection.
Overexpression of Membrane-Bound Fas Ligand (CD95L) Exacerbates Autoimmune Disease and Renal Pathology in Pristane-Induced Lupus
Authors: Bossaller Lukas , Rathinam Vijay A. K. , Bonegio Ramon , Chiang Ping-I , Busto Patricia , Wespiser Adam R. , Caffrey Daniel R. , Li Quan-Zhen , Mohan Chandra , Fitzgerald Katherine A. , Latz Eicke , Marshak-Rothstein Ann 
Published: August 2013

Abstract
Loss-of-function mutations in the Fas death receptor or its ligand result in a lymphoproliferative syndrome and exacerbate clinical disease in most lupus-prone strains of mice. One exception is mice injected with 2,6,10,14-tetramethylpentadecane (TMPD), a hydrocarbon oil commonly known as pristane, which induces systemic lupus erythematosus–like disease. Although Fas/Fas ligand (FasL) interactions have been strongly implicated in the activation-induced cell death of both lymphocytes and other APCs, FasL can also trigger the production of proinflammatory cytokines. FasL is a transmembrane protein with a matrix metalloproteinase cleavage site in the ectodomain. Matrix metalloproteinase cleavage inactivates membrane-bound FasL and releases a soluble form reported to have both antagonist and agonist activity. To better understand the impact of FasL cleavage on both the proapoptotic and proinflammatory activity of FasL, its cleavage site was deleted through targeted mutation to produce the deleted cleavage site (ΔCS) mouse line. ΔCS mice express higher levels of membrane-bound FasL than do wild-type mice and fail to release soluble FasL. To determine to what extent FasL promotes inflammation in lupus mice, TMPD-injected FasL-deficient and ΔCS BALB/c mice were compared with control TMPD-injected BALB/c mice. We found that FasL deficiency significantly reduced the early inflammatory exudate induced by TMPD injection. In contrast, ΔCS mice developed a markedly exacerbated disease profile associated with a higher frequency of splenic neutrophils and macrophages, a profound change in anti-nuclear Ab specificity, and markedly increased proteinuria and kidney pathology compared with controls. These results demonstrate that FasL promotes inflammation in TMPD-induced autoimmunity, and its cleavage limits FasL proinflammatory activity.
Paradoxical Effect of Cortistatin Treatment and Its Deficiency on Experimental Autoimmune Encephalomyelitis
Authors: Souza-Moreira Luciana , Morell Maria , Delgado-Maroto Virginia , Pedreño Marta , Martinez-Escudero Laura , Caro Marta , O’Valle Francisco , Luque Raul , Gallo Milagros , de Lecea Luis , Castaño Justo P. , Gonzalez-Rey Elena 
Published: August 2013

AbstractCortistatin is a cyclic-neuropeptide produced by brain cortex and immune cells that shows potent anti-inflammatory activity. In this article, we investigated the effect of cortistatin in two models of experimental autoimmune encephalomyelitis (EAE) that mirror chronic and relapsing-remitting multiple sclerosis. A short-term systemic treatment with cortistatin reduced clinical severity and incidence of EAE, the appearance of inflammatory infiltrates in spinal cord, and the subsequent demyelination and axonal damage. This effect was associated with a reduction of the two deleterious components of the disease, namely, the autoimmune and inflammatory response. Cortistatin decreased the presence/activation of encephalitogenic Th1 and Th17 cells in periphery and nervous system, and downregulated various inflammatory mediators, whereas it increased the number of regulatory T cells with suppressive effects on the encephalitogenic response. Moreover, cortistatin regulated glial activity and favored an active program of neuroprotection/regeneration. We further used cortistatin-deficient mice to investigate the role of endogenous cortistatin in the control of immune responses. Surprisingly, cortistatin-deficient mice were partially resistant to EAE and other inflammatory disorders, despite showing competent inflammatory/autoreactive responses. This unexpected phenotype was associated with elevated circulating glucocorticoids and an anxiety-like behavior. Our findings provide a powerful rationale for the assessment of the efficacy of cortistatin as a novel multimodal therapeutic approach to treat multiple sclerosis and identify cortistatin as a key endogenous component of neuroimmune system.
Divergent Immunomodulating Effects of Probiotics on T Cell Responses to Oral Attenuated Human Rotavirus Vaccine and Virulent Human Rotavirus Infection in a Neonatal Gnotobiotic Piglet Disease Model
Authors: Chattha Kuldeep S. , Vlasova Anastasia N. , Kandasamy Sukumar , Rajashekara Gireesh , Saif Linda J. 
Published: August 2013

AbstractRotaviruses (RVs) are a leading cause of childhood diarrhea. Current oral vaccines are not effective in impoverished countries where the vaccine is needed most. Therefore, alternative affordable strategies are urgently needed. Probiotics can alleviate diarrhea in children and enhance specific systemic and mucosal Ab responses, but the T cell responses are undefined. In this study, we elucidated the T cell and cytokine responses to attenuated human RV (AttHRV) and virulent human RV (HRV) in gnotobiotic pigs colonized with probiotics (Lactobacillus rhamnosus strain GG [LGG] and Bifidobacterium lactis Bb12 [Bb12]), mimicking gut commensals in breastfed infants. Neonatal gnotobiotic pigs are the only animal model susceptible to HRV diarrhea. Probiotic colonized and nonvaccinated (Probiotic) pigs had lower diarrhea and reduced virus shedding postchallenge compared with noncolonized and nonvaccinated pigs (Control). Higher protection in the Probiotic group coincided with higher ileal T regulatory cells (Tregs) before and after challenge, and higher serum TGF-β and lower serum and biliary proinflammatory cytokines postchallenge. Probiotic colonization in vaccinated pigs enhanced innate serum IFN-α, splenic and circulatory IFN-γ–producing T cells, and serum Th1 cytokines, but reduced serum Th2 cytokines compared with noncolonized vaccinated pigs (Vac). Thus, LGG+Bb12 induced systemic Th1 immunostimulatory effects on oral AttHRV vaccine that coincided with lower diarrhea severity and reduced virus shedding postchallenge in Vac+Pro compared with Vac pigs. Previously unreported intestinal CD8 Tregs were induced in vaccinated groups postchallenge. Thus, probiotics LGG+Bb12 exert divergent immunomodulating effects, with enhanced Th1 responses to oral AttHRV vaccine, whereas inducing Treg responses to virulent HRV.
Activation of p38α in T Cells Regulates the Intestinal Host Defense against Attaching and Effacing Bacterial Infections
Authors: Shim Eun-Jin , Bang Bo-Ram , Kang Seung-Goo , Ma Jianhui , Otsuka Motoyuki , Kang Jiman , Stahl Martin , Han Jiahuai , Xiao Changchun , Vallance Bruce A. , Kang Young Jun 
Published: August 2013

Abstract
Intestinal infections by attaching and effacing (A/E) bacterial pathogens cause severe colitis and bloody diarrhea. Although p38α in intestinal epithelial cells (IEC) plays an important role in promoting protection against A/E bacteria by regulating T cell recruitment, its impact on immune responses remains unclear. In this study, we show that activation of p38α in T cells is critical for the clearance of the A/E pathogen Citrobacter rodentium. Mice deficient of p38α in T cells, but not in macrophages or dendritic cells, were impaired in clearing C. rodentium. Expression of inflammatory cytokines such as IFN-γ by p38α-deficient T cells was reduced, which further reduced the expression of inflammatory cytokines, chemokines, and antimicrobial peptide by IECs and led to reduced infiltration of T cells into the infected colon. Administration of IFN-γ activated the mucosal immunity to C. rodentium infection by increasing the expression of inflammation genes and the recruitment of T cells to the site of infection. Thus, p38α contributes to host defense against A/E pathogen infection by regulating the expression of inflammatory cytokines that activate host defense pathways in IECs.
Induction of HIV-1 Broad Neutralizing Antibodies in 2F5 Knock-in Mice: Selection against Membrane Proximal External Region–Associated Autoreactivity Limits T-Dependent Responses
Authors: Verkoczy Laurent , Chen Yao , Zhang Jinsong , Bouton-Verville Hilary , Newman Amanda , Lockwood Bradley , Scearce Richard M. , Montefiori David C. , Dennison S. Moses , Xia Shi-Mao , Hwang Kwan-Ki , Liao Hua-Xin , Alam S. Munir , Haynes Barton F. 
Published: August 2013

Abstract
A goal of HIV-1 vaccine development is to elicit broadly neutralizing Abs (BnAbs). Using a knock-in (KI) model of 2F5, a human HIV-1 gp41 membrane proximal external region (MPER)–specific BnAb, we previously demonstrated that a key obstacle to BnAb induction is clonal deletion of BnAb-expressing B cells. In this study of this model, we provide a proof-of-principle that robust serum neutralizing IgG responses can be induced from pre-existing, residual, self-reactive BnAb-expressing B cells in vivo using a structurally compatible gp41 MPER immunogen. Furthermore, in CD40L-deficient 2F5 KI mice, we demonstrate that these BnAb responses are elicited via a type II T-independent pathway, coinciding with expansion and activation of transitional splenic B cells specific for 2F5's nominal gp41 MPER-binding epitope (containing the 2F5 neutralization domain ELDKWA). In contrast, constitutive production of nonneutralizing serum IgGs in 2F5 KI mice is T dependent and originates from a subset of splenic mature B2 cells that have lost their ability to bind 2F5's gp41 MPER epitope. These results suggest that residual, mature B cells expressing autoreactive BnAbs, like 2F5 as BCR, may be limited in their ability to participate in T-dependent responses by purifying selection that selectively eliminates reactivity for neutralization epitope-containing/mimicked host Ags.
Acute visual loss as the initial presentation in a child with systemic Burkitt lymphoma
Authors: Kourti Maria , Mantadakis Elpidoforos , Anastasiou Athanassia , Koliouskas Dimitrios 
Published: August 2013

AbstractNon-Hodgkin lymphoma (NHL) accounts for 10% of pediatric malignancies and is the third most common malignancy in childhood. We report a previous healthy 3-year-old boy with stage IV Burkitt lymphoma presenting with acute visual loss. In funduscopy his pupils were fixed at 6 mm in diameter without light perception. He started therapy according to the UKCCSG 9003 protocol. The boy didn′t show any visual improvement but some slight light perception despite his partial remission after CYVE II. He died of neutropenic septicemia before his scheduled radiotherapy. In conclusion, loss of vision is a rare presenting sign in NHL. Differential diagnosis is crucial as early diagnosis and effective treatment are important for survival as well as for visual restoration.
Four rare extranodal sites seen on FDG PET/CT in a single patient of disseminated lymphoma
Authors: Puranik Ameya D. , Agrawal Archi , Purandare Nilendu , Shah Sneha , Rangarajan Venkatesh 
Published: August 2013

AbstractExtranodal disease refers to lymphomatous infiltration of anatomic sites other than lymph nodes. With the advent of FDG PET/CT for staging, rare sites of extranodal disease have been documented. We report a case of Non- Hodgkin′s lymphoma with four rare extranodal sites, namely adrenal, peripheral nerves, pancreas and prostate, in the same patient, detected on FDG PET/CT imaging.
Oral submucous fibrosis at pediatric age, now time to think: Series of two cases
Authors: Gupta Vinay K. , Malhotra Seema , Patil Ranjit , Tripathi Anurag 
Published: August 2013

AbstractThe younger generation is consuming areca nut and areca nut products, which is coming in the market with different multicolored attractive pouches and easily available in each and every corner of the road. For the children from the lower socioeconomic strata, areca nut use is rampant. Alarmingly, it has been seen that the highest period of risk for engaging in areca nut alone is between the ages of 5 and 12. Oral submucous fibrosis associated with areca nut in children is a great concern for the Society and the Government. Factors associated with this report for consuming areca nut are levels of awareness, household environment, peer pressure, low cost, easy availability etc.
Stomach metastasis of breast carcinoma mimicking primary gastric neoplasm on fluorodeoxy glucose-positron emission tomography-computed tomography
Authors: Joshi Prathamesh , Lele Vikram , Jain Reetu , Khubchandani Shaila , Sinhasan Shraddha 
Published: August 2013

AbstractWe present fluorodeoxy glucose positron emission tomography-computed tomography (FDG-PET/CT) findings in a case of breast carcinoma. The PET/CT findings in this case were suspicious of second primary neoplasm in the stomach. However, on endoscopic biopsy, the lesion was found to be stomach metastasis of breast carcinoma with estrogen receptor positivity. Stomach is a rare site of breast carcinoma metastasis. Our case suggests that it is difficult to distinguish a stomach metastasis of breast cancer from a primary gastric cancer on the basis of clinical and imaging features. However, this differential diagnosis must be kept in mind and it is important to make such distinction because of its implications on patient management.
Fatal hematogenous relapse of mucinous borderline ovarian tumor of intestinal type
Authors: Louis A Robert , Gupta Sunil Kumar , Gouda Chandra , Gupta Gurudutt 
Published: August 2013

AbstractWe describe an unusual case of fatal hematogenous relapse of borderline mucinous ovarian tumour of intestinal type after three years of primary optimal cytoreduction with dissemination to liver, bones and lymphangitic pattern of spread in lungs with resistance to standard chemotherapy.
Abruptio Placentae in Subsequent Pregnancy after Conservative Management of Hemorrhagic Cesarean Scar Pregnancy by Transcatheter Arterial Chemoembolization
Authors: Takeda Akihiro , Imoto Sanae , Nakamura Hiromi 
Published: August 2013

Introduction Cesarean scar pregnancy is a rare but dangerous type of ectopic pregnancy in which implantation occurs within the fibrous tissue of a cesarean scar defect. Conservative management of cesarean scar pregnancy is challenging, especially when future fertility preservation is a significant concern. Furthermore, reports on significant maternal morbidity in subsequent pregnancies after successful conservative management of cesarean scar pregnancy are limited. Case report A 31-year-old woman with previous history of 2 cesarean sections transferred due to massive uterine hemorrhage 7 weeks after dilatation and curettage performed under the diagnosis of missed abortion at 7 weeks of gestation. Cesarean scar pregnancy was diagnosed and was conservatively managed by emergent transcatheter arterial chemoembolization (TACE) followed by multiple doses of systemic methotrexate administration. Seven months after TACE, she spontaneously conceived. At 36 weeks and 5 days of pregnancy, emergency cesarean section was performed due to sudden massive hemorrhage. Abruptio placentae was diagnosed when hysterotomy was performed. After manual removal of the placenta, a healthy infant was delivered. The postoperative course was uneventful. Conclusion The pregnancy course should be carefully monitored for early detection of maternal morbidity associated with placental abnormalities to achieve successful outcome in subsequent gestations after conservative management of cesarean scar pregnancy.
Indicators, Chains, Antichains, Ramsey Property
Authors: Sokić Miodrag 
Published: August 2013

AbstractWe introduce two Ramsey classes of finite relational structures. The first class contains finite structures of the form , where ≤ is a total ordering on A and ⪯ is a linear ordering on the set fa 2 A : Ii (a)g. The second class contains structures of the form a , where (A,≤) is a weak ordering and ⪯ is a linear ordering on A such that A is partitioned by into maximal chains in the partial ordering ≤ and each is an interval with respect to .
RECLAIMING OF GROUND RUBBER TIRE BY SAFE MULTIFUNCTIONAL RUBBER ADDITIVES: II VIRGIN NATURAL RUBBER/RECLAIMED GROUND RUBBER TIRE VULCANIZATES
Authors: Mandal Swapan Kumar , Alam Md Najib , Roy Kumarjyoti , Debnath Subhas Chandra 
Published: August 2013

ABSTRACT
Mechanochemically reclaimed ground rubber tire (GRT) was revulcanized in combination with virgin natural rubber (NR). The NR/GRT vulcanizates with GRT content 20–50 wt% were prepared and studied. Reclaiming of GRT was successfully carried out by tetra benzyl thiuram disulfide (TBzTD) in the presence of spindle oil at around ambient temperature. The cure characteristics and mechanical properties of the virgin NR/reclaimed GRT blend were studied. Increasing the reclaimed rubber (RR) content in the blend decreases the optimum cure time without altering the scorch time. The effect of carbon black was studied in NR/RR (80/20) blend vulcanizate for the ultimate use of NR/RR blend vulcanizate. Aging characteristics of different NR/RR blends were evaluated. The swelling behavior, thermo-gravimetric analysis, and dynamic mechanical properties of NR/RR blend vulcanizates were examined. The equilibrium swelling of the NR vulcanizates was reduced with increasing reclaimed rubber content. Thermal stability of the blend vulcanizates was increased with increase in reclaimed rubber content. The elastic and storage modulus of the NR/RR vulcanizates improved with increasing reclaimed rubber content. Scanning electron microscopy studies further indicate the coherency and homogeneity in the NR/RR vulcanizate.