bluuebunny/crossref_metadata_2025_split huggingface dataset:
Update on innate lymphoid cells in atopic and non‐atopic inflammation in the airways and skin
Authors: Mjösberg J. , Eidsmo L. 
Published: June 2014

SummaryInnate lymphoid cells (ILC) is the collective term for a group of related innate lymphocytes, including NK cells and the more recently appreciated non‐NK ILC (ILC1, ILC2 and ILC3). ILC all depend on the common γ‐chain of the IL‐2 receptor and the transcription factor Id2. Furthermore, ILC lack rearranged antigen‐receptors such as those expressed by T and B cells. Recent data indicate that non‐NK ILC contribute to a wide range of homeostatic and pathophysiological processes primarily by virtue of cytokine production. A lot of effort has been put into understanding the role for the non‐NK ILC in mucosal homeostasis, including in the gut and lungs. Recent reports also point towards a role for ILC in skin inflammation. In the lung, ILC may propagate stromal‐derived danger signals, with subsequent induction of mainly type 2 cytokine production. This might represent an early trigger of type 2‐mediated pathology, which subsequently also engages the adaptive immune system. Similarly, in the skin, ILC are well placed to sense keratinocyte‐derived danger signals in an antigen‐independent manner. Recent findings link ILC2 to atopic dermatitis and ILC3 to psoriasis. In this review, we provide an updated perspective on the role for non‐NK ILC in atopic and non‐atopic inflammation in the airways as well as in the skin.
Pattern recognition pathways leading to a Th2 cytokine bias in allergic bronchopulmonary aspergillosis patients
Authors: Becker K. L. , Gresnigt M. S. , Smeekens S. P. , Jacobs C. W. , Magis‐Escurra C. , Jaeger M. , Wang X. , Lubbers R. , Oosting M. , Joosten L. A. B. , Netea M. G. , Reijers M. H. , van de Veerdonk F. L. 
Published: June 2014

SummaryBackgroundAllergic bronchopulmonary aspergillosis (ABPA) is characterised by an exaggerated Th2 response to Aspergillus fumigatus, but the immunological pathways responsible for this effect are unknown.ObjectiveThe aim of this study was to decipher the pattern recognition receptors (PRRs) and cytokines involved in the Aspergillus‐specific Th2 response and to study Aspergillus‐induced responses in healthy controls and ABPA patients.MethodsPeripheral blood mononuclear cells (PBMCs) were stimulated with heat‐killed Aspergillus conidia, various other pathogens, or PRR ligands. PRRs and cytokine pathways were blocked with PRR‐blocking reagents, anti‐TNF (Etanercept or Adalimumab), IL‐1Ra (Anakinra) or IFNγ (IFN‐gamma). ELISA and FACS were used to analyse cytokine responses.ResultsAspergillus was the only pathogen that stimulated the Th2 cytokines IL‐5 and IL‐13, while Gram‐negative bacteria, Gram‐positive bacteria, Candida albicans, chitin, β‐glucan or Toll‐like receptor (TLR) ligands did not. Depletion of CD4+ cells abolished IL‐13 production. Blocking complement receptor 3 (CR3) significantly reduced IL‐5 and IL‐13, while blocking TLR2, TLR4 or dectin‐1 had no effect. ABPA patients displayed increased Aspergillus‐induced IL‐5 and IL‐13 and decreased IFNγ production compared with healthy controls. All biological agents tested showed the capability to inhibit Th2 responses, but also decreased Aspergillus‐induced IFNγ.Conclusions and Clinical RelevanceAspergillus conidia are unique in triggering Th2 responses in human PBMCs, through a CR3‐dependent pathway. ABPA patients display a significantly increased Aspergillus‐induced Th2/Th1 ratio that can be modulated by biologicals. These data provide a rationale to explore IFNγ therapy in ABPA as a corticosteroid‐sparing treatment option, by dampening Th2 responses and supplementing the IFNγ deficiency at the same time.
Mediation or Moderation? The Role of R&D Investment in the Relationship between Corporate Governance and Firm Performance: Empirical Evidence from the Chinese IT Industry
Authors: Zhang Qing , Chen Lilin , Feng Tianjun 
Published: June 2014

AbstractManuscript TypeEmpiricalResearch Question/IssueThis paper explores whether R&D investment has a mediating and/or moderating effect on the relationship between corporate governance and firm performance.Research Findings/InsightsThis empirical study of Chinese IT‐industry listed companies during the 2007–2008 period shows that R&D investment does not moderate, but instead mediates the relationship between corporate governance and firm performance.Theoretical/Academic ImplicationsThis paper takes the perspective of technological innovation to empirically examine the effect of corporate governance on firm performance. This study makes a contribution to the literature by showing that technological innovation (i.e., R&D investment) mediates the effects of various governance mechanisms (i.e., ownership concentration, managerial compensation, and asset‐debt ratio) on firm performance.Practitioner/Policy ImplicationsThe results provide important managerial implications for the practice of corporate governance in emerging economies. Companies in emerging economies can enhance technological innovation through maintaining relatively high ownership concentration, designing effective managerial compensation systems, and optimizing capital structure. In addition, emerging economies should adopt effective public policies on technological innovation to improve the relationship between corporate governance and firm performance.
How credible is the North Korean threat?
Authors: Kim Byung‐Yeon , Roland Gérard 
Published: June 2014

AbstractWe perform event analysis on particular episodes of tension in the Korean peninsula between 2000 and 2008, and investigate the effect of the events on South Korean financial markets (stock markets, bond yield spreads and the exchange rate) given that South Korea would be the first affected by a military aggression from North Korea. Surprisingly, in nearly all cases, these events, which have often been dramatized in the world media, have no significant impact on either of these variables or only a very small one. We also find no significant impact of events on listed firms that would a priori be likely to suffer from increased tension between the two Koreas. Since financial markets often contain better predictions than expert opinions or surveys, these results strongly suggest that the North Korean threat is non‐credible.
Regional differences in the production processes of financial and social outputs of microfinance institutions
Authors: Bolli Thomas , Vo Thi Anh 
Published: June 2014

AbstractThis study uses panel data of microfinance institutions across the world to compare production processes across regions, assess the relevance of unobserved heterogeneity and estimate economies of scale. Comparing a financial production process to a multidimensional production process that accounts for the presence of outreach in the objective function suggests that financial and social output reflect complements in South Asia but not in other regions. Furthermore, we find substantial economies of scale for a pure financial production process. However, accounting for outreach lowers estimated economies of scale, suggesting that producing outreach creates high transaction costs and requires exploitation of local knowledge.
Microcredit market structure and financing obstacles for micro firms
Authors: Sonnekalb Simon 
Published: June 2014

AbstractUsing rich survey data of micro firms in Eastern Europe and Central Asia, I analze the effect of recent changes in microcredit market structure on perceived financing obstacles. Controlling for country, time and firm characteristics, lower microcredit market concentration is associated with firms reporting financing as a more severe obstacle to their operations. This indicates that rising competition between microfinance institutions may have led to reduced financial access. The results are consistent with information‐based theoretical predictions that lenders with less market power have weaker incentives to invest in lending relationships with opaque firms and that greater competition aggravates borrower screening.
Acute multilineage (B/myeloid) leukemia with RUNX1 duplication/amplification and hypereosinophilia
Authors: Holmes Allen , Coviello Jean , Velagaleti Gopalrao 
Published: June 2014

AbstractA 14–year‐old girl presented with myalgias and decreased energy and was found to have a white count of 73 000 with 75% eosinophils. Flow cytometry and immunostains showed the blasts in the bone marrow expressed both myeloid and lymphoid markers. Patient was diagnosed with acute multilineage (B/Myeloid) leukemia. Genetic testing revealed four copies of the RUNX1 gene region in 25.5%, with a normal karyotype and no evidence of t(8;21) or t(12;21) by fluorescence in situ hybridization. RUNX1 translocations and amplifications have been implicated in acute myeloblastic leukemia, acute lymphoblastic leukemia, and MDS, but have not yet been seen with acute multilineage leukemia. Additionally, it is unclear what the risk stratification of this unique presentation will turn out to be.
Sensitivity and specificity of Single‐Tube Osmotic Fragility Test and its different methods as screening test for thalassemia trait: an alternative to expensive laboratory tests for resource‐limited countries
Authors: Ansari Saqib H. , Hanifa Anny , Saleem Ayesha , Ali Salima M. , Hussain Zeeshan , Zohaib Mohammad , Akbar Mohammad , Rehman Saif , Hussain Syed R. 
Published: June 2014

AbstractObjectiveTo determine the sensitivity and specificity of single‐tube osmotic fragility (SOFT) and its different methods as screening test for thalassemia trait.MethodsA cross‐sectional study was conducted at Omair Sana Foundation. A total of 400 participants were included in the study. Three hundred were known thalassemia carriers (parents with at least one child with thalassemia major), while 100 were healthy blood donors. SOFT was performed on all 400 participants. Serum iron, ferritin, and DNA tests were performed on 100 participants (donors). ARMS technique was used for detecting thalassemia mutations.ResultsSensitivity and specificity of SOFT (venous method) were found to be 99.6% and 86%, respectively, while with EDTA method, sensitivity was 95% and specificity was 96%. For venous and EDTA methods, positive predictive values were 95.5% and 98.6%, respectively, while negative predictive values were 98.8% and 86.6%, respectively. Use of EDTA and storage had an effect on the results. Sensitivity of SOFT was 95% at 5 min, while it decreased to 87% with EDTA method at 240 min. Sensitivity of SOFT for iron deficiency anemia was found to be 14%.ConclusionSOFT can be used as screening test for thalassemia trait in a cost‐effective way. Moreover, we also found that SOFT should be performed on venous blood without adding preservatives (EDTA) that can interfere with the results.
Impact of exercise on pro inflammatory cytokine levels and epigenetic modulations of tumor‐competitive lymphocytes in Non‐Hodgkin‐Lymphoma patients‐randomized controlled trial
Authors: Zimmer Philipp , Baumann Freerk T. , Bloch Wilhelm , Schenk Alexander , Koliamitra Christine , Jensen Patrizia , Mierau Andreas , Hülsdünker Thorben , Reinart Nina , Hallek Michael , Elter Thomas 
Published: June 2014

AbstractIntroductionPhysical activity is associated with decreased cancer (recurrence) risk and a reduction in treatment‐specific side effects. Exercise modulates cytokine expression and shows beneficial effects on cancer patients’ immune system. We investigated the following: (i) whether Non‐Hodgkin‐Lymphoma patients have increased serum macrophage migration inhibiting factor (MIF) and Interleukin‐6 (IL‐6) levels after immunochemotherapy; (ii) whether physical activity influences cytokine serum levels; and (iii) whether serum cytokine levels are associated with histone modifications in tumor‐competitive immune cells.MethodsThirty patients and 10 healthy controls were randomised into an intervention and a control group. Participants of the intervention group exercised once for 30 min at moderate intensity on a bicycle ergometer. Blood samples were collected twice, before and after the intervention. MIF and IL‐6 serum concentrations were detected by ELISA. Natural killer cells and CD8+ T‐lymphocytes were isolated by magnetic labeled cell sorting. Isolated cells were stained and analyzed for global histone acetylation at histone 4, lysine 5 and histone three, lysine 9.ResultsPatients showed higher serum MIF and IL‐6 baseline levels, and reduced NK‐cell histone acetylation, indicating a reduced transcriptional activity of tumor‐competitive lymphocytes. Changes in MIF correlated with altered NK‐cell histone acetylation, leading to the hypothesis that MIF impacts NK‐cells via epigenetic modifications. Further, the exercise intervention was associated with an increase in IL‐6 and CD8+ T‐lymphocyte histone acetylation.ConclusionsWe conclude that exercise induces changes in cytokine levels, thereby possibly affecting epigenetic patterns and activity of tumor‐competitive lymphocytes.
Severe cytokine release syndrome after the first dose of Brentuximab Vedotin in a patient with relapsed systemic anaplastic large cell lymphoma (sALCL): a case report and review of literature
Authors: Alig Stefan K. , Dreyling Martin , Seppi Bettina , Aulinger Benedikt , Witkowski Lukas , Rieger Christina T. 
Published: June 2014

AbstractBrentuximab Vedotin is an antibody – drug conjugate targeting CD30. We report a case of severe cytokine release syndrome (CRS) after administration of the first dose of Brentuximab Vedotin in a 64‐yr‐old patient with relapsed systemic anaplastic large cell lymphoma (sALCL). To our knowledge, this is the first case of CRS to Brentuximab Vedotin described in the literature. However, CRS to Brentuximab Vedotin might be underestimated, as the drug has not been tested in large phase III trials yet.
Detection of bacteraemia and host response in healthy neonatal foals
Authors: Hackett E. S. , Lunn D. P. , Ferris R. A. , Horohov D. W. , Lappin M. R. , McCue P. M. 
Published: June 2014

SummaryReasons for performing the studyNeonatal sepsis is a common problem in foals and is a primary cause of death in the post natal period. Transient bacteraemia and subsequent host responses have not been described in the equine neonate.ObjectivesThe primary objective of this study was to determine if transient bacteraemia occurs in foals within the first 72 h of life. Additional objectives included description of bacterial organisms associated with transient bacteraemia and concurrent cytokine gene expression in healthy foals.Study designProspective observational study in healthy foals.MethodsBlood was aseptically collected for bacterial culture from observed spontaneously born foals at birth and 1, 2, 3, 4, 8, 12, 24, 48 and 72 h following birth. Samples taken at birth, 4, 12, 24, 48 and 72 h were analysed for interferon gamma (IFNγ), interleukin (IL)‐1,IL‐2,IL‐6,IL‐8,IL‐10,IL‐18 and monocyte chemotactic protein 1 (MCP1) cytokine gene expression quantified byRT‐PCR.ResultsBacteria were cultured from 9 of 70 samples submitted for blood culture. The positive samples were from 4 of the 7 foals, all of which remained healthy throughout and subsequent to the study. All positive blood cultures were from blood samples obtained at 12 h of age or earlier andIL‐10 elevation coincided with positive blood cultures in healthy foals. Cytokine gene expression fluctuated with age.ConclusionsPositive blood cultures suggest transient bacteraemia may occur in healthy foals early in the post natal period. Age corrected normal values may be necessary to interpret cytokine concentration in diseased populations.
Genetic polymorphisms altering microRNA activity in psoriasis – a key to solve the puzzle of missing heritability?
Authors: Pivarcsi Andor , Ståhle Mona , Sonkoly Enikő 
Published: June 2014

AbstractPsoriasis is a chronic immune‐mediated skin disease in which the balance in the interplay of immune cells and keratinocytes is disturbed. MicroRNAs (miRNAs) are endogenous small regulatory RNAs that stabilize cellular phenotypes and fine‐tune signal transduction feedback loops through the regulation of gene networks. Through the regulation of their multiple target genes, miRNAs regulate the development of inflammatory cell subsets and have a significant impact on the magnitude of inflammatory responses. Since the discovery of deregulated miRNA expression in psoriasis, we have learned that they can regulate differentiation, proliferation and cytokine response of keratinocytes, activation and survival of T cells and the crosstalk between immunocytes and keratinocytes through the regulation of chemokine production. In recent years, it became apparent that genetic polymorphisms in miRNA genes and/or in miRNA binding sites of target genes can affect miRNA activity and contribute to disease susceptibility. Psoriasis has a strong genetic background; however, the contribution of genetic variants involving miRNAs is largely unexplored in psoriasis. We propose that changes in miRNA‐mediated gene regulation may be a major contributor to the disturbed balance in immune regulation that results in chronic skin inflammation. In this viewpoint essay, we focus on the emerging new aspects of the role of miRNAs in psoriasis and propose that genetic polymorphisms that affect miRNA activity might be important in the pathogenesis of psoriasis.
Modeling cancer glycolysis under hypoglycemia, and the role played by the differential expression of glycolytic isoforms
Authors: Marín‐Hernández Alvaro , López‐Ramírez Sayra Y. , Del Mazo‐Monsalvo Isis , Gallardo‐Pérez Juan C. , Rodríguez‐Enríquez Sara , Moreno‐Sánchez Rafael , Saavedra Emma 
Published: June 2014

The effect of hypoglycemia on the contents of glycolytic proteins, activities of enzymes/transporters and flux of HeLa and MCF‐7 tumor cells was experimentally analyzed and modeled in silico. After 24 h hypoglycemia (2.5 mm initial glucose), significant increases in the protein levels of glucose transporters 1 and 3 (GLUT 1 and 3) (3.4 and 2.1‐fold, respectively) and hexokinase I (HKI) (2.3‐fold) were observed compared to the hyperglycemic standard cell culture condition (25 mm initial glucose). However, these changes did not bring about a significant increase in the total activities (Vmax) of GLUT and HK; instead, the affinity of these proteins for glucose increased, which may explain the twofold increased glycolytic flux under hypoglycemia. Thus, an increase in more catalytically efficient isoforms for two of the main controlling steps was sufficient to induce increased flux. Further, a previous kinetic model of tumor glycolysis was updated by including the ratios of GLUT and HK isoforms, modified pyruvate kinase kinetics and an oxidative phosphorylation reaction. The updated model was robust in terms of simulating most of the metabolite levels and fluxes of the cells exposed to various glycemic conditions. Model simulations indicated that the main controlling steps were glycogen degradation > HK > hexosephosphate isomerase under hyper‐ and normoglycemia, and GLUT > HK > glycogen degradation under hypoglycemia. These predictions were experimentally evaluated: the glycolytic flux of hypoglycemic cells was more sensitive to cytochalasin B (a GLUT inhibitor) than that of hyperglycemic cells. The results indicated that cancer glycolysis should be inhibited at multiple controlling sites, regardless of external glucose levels, to effectively block the pathway.DatabaseThe mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.mib.ac.uk/database/achcar/index.html.[Database section added 21 July 2014 after original online publication]
Contrasting topoclimate, long‐term macroclimatic averages, and habitat variables for modelling ant biodiversity at landscape scales
Authors: Gollan John R. , Ramp Daniel , Ashcroft Michael B. 
Published: June 2014

Abstract

Spatial modelling is part of the solution for incorporating insects into conservation policy. Uptake, however, rests on identifying robust environmental predictors. Coarse‐grained climate models based on long‐term averages and similarly coarse environmental features may not be adequate, especially at regional scales where most planning is done. Here, we test whether topoclimatic variables, which are derived from local‐scale climate forcing factors, are more important for structuring ant assemblages.

We quantified ant richness and species composition at 86 sites across a large (200 × 300 km) temperate region of southeast Australia, and tested the explanatory power of three groups of environmental variables: (i) topoclimatic variables, (ii) long‐term climatic averages modelled from global data, and (iii) habitat features, namely, habitat complexity, soil pH, and soil texture. Generalised Additive and Generalised Dissimilarity Models were used to test predictors.

In univariate models, the topoclimatic estimator of maximum temperature (95maxT) explained the largest amount of variance in both richness and compositional turnover (20% and 24% of deviance respectively). The plot for richness indicated a positive but decelerating function of 95maxT. This was consistent for two of three habitat types. Habitat complexity was the most important predictor in cleared habitat (28%).

While a topoclimatic variable was a strong predictor of ant biodiversity across the landscape, this was not a ‘magic bullet’. Other predictors such as complexity may be more applicable in certain habitat types. We concluded that tailored predictors are needed for landscapes with a mosaic of different land use.
Assessing in vitro stem‐cell function and tracking engraftment of stem cells in ischaemic hearts by using novel iRFP gene labelling
Authors: Wang Yingjie , Zhou Mi , Wang Xiaolong , Qin Gangjian , Weintraub Neal L. , Tang Yaoliang 
Published: June 2014

AbstractNear‐infrared fluorescence (NIRF) imaging by using infrared fluorescent protein (iRFP) gene labelling is a novel technology with potential value for in vivo applications. In this study, we expressed iRFP in mouse cardiac progenitor cells (CPC) by lentiviral vector and demonstrated that the iRFP‐labelled CPC (CPCiRFP) can be detected by flow cytometry and fluorescent microscopy. We observed a linear correlation in vitro between cell numbers and infrared signal intensity by using the multiSpectral imaging system. CPCiRFP injected into the non‐ischaemic mouse hindlimb were also readily detected by whole‐animal NIRF imaging. We then compared iRFP against green fluorescent protein (GFP) for tracking survival of engrafted CPC in mouse ischaemic heart tissue. GFP‐labelled CPC (CPCGFP) or CPC labelled with both iRFP and GFP (CPCiRFP GFP) were injected intramyocardially into mouse hearts after infarction. Three days after cell transplantation, a strong NIRF signal was detected in hearts into which CPCiRFP GFP, but not CPCGFP, were transplanted. Furthermore, iRFP fluorescence from engrafted CPCiRFP GFP was detected in tissue sections by confocal microscopy. In conclusion, the iRFP‐labelling system provides a valuable molecular imaging tool to track the fate of transplanted progenitor cells in vivo.