bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-17 superfamily cytokines modulate normal germinal center B cell migration
Authors: Ferretti Elisa , Ponzoni Maurilio , Doglioni Claudio , Pistoia Vito 
Published: August 2016

Abstract
The germinal center (GC) is a dynamic structure formed by proliferating B cells in the follicles of secondary lymphoid organs during T cell-dependent antibody responses to exogenous antigens. GC is composed by a dark zone, enriched in proliferating centroblasts (CBs), and a light zone where CBs migrate and transform into centrocytes (CCs), a minority of which is selected to survive, undergoes Ig class-switch recombination, and differentiates into memory B cells or long-lived plasma cells. CBs express CXCR4 and are attracted to the dark zone by stromal cell-derived CXCL12, whereas CCs express CXCR5 and are recruited to the light zone along a gradient of CXCL13 produced by follicular dendritic cells (FDCs). Therefore, CXCL12 and CXCL13 play crucial roles in the regulation of GC B cell trafficking. Among the numerous molecules involved in GC formation, IL-17A represents a recent addition. Its involvement has been demonstrated in mouse models of human autoimmune or infectious diseases. IL-17A belongs to the IL-17 cytokine superfamily, together with 5 additional structurally related cytokines. We have recently demonstrated that IL-17A renders freshly isolated tonsil GC B cells competent to migrate to CXCL12 and CXCL13 through a NF-κBp65-dependent mechanism. Here, we review the role of IL-17A on GC cells and discuss, for the first time, common effects of the cognate cytokines IL-25 and IL-17B on GC B cell function.
Coordination between T helper cells, iNKT cells, and their follicular helper subsets in the humoral immune response against Clostridium difficile toxin B
Authors: Rampuria Pragya , Lang Gillian A , Devera T Scott , Gilmore Casey , Ballard Jimmy D , Lang Mark L 
Published: August 2016

Abstract
Activation of iNKT cells with the CD1d-binding glycolipid adjuvant α-galactosylceramide (α-GC) enhances humoral immunity specific for coadministered T-dependent Ag. However, the relationship between the iNKT cell and the classic T helper (Th) or T follicular helper (Tfh) function following this immunization modality remains unclear. We show that immunization with the C-terminal domain (CTD) of Clostridium difficile toxin B (TcdB), accompanied by activation of iNKT cells with α-GC, led to enhanced production of CTD-specific IgG, which was CD1d- and iNKT cell-dependent and associated with increased neutralization of active TcdB. Immunization with CTD plus α-GC followed by NP hapten-linked CTD increased NP-specific IgG1 titers in an NKT-dependent manner, suggesting that iNKT activation could enhance Th or Tfh function or that iNKT and iNKTfh cells could provide supplemental, yet independent, B cell help. Th, Tfh, iNKT, and iNKTfh cells were, therefore, examined quantitatively, phenotypically, and functionally following immunization with CTD or with CTD plus α-GC. Our results demonstrated that α-GC–activated iNKT cells had no direct effect on the numbers, phenotype, or function of Th or Tfh cells. However, CD4+ T cell–specific ablation of the Bcl6 transcription factor demonstrated that Tfh and iNKTfh cells both contributed to B cell help. This work extends our understanding of the immune response to vaccination and demonstrates an important contribution by NKTfh cells to humoral immunity.
Cystic Craniopharyngiomas: Microsurgical or Stereotactic Treatment?
Authors: Rachinger Walter , Oehlschlaegel Florian , Kunz Mathias , Fuetsch Manuel , Schichor Christian , Thurau Stephan , Schopohl Jochen , Seelos Klaus , Tonn Jörg-Christian , Kreth Friedrich-Wilhelm 
Published: August 2016

AbstractBACKGROUND:Prognosis and treatment of cystic craniopharyngiomas are poorly defined.OBJECTIVE:To analyze progression-free survival (PFS) and safety profile of cystic craniopharyngiomas undergoing resection or minimally invasive drainage procedures. We compared further outcome measurements for cystic and solid tumors undergoing resection to elucidate the impact of the initial tumor composition on both PFS and the toxicity profile.METHODS:All patients with craniopharyngiomas consecutively treated between 1999 and 2014 were included. A treatment decision in favor of microsurgery or stereotactic treatment was made interdisciplinarily. For stereotactic drainage, a catheter was implanted, allowing both permanent upstream (into ventricular spaces) and downstream (into prepontine cistern) drainage. Study endpoints were tumor progression, functional outcome, and treatment toxicity. Functional endocrinological and visual outcome analyses referred to data obtained preoperatively and 6 weeks after treatment. The Kaplan-Meier method was used for survival analysis. Prognostic factors were obtained from proportional hazard models.RESULTS:Seventy-nine patients were included. The distribution of clinical and tumor-related data was well balanced among patients with solid (n = 35) and cystic (n = 44) tumors and those undergoing microsurgical or stereotactic treatment. Cystic tumors had shorter PFS (5-year PFS: 53.6% vs 66.8%,P= .10) and needed significantly more therapeutic interventions, which was independent of the initial treatment mode. The endocrinological deterioration rate was high for both solid and cystic tumors after microsurgery (59.4% and 85.7%, respectively), whereas it was significantly lower for cystic tumors undergoing stereotactic treatment (23.1%,P< .001).CONCLUSION:Stereotactic bidirectional drainage of cystic craniopharyngiomas is effective and provides a better endocrinological outcome than conventional microsurgery.
Acute and long-term outcomes in a Drosophila melanogaster model of classic galactosemia occur independently of galactose-1-phosphate accumulation
Authors: Daenzer Jennifer M. I. , Jumbo-Lucioni Patricia P. , Hopson Marquise L. , Garza Kerry R. , Ryan Emily L. , Fridovich-Keil Judith L. 
Published: August 2016

ABSTRACT
Classic galactosemia (CG) is a potentially lethal inborn error of metabolism that results from the profound loss of galactose-1-phosphate uridylyltransferase (GALT), the second enzyme in the Leloir pathway of galactose metabolism. Neonatal detection and dietary restriction of galactose minimizes or resolves the acute sequelae of CG, but fails to prevent the long-term complications experienced by a majority of patients. One of the substrates of GALT, galactose-1-phosphate (Gal-1P), accumulates to high levels in affected infants, especially following milk exposure, and has been proposed as the key mediator of acute and long-term pathophysiology in CG. However, studies of treated patients demonstrate no association between red blood cell Gal-1P level and long-term outcome severity. Here, we used genetic, epigenetic and environmental manipulations of a Drosophila melanogaster model of CG to test the role of Gal-1P as a candidate mediator of outcome in GALT deficiency. Specifically, we both deleted and knocked down the gene encoding galactokinase (GALK) in control and GALT-null Drosophila, and assessed the acute and long-term outcomes of the resulting animals in the presence and absence of dietary galactose. GALK is the first enzyme in the Leloir pathway of galactose metabolism and is responsible for generating Gal-1P in humans and Drosophila. Our data confirmed that, as expected, loss of GALK lowered or eliminated Gal-1P accumulation in GALT-null animals. However, we saw no concomitant rescue of larval survival or adult climbing or fecundity phenotypes. Instead, we saw that loss of GALK itself was not benign and in some cases phenocopied or exacerbated the outcome seen in GALT-null animals. These findings strongly contradict the long-standing hypothesis that Gal-1P alone underlies pathophysiology of acute and long-term outcomes in GALT-null Drosophila and suggests that other metabolite(s) of galactose, and/or other pathogenic factors, might be involved.
Insulin receptor isoform A ameliorates long-term glucose intolerance in diabetic mice
Authors: Diaz-Castroverde Sabela , Gómez-Hernández Almudena , Fernández Silvia , García-Gómez Gema , Di Scala Marianna , González-Aseguinolaza Gloria , Fernández-Millán Elisa , González-Rodríguez Águeda , García-Bravo María , Chambon Pierre , Álvarez Carmen , Perdomo Liliana , Beneit Nuria , Escribano Oscar , Benito Manuel 
Published: August 2016

ABSTRACT
Type 2 diabetes mellitus is a complex metabolic disease and its pathogenesis involves abnormalities in both peripheral insulin action and insulin secretion. Previous in vitro data showed that insulin receptor isoform A, but not B, favours basal glucose uptake through its specific association with endogenous GLUT1/2 in murine hepatocytes and beta cells. With this background, we hypothesized that hepatic expression of insulin receptor isoform A in a mouse model of type 2 diabetes could potentially increase the glucose uptake of these cells, decreasing the hyperglycaemia and therefore ameliorating the diabetic phenotype. To assure this hypothesis, we have developed recombinant adeno-associated viral vectors expressing insulin receptor isoform A (IRA) or isoform B (IRB) under the control of a hepatocyte­-specific promoter. Our results demonstrate that in the long term, hepatic expression of IRA in diabetic mice is more efficient than IRB in ameliorating glucose intolerance. Consequently, it impairs the induction of compensatory mechanisms through beta cell hyperplasia and/or hypertrophy that finally lead to beta cell failure, reverting the diabetic phenotype in about 8 weeks. Our data suggest that long-term hepatic expression of IRA could be a promising therapeutic approach for the treatment of type 2 diabetes mellitus.
TRIM17 contributes to autophagy of midbodies while actively sparing other targets from degradation
Authors: Mandell Michael A. , Jain Ashish , Kumar Suresh , Castleman Moriah J. , Anwar Tahira , Eskelinen Eeva-Liisa , Johansen Terje , Prekeris Rytis , Deretic Vojo 
Published: August 2016

ABSTRACT
TRIM proteins contribute to selective autophagy, a process whereby cells target specific cargo for autophagic degradation. In a previously reported screen, TRIM17 acted as a prominent inhibitor of bulk autophagy, unlike the majority of TRIMs, which had positive roles. Nevertheless, TRIM17 showed biochemical hallmarks of autophagy-inducing TRIMs. To explain this paradox, here, we investigated how TRIM17 inhibits selective autophagic degradation of a subset of targets while promoting degradation of others. We traced the inhibitory function of TRIM17 to its actions on the anti-autophagy protein Mcl-1, which associates with and inactivates Beclin 1. TRIM17 expression stabilized Mcl-1–Beclin-1 complexes. Despite its ability to inhibit certain types of selective autophagy, TRIM17 promoted the removal of midbodies, remnants of the cell division machinery that are known autophagy targets. The selective loss of anti-autophagy Mcl-1 from TRIM17–Beclin-1 complexes at midbodies correlated with the ability of TRIM17 to promote midbody removal. This study further expands the roles of TRIMs in regulating selective autophagy by showing that a single TRIM can, depending upon a target, either positively or negatively regulate autophagy.
Price-Matching Guarantees with Endogenous Consumer Search
Authors: Jiang Juncai , Kumar Nanda , Ratchford Brian T. 
Published: August 2016

Price-matching guarantees (PMGs) are offered in a wide array of product categories in retail markets. PMGs offer consumers the assurance that, should they find a lower price elsewhere within a specified period after purchase the retailer will match that price and refund the price difference. The goal of this study is to explain the following stylized facts: (1) many retailers that operate both online and offline implement PMG offline but not online; (2) the practices of PMG vary considerably across retail categories; and (3) some retailers launch specialized websites that automatically check competitors’ prices for consumers after purchase. To this end, we build a sequential search model that endogenizes consumers’ pre- and postpurchase search decisions. We find that PMG expands retail demand but intensifies price competition on two dimensions. PMG drives retailers to offer deeper promotions because it increases the overall extent of consumer search, which we call the primary competition-intensifying effect. We also find a new secondary competition-intensifying effect, which results from endogenous consumer search. As deeper promotions incentivize consumers to continue price search, retailers are forced to lower the “regular” price to deter consumers from searching. The strength of the secondary competition-intensifying effect increases with the ratio of product valuation to search cost, which explains the variation in PMG practices online versus offline and across retail categories. We show that an asymmetric equilibrium exists such that one retailer offers PMG while the other does not. In this equilibrium, the PMG retailer may benefit from launching a price check website to facilitate consumers’ postpurchase search. This paper was accepted by J. Miguel Villas-Boas, marketing.
Early Task Initiation and Other Load-Adaptive Mechanisms in the Emergency Department
Authors: Batt Robert J. , Terwiesch Christian 
Published: August 2016

We study a multistage service process that adapts to system occupancy level. Using operational data from more than 140,000 patient visits to a hospital emergency department, we show that the system-level performance of the emergency department is an aggregation of several simultaneous server-level workload response mechanisms. We identify early task initiation as a between-stage adaptive response mechanism that occurs when an upstream stage initiates tasks that are normally handled by a downstream stage. We show that having some diagnostic tests ordered during the triage process reduces treatment time by 20 minutes, on average. However, ordering too many tests at triage can lead to an increase in the total number of tests performed on the patient. We also demonstrate the presence of other response mechanisms such as queuing delays for tasks such as medication delivery, and rushing as nurses spend less time with their patients when the queue length is high. This paper was accepted by Serguei Netessine, operations management.
Carer experiences of inpatient hospice care for people with dementia, delirium and related cognitive impairment
Authors: Bolton Leanne , Loveard Tanya , Brander Penny 
Published: August 2016

Aim: This study aimed to explore carer experiences of inpatient unit (IPU) hospice care for people with dementia, delirium and related cognitive impairment, following implementation of the Te Kete Marie (TKM) initiative aimed at improving care for this patient group. Methods: Semi-structured interviews were undertaken with 10 carers of people affected by these conditions to ascertain their experiences of the care provided during the IPU stay. Results: Analysis of interviews found carer experience could be described by three underlying themes: staff attunement, environmental support, and discharge preparedness, which contributed to a central theme of carer confidence. Conclusion: The findings suggest that carer confidence is enhanced by: staff awareness and response to individual patient needs, interests and preferences, as well as carer requirements for information and consultation; an environment that engenders experience of comfort, safety, flexibility, privacy and outdoor connection; carer preparedness for patients who subsequently transition home or to alternative residential care.
Young citizens in South Africa: A paradox of engagement with politics and the media
Authors: Malila Vanessa , Oelofsen Marietjie 
Published: August 2016

Abstract
In 2014, South Africa’s democracy turned 20. Just like the young democracy is learning to find its feet, young citizens are negotiating the unknown territory of full citizenship rights while confronting a ‘totally different world than that of their parents’. Whether their parents were black and not entitled to full citizenship or whether their parents were white and therefore implicated in a system that withheld full citizenship from the majority of the population, young people do not have a template to draw on for meaning and form of citizenship in a new and liberated South Africa. This article examines political participation amongst young South Africans and their negotiated participation in both political and civic activities within the context of media use and consumption. Their paradoxical relationship with both politics and the media is detailed in an attempt to understand how to deepen a culture of meaningful citizenship amongst South African youth.
Capacity building, tertiary postgraduate interventions and the changing media environment in southern and eastern Africa
Authors: Teer-Tomaselli Ruth 
Published: August 2016

Abstract
An academic revolution in higher education during the past half century has been marked by transformations unprecedented in scope and diversity. Simultaneously, the significant changes in the ‘mediascape’ of southern and eastern Africa over the past two decades have replaced total state control with a degree of liberalization, while the digital revolution has changed the access to, and the content of, media programming. The article argues that the production of postgraduate scholars, particularly at the doctoral level, is a useful indicator of the way in which capacity building in higher education – specifically, higher education for media and journalism studies – is being undertaken. This desk research article synthesizes the trends in media and academia under six headings: 1. structure and regulation; 2. end users – audiences, readers and viewers and students; 3. content delivery – programmes and curricula; 4. human resources; 5. digital technology and new media; and 6. financial sustainability.
Sherlock’s violin: Making the Victorian modern through musical fan culture
Authors: Clendinning Elizabeth A. 
Published: August 2016

Abstract
In the past decade, numerous film and television adaptations of Sir Arthur Conan Doyle’s Sherlock Holmes detective stories have inspired fans across the world to form vibrant communities devoted to creating Sherlockian fiction, art and music. These fans join a lineage of fandom as old as Doyle’s stories themselves, a lineage within which the interpretation of music within Doyle’s original stories, as well as performing Sherlock-related songs, constituted important acts of fandom. Through examining archival records of Sherlockian correspondence, publications and recordings as well as the textual, visual and audio-visual creations of online fan communities, I analyse the musical representation in Doyle’s original stories, and then document how Sherlockians from the nineteenth century to the present have integrated music into their fan activities. Expanding on the work of Small, I suggest that Sherlock Holmes fans engage not only in live music-making activities but also in what I term textual musicking – the fictional interpretation of canonical diegetic music in the written word. Finally, I identify how historical shifts in musical fandom embody and reflect a more fundamental recent shift in perception of the Sherlockian textual canon, but also what it means to be a Sherlock fan.
‘Reading the territory’: Psychogeography and urban intertextuality
Authors: Mudie Ella 
Published: August 2016

Abstract
This review article looks at three recent publications that manifest the intertextual nature of psychogeography, focusing on how the influence of place cuts across disciplinary boundaries to critical effect. In London Overground: A Day’s Walk around the Ginger Line (2015), Iain Sinclair continues to harness the oppositional power of conceiving of the city as inherently intertextual. A new volume edited by Tina Richardson, Walking Inside Out: Contemporary British Psychogeography (2015), is largely concerned with psychogeography as method yet its contributions reveal the extent to which the literary character of psychogeography resists supersession. And notwithstanding his disdain for the term, Patrick Keiller’s The View from the Train: Cities and Other Landscapes (2013) is nonetheless suggestive of the mutual imbrication of quotation, literary association and the critique of urban space. Revealing contradictory attitudes towards the literary dimensions of psychogeography, these publications raise timely questions about the capacity of psychogeographical texts and methods to effect social change.
O conceito de letramento multimodal crítico na escola: o que dizem os professores de inglês
Authors: Kummer Daiane Aline 
Published: August 2016

Para uma participação bem-sucedida em sociedade, precisamos de conhecimentos de letramento multimodal crítico (LMC), ou seja, conhecimentos sobre a combinação crítica e reflexiva de diferentes recursos semióticos, dentre os quais destacamos os visuais, em diversos gêneros discursivos. A escola tem papel fundamental no desenvolvimento dos conhecimentos de LMC nos estudantes, para tanto, o objetivo deste trabalho é verificar como professores de inglês recontextualizam esses conhecimentos na escola. Neste estudo, tomamos como base teórica e metodológica a Análise Crítica de Gênero (MOTTA-ROTH, 2008a), e como corpus respostas a entrevistas de professores inglês de escolas públicas de XXX, Brasil. A análise das respostas às entrevistas revela que a necessidade de conhecer e de mobilizar os recursos semióticos ao agir socialmente, assim como a necessidade de promover conhecimentos de LMC na escola, são reconhecidas pelos professores. Porém, o elemento crítico do conceito parece ser deixado de lado, o que indica a necessidade de refletirmos sobre nosso papel como professores de inglês, no sentido de possibilitar aos estudantes conhecimentos para a combinação de diversos recursos semióticos em diferentes gêneros e contextos de maneira crítica e reflexiva.
Intersonoridade no Discurso Audiovisual: por uma memória no âmbito sonoro
Authors: Marques Welisson 
Published: August 2016

Este artigo apresenta algumas considerações a que chegamos, a partir de uma pesquisa mais ampla, cujo enfoque foi observar o funcionamento do som no discurso publicitário audiovisual. Pesquisas em Análise do discurso atualmente têm se voltado para o estudo da imagem em diferentes corpora, todavia o som – tomado como objeto analítico –, ainda é, certamente, uma materialidade que demanda maior investigação em virtude de sua complexidade. Assim, propusemo-nos a investigar o funcionamento do discurso audiovisual com enfoque no âmbito sonoro. Tomamos como corpus, neste artigo, uma peça publicitária de curso de idiomas veiculada em diferentes mídias no Brasil. Em nossa conclusão destacamos que para se proceder a uma análise discursiva de cunho histórico, não é possível tomar a forma sonora destituída de sua historicidade. Verificamos que os sons produzidos na propaganda, notadamente as formas artificiais, se assemelham ou se avizinham a outros. Isso possibilita a compreensão dos diversos sons que animam e dão sentido à propaganda de modo particular e, sem dúvidas, ao discurso de modo geral.