bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD28 Promotes CD4+ T Cell Clonal Expansion during Infection Independently of Its YMNM and PYAP Motifs
Authors: Pagán Antonio J. , Pepper Marion , Chu H. Hamlet , Green Jonathan M. , Jenkins Marc K. 
Published: August 2012

AbstractCD28 is required for maximal proliferation of CD4+ T cells stimulated through their TCRs. Two sites within the cytoplasmic tail of CD28, a YMNM sequence that recruits PI3K and activates NF-κB and a PYAP sequence that recruits Lck, are candidates as transducers of the signals responsible for these biological effects. We tested this proposition by tracking polyclonal peptide:MHCII-specific CD4+ T cells in vivo in mice with mutations in these sites. Mice lacking CD28 or its cytoplasmic tail had the same number of naive T cells specific for a peptide:MHCII ligand as wild-type mice. However, the mutant cells produced one tenth as many effector and memory cells as wild-type T cells after infection with bacteria expressing the antigenic peptide. Remarkably, T cells with a mutated PI3K binding site, a mutated PYAP site, or both mutations proliferated to the same extent as wild-type T cells. The only observed defect was that T cells with a mutated PYAP or Y170F site proliferated even more weakly in response to peptide without adjuvant than wild-type T cells. These results show that CD28 enhances T cell proliferation during bacterial infection by signals emanating from undiscovered sites in the cytoplasmic tail.
Role of Caspases in Cytokine-Induced Barrier Breakdown in Human Brain Endothelial Cells
Authors: Lopez-Ramirez M. Alejandro , Fischer Roman , Torres-Badillo Claudia C. , Davies Heather A. , Logan Karen , Pfizenmaier Klaus , Male David K. , Sharrack Basil , Romero Ignacio A. 
Published: August 2012

Abstract
During neuroinflammation, cytokines such as TNF-α and IFN-γ secreted by activated leukocytes and/or CNS resident cells have been shown to alter the phenotype and function of brain endothelial cells (BECs) leading to blood–brain barrier breakdown. In this study, we show that the human BEC line hCMEC/D3 expresses the receptors for TNF-α, TNF receptor 1 and TNF receptor 2, and for IFN-γ. BEC activation with TNF-α alone or in combination with IFN-γ induced endothelial leakage of paracellular tracers. At high cytokine concentrations (10 and 100 ng/ml), this effect was associated with caspase-3/7 activation and apoptotic cell death as evidenced by annexin V staining and DNA fragmentation (TUNEL) assays. In addition, inhibition of JNK and protein kinase C activation at these doses partially prevented activation of caspase-3/7, although only JNK inhibition was partially able to prevent the increase in BEC paracellular permeability induced by cytokines. By contrast, lower cytokine concentrations (1 ng/ml) also led to effector caspase activation, increased paracellular flux, and redistribution of zonula occludens-1 and VE-cadherin but failed to induce apoptosis. Under these conditions, specific caspase-3 and caspase-9, but not caspase-8, inhibitors partially blocked cytokine-induced disruption of tight and adherens junctions and BEC paracellular permeability. Our results suggest that the concentration of cytokines in the CNS endothelial microenvironment determines the extent of caspase-mediated barrier permeability changes, which may be generalized as a result of apoptosis or more subtle as a result of alterations in the organization of junctional complex molecules.
MyD88 Drives the IFN-β Response to Lactobacillus acidophilus in Dendritic Cells through a Mechanism Involving IRF1, IRF3, and IRF7
Authors: Weiss Gudrun , Maaetoft-Udsen Kristina , Stifter Sebastian A. , Hertzog Paul , Goriely Stanislas , Thomsen Allan R. , Paludan Søren R. , Frøkiær Hanne 
Published: August 2012

Abstract
Type I IFNs are induced by pathogens to protect the host from infection and boost the immune response. We have recently demonstrated that this IFN response is not restricted to pathogens, as the Gram-positive bacterium Lactobacillus acidophilus, a natural inhabitant of the intestine, induces high levels of IFN-β in dendritic cells. In the current study, we investigate the intracellular pathways involved in IFN-β upon stimulation of dendritic cells with L. acidophilus and reveal that this IFN-β induction requires phagosomal uptake and processing but bypasses the endosomal receptors TLR7 and TLR9. The IFN-β production is fully dependent on the TIR adapter molecule MyD88, partly dependent on IFN regulatory factor (IRF)1, but independent of the TIR domain-containing adapter inducing IFN-β MyD88 adapter-like, IRF and IRF7. However, our results suggest that IRF3 and IRF7 have complementary roles in IFN-β signaling. The IFN-β production is strongly impaired by inhibitors of spleen tyrosine kinase (Syk) and PI3K. Our results indicate that L. acidophilus induces IFN-β independently of the receptors typically used by bacteria, as it requires MyD88, Syk, and PI3K signaling and phagosomal processing to activate IRF1 and IRF3/IRF7 and thereby the release of IFN-β.
Immune Mechanism of the Antitumor Effects Generated by Bortezomib
Authors: Chang Chih-Long , Hsu Yun-Ting , Wu Chao-Chih , Yang Yuh-Cheng , Wang Connie , Wu T.-C. , Hung Chien-Fu 
Published: August 2012

Abstract
Bortezomib, a proteasome inhibitor, is a chemotherapeutic drug that is commonly used to treat a variety of human cancers. The antitumor effects of bortezomib-induced tumor cell immunogenicity have not been fully delineated. In this study, we examined the generation of immune-mediated antitumor effects in response to treatment by bortezomib in a murine ovarian tumor model. We observed that tumor-bearing mice that were treated with bortezomib had CD8+ T cell-mediated inhibition of tumor growth. Furthermore, the comparison of tumor cell-based vaccines that were produced from tumor cells treated or untreated with bortezomib showed vaccination with drug-treated tumor cell-based vaccines elicited potent tumor-specific CD8+ T cell immune response with improved therapeutic antitumor effect in tumor-bearing mice. Conversely, the untreated tumor cell-based vaccines led to no appreciable antitumor response. Treatment of tumor cells with bortezomib led to the upregulation of Hsp60 and Hsp90 on the cell surface and promoted their phagocytosis by dendritic cells (DCs). However, cell surface expression of Hsp60, instead of Hsp90, is the more important determinant of whether bortezomib-treated tumor cells can generate tumor-specific CD8+ T cells. CD11c+ DCs that were treated with bortezomib in vitro had enhanced phagocytic activities. In addition, CD11c+ DCs from bortezomib-treated tumor-bearing mice had increased maturation. At lower concentrations, bortezomib had no inhibitory effects on T cell proliferation. Taken together, our data indicate that bortezomib can render tumor cells immunogenic by upregulating the cell surface expression of heat shock protein 60 and heat shock protein 90, as well as improve DC function, which results in potent immune-mediated antitumor effects.
The Adaptor 3BP2 Is Required for Early and Late Events in FcεRI Signaling in Human Mast Cells
Authors: Ainsua-Enrich Erola , Álvarez-Errico Damiana , Gilfillan Alasdair M. , Picado César , Sayós Joan , Rivera Juan , Martín Margarita 
Published: August 2012

Abstract
Adaptor molecules are essential in organizing signaling molecules and in coordinating and compartmentalizing their activity. SH3-binding protein 2 (3BP2) is a cytoplasmic adaptor protein mainly expressed by hematopoietic cells that has been shown to act as a positive regulator in T, B, and NK cell signal transduction. 3BP2 is an important regulator of cytotoxic granule release in NK cells. Mast cells (MCs) similarly degranulate following Ag-dependent aggregation of the FcεRI on the cell surface. Activation of these cells induces the release of preformed inflammatory mediators and the de novo synthesis and secretion of cytokines and chemokines. Thus, MCs participate in both innate and acquired responses. We observed that 3BP2 is expressed in human MCs (huMCs) from diverse origins. Moreover, 3BP2 coimmunoprecipitates with essential MC signaling mediators such as Lyn, Syk, and phospholipase C γ; thus, a role for this adaptor in MC function was postulated. In the present work, we used the short hairpin RNA lentiviral targeting approach to silence 3BP2 expression in huMCs. Our findings point to a requirement for 3BP2 in optimal immediate and late MCs responses such as degranulation and IL-8 or GM-CSF secretion. 3BP2 was determined to be necessary for optimal phosphorylation of Syk, linker for activation of T cells, and phospholipase C γ1, critical signals for calcium release from intracellular stores. Taken together, our results show that by participating in FcεRI- mediated signal transduction 3BP2 is an important regulator of huMC activation. Thus, 3BP2 could be a potential therapeutic target for IgE-dependent MC-mediated inflammatory disease.
Cyclin-Dependent Kinase Inhibitor Cdkn2c Deficiency Promotes B1a Cell Expansion and Autoimmunity in a Mouse Model of Lupus
Authors: Potula Hari-Hara S. K. , Xu Zhiwei , Zeumer Leilani , Sang Allison , Croker Byron P. , Morel Laurence 
Published: August 2012

Abstract
The lupus-prone NZM2410 mice present an expanded B1a cell population that we have mapped to the Sle2c1 lupus susceptibility locus. The expression of Cdkn2c, a gene encoding for cyclin-dependent kinase inhibitor p18Ink4c and located within Sle2c1, is significantly lower in B6.Sle2c1 B cells than in B6 B cells. To test the hypothesis that the B1a cell expansion in B6.Sle2c1 mice was due to a defective p18 expression, we analyzed the B1a cell phenotypes of p18-deficient C57BL/6 mice. We found a dose-dependent negative correlation between the number of B1a cells and p18 expression in B cells, with p18-deficient mice showing an early expansion of the peritoneal B1a cell pool. p18 deficiency enhanced the homeostatic expansion of B1a cells but not of splenic conventional B cells, and the elevated number of B6.Sle2c1 B1a cells was normalized by cyclin D2 deficiency. These data demonstrated that p18 is a key regulator of the size of the B1a cell pool. B6.p18−/− mice produced significant amounts of anti-DNA IgM and IgG, indicating that p18 deficiency contributes to humoral autoimmunity. Finally, we have shown that Sle2c1 increases lpr-associated lymphadenopathy and T cell–mediated pathology. B6.p18−/−.lpr mice showed a greater lymphadenopathy than B6.Sle2c1.lpr mice, but their renal pathology was intermediate between that of B6.lpr and B6.Sle2c1.lpr mice. This indicated that p18-deficiency synergizes, at least partially, with lpr-mediated pathology. These results show that Cdkn2c contributes to lupus susceptibility by regulating the size of the B1a cell compartment and hence their contribution to autoimmunity.
Tryptophan Depletion and the Kinase GCN2 Mediate IFN-γ–Induced Autophagy
Authors: Fougeray Sophie , Mami Iadh , Bertho Gildas , Beaune Philippe , Thervet Eric , Pallet Nicolas 
Published: August 2012

Abstract
IFN-γ is a master regulator of the immune responses that occur in the transplanted kidney, acting both on the immune system and on the graft itself. The cellular responses to IFN-γ are complex, and emerging evidence suggests that IFN-γ may regulate autophagic functions. Conversely, autophagy modulates innate and adaptive immune functions in various contexts. In this study, we identify a novel mechanism by which IFN-γ activates autophagy in human kidney epithelial cells and provide new insights into how autophagy regulates immune functions in response to IFN-γ. Our results indicate that IFN-γ promotes tryptophan depletion, activates the eIF2α kinase general control nonderepressible-2 (GCN2), and leads to an increase in the autophagic flux. Further, tryptophan supplementation and RNA interference directed against GCN2 inhibited IFN-γ–induced autophagy. This process is of functional relevance because autophagy regulates the secretion of inflammatory cytokines and growth factors by human kidney epithelial cells in response to IFN-γ. These findings assign to IFN-γ a novel function in the regulation of autophagy, which, in turn, modulates IFN-γ–induced secretion of inflammatory cytokines.
Cutting Edge: 4-1BB Controls Regulatory Activity in Dendritic Cells through Promoting Optimal Expression of Retinal Dehydrogenase
Authors: Lee Seung-Woo , Park Yunji , Eun So-Young , Madireddi Shravan , Cheroutre Hilde , Croft Michael 
Published: August 2012

Abstract
Dendritic cells (DC) in the gut promote immune tolerance by expressing retinal dehydrogenase (RALDH), an enzyme that promotes retinoic acid, which aids differentiation of Foxp3+ inducible regulatory T cells (iTreg) in the intestinal mucosa. How RALDH expression is regulated is unclear. We found that 4-1BB (CD137), a member of the TNFR family, together with CD103, marked mesenteric lymph node DC with the highest level of RALDH activity, and ligation of 4-1BB maintained RALDH expression in these gut DC. Moreover, 4-1BB signals synergized with those through TLR2 or GM-CSFR to promote RALDH activity in undifferentiated DC. Correspondingly, 4-1BB–deficient mice were impaired in their ability to generate iTreg in the GALT when exposed to oral Ag, and 4-1BB–deficient mesenteric lymph node DC displayed weak RALDH activity and were poor at promoting iTreg development. Thus, our data demonstrate a novel activity of 4-1BB in controlling RALDH expression and the regulatory activity of DC.
Advances and Applications in Stem Cell Biology
Authors: Bhattacharyya Shamoli 
Published: August 2012

ABSTRACT
Mesenchymal stem cells have shown great promise as the source of adult stem cells for regenerative medicine. Present research efforts are directed at isolating these cells from various sources, growing them in vitro and maintaining their pluripotency as well as capacity for self renewal. It is crucial to identify the regulatory molecules which directly or indirectly control the proliferative status or influence the niche microenvironment. The main challenge is to understand the basic biology of the stem cells and manipulate them for further therapeutic applications. Considering their malignant potential, stem cells may be a double edged sword. While the benefits of these cells need to be harnessed judiciously, a significant amount of research is required before embarking on widespread use of this tool for the benefit of humanity.

How to cite this article
Bhattacharyya S. Advances and Applications in Stem Cell Biology. J Postgrad Med Edu Res 2012;46(2):75-80.
Prospective Single-Arm Study of Radioprotection by Amifostine in High Dose Radioactive Iodine Therapy for Thyroid Cancer
Authors: Sandhu Ajay , Ioffe Vladimir , Karakla Daniel , Wadsworth J Trad , Mendoza April , Rao Nikhil , Dignan Kathleen , Mason Elizabeth , Goffman Thomas E 
Published: August 2012

ABSTRACT

Purpose
Xerostomia, sialoadenitis, taste dysfunction and nausea are well known toxicities following high dose radioactive iodine (RAI) treatment for well-differentiated thyroid cancer. This prospective study sought to determine the incidence rates for RAI adverse effects and to determine, whether the radioprotector, amifostine could decrease the duration of the adverse effects in single treatment patients.

Materials and methods
Patients with differentiated thyroid cancer received 150 mCi RAI after total thyroidectomy. All patients were pretreated with 1 mg granisetron and 4 mg dexamethasone. Patients in the amifostine arm (n = 27) were prospectively enrolled and received 500 mg amifostine subcutaneously. Adverse effects were scored based on the CTCAE at 1 month, 6 months, and yearly intervals using a physician administered questionnaire. The results were compared with a retrospective no amifostine cohort (n = 22) for whom data was collected with the identical questionnaire.

Results
The overall incidence of xerostomia, sialadenitis, taste dysfunction and nausea in the treatment group was 26, 22, 52 and 26% respectively. Only grades 1 and 2 adverse effects were observed. The mean duration (days) of xerostomia (control vs treatment)—37.3 vs 21.9 (F test, p = 0.016), taste dysfunction—45.5 vs 23.5 (F test, p = 0.001), sialadenitis— 16.8 vs 7.5 and nausea—18.7 vs 5.1.

Conclusion
In patients treated once with high dose RAI, who develop xerostomia, sialoadenitis, taste dysfunction, and/or nausea, the duration of symptoms appears to be reduced by pretreatment with 500 mg of subcutaneous amifostine without significant treatment related adverse effects.

How to cite this article
Sandhu A, Ioffe V, Karakla D, Wadsworth JT, Mendoza A, Rao N, Dignan K, Mason E, Goffman TE. Prospective Single-Arm Study of Radioprotection by Amifostine in High Dose Radioactive Iodine Therapy for Thyroid Cancer. J Postgrad Med Edu Res 2012;46(2):90-94.
Aggressive Angiomyxoma Pelvis Presenting as an Ovarian Tumor with Vault Prolapse
Authors: Dhaliwal Lakhbir , Aggarwal Neelam , Nijhawan Raje , Siwatch Sujata , Saha Subhas Chandra 
Published: August 2012

ABSTRACT

Background
Angiomyxoma is a rare tumor arising from the pelvis. Preoperative diagnosis and treatment may be difficult.

Case report
We report a rare case of aggressive angiomyxoma pelvis that presented as vault prolapse and was misdiagnosed as ovarian tumor.

Conclusion
As surgery is the main treatment, preoperative diagnosis and assessment of extent of the tumor for planning surgery cannot be overemphasized.

Synopsis
Angiomyxoma is a rare pelvic tumor with varied presentation. Preoperative diagnosis and assessment of extent of the tumor are important for its management.

How to cite this article
Siwatch S, Saha SC, Aggarwal N, Dhaliwal L, Nijhawan R. Aggressive Angiomyxoma Pelvis Presenting as an Ovarian Tumor with Vault Prolapse. J Postgrad Med Edu Res 2012;46(2):102-103.
Collective Action Control by Goals and Plans: Applying a Self-Regulation Perspective to Group Performance
Authors: Wieber Frank , Thürmer J. Lukas , Gollwitzer Peter M. 
Published: August 2012

Abstract
In celebration of the 125th anniversary of The American Journal of Psychology, this article discusses a seminal publication by Marjorie Shaw (1932) on small group performance in the rational solution of complex problems. We then propose an approach for the effective regulation of group goal striving based on the collective action control perspective. From this perspective, group performance might be hindered by a collective intention-behavior gap: Groups fail to act on their intentions despite being strongly committed to the collective goal, knowing what the necessary actions are, and being capable of performing them. To reduce this gap, we suggest specific if-then plans (implementation intentions) in which groups specify when, where, and how to act toward their collective goal as an easily applicable self-regulation strategy to automate collective action control. Studies in which implementation intentions improved group performance in hidden profile, escalation of commitment, and cooperation task paradigms are reported and discussed.
Synthesis and Reactions of New Chiral Linear and Macrocyclic Tetraand Penta-peptide Candidates
Authors: Ghalia Mohamed H. , El-Hamid Mohamed Abd , Zweil Mohamed A. , Amr Abd El-Galil E. , Moafi Shimaa A. 
Published: August 2012

9a
A series of linear and macrocyclic pentapeptide derivatives have been prepared via the coupling of pyridine-2,6-dicarboxylic acid (1) or pyridine-2,6-dicarbonyl dichloride (2) with appropriate amino acid methyl esters. The coupling of 1or 2with aminoacid methyl esters gave the corresponding pyridine dipeptide methyl esters 3, which were hydrolyzed with sodium hydroxide to the corresponding acids 4. The latter compounds 4were coupled with other amino acid methyl esters to afford the corresponding tetrapeptide esters 5, which were hydrolyzed with sodium hydroxide to the corresponding acids 6. Cyclization of tetrapeptide acids with L-lysine methyl ester or with aliphatic diamide derivatives afforded the corresponding cyclic pentapeptide methyl ester derivatives 7and cyclic tetrapeptide diamines 8, respectively. Finally, hydrolysis with 1 N sodium hydroxide or hydrazinolysis with hydrazine hydrate of methyl esters 7afforded the corresponding acids - e and hydrazides 10a - e, respectively
Ammonius on Universals and Abstraction
Authors: Fortier Simon 
Published: August 2012

Ammonius’ is the earliest exegesis we possess of Porphyry’s Isagoge, as is his interpretation of lines 1.9-12, over which so much ink was subsequently spilt. Although the essence of this interpretation, the so-called doctrine of the three states of the universal, is now widely known, the section of commentary in which it appears has hitherto never been translated in its entirety. The following article therefore presents a complete translation of Ammonius’ commentary upon Isagoge 1.9-12, preceded by a brief introduction.
Alexandre d’Aphrodise et l’abstraction selon l’exposé sur les universaux chez Boèce dans son Second commentaire sur l’« Isagoge » de Porphyre
Authors: Lafleur Claude , Carrier Joanne 
Published: August 2012

Cette première traduction française d’une portion significative de l’In « Isagogen » Porphyrii Commentorum Editio secunda, en regard d’un texte latin reponctué en conséquence et accompagné d’annotations critiques, est précédée d’une présentation historico-doctrinale mettant en relief le rôle — à la fois central et problématique — de l’abstraction dans la solution boécienne, ouvertement rattachée à Alexandre d’Aphrodise (dont le traité De l’âme est ici examiné), du statut des genres et des espèces dans ce texte qui, à travers l’exégèse du célèbre questionnaire porphyrien, a fait connaître le problème des universaux à l’Occident latin et en est demeuré l’expression la plus achevée jusqu’au xiie siècle, où Abélard en a donné un méta-commentaire particulièrement brillant dans sa Logica « Ingredientibus » : Super Porphyrium, éditée, traduite et étudiée ci-après dans ce numéro thématique.
Abélard et les universaux : édition et traduction du début de la Logica « Ingredientibus » : Super Porphyrium
Authors: Lafleur Claude , Carrier Joanne 
Published: August 2012

Appuyée sur une collation systématique — incluant l’orthographe — de l’unique manuscrit subsistant (le ms. Milano, Biblioteca Ambrosiana, M 63 sup., fol. 1ra-5rb), cette nouvelle édition critique du début de la Logica « Ingredientibus » : Super Porphyrium, accompagnée d’une traduction française inédite et complétée par une abondante annotation, rend ainsi accessible l’exposé le plus détaillé d’Abélard sur les universaux, des pages célèbres où, dans une approche sémantique non exempte de perspectives métaphysiques, on trouve, comme l’étude précédente l’a laissé voir, des développements philosophiques importants relatifs à l’intellection et à l’abstraction.
Interjection, concept et signification dans les Communia gramatice
Authors: Létourneau René 
Published: August 2012

Les Communia gramatice, un compendium grammatical anonyme rédigé autour de 1250 dans le milieu éclectique de la Faculté des arts de Paris et contenu aujourd’hui uniquement dans le manuscrit 16617 du fonds latin de la Bibliothèque nationale de France, traitent entre autres du statut linguistique de l’interjection. La notion de signification, au sens de contenu de connaissances et de rapport référentiel entre un mot et son signifié, y joue un rôle fondamental : la principale difficulté onto-grammaticale présentée par l’interiectio étant précisément de déterminer la nature de sa signification. L’auteur anonyme des Communia gramatice pose clairement la distinction classique entre la signification d’une émotion (affectus) et la signification d’un concept (conceptus), mais y apporte des nuances intéressantes de nature cognitive : nous sommes à une époque où la philosophie naturelle aristotélicienne vient tout juste de rencontrer la grammaire spéculative typiquement parisienne (vers 1240).