Miracle-dz/UniFAR-FTUs huggingface dataset:
Superantigen-Induced Steroid Resistance Depends on Activation of Phospholipase Cβ2

The glucocorticoid receptor is present in a TCR-associated complex, which includes the Src family tyrosine kinase Lck. Glucocorticoids rapidly dissociate this complex, resulting in the inhibition of canonical Lck-phospholipase C (PLC)γ–dependent TCR signaling. The relative importance of this nongenomic role for the glucocorticoid receptor compared with its direct transcriptional effects is not known. Superantigens induce a state of steroid resistance in activated T cells. It was reported that, in addition to canonical Lck-PLCγ signaling, superantigens can activate a noncanonical G protein–PLCβ–dependent signaling pathway. In this study, we show that staphylococcal enterotoxin B activates a Gαq and PLCβ2–dependent pathway in human T cells. We find that this pathway bypasses the need for canonical Lck-PLCγ signaling in T cell activation and renders superantigen-stimulated T cells insensitive to glucocorticoids in vitro. We show that the PLCβ inhibitor U-73122 sensitizes staphylococcal enterotoxin B–treated mice to dexamethasone in vivo. In conclusion, we find that effects of glucocorticoids on TCR-induced T cell proliferation are mainly nongenomic and can be bypassed by the activation of an Lck-independent signaling pathway.
Intrinsic Molecular Factors Cause Aberrant Expansion of the Splenic Marginal Zone B Cell Population in Nonobese Diabetic Mice

Marginal zone (MZ) B cells are an innate-like population that oscillates between MZ and follicular areas of the splenic white pulp. Differentiation of B cells into the MZ subset is governed by BCR signal strength and specificity, NF-κB activation through the B cell–activating factor belonging to the TNF family (BAFF) receptor, Notch2 signaling, and migration signals mediated by chemokine, integrin, and sphingosine-1-phosphate receptors. An imbalance in splenic B cell development resulting in expansion of the MZ subset has been associated with autoimmune pathogenesis in various murine models. One example is the NOD inbred mouse strain, in which MZ B cell expansion has been linked to development of type 1 diabetes and Sjögren’s syndrome. However, the cause of MZ B cell expansion in this strain remains poorly understood. We have determined that increased MZ B cell development in NOD mice is independent of T cell autoimmunity, BCR specificity, BCR signal strength, and increased exposure to BAFF. Rather, mixed bone marrow chimeras showed that the factor(s) responsible for expansion of the NOD MZ subset is B cell intrinsic. Analysis of microarray expression data indicated that NOD MZ and precursor transitional 2-MZ subsets were particularly dysregulated for genes controlling cellular trafficking, including Apoe, Ccbp2, Cxcr7, Lgals1, Pla2g7, Rgs13, S1pr3, Spn, Bid, Cd55, Prf1, and Tlr3. Furthermore, these B cell subsets exhibited an increased steady state dwell time within splenic MZ areas. Our data therefore reveal that precursors of mature B cells in NOD mice exhibit an altered migration set point, allowing increased occupation of the MZ, a niche favoring MZ B cell differentiation.
A TNF-α–CCL20–CCR6 Axis Regulates Nod1-Induced B Cell Responses

Innate immune responses provoke the accumulation of leukocytes at sites of inflammation. In addition to monocytes and granulocytes, B cells also participate in antimicrobial innate immune responses; however, the mechanisms for accumulation of B cells to sites of inflammation are not well understood. To study B cell accumulation following systemic inflammation, we used a model synthetic ligand that stimulates a specific pattern recognition molecule, nucleotide-binding oligomerization domain–containing protein 1 (Nod1). Upon exposure to Nod1 agonists, both B cells and neutrophils rapidly accumulate within the spleen, and dendritic cells migrate into the periarterial lymphoid sheath. Nod1 stimulation led to a marked increase in several chemokines within the spleen, including CXCL13, CCL2, and CCL20. Whereas the lymphotoxin pathway was critical for the induction of the B cell chemoattractant CXCL13 in response to Nod1 agonists, B cell accumulation within the spleen following Nod1-induced systemic inflammation was independent of the lymphotoxin pathway. In contrast, a CCR6/CCL20 chemokine loop instructed rapid increase of B cells in the spleen in response to systemic administration of Nod1 agonists in a TNF-α–dependent manner. Moreover, CCR6 was required to regulate Nod1-mediated B cell responses. These results reveal a novel mechanism of B cells during inflammation and shed light on how B cells participate in innate immune responses to microbial stimulation.
Pulmonary Expression of Oncostatin M (OSM) Promotes Inducible BALT Formation Independently of IL-6, Despite a Role for IL-6 in OSM-Driven Pulmonary Inflammation

Inducible BALT (iBALT) is associated with immune responses to respiratory infections as well as with local pathology derived from chronic inflammatory lung diseases. In this study, we assessed the role of oncostatin M (OSM) in B cell activation and iBALT formation in mouse lungs. We found that C57BL/6 mice responded to an endotracheally administered adenovirus vector expressing mouse OSM, with marked iBALT formation, increased cytokine (IL-4, IL-5, IL-6, IL-10, TNF-α, and IL-12), and chemokine (CXCL13, CCL20, CCL21, eotaxin-2, KC, and MCP-1) production as well as inflammatory cell accumulation in the airways. B cells, T cells, and dendritic cells were also recruited to the lung, where many displayed an activated phenotype. Mice treated with control adenovirus vector (Addl70) were not affected. Interestingly, IL-6 was required for inflammatory responses in the airways and for the expression of most cytokines and chemokines. However, iBALT formation and lymphocyte recruitment to the lung tissue occurred independently of IL-6 and STAT6 as assessed in gene-deficient mice. Collectively, these results support the ability of OSM to induce B cell activation and iBALT formation independently of IL-6 and highlight a role for IL-6 downstream of OSM in the induction of pulmonary inflammation.
How artefacts rule web-based communities: practices of free software development

This paper seeks to understand how complex tasks are accomplished by large web-based communities. In order to do so, we consider that technologies may embody organisational rules, hence becoming the core of coordination efforts in such communities. Our analysis is based on the concepts of translation and inscription taken from the Actor-Network Theory, while the data have been gathered using an ethnographic approach. We base our observation on the case of a Geographic Information System (GIS): the Geographic Resources Analysis Support System (GRASS) is a system developed by a small group of developers but sustained by a very large users' base located worldwide. In particular, we focus on small explanatory examples of everyday development activities of the GRASS community in relation to the internationalisation process. We focus on artefacts, such as the Concurrent Versioning System and the GRASS source code, that greatly affect the everyday activities of the community. The main result of our research is the illustration that complex tasks are accomplished by large web-based communities, thanks to many small contributions shaped and organised by the rules embodied in artefacts.
The Nature and Extent of Flavored Alcoholic Beverage Consumption among Underage Youth: Results of a National Brand-Specific Survey

Background: Flavored alcoholic beverages are popular among underage drinkers. Existing studies that assessed flavored alcoholic beverage use among youth relied upon respondents to correctly classify the beverages they consume, without defining what alcohol brands belong to this category. Objectives: The aim is to demonstrate a new method for analyzing the consumption of flavored alcoholic beverages among youth on a brand-specific basis, without relying upon youth to correctly classify brands they consume. Methods: Using a prerecruited Internet panel developed by Knowledge Networks, we measured the brands of alcohol consumed by a national sample of youth drinkers, aged 16–20 years, in the United States. The sample consisted of 108 youths who had consumed at least one drink of an alcoholic beverage in the past 30 days. We measured the brand-specific consumption of alcoholic beverages within the past 30 days, ascertaining the consumption of 380 alcohol brands, including 14 brands of flavored alcoholic beverages. Results: Measuring the brand-specific consumption of flavored alcoholic beverages was feasible. Based on a brand-specific identification of flavored alcoholic beverages, nearly half of the youth drinkers in the sample reported having consumed such beverages in the past 30 days. Flavored alcoholic beverage preference was concentrated among the top four brands, which accounted for almost all of the consumption volume reported in our study. Conclusions and scientific significance: These findings underscore the need to assess youth alcohol consumption at the brand level and the potential value of such data in better understanding underage youth drinking behavior and the factors that influence it.
Different Stages of Primary Sjögren’s Syndrome Involving Lymphotoxin and Type 1 IFN

Primary Sjögren’s syndrome (pSS) is a complex autoimmune disease starting in the salivary and lacrimal glands and continuing to involve the lungs and kidneys with the eventual development of lymphoma. Many studies have emphasized the role of type 1 IFN (IFN-α) and lymphotoxin α (LTα) in the pathogenesis of the disease. The present studies were designed to delineate the role of IFN-α in pSS using an animal model, the IL-14α (IL14αTG) transgenic mouse. IL14αTG mice lacking the type 1 IFNR (IL14αTG.IFNR−/−) had the same submandibular gland and lacrimal gland injury as did the IL14αTG mice, but they lacked the later parotid gland and lung injury. Development of lymphoma was delayed in IL14αTG. IFNR−/− mice. The switch from IgM to IgG autoantibodies as well as the increase in serum IgG2a seen is IL14αTG mice was inhibited in IL14αTG. IFNR−/− mice. Production of LTα was identified in both IL14αTG mice and IL14αTG. IFNR−/− mice at the time that salivary gland injury was occurring. These and previous studies suggest a model for pSS that separates the disease into several stages: 1) initial injury to the submandibular and lacrimal glands via an environmental insult and LTα; 2) amplification of local injury via the production of type 1 IFN; injury to the parotid glands, lungs, and kidneys is seen; 3) progression of systemic inflammation with the eventual development of large B cell lymphoma. Understanding these different stages will help to develop strategies for treatment of patients with pSS based on the status of their disease.
Antibody-Secreting Cells with a Phenotype of Ki-67low, CD138high, CD31high, and CD38high Secrete Nonspecific IgM during Primary Hepatitis A Virus Infection

Although studies investigating the nature of Ab-secreting cells (ASCs) during acute infection with influenza or dengue virus found that the ASC response was dominated by virus-specific IgG secretion, the Ag specificity and phenotype of ASCs during primary acute viral infection were not identified. To this end, we investigated the nature of ASCs in direct ex vivo assays from patients with acute hepatitis A caused by primary infection with hepatitis A virus (HAV). We found that the frequency of CD27highCD38high ASCs was markedly increased in the peripheral blood during the acute phase of HAV infection. Moreover, substantial numbers of ASCs were non-HAV–specific and dominantly secreted IgM. We detected HAV-specific ASCs by staining with fluorochrome-tagged HAV-VP1 protein. As compared with HAV-specific ASCs, non-HAV–specific ASCs were Ki-67lowCD138highCD31highCD38high, demonstrating that non-HAV–specific ASCs had a bone marrow plasma cell–like phenotype whereas HAV-specific ASCs had a phenotype typical of circulating plasmablasts. These data suggest that non-HAV–specific ASCs might be mobilized plasma cells from the bone marrow or the spleen, whereas HAV-specific ASCs were newly generated plasmablasts. In this study, we provide evidence that pre-existing plasma cells are released into the circulation and contribute to Ag-nonspecific secretion of IgM during primary HAV infection.
IL-22 Deficiency Alters Colonic Microbiota To Be Transmissible and Colitogenic

IL-22 is a good candidate to play a critical role in regulating gut microbiota because it is an important inducer of antimicrobial peptides and mucins in the gut. However, whether IL-22 participates in immune homeostasis by way of modulating gut microbiota remains to be elucidated. In this study, we find, through 16S rRNA gene-pyrosequencing analysis, that healthy IL-22–deficient mice had altered colonic microbiota, notably with decreased abundance of some genera, including Lactobacillus, and increased levels of others. Mice harboring this altered microbiota exhibited more severe disease during experimentally induced colitis. Interestingly, this altered gut microbiota can be transmitted to cohoused wild-type animals along with the increased susceptibility to this colitis, indicating an important role for IL-22 in shaping the homeostatic balance between immunity and colonic microbiota for host health.
A typology of social networking sites users

Social networking sites (SNSs) are said to be new important means of participating, communicating, and gaining social capital. Thus, increasingly fragmented user population and user behaviours in SNSs make it important to achieve more knowledge about SNS users and their participation inequality. This article proposes a user typology for SNSs, which identifies and describes the variety of ways in which people use SNSs. An analysis of the survey data from 5,233 respondents in four major Norwegian SNSs showed five distinct user types: 1) sporadics; 2) lurkers; 3) socialisers; 4) debaters; 5) actives. Both quantitative and qualitative analysis validates the typology. The SNS user typology contributes to a more nuanced and precise measure of how future research should identify and predict SNS use and better understand participation inequality in SNSs. The identification of various user types indicates a 50-30-20 rule for participation in small and locally bounded online communities compared to the existing 90-9-1 rule. Finally, the results could help the design of SNSs in tailoring them to user type.
What is the most important factor in switching blogs?

The purpose of this study is to analyse various factors of switching blogs. The switching costs theory has been applied to develop the research model. Bloggers using such blogs as: Cyworld's minihompy, Naver's blog, Daum's Tistory, and Tattertools were selected as subjects for the sample frame. A total of 290 surveys were collected, from which 243 were used as data for analysis. Results of the survey by SPSS 12.0 showed that the attractiveness of alternatives and attachment affected blog switching intention, and attractiveness of alternatives had a moderating effect between user satisfaction and switching intention.
A survey on social network sites to determine requirements for learning networks for professional development of university staff

Learning networks – online social networks where the learner is put central – are well suited for the non-formal professional development of academic staff. Our assumption is that learning networks can build on social network sites. Social network sites are becoming very popular and are very effective in connecting people, allowing exchange and sharing of all kinds of information and resources. Therefore, we designed a survey to explore the use and perception of social network sites among academic staff and to relate this to the functionalities required for learning networks for professional development. The survey results indicate that a learning network should cater for the desired social aspects along with facilities to organise and maintain resources and contacts.
Twitter for crisis communication: lessons learned from Japan's tsunami disaster

Two weeks after the Great Tohoku earthquake followed by the devastating tsunami, we have sent open-ended questionnaires to a randomly selected sample of Twitter users and also analysed the tweets sent from the disaster-hit areas. We found that people in directly affected areas tend to tweet about their unsafe and uncertain situation while people in remote areas post messages to let their followers know that they are safe. Our analysis of the open-ended answers has revealed that unreliable retweets (RTs) on Twitter was the biggest problem the users have faced during the disaster. Some of the solutions offered by the respondents included introducing official hash tags, limiting the number of RTs for each hash tag and adding features that allow users to trace information by maintaining anonymity.
Central Role of Conventional Dendritic Cells in Regulation of Bone Marrow Release and Survival of Neutrophils

Neutrophils are the most abundant cell type in the immune system and play an important role in the innate immune response. Using a diverse range of mouse models with either defective dendritic cell (DC) development or conditional DC depletion, we provide in vivo evidence indicating that conventional DCs play an important role in the regulation of neutrophil homeostasis. Flk2, Flt3L, and Batf3 knockout mice, which have defects in DC development, have increased numbers of liver neutrophils in the steady state. Conversely, neutrophil frequency is reduced in DC-specific PTEN knockout mice, which have an expansion of CD8+ and CD103+ DCs. In chimeric CD11c-DTR mice, conventional DC depletion results in a systemic increase of neutrophils in peripheral organs in the absence of histological inflammation or an increase in proinflammatory cytokines. This effect is also present in splenectomized chimeric CD11c-DTR mice and is absent in chimeric mice with 50% normal bone marrow. In chimeric CD11c-DTR mice, diphtheria toxin treatment results in enhanced neutrophil trafficking from the bone marrow into circulation and increased neutrophil recruitment. Moreover, there is an increased expression of chemokines/cytokines involved in neutrophil homeostasis and reduced neutrophil apoptosis. These data underscore the role of the DC pool in regulating the neutrophil compartment in nonlymphoid organs.
Phosphatase Wip1 Is Essential for the Maturation and Homeostasis of Medullary Thymic Epithelial Cells in Mice

Thymic epithelial cells (TECs) are a key cell type in the thymic microenvironment essential for T cell development. However, intrinsic molecular mechanisms controlling TEC differentiation and activities are poorly defined. In this study, we found that deficiency of p53-induced phosphatase 1 (Wip1) in mice selectively caused severe medullary TEC (mTEC) maturation defects in an intrinsic manner. Wip1 knockout (KO) mice had decreased mature epithelial cell adhesion molecule+Ulex europaeus agglutinin-1 (UEA-1)+ mTECs, including UEA-1+MHC class IIhigh, UEA-1+CD80+, UEA-1+CD40+, and UEA-1+Aire+ cells, but not decreased numbers of cortical epithelial cell adhesion molecule+BP-1+ TECs, in the postnatal stage but not in the fetal stage. Wip1-deficient mTECs express fewer tissue-restricted Ags and UEA-1+involucrin+ terminal-differentiated cells. Animal models, including grafting fetal Wip1-deficient thymic tissue into T cell–deficient nude mice and reconstitution of lethally irradiated Wip1KO mouse recipients with wild-type bone marrow cells, also showed the impaired mTEC components in Wip1KO thymi, indicating the intrinsic regulatory role of Wip1 in mTEC maturation. Furthermore, thymus regeneration was significantly less efficient in adult Wip1KO mice than in wild-type mice after cyclophosphamide treatment. Wip1 deficiency resulted in elevated p38 MAPK activity in mTECs. Activated p38 MAPK has the ability to suppress CD40 expression on mTECs. Wip1-deficient thymi displayed poor response to CD40L in the fetal thymus organ culture system. Thus, Wip1 positively controls mTEC maturation, homeostasis, and regeneration through limiting the p38 MAPK pathway.
The effects of training medical students in motivational interviewing

Objective To explore the effects of brief training in Motivational interviewing (MI) for medical students. Design Video recordings of consultations between 113 final-year medical students and simulated patients were scored blind by two independent raters with the Motivational Interviewing Skill Code (MISC). Half of the students participated in a four-hour motivational interviewing workshop while the other half did not. Results Differences between the two groups were statistically significant for five of six global MISC variables. All differences were in the expected direction, with higher scores in the group that had received MI training. There were also statistically significant group differences in the expected direction on several behavioural measures. The group that received MI training asked fewer closed questions and more open questions; they summarized, affirmed and emphasized patient control more often, and directed and confronted less often. Conclusion Four hours of training has a measurable effect on medical students’ style and verbal behaviour in simulated patient consultations, but is not sufficient to become proficient in motivational interviewing.
Targeting CD137 Enhances Vaccine-Elicited Anti–Respiratory Syncytial Virus CD8+ T Cell Responses in Aged Mice

Respiratory syncytial virus (RSV) causes significant morbidity and mortality in children and the elderly. No vaccines for RSV are in use. Because of immunosenescence, the immunologic requirements for a successful RSV vaccine in the elderly might differ from a RSV vaccine for young children. Using an aged mouse model of RSV pathogenesis, we found that aged mice had impaired Ag-specific CD8+ T cell responses and delayed RSV clearance compared with young mice. To study vaccine-elicited RSV-specific CD8+ T cells in aged mice, we used a peptide vaccine approach. TriVax is a commixture of a peptide representing immunodominant RSV CD8+ T cell epitope M282–90, a TLR agonist (polyinosinic-polycytidylic acid), and a costimulatory anti-CD40 Ab. TriVax vaccination generated robust, polyfunctional, and protective CD8+ T cell responses in young BALB/c mice, but not in 18-mo-old (aged) BALB/c mice. We hypothesized that treatment of aged mice with agonistic anti-CD137 (41BB) mAb will partially restore T cell responses and TriVax efficacy in aged mice. We immunized 18-mo-old BALB/c mice twice with TriVax + anti-41BB mAb or TriVax + isotype control Ab. Coadministration of anti-41BB mAb with TriVax enhanced RSV-specific CD8+ T cell responses and TriVax efficacy in challenge experiments. Triggering the 41BB costimulatory pathway may be a strategy for enhancing T cell responses to vaccines in the elderly.