bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered Distribution and Increased IL-17 Production by Mucosal-Associated Invariant T Cells in Adult and Childhood Obesity
Authors: Carolan Eirin , Tobin Laura M. , Mangan Bozgana A. , Corrigan Michelle , Gaoatswe Gadinthsware , Byrne Greg , Geoghegan Justin , Cody Declan , O’Connell Jean , Winter Desmond C. , Doherty Derek G. , Lynch Lydia , O’Shea Donal , Hogan Andrew E. 
Published: May 2015

Abstract
Mucosal-associated invariant T (MAIT) cells are innate MHC-unrestricted cells that regulate inflammatory responses through the rapid production of cytokines. In this article, we show that circulating MAIT cells are depleted in obese adults, and depletion is associated with diabetic status. Circulating MAIT cells more frequently produced IL-17 upon stimulation ex vivo, a cytokine implicated in insulin resistance. MAIT cells were enriched in adipose tissue (AT) compared with blood. AT MAIT cells, but not circulating MAIT cells, were capable of producing IL-10. In AT from obese subjects, MAIT cells were depleted, were less likely to produce IL-10, and more frequently produced IL-17. Finally, we show that IL-17+ MAIT cells are also increased in childhood obesity, and altered MAIT cell frequencies in obese children are positively associated with insulin resistance. These data indicate that MAIT cells are enriched in human AT and display an IL-17+ phenotype in both obese adults and children, correlating with levels of insulin resistance. The alterations in MAIT cells may be contributing to obesity-related sterile inflammation and insulin resistance.
A Synthetic M Protein Peptide Synergizes with a CXC Chemokine Protease To Induce Vaccine-Mediated Protection against Virulent Streptococcal Pyoderma and Bacteremia
Authors: Pandey Manisha , Langshaw Emma , Hartas Jon , Lam Alfred , Batzloff Michael R. , Good Michael F. 
Published: May 2015

Abstract
Infections caused by Streptococcus pyogenes (group A Streptococcus [GAS]) are highly prevalent in the tropics, in developing countries, and in the Indigenous populations of developed countries. These infections and their sequelae are responsible for almost 500,000 lives lost prematurely each year. A synthetic peptide vaccine (J8-DT) from the conserved region of the M protein has shown efficacy against disease that follows i.p. inoculation of bacteria. By developing a murine model for infection that closely mimics human skin infection, we show that the vaccine can protect against pyoderma and subsequent bacteremia caused by multiple GAS strains, including strains endemic in Aboriginal communities in the Northern Territory of Australia. However, the vaccine was ineffective against a hypervirulent cluster of virulence responder/sensor mutant GAS strain; this correlated with the strain’s ability to degrade CXC chemokines, thereby preventing neutrophil chemotaxis. By combining J8-DT with an inactive form of the streptococcal CXC protease, S. pyogenes cell envelope proteinase, we developed a combination vaccine that is highly effective in blocking CXC chemokine degradation and permits opsonic Abs to kill the bacteria. Mice receiving the combination vaccine were strongly protected against pyoderma and bacteremia, as evidenced by a 100–1000-fold reduction in bacterial burden following challenge. To our knowledge, a vaccine requiring Abs to target two independent virulence factors of an organism is unique.
Haploinsufficiency for Stard7 Is Associated with Enhanced Allergic Responses in Lung and Skin
Authors: Yang Li , Lewkowich Ian , Apsley Karen , Fritz Jill M. , Wills-Karp Marsha , Weaver Timothy E. 
Published: May 2015

Abstract
Allergic asthma is a chronic inflammatory disorder that affects ∼20% of the population worldwide. Microarray analyses of nasal epithelial cells from acute asthmatic patients detected a 50% decrease in expression of Stard7, an intracellular phosphatidylcholine transport protein. To determine whether loss of Stard7 expression promotes allergic responses, mice were generated in which one allele of the Stard7 locus was globally disrupted (Stard7+/− mice). OVA sensitization and challenge of Stard7+/− mice resulted in a significant increase in pulmonary inflammation, mucous cell metaplasia, airway hyperresponsiveness, and OVA-specific IgE compared with OVA-sensitized/challenged wild-type (WT) mice. This exacerbation was largely Th2-mediated with a significant increase in CD4+IL-13+ T cells and IL-4, IL-5, and IL-13 cytokines. The loss of Stard7 was also associated with increased lung epithelial permeability and activation of proinflammatory dendritic cells in sensitized and/or challenged Stard7+/− mice. Notably, OVA-pulsed dendritic cells from Stard7+/− mice were sufficient to confer an exaggerated allergic response in OVA-challenged WT mice, although airway hyperresponsiveness was greater in Stard7+/− recipients compared with WT recipients. Enhanced allergic responses in the lung were accompanied by age-dependent development of spontaneous atopic dermatitis. Overall, these data suggest that Stard7 is an important component of a novel protective pathway in tissues exposed to the extracellular environment.
Amino Acid Metabolism Inhibits Antibody-Driven Kidney Injury by Inducing Autophagy
Authors: Chaudhary Kapil , Shinde Rahul , Liu Haiyun , Gnana-Prakasam Jaya P. , Veeranan-Karmegam Rajalakshmi , Huang Lei , Ravishankar Buvana , Bradley Jillian , Kvirkvelia Nino , McMenamin Malgorzata , Xiao Wei , Kleven Daniel , Mellor Andrew L. , Madaio Michael P. , McGaha Tracy L. 
Published: May 2015

Abstract
Inflammatory kidney disease is a major clinical problem that can result in end-stage renal failure. In this article, we show that Ab-mediated inflammatory kidney injury and renal disease in a mouse nephrotoxic serum nephritis model was inhibited by amino acid metabolism and a protective autophagic response. The metabolic signal was driven by IFN-γ–mediated induction of indoleamine 2,3-dioxygenase 1 (IDO1) enzyme activity with subsequent activation of a stress response dependent on the eIF2α kinase general control nonderepressible 2 (GCN2). Activation of GCN2 suppressed proinflammatory cytokine production in glomeruli and reduced macrophage recruitment to the kidney during the incipient stage of Ab-induced glomerular inflammation. Further, inhibition of autophagy or genetic ablation of Ido1 or Gcn2 converted Ab-induced, self-limiting nephritis to fatal end-stage renal disease. Conversely, increasing kidney IDO1 activity or treating mice with a GCN2 agonist induced autophagy and protected mice from nephritic kidney damage. Finally, kidney tissue from patients with Ab-driven nephropathy showed increased IDO1 abundance and stress gene expression. Thus, these findings support the hypothesis that the IDO–GCN2 pathway in glomerular stromal cells is a critical negative feedback mechanism that limits inflammatory renal pathologic changes by inducing autophagy.
Cutting Edge: Caspase-11 Limits the Response of CD8+ T Cells to Low-Abundance and Low-Affinity Antigens
Authors: Bergsbaken Tessa , Bevan Michael J. 
Published: May 2015

Abstract
Inflammatory caspases, including caspase-11, are upregulated in CD8+ T cells after Ag-specific activation, but little is known about their function in T cells. We report that caspase-11–deficient (Casp11−/−) T cells proliferated more readily in response to low-affinity and low-abundance ligands both in vitro and in vivo due to an increased ability to signal through the TCR. In addition to increased numbers, Casp11−/− T cells had enhanced effector function compared with wild-type cells, including increased production of IL-2 and reduced expression of CD62L. Casp11−/− T cells specific for endogenous Ags were more readily deleted than wild-type cells. These data indicate that caspase-11 negatively regulates TCR signaling, possibly through its ability to regulate actin polymerization, and inhibiting its activity could enhance the expansion and function of low-affinity T cells.
Oxygen Tension Regulates Human Mesenchymal Stem Cell Paracrine Functions
Authors: Paquet Joseph , Deschepper Mickael , Moya Adrien , Logeart-Avramoglou Delphine , Boisson-Vidal Catherine , Petite Hervé 
Published: May 2015

Abstract

Mesenchymal stem cells (MSCs) have captured the attention and research endeavors of the scientific world because of their differentiation potential. However, there is accumulating evidence suggesting that the beneficial effects of MSCs are predominantly due to the multitude of bioactive mediators secreted by these cells. Because the paracrine potential of MSCs is closely related to their microenvironment, the present study investigated and characterized select aspects of the human MSC (hMSC) secretome and assessed its in vitro and in vivo bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2), conditions that reflect the environment to which MSCs are exposed during MSC-based therapies in vivo. In contrast to supernatant conditioned media (CM) obtained from hMSCs cultured at either 5% or 21% of O2, CM from hMSCs cultured under near anoxia exhibited significantly (p &lt; .05) enhanced chemotactic and proangiogenic properties and a significant (p &lt; .05) decrease in the inflammatory mediator content. An analysis of the hMSC secretome revealed a specific profile under near anoxia: hMSCs increase their paracrine expression of the angiogenic mediators vascular endothelial growth factor (VEGF)-A, VEGF-C, interleukin-8, RANTES, and monocyte chemoattractant protein 1 but significantly decrease expression of several inflammatory/immunomodulatory mediators. These findings provide new evidence that elucidates aspects of great importance for the use of MSCs in regenerative medicine and could contribute to improving the efficacy of such therapies.

Significance
The present study investigated and characterized select aspects of the human mesenchymal stem cell (hMSC) secretome and assessed its in vitro and in vivo biological bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2), conditions that reflect the environment to which MSCs are exposed during MSC-based therapies in vivo. The present study provided the first evidence of a shift of the hMSC cytokine signature induced by oxygen tension, particularly near anoxia (0.1% O2). Conditioned media obtained from hMSCs cultured under near anoxia exhibited significantly enhanced chemotactic and proangiogenic properties and a significant decrease in the inflammatory mediator content. These findings provide new evidence that elucidates aspects of great importance for the use of MSCs in regenerative medicine, could contribute to improving the efficacy of such therapies, and most importantly highlighted the interest in using conditioned media in therapeutic modalities.
Transplantation of Induced Pluripotent Stem Cell-Derived Neural Stem Cells Mediate Functional Recovery Following Thoracic Spinal Cord Injury Through Remyelination of Axons
Authors: Salewski Ryan P. , Mitchell Robert A. , Li Lijun , Shen Carl , Milekovskaia Maria , Nagy Andras , Fehlings Michael G. 
Published: May 2015

Abstract

Neural stem cells (NSCs) from embryonic or fetal/adult tissue sources have shown considerable promise in regenerative strategies for traumatic spinal cord injury (SCI). However, there are limitations with their use related to the availability, immunogenicity, and uncertainty of the mechanisms involved. To address these issues, definitive NSCs derived from induced pluripotent stem (iPS) cells generated using a nonviral, piggyBac transposon approach, were investigated. Committed NSCs were generated from iPS cells using a free-floating neurosphere methodology previously described by our laboratory. To delineate the mechanism of action, specifically the role of exogenous myelination, NSCs derived from wildtype (wt) and nonmyelinating Shiverer (shi) iPS cell lines were used following thoracic SCI with subacute intraspinal transplantation. Behavioral, histological, and electrophysiological outcomes were analyzed to assess the effectiveness of this treatment. The wt- and shi-iPS-NSCs were validated and shown to be equivalent except in myelination capacity. Both iPS-NSC lines successfully integrated into the injured spinal cord and predominantly differentiated to oligodendrocytes, but only the wt-iPS-NSC treatment resulted in a functional benefit. The wt-iPS-dNSCs, which exhibited the capacity for remyelination, significantly improved neurobehavioral function (Basso Mouse Scale and CatWalk), histological outcomes, and electrophysiological measures of axonal function (sucrose gap analysis) compared with the nonmyelinating iPS-dNSCs and cell-free controls. In summary, we demonstrated that iPS cells can generate translationally relevant NSCs for applications in SCI. Although NSCs have a diverse range of functions in the injured spinal cord, remyelination is the predominant mechanism of recovery following thoracic SCI.

Significance
Gain-of-function/loss-of-function techniques were used to examine the mechanistic importance of graft-derived remyelination following thoracic spinal cord injury (SCI). The novel findings of this study include the first use of neural stem cells (NSCs) from induced pluripotent stem cells (iPSCs) derived using the clonal neurosphere expansion conditions, for the treatment of SCI, the first characterization and in vivo application of iPSCs from Shiverer mouse fibroblasts, and the first evidence of the importance of remyelination by pluripotent-sourced NSCs for SCI repair and regeneration.
Evaluating the Effectiveness of Cryopreserved Acellular Dermal Matrix in Immediate Expander-Based Breast Reconstruction: A Comparison Study
Authors: Kim So-Young , Lim So Young , Mun Goo-Hyun , Bang Sa-Ik , Oh Kap Sung , Pyon Jai-Kyong 
Published: May 2015

Background CGCryoDerm was first introduced in 2010 and offers a different matrix preservation processes for freezing without drying preparation. From a theoretical perspective, CGCryoDerm has a more preserved dermal structure and more abundant growth factors for angiogenesis and recellularization. In the current study, the authors performed a retrospective study to evaluate freezing- and freeze-drying-processed acellular dermal matrix (ADM) to determine whether any differences were present in an early complication profile.
Methods Patients who underwent ADM-assisted tissue expander placement for two stage breast reconstruction between January of 2013 and March of 2014 were retrospectively reviewed and divided into two groups based on the types of ADM-assisted expander reconstruction (CGDerm vs. CGCryoDerm). Complications were divided into four main categories and recorded as follows: seroma, hematoma, infection, and mastectomy skin flap necrosis.
Results In a total of 82 consecutive patients, the CGCryoDerm group had lower rates of seroma when compared to the CGDerm group without statistical significance (3.0% vs. 10.2%, P=0.221), respectively. Other complications were similar in both groups. Reconstructions with CGCryoDerm were found to have a significantly longer period of drainage when compared to reconstructions with CGDerm (11.91 days vs. 10.41 days, P=0.043).
Conclusions Preliminary findings indicate no significant differences in early complications between implant/expander-based reconstructions using CGCryoderm and those using CGDerm.
Diagnostiquer la « schizophrénie spirituelle » du Canada français1 : la politique spirituelle de Claude Ryan, 1952-1958
Authors: Gauvreau Michael , Warren Jean-Philippe 
Published: May 2015

Cet article analyse le rôle intellectuel de Claude Ryan dans une transformation culturelle de grande envergure au sein de l’Action catholique au Québec de 1945 à 1958. Durant ces années, la pensée de Ryan fut fortement influencée par de nouveaux courants de théologie catholique et la psychologie sociale dominant l’horizon de nombreux intellectuels américains. Sous son inspiration, l’Action catholique abandonne progressivement sa préoccupation initiale avec la réforme sociale, dominée par la « question des travailleurs » et la notion de la jeunesse comme classe à part dans la société moderne, pour une inquiétude centrée sur la classe moyenne québécoise, une orientation plus psychologique, centrée sur l’existence des mentalités religieuses et culturelles conflictuelles. Dès le milieu des années 1950, Ryan décerna dans ce conflit un vecteur dynamique de la sécularisation, mais il demeura plutôt optimiste que ces contemporains trouveraient, par le biais d’un catholicisme plus centré sur le spirituel, les ressources culturelles pour surmonter ce qu’il identifiait comme la « crise de l’adolescence » du Canada français.
La déploration, de Sarah Bernhardt à Al Pacino. Permanence et migration d’une posture codifiée (arts visuels, théâtre, cinéma1)
Authors: Damour Christophe 
Published: May 2015

L’acteur demeure au coeur de la palette expressive d’artistes (qu’ils soient cinéastes, photographes ou metteurs en scène) recourant à des procédés rhétoriques similaires fondés sur la puissance iconique de certains gestes. Cet article ébauche une enquête figurative sur la reprise stylistique d’un motif partagé par différents champs scéniques et visuels (du théâtre classique au photojournalisme) et des cinématographies diverses (des cinémas muets européen et russe au cinéma hollywoodien contemporain) : la gestuelle codifiée et esthétisée de la déploration (affaissement, cris, mains portées aux tempes ou levées vers le ciel). L’analyse comparative et généalogique de telles survivances de la peinture romantique, de l’expressionnisme, de l’opéra et du mélodrame, qui révèle l’existence de véritables filiations artistiques, va ici de la Sarah Bernhardt de La Tosca (1887) au Pacino du troisième volet du Parrain (1990), en passant par certaines images-choc redondantes qui prolifèrent dans le champ médiatique.
Implications of freshwater flux data from the CMIP5 multimodel output across a set of Northern Hemisphere drainage basins
Authors: Bring Arvid , Asokan Shilpa M. , Jaramillo Fernando , Jarsjö Jerker , Levi Lea , Pietroń Jan , Prieto Carmen , Rogberg Peter , Destouni Georgia 
Published: May 2015

AbstractThe multimodel ensemble of the Coupled Model Intercomparison Project, Phase 5 (CMIP5) synthesizes the latest research in global climate modeling. The freshwater system on land, particularly runoff, has so far been of relatively low priority in global climate models, despite the societal and ecosystem importance of freshwater changes, and the science and policy needs for such model output on drainage basin scales. Here we investigate the implications of CMIP5 multimodel ensemble output data for the freshwater system across a set of drainage basins in the Northern Hemisphere. Results of individual models vary widely, with even ensemble mean results differing greatly from observations and implying unrealistic long‐term systematic changes in water storage and level within entire basins. The CMIP5 projections of basin‐scale freshwater fluxes differ considerably more from observations and among models for the warm temperate study basins than for the Arctic and cold temperate study basins. In general, the results call for concerted research efforts and model developments for improving the understanding and modeling of the freshwater system and its change drivers. Specifically, more attention to basin‐scale water flux analyses should be a priority for climate model development, and an important focus for relevant model‐based advice for adaptation to climate change.
Persistent millennial‐scale climate variability in the eastern tropical North Pacific over the last two glacial cycles
Authors: Arellano‐Torres Elsa , Ganeshram Raja S. , Pichevin Laetitia E. , Salas‐de‐Leon David Alberto 
Published: May 2015

AbstractHigh‐resolution sediment records from the eastern tropical North Pacific (ETNP) spanning the last ~240 ka B.P. were studied to document the nature of millennial‐scale climatic events in the tropical Pacific and to investigate teleconnection mechanisms. We present organic carbon (%OC) and diffuse spectral reflectivity records as indicative of upwelling and productivity changes off NW Mexico over the middle to late Pleistocene. The new productivity records document the persistence of abrupt millennial‐scale changes over the last two glacial cycles. Detailed spectral and wavelet time series analyses show the predominance of longer climatic cycles (2–6 ka) during the last and the penultimate glacial periods. The persistence of millennial variability during the penultimate glacial, in absence of large ice rafted debris events in the North Atlantic, suggests that freshwater input through ice sheet dynamics is not essential for millennial‐scale climate variability. Given the worldwide emerging picture of remarkable similar millennial‐scale records over long time periods, we suggest that the pacing of this climate variability may represent a natural resonance in the climate system, amplified by a tightly coupled oceanic and atmospheric teleconnection processes. We present a schematic scenario of millennial‐scale climate change depicting the role of the tropical Pacific in this global teleconnection system by linking productivity and upwelling changes in the ETNP with shifts in the position of the Intertropical Convergence Zone and the strength of the subtropical North Pacific High.