bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrahepatic Activation of Naive CD4+ T Cells by Liver-Resident Phagocytic Cells
Authors: Tay Szun S. , Wong Yik Chun , Roediger Ben , Sierro Frederic , Lu Bo , McDonald David M. , McGuffog Claire M. , Meyer Nicholas J. , Alexander Ian E. , Parish Ian A. , Heath William R. , Weninger Wolfgang , Bishop G. Alex , Gamble Jennifer R. , McCaughan Geoffrey W. , Bertolino Patrick , Bowen David G. 
Published: July 2014

Abstract
Naive T cell activation is normally restricted to the lymphoid organs, in part because of their limited ability to migrate into the parenchyma of peripheral tissues. The liver vasculature is unique, however, and circulating leukocytes within the hepatic sinusoids have direct access to liver-resident cells, which include an abundant population of Kupffer cells. It is well accepted that recognition of cognate Ag within the liver leads to naive CD8+ T cell activation in situ, but it is unclear whether the liver also supports naive CD4+ T cell activation. In this study, we show that naive CD4+ T cells can be activated to proliferate in the liver when cognate Ag expression is induced in hepatocytes by recombinant adeno-associated viral vectors. Ag-specific retention and activation of naive CD4+ T cells within the liver are independent of lymphoid tissues but dependent on a clodronate liposome–sensitive population of liver-resident phagocytic cells. To our knowledge, this study provides the first unequivocal evidence that naive CD4+ T cells can be activated in a nonlymphoid organ. It also gives critical insight into how CD4+ T cells specific for Ag expressed in the liver are recruited to participate in protective or pathological responses during hepatotropic infections and autoimmune liver disease.
Independent of Plasmacytoid Dendritic Cell (pDC) infection, pDC Triggered by Virus-Infected Cells Mount Enhanced Type I IFN Responses of Different Composition as Opposed to pDC Stimulated with Free Virus
Authors: Frenz Theresa , Graalmann Lukas , Detje Claudia N. , Döring Marius , Grabski Elena , Scheu Stefanie , Kalinke Ulrich 
Published: July 2014

Abstract
Upon treatment with vesicular stomatitis virus (VSV) particles, plasmacytoid dendritic cells (pDC) are triggered to mount substantial type I IFN responses, whereas myeloid DC (mDC) are only minor producers. Interestingly, bone marrow–derived (BM-)mDC were more vulnerable to infection with enhanced GFP (eGFP)–expressing VSV (VSVeGFP) than BM-pDC. BM-pDC stimulated with wild-type VSV mounted TLR-dependent IFN responses that were independent of RIG-I–like helicase (RLH) signaling. In contrast, in BM-pDC the VSV variant M2 induced particularly high IFN responses triggered in a TLR- and RLH-dependent manner, whereas BM-mDC stimulation was solely RLH-dependent. Importantly, VSVeGFP treatment of BM-pDC derived from IFN-β yellow fluorescent protein (YFP) reporter mice (messenger of IFN-β) resulted in YFP+ and eGFP+ single-positive cells, whereas among messenger of IFN-β–BM-mDC most YFP+ cells were also eGFP+. This observation indicated that unlike mDC, direct virus infection was not required to trigger IFN responses of pDC. VSV-infected BM-mDC triggered BM-pDC to mount significantly higher IFN responses than free virus particles. Stimulation with infected cells enhanced the percentages of pDC subsets expressing either IFN-β+ or IFN-α6+ plus IFN-β+. Irrespective of whether stimulated with free virus or infected cells, IFN induction was dependent on autophagy of pDC, whereas autophagy of the infected mDC was dispensable. Collectively, these results indicated that productive VSV infection was needed to trigger IFN responses of mDC, but not of pDC, and that IFN responses were primarily induced by virus-infected cells that stimulated pDC in a TLR-dependent manner.
JNK2 Regulates the Functional Plasticity of Naturally Occurring T Regulatory Cells and the Enhancement of Lung Allergic Responses
Authors: Joetham Anthony , Schedel Michaela , Takeda Katsuyuki , Jia Yi , Ashino Shigeru , Dakhama Azzeddine , Lluis Anna , Okamoto Masakazu , Gelfand Erwin W. 
Published: July 2014

Abstract
Glucocorticoid-induced TNFR family–related protein (GITR)–mediated activation of JNK was shown to regulate the suppressive activity of CD4+CD25+ naturally occurring T regulatory cells (nTregs) in wild-type (WT) hosts. In this study, CD4+CD25+ T cells were shown to be capable of becoming pathogenic effector cells in sensitized and challenged CD8−/− recipient mice. Only GITR-expressing CD4+CD25+ T cells, but neither GITR knocked-in CD4+CD25− T cells nor GITR-silenced CD4+CD25+ T cells, enhanced development of lung allergic responses. Inhibition of JNK in WT nTregs or nTregs from GITR−/−and JNK2−/− mice failed to enhance lung allergic responses in sensitized and challenged CD8−/− recipient mice. The failure to enhance responses was associated with increased bronchoalveolar lavage fluid levels of IL-10 and TGF-β and decreased levels of IL-5, IL-6, and IL-13. In contrast, nTregs from JNK1−/− mice, similar to WT nTregs, were fully effective in enhancing responses. Thus, GITR stimulation of nTregs and signaling through JNK2, but not JNK1, triggered the loss of regulatory function while concomitantly gaining pathogenic CD4+ T effector cell function responsible for exacerbating asthma-like immunopathology.
Inhibition of Two Temporal Phases of HIV-1 Transfer from Primary Langerhans Cells to T Cells: The Role of Langerin
Authors: Nasr Najla , Lai Joey , Botting Rachel A. , Mercier Sarah K. , Harman Andrew N. , Kim Min , Turville Stuart , Center Rob J. , Domagala Teresa , Gorry Paul R. , Olbourne Norman , Cunningham Anthony L. 
Published: July 2014

Abstract
Epidermal Langerhans cells (eLCs) uniquely express the C-type lectin receptor langerin in addition to the HIV entry receptors CD4 and CCR5. They are among the first target cells to encounter HIV in the anogenital stratified squamous mucosa during sexual transmission. Previous reports on the mechanism of HIV transfer to T cells and the role of langerin have been contradictory. In this study, we examined HIV replication and langerin-mediated viral transfer by authentic immature eLCs and model Mutz-3 LCs. eLCs were productively infected with HIV, whereas Mutz-3 LCs were not susceptible because of a lack of CCR5 expression. Two successive phases of HIV viral transfer to T cells via cave/vesicular trafficking and de novo replication were observed with eLCs as previously described in monocyte-derived or blood dendritic cells, but only first phase transfer was observed with Mutz-3 LCs. Langerin was expressed as trimers after cross-linking on the cell surface of Mutz-3 LCs and in this form preferentially bound HIV envelope protein gp140 and whole HIV particles via the carbohydrate recognition domain (CRD). Both phases of HIV transfer from eLCs to T cells were inhibited when eLCs were pretreated with a mAb to langerin CRD or when HIV was pretreated with a soluble langerin trimeric extracellular domain or by a CRD homolog. However, the langerin homolog did not inhibit direct HIV infection of T cells. These two novel soluble langerin inhibitors could be developed to prevent HIV uptake, infection, and subsequent transfer to T cells during early stages of infection.
Differentiation of Human Limbal-Derived Induced Pluripotent Stem Cells Into Limbal-Like Epithelium
Authors: Sareen Dhruv , Saghizadeh Mehrnoosh , Ornelas Loren , Winkler Michael A. , Narwani Kavita , Sahabian Anais , Funari Vincent A. , Tang Jie , Spurka Lindsay , Punj Vasu , Maguen Ezra , Rabinowitz Yaron S. , Svendsen Clive N. , Ljubimov Alexander V. 
Published: July 2014

Abstract

Limbal epithelial stem cell (LESC) deficiency (LSCD) leads to corneal abnormalities resulting in compromised vision and blindness. LSCD can be potentially treated by transplantation of appropriate cells, which should be easily expandable and bankable. Induced pluripotent stem cells (iPSCs) are a promising source of transplantable LESCs. The purpose of this study was to generate human iPSCs and direct them to limbal differentiation by maintaining them on natural substrata mimicking the native LESC niche, including feederless denuded human amniotic membrane (HAM) and de-epithelialized corneas. These iPSCs were generated with nonintegrating vectors from human primary limbal epithelial cells. This choice of parent cells was supposed to enhance limbal cell differentiation from iPSCs by partial retention of parental epigenetic signatures in iPSCs. When the gene methylation patterns were compared in iPSCs to parental LESCs using Illumina global methylation arrays, limbal-derived iPSCs had fewer unique methylation changes than fibroblast-derived iPSCs, suggesting retention of epigenetic memory during reprogramming. Limbal iPSCs cultured for 2 weeks on HAM developed markedly higher expression of putative LESC markers ABCG2, ΔNp63α, keratins 14, 15, and 17, N-cadherin, and TrkA than did fibroblast iPSCs. On HAM culture, the methylation profiles of select limbal iPSC genes (including NTRK1, coding for TrkA protein) became closer to the parental cells, but fibroblast iPSCs remained closer to parental fibroblasts. On denuded air-lifted corneas, limbal iPSCs even upregulated differentiated corneal keratins 3 and 12. These data emphasize the importance of the natural niche and limbal tissue of origin in generating iPSCs as a LESC source with translational potential for LSCD treatment.
Storm time response of the midlatitude thermosphere: Observations from a network of Fabry‐Perot interferometers
Authors: Makela Jonathan J. , Harding Brian J. , Meriwether John W. , Mesquita Rafael , Sanders Samuel , Ridley Aaron J. , Castellez Michael W. , Ciocca Marco , Earle Gregory D. , Frissell Nathaniel A. , Hampton Donald L. , Gerrard Andrew J. , Noto John , Martinis Carlos R. 
Published: July 2014

AbstractObservations of thermospheric neutral winds and temperatures obtained during a geomagnetic storm on 2 October 2013 from a network of six Fabry‐Perot interferometers (FPIs) deployed in the Midwest United States are presented. Coincident with the commencement of the storm, the apparent horizontal wind is observed to surge westward and southward (toward the equator). Simultaneous to this surge in the apparent horizontal winds, an apparent downward wind of approximately 100 m/s lasting for 6 h is observed. The apparent neutral temperature is observed to increase by approximately 400 K over all of the sites. Observations from an all‐sky imaging system operated at the Millstone Hill observatory indicate the presence of a stable auroral red (SAR) arc and diffuse red aurora during this time. We suggest that the large sustained apparent downward winds arise from contamination of the spectral profile of the nominal thermospheric 630.0 nm emission by 630.0 nm emission from a different (nonthermospheric) source. Modeling demonstrates that the effect of an additional population of 630.0 nm photons, with a distinct velocity and temperature distribution, introduces an apparent Doppler shift when the combined emissions from the two sources are analyzed as a single population. Thus, the apparent Doppler shifts should not be interpreted as the bulk motion of the thermosphere, calling into question results from previous FPI studies of midlatitude storm time thermospheric winds. One possible source of contamination could be fast O related to the infusion of low‐energy O+ ions from the magnetosphere. The presence of low‐energy O+ is supported by observations made by the Helium, Oxygen, Proton, and Electron spectrometer instruments on the twin Van Allen Probes spacecraft, which show an influx of low‐energy ions during this period. These results emphasize the importance of distributed networks of instruments in understanding the complex dynamics that occur in the upper atmosphere during disturbed conditions.
Aberrant fetal macrophage/microglial reactions to cytomegalovirus infection
Authors: Sakao‐Suzuki Makiko , Kawasaki Hideya , Akamatsu Taisuke , Meguro Shiori , Miyajima Hiroaki , Iwashita Toshihide , Tsutsui Yoshihiro , Inoue Naoki , Kosugi Isao 
Published: July 2014

AbstractObjectiveCongenital cytomegalovirus (CMV) infection is the leading viral cause of neurodevelopmental disorders in humans, with the most severe and permanent sequelae being those affecting the cerebrum. As the fetal immune reactions to congenital CMV infection in the brain and their effects on cerebral development remain elusive, our aim was to investigate primitive innate immunity to CMV infection and its effects on cerebral corticogenesis in a mouse model for congenital CMV infection using a precise intraplacental inoculation method.MethodsAt 13.5 embryonic days (E13.5), pregnant C57BL/6 mice were intraplacentally infected with murine CMV (MCMV). Placentas and fetal organs were collected at 1, 3, and 5 days postinfection and analyzed.ResultsMCMV antigens were found frequently in perivascular macrophages, and subsequently in neural stem/progenitor cells (NSPCs). With increased expression of inducible nitric oxide synthase and proinflammatory cytokines, activated macrophages infiltrated into the infectious foci. In addition to the infected area, the numbers of both meningeal macrophages and parenchymal microglia increased even in the uninfected areas of MCMV‐infected brain due to recruitment of their precursors from other sites. A bromodeoxyuridine (BrdU) incorporation experiment demonstrated that MCMV infection globally disrupted the self‐renewal of NSPCs. Furthermore, BrdU‐labeled neurons, particularly Brn2+ neurons of upper layers II/III in the cortical plate, decreased in number significantly in the MCMV‐infected E18.5 cerebrum.InterpretationBrain macrophages are crucial for innate immunity during MCMV infection in the fetal brain, while their aberrant recruitment and activation may adversely impact on the stemness of NSPCs, resulting in neurodevelopmental disorders.
A novel scaffold geometry for chondral applications: Theoretical model and in vivo validation
Authors: Scaglione Silvia , Ceseracciu Luca , Aiello Maurizio , Coluccino Luca , Ferrazzo Federica , Giannoni Paolo , Quarto Rodolfo 
Published: July 2014

ABSTRACTA theoretical model of the 3D scaffold internal architecture has been implemented with the aim to predict the effects of some geometrical parameters on total porosity, Young modulus, buckling resistance and permeability of the graft. This model has been adopted to produce porous poly‐caprolacton based grafts for chondral tissue engineering applications, best tuning mechanical and functional features of the scaffolds. Material prototypes were produced with an internal geometry with parallel oriented cylindrical pores of 200 μm of radius (r) and an interpore distance/pores radius (d/r) ratio of 1. The scaffolds have been then extensively characterized; progenitor cells were then used to test their capability to support cartilaginous matrix deposition in an ectopic model. Scaffold prototypes fulfill both the chemical‐physical requirements, in terms of Young's modulus and permeability, and the functional needs, such as surface area per volume and total porosity, for an enhanced cellular colonization and matrix deposition. Moreover, the grafts showed interesting chondrogenic potential in vivo, besides offering adequate mechanical performances in vitro, thus becoming a promising candidate for chondral tissues repair. Finally, a very good agreement was found between the prediction of the theoretical model and the experimental data. Many assumption of this theoretical model, hereby applied to cartilage, may be transposed to other tissue engineering applications, such as bone substitutes. Biotechnol. Bioeng. 2014;111: 2107–2119. © 2014 Wiley Periodicals, Inc.
Developing services for people with dangerous and severe personality disorders
Authors: Lavender Anthony 
Published: July 2014

AbstractThis paper describes the conflicting attitudes that exist within wider society and the people who deliver services for people with dangerous and severe personality disorder. The importance of recognizing the nature of these conflicting attitudes that are based on the desire for ‘punishment’, ‘keeping society safe’ and ‘treatment and care’ is discussed. Potential ways of resolving these conflicts at an organizational and practice level are explored. The resolution might involve replacing the notions and associated practices of ‘punishment’ and ‘safety’ with ‘containment’, and ‘treatment and care’ with psychosocial therapy and rehabilitation.
Concurrent Oxidation of Alcohols and the Passerini Three‐Component Polymerization for the Synthesis of Functional Poly(ester amide)s
Authors: Kan Xiao‐Wei , Deng Xin‐Xing , Du Fu‐Sheng , Li Zi‐Chen 
Published: July 2014

A new polymerization method based on the Passerini three‐component reaction of a dicarboxylic acid, an alcohol, and a diisocyanide in the presence of an oxidant is reported. This polymerization involves the concurrent oxidation of alcohols by o‐iodoxybenzoic acid (IBX) and the Passerini three‐component polymerization. The kinetics of the alcohol oxidation and the Passerini reaction are investigated, and the results indicate that the cascade process can occur efficiently. The reaction conditions are optimized, and various functional alcohols are examined to get insight into the applicability of the method. Based on the optimized conditions, a variety of functional poly(ester amide)s are prepared in a one‐pot fashion via using 1,6‐diisocyanohexane, 1,6‐hexanedioic acid, different functional alcohols, and iodoxybenzoic acid. The introduction of functional pendant groups, especially alkynyl, alkenyl and epoxy groups, to the final poly(ester amide)s, provides an efficient way for further modification of the polymers.
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Rethinking the Context of Language in the Schools
Authors: Kovarsky Dana , Maxwell Madeline 
Published: July 2014

When taken together, the involvement strategies that operate on sound and meaning, coupled with the historical, spatial, thematic, and relational frames that make up the human world, help form an intricate web that displays how language and context mutually constitute one another. These ideas are not new and have been articulated in various ways through different academic fields of study concerned with the relations between language and social life, including the ethnography of communication, conversation analysis, and systemic linguistics. The location of talk in communities of practice recognizes that language is embodied action that is accomplished within fields in habits of expression and provides a framework for using empirically discovered, natural processes to highlight (rather than disembed) meaning-making resources.That language and context cannot be separated from one another when seeking to understand communication and meaning is a theme that weaves it way throughout the ideas of the authors presented here. Language is more than a tool. It is a primary way of being human and transforming experience in the construction of social reality: "To be human is to be an understander, which is to engage in processes of coherence building or sense making, processes that occur communicatively and that enable humans to constitute, maintain, and develop the worlds we inhabit" (Stewart, 1995, p. 115).By the same token, language incompetence and disorder are socially constituted and manifest themselves by the degree to which they marginalize, alienate, and disassociate individuals from the social world. This does not mean that the grammar and the dictionary of language are unimportant for those seeking to amend communication problems faced by students in schools; rather, they must be contextualized as part of a set of resources for building coherence, participation, and reality in the human world.
A Comparison of the Oral Narrative Abilities of Underachieving and High-Achieving Gifted Adolescents
Authors: Hayes Phebe Archon , Norris Janet , Flaitz James R. 
Published: July 2014

Few researchers have examined the narrative abilities of underachieving gifted students. This study investigated the ability of eighth-grade underachieving gifted adolescents to spontaneously produce oral narratives by comparing their stories to those that were produced by achieving gifted peers. It was hypothesized that evidence of difficulty generating the stories relative to the macrostructure (organization of ideas across sentences) and the microstructure (organization of ideas within sentences) would be exhibited by the underachieving gifted subjects.
Twenty 13-year-old eighth-graders served as subjects in the present investigation. All were identified as gifted by their local school system and were enrolled in the gifted program at the time of their participation in the study. Ten of the subjects met criteria for the underachieving gifted group and ten met criteria for the achieving gifted group. The stories produced by the underachieving gifted subjects were compared to those produced by their achieving gifted peers for differences in 13 dependent measures of story length, episodic integrity, story grammar components, and sentence complexity.

Differences in the mean number of occurrences of each of the 13 variables were found. The result of the MANOVA revealed that when the 13 dependent variables were considered in combination, the stories told by the underachieving gifted subjects differed significantly from those produced by the achieving gifted subjects at the
p
< .05 level of significance. Results of the univariate analyses indicated that these differences were not accounted for by any one element of story macrostructure or microstructure, but rather that the stories differed across multiple dimensions, each of which contributed to the overall difference.

The results of this study suggest that the language of underachieving gifted children may differ from that of gifted peers when narrative language is examined. Results are discussed relative to the limitations of the study and implications for future research.
Language Testing in Adolescents With Brain Injury
Authors: Turkstra Lyn S. 
Published: July 2014

The validity of the Clinical Evaluation of Language Fundamentals-Third Edition (CELF-3, Semel, Wiig, & Secord, 1995) for the identification and description of language disorders following traumatic brain injury (TBI) was considered in 11 adolescents with TBI. In general, the CELF-3 identified only the individuals who had previously been diagnosed as language impaired, not the individuals with verbal information processing impairments but no diagnosis of language impairment. The test did not permit the identification of strengths and weaknesses.
Intercorrelations among subtest standard scores were as high in the TBI group as in the standardization sample, which is consistent with the CELF-3 being a one-factor test. Test performance may have been influenced by the interaction of the subjects’ memory abilities and the subtests’ memory demands, although this relationship was not statistically significant in the present data.