bluuebunny/crossref_metadata_2025_split huggingface dataset:
La diversification alimentaire à travers le monde
Authors: Perez Paola 
Published: February 2015

La diversification alimentaire de l’enfant est une étape importante dans la vie de l’enfant et de son entourage. Elle peut être source de questionnements et ce, d’autant plus si le comportement de l’enfant diffère des suggestions et recommandations données par les professionnels de santé et de la petite enfance. Est-il judicieux de poser comme modèle la façon communément admise dans notre société d’aborder la diversification ? Existe-t-il qu’une seule manière de procéder ? Afin de répondre à ces questions, il paraît pertinent de se pencher sur les comportements et les habitudes en matière de diversification alimentaire dans le monde.
Vers une politique française de compensation des impacts sur la biodiversité plus efficace : défis et perspectives
Authors: Jacob Céline , Quétier Fabien , Aronson James , Pioch Sylvain , Levrel Harold 
Published: February 2015

La question de la compensation des impacts résiduels des projets d’aménagement sur la biodiversité suscite de nombreux débats : droit à détruire pour les uns, taxe non assumée pour les autres. Les recommandations sur la bonne application de la séquence Eviter – Réduire – Compenser publiées en 2012 et 2013 par le ministère français en charge de l’environnement affichent une forte ambition, et de solides bases théoriques, afin de respecter le principe de « no net loss » (pas de perte nette) de biodiversité. Toutefois, l’analyse des textes et la comparaison avec les expériences internationales, montrent que la forte demande de solutions de compensation couplée à l’absence d’exigences clairement formulées en termes de moyens techniques, juridiques et financiers à mettre en œuvre, et d’évaluation des performances, conduisent les acteurs des procédures d’autorisation à se satisfaire trop souvent de mesures peu performantes en termes écologiques (pertes nettes), et avec de faibles garanties de pérennité. En France, ce travail de conception de la compensation a été transféré vers les services instructeurs de l’État en région, voire aux aménageurs eux-mêmes, ce qui génère des solutions de compensation, conçues au cas par cas, très hétérogènes dans leurs définitions et leurs mises en œuvre. Si les défis institutionnels et scientifiques soulevés par la mise en œuvre de la compensation ne sont pas résolus, alors les craintes d’un échec du pari d’un aménagement plus durable seront avérées : la France se sera satisfaite de compensations « de papier ».
Estradiol Promotes M1-like Macrophage Activation through Cadherin-11 To Aggravate Temporomandibular Joint Inflammation in Rats
Authors: Kou Xiao-Xing , Li Chen-Shuang , He Dan-Qing , Wang Xue-Dong , Hao Ting , Meng Zhen , Zhou Yan-Heng , Gan Ye-Hua 
Published: February 2015

Abstract
Macrophages play a major role in joint inflammation. Estrogen is involved in rheumatoid arthritis and temporomandibular disorders. However, the underlying mechanism is still unclear. This study was done to verify and test how estrogen affects M1/M2-like macrophage polarization and then contributes to joint inflammation. Female rats were ovariectomized and treated with increasing doses of 17β-estradiol for 10 d and then intra-articularly injected with CFA to induce temporomandibular joint (TMJ) inflammation. The polarization of macrophages and expression of cadherin-11 was evaluated at 24 h after the induction of TMJ inflammation and after blocking cadherin-11 or estrogen receptors. NR8383 macrophages were treated with estradiol and TNF-α, with or without blocking cadherin-11 or estrogen receptors, to evaluate the expression of the M1/M2-like macrophage-associated genes. We found that estradiol increased the infiltration of macrophages with a proinflammatory M1-like predominant profile in the synovium of inflamed TMJ. In addition, estradiol dose-dependently upregulated the expressions of the M1-associated proinflammatory factor inducible NO synthase (iNOS) but repressed the expressions of the M2-associated genes IL-10 and arginase in NR8383 macrophages. Furthermore, estradiol mainly promoted cadherin-11 expression in M1-like macrophages of inflamed TMJ. By contrast, blockage of cadherin-11 concurrently reversed estradiol-potentiated M1-like macrophage activation and TMJ inflammation, as well as reversed TNF-α–induced induction of inducible NO synthase and NO in NR8383 macrophages. The blocking of estrogen receptors reversed estradiol-potentiated M1-like macrophage activation and cadherin-11 expression. These results suggested that estradiol could promote M1-like macrophage activation through cadherin-11 to aggravate the acute inflammation of TMJs.
Set7 Facilitates Hepatitis C Virus Replication via Enzymatic Activity–Dependent Attenuation of the IFN-Related Pathway
Authors: Han Tao , Wan Yushun , Wang Jun , Zhao Peng , Yuan Yue , Wang Li , She Yinglong , Broering Ruth , Lu Mengji , Ye Linbai , Zhu Ying 
Published: February 2015

Abstract
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, usually resulting in persistent infection involving hepatic steatosis, cirrhosis, and hepatocellular carcinoma via escape of the host’s immune response. Set7 is a lysine-specific methyltransferase that is involved in gene regulation and virus replication. However, the mechanism underlying the immune evasion between HCV and Set7 is not well understood. In this study, we observed that the expression of Set7 in Huh7.5.1 cells was upregulated by HCV infection, and high levels of Set7 expression were also found in the sera, PBMCs, and liver tissue of HCV patients relative to healthy individuals. Further investigation showed that Set7 enhanced HCV replication in an enzymatic activity–dependent manner. Moreover, our data showed that Set7 decreased the expression of virus-induced IFN and IFN-related effectors, such as dsRNA-activated protein kinase and 2′,5′-oligoadenylate synthetase. Further investigation suggested that Set7 suppressed the endogenous IFN expression by reducing the nuclear translocation of IFN regulatory factor 3/7 and the p65 subunit of NF-κB and reduced IFN-induced dsRNA-activated protein kinase and 2′,5′-oligoadenylate synthetase via attenuation of the phosphorylation of STAT1 and STAT2. Additionally, IFN receptors, including IFNAR1 and IFNAR2, which are located upstream of the JAK/STAT pathway, were reduced by Set7. Taken together, our results reveal that Set7 facilitates HCV replication through the attenuation of IFN signaling pathways and IFN-related effectors.
RelB/p50 Complexes Regulate Cytokine-Induced YKL-40 Expression
Authors: Bhardwaj Reetika , Yester Jessie W. , Singh Sandeep K. , Biswas Debolina D. , Surace Michael J. , Waters Michael R. , Hauser Kurt F. , Yao Zhenqiang , Boyce Brendan F. , Kordula Tomasz 
Published: February 2015

Abstract
The secreted protein, YKL-40, has been proposed as a biomarker of a variety of human diseases characterized by ongoing inflammation, including chronic neurologic pathologies such as multiple sclerosis and Alzheimer’s disease. However, inflammatory mediators and the molecular mechanism responsible for enhanced expression of YKL-40 remained elusive. Using several mouse models of inflammation, we now show that YKL-40 expression correlated with increased expression of both IL-1 and IL-6. Furthermore, IL-1 together with IL-6 or the IL-6 family cytokine, oncostatin M, synergistically upregulated YKL-40 expression in both primary human and mouse astrocytes in vitro. The robust cytokine-driven expression of YKL-40 in astrocytes required both STAT3 and NF-κB binding elements of the YKL-40 promoter. In addition, YKL-40 expression was enhanced by constitutively active STAT3 and inhibited by dominant-negative IκBα. Surprisingly, cytokine-driven expression of YKL-40 in astrocytes was independent of the p65 subunit of NF-κB and instead required subunits RelB and p50. Mechanistically, we show that IL-1–induced RelB/p50 complex formation was further promoted by oncostatin M and that these complexes directly bound to the YKL-40 promoter. Moreover, we found that expression of RelB was strongly upregulated during inflammation in vivo and by IL-1 in astrocytes in vitro. We propose that IL-1 and the IL-6 family of cytokines regulate YKL-40 expression during sterile inflammation via both STAT3 and RelB/p50 complexes. These results suggest that IL-1 may regulate the expression of specific anti-inflammatory genes in nonlymphoid tissues via the canonical activation of the RelB/p50 complexes.
Cutting Edge: Circulating Plasmablasts Induce the Differentiation of Human T Follicular Helper Cells via IL-6 Production
Authors: Chavele Konstantia-Maria , Merry Eve , Ehrenstein Michael R. 
Published: February 2015

Abstract
B cells require CD4+ T follicular helper (Tfh) cells to progress through the germinal center and provide protective Ab responses. In this article, we reveal a reciprocal interaction whereby circulating human plasmablasts are potent inducers of the Tfh cell–differentiation program, including the expression of their key transcription factor Bcl-6. The markedly increased propensity of plasmablasts, compared with naive B cells, to induce Tfh cell differentiation was due to their increased production of IL-6. Specific targeting of IL-6 using tocilizumab therapy in patients with rheumatoid arthritis led to a significant reduction in circulating Tfh cell numbers and IL-21 production, which was correlated with reduced plasmablast formation. Our data uncover a positive-feedback loop between circulating plasmablasts and Tfh cells that could sustain autoimmunity and spread Ab-driven inflammation to unaffected sites; this represents an important therapeutic target, as well as reveals a novel mechanism of action for tocilizumab.
CD73 Plays a Protective Role in Collagen-Induced Arthritis
Authors: Chrobak Pavel , Charlebois Roxanne , Rejtar Pavel , El Bikai Rana , Allard Bertrand , Stagg John 
Published: February 2015

Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease with significant morbidity and mortality. Recent studies suggest that modulation of adenosine signaling, a potent immunosuppressive pathway, is a promising approach for treatment of RA. Extracellular adenosine can come from two sources: transport of intracellular adenosine and hydrolysis of extracellular adenine nucleotides by CD73. In this study, we investigated the susceptibility of CD73-deficient C57BL/6 mice to collagen-induced arthritis (CIA), a well-established mouse model of RA. Our data demonstrated that CD73-deficient mice are significantly more susceptible to CIA than wild-type mice. CD73 deficiency resulted in an increased production of proinflammatory cytokines in the joints, increased Th1 T cell responses, and increased joint destruction. Surprisingly, this was accompanied by delayed anticollagen IgG responses, suggesting defective isotype class switching in CD73-deficient mice. Using bone marrow chimera mice, we demonstrated that CD73 expression on nonhematopoietic cells, but not on hematopoietic cells, was important for protection from CIA. We further demonstrated that administration of a selective A2A adenosine receptor agonist to CD73-deficient mice resulted in arthritis incidence similar to wild-type mice in support of a protective role for A2A signaling. Taken together, our study identifies CD73 as an important regulator of CIA in mice. It also strengthens the notion that CD73-generated adenosine by nonhematopoietic cells plays a protective role in RA and suggests that strategies able to enhance CD73 activity or expression levels may be a valid therapeutic option.
Genetic Investigation of MHC-Independent Missing-Self Recognition by Mouse NK Cells Using an In Vivo Bone Marrow Transplantation Model
Authors: Chen Peter , Aguilar Oscar A. , Rahim Mir Munir A. , Allan David S. J. , Fine Jason H. , Kirkham Christina L. , Ma Jaehun , Tanaka Miho , Tu Megan M. , Wight Andrew , Kartsogiannis Vicky , Gillespie Matthew T. , Makrigiannis Andrew P. , Carlyle James R. 
Published: February 2015

Abstract
MHC-I–specific receptors play a vital role in NK cell–mediated “missing-self” recognition, which contributes to NK cell activation. In contrast, MHC-independent NK recognition mechanisms are less well characterized. In this study, we investigated the role of NKR-P1B:Clr-b (Klrb1:Clec2d) interactions in determining the outcome of murine hematopoietic cell transplantation in vivo. Using a competitive transplant assay, we show that Clr-b−/− bone marrow (BM) cells were selectively rejected by wild-type B6 recipients, to a similar extent as H-2Db−/− MHC-I–deficient BM cells. Selective rejection of Clr-b−/− BM cells was mitigated by NK depletion of recipient mice. Competitive rejection of Clr-b−/− BM cells also occurred in allogeneic transplant recipients, where it was reversed by selective depletion of NKR-P1Bhi NK cells, leaving the remaining NKR-P1Blo NK subset and MHC-I–dependent missing-self recognition intact. Moreover, competitive rejection of Clr-b−/− hematopoietic cells was abrogated in Nkrp1b-deficient recipients, which lack the receptor for Clr-b. Of interest, similar to MHC-I–deficient NK cells, Clr-b−/− NK cells were hyporesponsive to both NK1.1 (NKR-P1C)–stimulated and IL-12/18 cytokine–primed IFN-γ production. These findings support a unique and nonredundant role for NKR-P1B:Clr-b interactions in missing-self recognition of normal hematopoietic cells and suggest that optimal BM transplant success relies on MHC-independent tolerance mechanisms. These findings provide a model for human NKR-P1A:LLT1 (KLRB1:CLEC2D) interactions in human hematopoietic cell transplants.
The Cyclopentenone Prostaglandin 15d-PGJ2 Inhibits the NLRP1 and NLRP3 Inflammasomes
Authors: Maier Nolan K. , Leppla Stephen H. , Moayeri Mahtab 
Published: February 2015

Abstract
Inflammasomes are cytosolic protein complexes that respond to diverse danger signals by activating caspase-1. The sensor components of the inflammasome, often proteins of the nucleotide-binding oligomerization domain–like receptor (NLR) family, detect stress, danger stimuli, and pathogen-associated molecular patterns. We report that the eicosanoid 15-deoxy-Δ12,14–PGJ2 (15d-PGJ2) and related cyclopentenone PGs inhibit caspase-1 activation by the NLR family leucine-rich repeat protein (NLRP)1 and NLRP3 inflammasomes. This inhibition was independent of the well-characterized role of 15d-PGJ2 as a peroxisome proliferator receptor-γ agonist, its activation of NF erythroid 2–related factor 2, or its anti-inflammatory function as an inhibitor of NF-κB. Instead, 15d-PGJ2 prevents the autoproteolytic activation of caspase-1 and the maturation of IL-1β through induction of a cellular state inhibitory to caspase-1 proteolytic function. The eicosanoid does not directly modify or inactivate the caspase-1 enzyme. Rather, inhibition is dependent on de novo protein synthesis. In a mouse peritonitis model of gout, using monosodium urate crystals to activate NLRP3, 15d-PGJ2 caused a significant inhibition of cell recruitment and associated IL-1β release. Furthermore, in a murine anthrax infection model, 15d-PGJ2 reversed anthrax lethal toxin-mediated NLRP1-dependent resistance. The findings reported in this study suggest a novel mechanism for the anti-inflammatory properties of the cyclopentenone PGs through inhibition of caspase-1 and the inflammasome.
Hydroxypropyl-β-Cyclodextrin Spikes Local Inflammation That Induces Th2 Cell and T Follicular Helper Cell Responses to the Coadministered Antigen
Authors: Onishi Motoyasu , Ozasa Koji , Kobiyama Kouji , Ohata Keiichi , Kitano Mitsutaka , Taniguchi Keiichi , Homma Tomoyuki , Kobayashi Masanori , Sato Akihiko , Katakai Yuko , Yasutomi Yasuhiro , Wijaya Edward , Igarashi Yoshinobu , Nakatsu Noriyuki , Ise Wataru , Inoue Takeshi , Yamada Hiroshi , Vandenbon Alexis , Standley Daron M. , Kurosaki Tomohiro , Coban Cevayir , Aoshi Taiki , Kuroda Etsushi , Ishii Ken J. 
Published: February 2015

Abstract
Cyclodextrins are commonly used as a safe excipient to enhance the solubility and bioavailability of hydrophobic pharmaceutical agents. Their efficacies and mechanisms as drug-delivery systems have been investigated for decades, but their immunological properties have not been examined. In this study, we reprofiled hydroxypropyl-β-cyclodextrin (HP-β-CD) as a vaccine adjuvant and found that it acts as a potent and unique adjuvant. HP-β-CD triggered the innate immune response at the injection site, was trapped by MARCO+ macrophages, increased Ag uptake by dendritic cells, and facilitated the generation of T follicular helper cells in the draining lymph nodes. It significantly enhanced Ag-specific Th2 and IgG Ab responses as potently as did the conventional adjuvant, aluminum salt (alum), whereas its ability to induce Ag-specific IgE was less than that of alum. At the injection site, HP-β-CD induced the temporary release of host dsDNA, a damage-associated molecular pattern. DNase-treated mice, MyD88-deficient mice, and TBK1-deficient mice showed significantly reduced Ab responses after immunization with this adjuvant. Finally, we demonstrated that HP-β-CD–adjuvanted influenza hemagglutinin split vaccine protected against a lethal challenge with a clinically isolated pandemic H1N1 influenza virus, and the adjuvant effect of HP-β-CD was demonstrated in cynomolgus macaques. Our results suggest that HP-β-CD acts as a potent MyD88- and TBK1-dependent T follicular helper cell adjuvant and is readily applicable to various vaccines.
Cutting Edge: STAT6 Signaling in Eosinophils Is Necessary for Development of Allergic Airway Inflammation
Authors: Stokes Kindra , LaMarche Nelson M. , Islam Nasif , Wood Amie , Huang Weishan , August Avery 
Published: February 2015

Abstract
Eosinophils are critical cellular mediators in allergic asthma and inflammation; however, the signals that regulate their functions are unclear. The transcription factor STAT6 regulates Th2 cytokine responses, acting downstream of IL-4 and IL-13. We showed previously that eosinophil-derived IL-13 plays an important role in the recruitment of T cells to the lung and the subsequent development of allergic asthma. However, whether eosinophils respond to Th2 signals to control allergic airway inflammation is unclear. In this report, we show that STAT6−/− eosinophils are unable to induce the development of allergic lung inflammation, including recruitment of CD4+ T cells, mucus production, and development of airways hyperresponsiveness. This is likely due to the reduced migration of STAT6−/− eosinophils to the lung and in response to eotaxin. These data indicate that, like Th cells, eosinophils need to respond to Th2 cytokines via STAT6 during the development of allergic airway inflammation.
SHP-1–Dependent Macrophage Differentiation Exacerbates Virus-Induced Myositis
Authors: Watson Neva B. , Schneider Karin M. , Massa Paul T. 
Published: February 2015

Abstract
Virus-induced myositis is an emerging global affliction that remains poorly characterized with few treatment options. Moreover, muscle-tropic viruses often spread to the CNS, causing dramatically increased morbidity. Therefore, there is an urgent need to explore genetic factors involved in this class of human disease. This report investigates critical innate immune pathways affecting murine virus–induced myositis. Of particular importance, the key immune regulator src homology region 2 domain–containing phosphatase 1 (SHP-1), which normally suppresses macrophage-mediated inflammation, is a major factor in promoting clinical disease in muscle. We show that Theiler’s murine encephalomyelitis virus (TMEV) infection of skeletal myofibers induces inflammation and subsequent dystrophic calcification, with loss of ambulation in wild-type (WT) mice. Surprisingly, although similar extensive myofiber infection and inflammation are observed in SHP-1−/− mice, these mice neither accumulate dead calcified myofibers nor lose ambulation. Macrophages were the predominant effector cells infiltrating WT and SHP-1−/− muscle, and an increased infiltration of immature monocytes/macrophages correlated with an absence of clinical disease in SHP-1−/− mice, whereas mature M1-like macrophages corresponded with increased myofiber degeneration in WT mice. Furthermore, blocking SHP-1 activation in WT macrophages blocked virus-induced myofiber degeneration, and pharmacologic ablation of macrophages inhibited muscle calcification in TMEV-infected WT animals. These data suggest that, following TMEV infection of muscle, SHP-1 promotes M1 differentiation of infiltrating macrophages, and these inflammatory macrophages are likely involved in damaging muscle fibers. These findings reveal a pathological role for SHP-1 in promoting inflammatory macrophage differentiation and myofiber damage in virus-infected skeletal muscle, thus identifying SHP-1 and M1 macrophages as essential mediators of virus-induced myopathy.
Bone Marrow Plasma Cells Are a Primary Source of Serum HIV-1–Specific Antibodies in Chronically Infected Individuals
Authors: Montezuma-Rusca Jairo M. , Moir Susan , Kardava Lela , Buckner Clarisa M. , Louie Aaron , Kim Leo J. Y. , Santich Brian H. , Wang Wei , Fankuchen Olivia R. , Diaz Gabriella , Daub Janine R. , Rosenzweig Sergio D. , Chun Tae-Wook , Li Yuxing , Braylan Raul C. , Calvo Katherine R. , Fauci Anthony S. 
Published: February 2015

Abstract
Several potent and broadly neutralizing Abs to HIV-1 have been isolated recently from peripheral blood B cells of infected individuals, based on prescreening of Ab activity in the serum. However, little is known regarding the cells that make the Abs that circulate in the blood. Accordingly, we investigated the most likely source, the bone marrow, of chronically HIV-1–infected individuals who were not receiving antiretroviral therapy. Increased frequencies of plasma cells, as well as B cell precursors, namely preB-I and preB-II, and decreased frequencies of mature B cells were observed in bone marrow aspirates of these individuals compared with HIV-negative counterparts. Increased frequencies of bone marrow plasma cells are consistent with known hallmarks of HIV-1 infection, namely hypergammaglobulinemia and increased frequencies of peripheral blood plasmablasts. Levels of HIV-1 envelope (Env)-binding and HIV-1–neutralizing Abs were measured in serum, and corresponding frequencies of Ab-secreting or Env-binding cells were measured in the blood (plasmablasts and memory B cells) and in the bone marrow (plasma cells). A strong correlation was observed between serum HIV-1–specific Abs and Env-specific bone marrow–derived plasma cells, but not circulating plasmablasts or memory B cells. These findings demonstrate that, despite HIV-1–induced phenotypic and functional B cell dysregulation in the peripheral blood and secondary lymphoid tissues, bone marrow plasma cells remain a primary source for circulating HIV-1–specific Abs in HIV-1–infected individuals.