bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Human NK Cell Activation/Inhibition Threshold Allows Small Changes in the Target Cell Surface Phenotype To Dramatically Alter Susceptibility to NK Cells
Authors: Holmes Tim D. , El-Sherbiny Yasser M. , Davison Adam , Clough Sally L. , Blair G. Eric , Cook Graham P. 
Published: December 2010

Abstract
NK cell activation is negatively regulated by the expression of target cell MHC class I molecules. We show that this relationship is nonlinear due to an NK cell activation/inhibition threshold. Ewing’s sarcoma family tumor cell monolayers, which were highly susceptible to NK cells in vitro, developed a highly resistant phenotype when cultured as three-dimensional multicellular tumor spheroid structures. This suggested that tumor architecture is likely to influence the susceptibility to NK cells in vivo. Resistance of the multicellular tumor spheroid was associated with the increased expression of MHC class I molecules and greatly reduced NK cell activation, implying that a threshold of NK cell activation/inhibition had been crossed. Reducing MHC class I expression on Ewing’s sarcoma family tumor monolayers did not alter their susceptibility to NK cells, whereas increased expression of MHC class I rendered them resistant and allowed the threshold point to be identified. This threshold, as defined by MHC class I expression, was predictive of the number of NK-resistant target cells within a population. A threshold permits modest changes in the target cell surface phenotype to profoundly alter the susceptibility to NK cells. Whereas this allows for the efficient detection of target cells, it also provides a route for pathogens and tumors to evade NK cell attack.
Autophagy Regulates Endoplasmic Reticulum Homeostasis and Calcium Mobilization in T Lymphocytes
Authors: Jia Wei , Pua Heather H. , Li Qi-Jing , He You-Wen 
Published: December 2010

Abstract
Macroautophagy (hereafter referred to as autophagy) is an evolutionarily conserved intracellular bulk degradation pathway that plays critical roles in eliminating intracellular pathogens, presenting endogenous Ags, and regulating T lymphocyte survival and proliferation. In this study, we have investigated the role of autophagy in regulating the endoplasmic reticulum (ER) compartment in T lymphocytes. We found that ER content is expanded in mature autophagy-related protein (Atg) 7-deficient T lymphocytes. Atg7-deficient T cells stimulated through the TCR display impaired influx, but not efflux, of calcium, and ER calcium stores are increased in Atg7-deficient T cells. Treatment with the ER sarco/ER Ca2+-ATPase pump inhibitor thapsigargin rescues the calcium influx defect in Atg7-deficient T lymphocytes, suggesting that this impairment is caused by an intrinsic defect in ER. Furthermore, we found that the stimulation-induced redistribution of stromal interaction molecule-1, a critical event for the store-operated Ca2+ release-activated Ca2+ channel opening, is impaired in Atg7-deficient T cells. Together, these findings indicate that the expanded ER compartment in Atg7-deficient T cells contains increased calcium stores, and the inability of these stores to be depleted causes defective calcium influx in these cells. Our results demonstrate that autophagy plays an important role in maintaining ER and calcium homeostasis in T lymphocytes.
Senescent CD14+CD16+ Monocytes Exhibit Proinflammatory and Proatherosclerotic Activity
Authors: Merino Ana , Buendia Paula , Martin-Malo Alejandro , Aljama Pedro , Ramirez Rafael , Carracedo Julia 
Published: December 2010

Abstract
In elderly subjects and in patients with chronic inflammatory diseases, there is an increased subset of monocytes with a CD14+CD16+ phenotype, whose origin and functional relevance has not been well characterized. In this study, we determined whether prolonged survival of human CD14++CD16− monocytes promotes the emergence of senescent cells, and we analyzed their molecular phenotypic and functional characteristics. We used an in vitro model to prolong the life span of healthy monocytes. We determined cell senescence, intracellular cytokine expression, ability to interact with endothelial cells, and APC activity. CD14+CD16+ monocytes were senescent cells with shortened telomeres (215 ± 37 relative telomere length) versus CD14++CD16− cells (339 ± 44 relative telomere length; p &lt; 0.05) and increased expression of β-galactosidase (86.4 ± 16.4% versus 10.3 ± 7.5%, respectively; p = 0.002). CD14+CD16+ monocytes exhibited features of activated cells that included expression of CD209, release of cytokines in response to low-intensity stimulus, and increased capacity to sustain lymphocyte proliferation. Finally, compared with CD14++CD16− cells, CD14+CD16+ monocytes showed elevated expression of chemokine receptors and increased adhesion to endothelial cells (19.6 ± 8.1% versus 5.3 ± 4.1%; p = 0.033). In summary, our data indicated that the senescent CD14+CD16+ monocytes are activated cells, with increased inflammatory activity and ability to interact with endothelial cells. Therefore, accumulation of senescent monocytes may explain, in part, the development of chronic inflammation and atherosclerosis in elderly subjects and in patients with chronic inflammatory diseases.
Lung Cancer-Derived Galectin-1 Mediates Dendritic Cell Anergy through Inhibitor of DNA Binding 3/IL-10 Signaling Pathway
Authors: Kuo Po-Lin , Hung Jen-Yu , Huang Shau-Ku , Chou Shah-Hwa , Cheng Da-En , Jong Yuh-Jyh , Hung Chih-Hsing , Yang Chih-Jen , Tsai Ying-Ming , Hsu Ya-Ling , Huang Ming-Shyan 
Published: December 2010

Abstract
Lung cancer, one of the leading causes of death worldwide, is often associated with a state of immune suppression, but the molecular and functional basis remains enigmatic. Evidence is provided in this paper supporting the role of lung cancer-derived soluble lectin, galectin-1, as a culprit in dendritic cell (DC) anergy. We have shown that galectin-1 is highly expressed in lung cancer cell lines, together with the serum and surgical samples from lung cancer patients. Functionally, lung cancer-derived galectin-1 has been shown to alter the phenotypes of monocyte-derived DCs (MdDCs) and impair alloreactive T cell response, concomitant with the increase of CD4+CD25+FOXP3+ regulatory T cells. The regulatory effect of galectin-1 is mediated, in part, through its ability to induce, in an Id3 (inhibitor of DNA binding 3)-dependent manner, the expression of IL-10 in monocytes and MdDCs. This effect is inhibited by the addition of lactose, which normalizes the phenotypic and functional alterations seen in MdDCs. Of note, significant upregulation of IL-10 was seen in tumor-infiltrating CD11c+ DCs in human lung cancer samples. This was also noted in mice transplanted with lung cancer cells, but not in those receiving tumor cells with galectin-1 knockdown. Furthermore, a significant reduction was noted in lung cancer incidence and in the levels of IL-10–expressing, tumor-infiltrating DCs, in mice receiving galectin-1–silenced tumor cells. These results thus suggest that the galectin-1/IL-10 functional axis may be crucial in lung cancer-mediated immune suppression, and that galectin-1 may serve as a target in the development of lung cancer immunotherapy.
Cutting Edge: NLRC5-Dependent Activation of the Inflammasome
Authors: Davis Beckley K. , Roberts Reid A. , Huang Max T. , Willingham Stephen B. , Conti Brian J. , Brickey W. June , Barker Brianne R. , Kwan Mildred , Taxman Debra J. , Accavitti-Loper Mary-Ann , Duncan Joseph A. , Ting Jenny P.-Y. 
Published: December 2010

Abstract
The nucleotide-binding domain leucine-rich repeat-containing proteins, NLRs, are intracellular sensors of pathogen-associated molecular patterns and damage-associated molecular patterns. A subgroup of NLRs can form inflammasome complexes, which facilitate the maturation of procaspase 1 to caspase 1, leading to IL-1β and IL-18 cleavage and secretion. NLRC5 is predominantly expressed in hematopoietic cells and has not been studied for inflammasome function. RNA interference-mediated knockdown of NLRC5 nearly eliminated caspase 1, IL-1β, and IL-18 processing in response to bacterial infection, pathogen-associated molecular patterns, and damage-associated molecular patterns. This was confirmed in primary human monocytic cells. NLRC5, together with procaspase 1, pro–IL-1β, and the inflammasome adaptor ASC, reconstituted inflammasome activity that showed cooperativity with NLRP3. The range of pathogens that activate NLRC5 inflammasome overlaps with those that activate NLRP3. Furthermore, NLRC5 biochemically associates with NLRP3 in a nucleotide-binding domain-dependent but leucine-rich repeat-inhibitory fashion. These results invoke a model in which NLRC5 interacts with NLRP3 to cooperatively activate the inflammasome.
CD1d-Restricted IFN-γ–Secreting NKT Cells Promote Immune Complex-Induced Acute Lung Injury by Regulating Macrophage-Inflammatory Protein-1α Production and Activation of Macrophages and Dendritic Cells
Authors: Kim Ji Hyung , Chung Doo Hyun 
Published: December 2010

Abstract
Immune complex-induced acute lung injury (IC-ALI) has been implicated in various pulmonary disease states. However, the role of NKT cells in IC-ALI remains unknown. Therefore, we explored NKT cell functions in IC-ALI using chicken egg albumin and anti-chicken egg albumin IgG. The bronchoalveolar lavage fluid of CD1d−/− and Jα18−/− mice contained few Ly6G+CD11b+ granulocytes, whereas levels in B6 mice were greater and were increased further by α-galactosyl ceramide. IFN-γ and MIP-1α production in the lungs was greater in B6 than CD1d−/− mice. Adoptive transfer of wild type (WT) but not IFN-γ–, MIP-1α–, or FcγR-deficient NKT cells into CD1d−/− mice caused recruitment of inflammatory cells to the lungs. Moreover, adoptive transfer of IFN-γR–deficient NKT cells enhanced MIP-1α production and cell recruitment in the lungs of CD1d−/− or CD1d−/−IFN-γ−/− mice, but to a lesser extent than WT NKT cells. This suggests that IFN-γ–producing NKT cells enhance MIP-1α production in both an autocrine and a paracrine manner. IFN-γ–deficient NKT cells induced less IL-1β and TNF-α production by alveolar macrophages and dendritic cells in CD1d−/− mice than did WT NKT cells. Taken together, these data suggest that CD1d-restricted IFN-γ–producing NKT cells promote IC-ALI by producing MIP-1α and enhancing proinflammatory cytokine production by alveolar macrophages and dendritic cells.
Glycogen Synthase Kinase-3 Is an Early Determinant in the Differentiation of Pathogenic Th17 Cells
Authors: Beurel Eléonore , Yeh Wen-I , Michalek Suzanne M. , Harrington Laurie E. , Jope Richard S. 
Published: December 2010

Abstract
CD4+ T cells are critical for host defense but are also major drivers of immune-mediated diseases. The classical view of Th1 and Th2 subtypes of CD4+ T cells was recently revised by the identification of the Th17 lineage of CD4+ T cells that produce IL-17, which have been found to be critical in the pathogenesis of autoimmune and other diseases. Mechanisms controlling the differentiation of Th17 cells have been well described, but few feasible targets for therapeutically reducing Th17 cells are known. The generation of Th17 cells requires IL-6 and activation of STAT3. During polarization of CD4+ T cells to Th17 cells, we found that inhibition of glycogen synthase kinase-3 (GSK3) blocked IL-6 production, STAT3 activation, and polarization to Th17 cells. Polarization of CD4+ T cells to Th17 cells increased by 10-fold the expression of GSK3β protein levels in Th17 cells, whereas GSK3β was unaltered in regulatory T cells. Diminishing GSK3 activity either pharmacologically or molecularly blocked Th17 cell production, and increasing GSK3 activity promoted polarization to Th17 cells. In vivo inhibition of GSK3 in mice depleted constitutive Th17 cells in intestinal mucosa, blocked Th17 cell generation in the lung after Francisella tularensis infection, and inhibited the increase in spinal cord Th17 cells and disease symptoms in the experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. These findings identify GSK3 as a critical mediator of Th17 cell production and indicate that GSK3 inhibitors provide a potential therapeutic intervention to control Th17-mediated diseases.
Effectiveness of a Worksite Telephone-Based Weight Management Program
Authors: Terry Paul E. , Seaverson Erin L. D. , Grossmeier Jessica , Anderson David R. 
Published: December 2010

Purpose. Examine the long-term impact of a telephone-based weight management program among participants recruited from worksite settings. Design. Pre/post quasi-experimental design comparing weight loss and related behaviors between program completers and noncompleters. Setting. Ten large private-sector and public-sector employers. Subjects. Overweight or obese participants (n = 1298) enrolled in a telephone-based weight management program. Intervention. Individually tailored telephone-based weight management coaching program that included up to five calls over a median of 250 days. Measures. Weight, body mass index, and lifestyle behaviors assessed via health risk assessment at baseline and 1-year follow-up. Analysis. Chi-square and one-way analysis of variance procedures were used to assess between-group differences in weight and associated behaviors, with criterion for significance set at p < .05. Results. Among weight management program participants, 48% of program completers and 47% of noncompleters lost weight, but program completers averaged 2.6 times more weight loss than noncompleters. Improvements in physical activity, eating habits, and overall health status were reported for completers. Conclusion. The weight loss attained among participants who lost weight, along with the improvements in physical activity and nutrition practices, suggests that a telephone-based weight management program of modest intensity can have a positive impact on the health of obese or overweight worksite participants. (Am J Health Promot 2011;25[3]:186–189.)
Active Commuting and Habit Strength: An Interactive and Discriminant Analyses Approach
Authors: de Bruijn Gert-Jan , Gardner Benjamin 
Published: December 2010

Purpose. Habits may be a mechanism linking environmental variables with active commuting. This study investigated the role of habit strength in the explanation of active commuting across profiles based on current active commuting, motivation, and habit strength within the framework of the theory of planned behavior (TPB). Design. Cross-sectional survey using validated questionnaires. Setting. Undergraduate students who participated for course credits. Subjects. Five hundred and thirty-eight students (mean age = 21.19 [SD = 2.57]; 28.45% males; response rate = 86.36%). Measures. Questionnaire included TPB items, underlying beliefs, and a validated measure of habit strength. Active commuting was assessed with relevant items from the International Physical Activity Questionnaire. Analysis. Hierarchical regression and interaction analyses, discriminant function analysis, and analyses of variance. Results. Habit strength was the strongest correlate of active commuting and interacted with intention: at low and medium levels of habit strength, the intention–bicycle use relationship was more than twice as strong as at high levels. Beliefs regarding situational barriers were amongst the most discriminating beliefs, whereas beliefs regarding health benefits did not distinguish profiles. Conclusions. Stronger active commuting habits are associated with a lower association between intention and bicycle use. Persuasive health campaigns might more usefully instill a sense of confidence in various commuting situations rather than merely emphasizing health benefits of active commuting. (Am J Health Promot 2011;25[3]:e27–e36.)
Corporate governance, corporate social responsibility and corporate performance
Authors: Huang Chi-Jui 
Published: December 2010

AbstractPrevious research has analyzed and debated corporate governance (CG) and corporate social responsibility (CSR) independently. This paper aims to empirically explore the interrelationship between CG, CSR, financial performance (FP) and Corporate Social Performance (CSP) using a sample of 297 electronics companies operating in Taiwan, a newly industrialized Asian economy. The results show that a CG model which includes independent outside directors and which has specific ownership characteristics has a significantly positive impact on both FP and CSP, whereas FP itself does not influence CSP. The presence of independent outside directors in the firm has the greatest impact on the social performance of the firm's worker, customer, supplier, community and society dimensions. Government shareholders enhance a firm's social performance extraordinarily because government shareholders will be more likely to request that companies fulfill their social responsibilities. Only government shareholders positively and significantly relate to a firm's environmental performance. Furthermore, foreign institutional stockholders help to increase worker and supplier performance by paying more attention to employee policies and supply chain relationships. Finally, independent outside directors, foreign institutional stockholders and domestic financial institutional stockholders are shown to improve financial performance.
A qualitative analysis of intellectual capital in social service non-profit organisations: A theory–practice divide
Authors: Kong Eric , Ramia Gaby 
Published: December 2010

AbstractThe paper contributes to debates on non-profit strategy, first by arguing that intellectual capital (IC) can be utilised as a non-profit strategic management conceptual framework and second by highlighting nuances in the meaning and significance of IC. In responding to the public management agendas of government, non-profit organisations (NPOs) have had to commercialise their strategies. On the basis of data from in-depth interviews with 35 senior non-profit managers across 22 large Australian social service non-profit organisations (SSNPOs), the analysis confirms that IC assists SSNPOs in managing the social–commercial divide, but that managers' understandings of the IC concept are often different to those contained in the IC literature. IC scholars suggest that IC is synergetic with its components being inter-dependent. The managers perceived that very few inter-relationships existed between IC components. Implications of the theory—practice divide for non-profit strategy are discussed. Research limitations and future research direction are presented in the paper.
Enhancing learning outcomes through group work in an internationalised undergraduate business education context
Authors: Hunter James D , Vickery Jo , Smyth Robyn 
Published: December 2010

AbstractEmployers of business graduates require them to be effective communicators and team members in twenty-first century work environments. As a means of developing these skills, we believe group work is important to an undergraduate business teaching pedagogy preparing graduates for the challenges of modern workplaces. Student responses to a series of qualitative and quantitative focus group activities highlighted the ‘big issues’ encountered in group activities involving an increasingly internationalised and diverse cohort of students. These issues related mainly to communication within the group and the fear of social-loafers. These insights established the basis on which proactive strategies were introduced in a subsequent teaching period to nurture and advance the quality of the learning experience within a tertiary undergraduate business education setting. Given that reduced Government funding to Australian universities has prompted the management of institutions to look to full-fee paying international students to offset shortfalls in their operating budgets, this paper explores the particular impact of increasing numbers of English as a Second Language (ESL) students on the quality of, and student receptiveness to, group based study activities.
Research in strategy–structure–performance construct: Review of trends, paradigms and methodologies
Authors: Amitabh Manu , Gupta Rajen K 
Published: December 2010

AbstractWith rising unpredictability of the business environment, the strategy–structure–performance construct is being questioned afresh. But cutting edge research evidence is still difficult to come by. One of the possible reasons is that few researchers are adopting new and innovative methodologies. This paper carries out a paradigmatic and methodological review of research on the topic for the last 10 years after classifying published research into three broad categories of enquiry. The study finds that contrary to expectations, the logical positivistic/empiricist paradigm of enquiry into the one way linear causality in the strategy–structure–performance relationship was still the favorite among researchers and may explain the lack of breakthrough contribution of recent research. This paper makes a case for more research on the challenging two-way causality using innovative designs and archival data, and suggests some future directions for research.
A 5-Year Follow-Up of Antioxidant Supplementation in Type 2 Diabetic Retinopathy
Authors: Garcia-Medina Jose Javier , Pinazo-Duran Maria Dolores , Garcia-Medina Manuel , Zanon-Moreno Vicente , Pons-Vazquez Sheila 
Published: December 2010

Purpose This study was designed to evaluate the effect of antioxidant supplementation on diabetic retinopathy (DR) over a 5-year follow-up period. To our knowledge, this is the first such clinical trial performed. Methods We recruited 105 type 2 diabetic patients with nonproliferative DR. A complete ophthalmic checkup and a plasma determination of oxidative (malonyldialdehyde [MDA]) and antioxidant parameters (total antioxidant status [TAS]) were obtained as the baseline. One part of the cohort was randomly assigned to oral antioxidant supplementation at nutritional doses. The same examinations were performed with 97 diabetic patients who completed the 5-year follow-up period. The best-corrected visual acuity, DR score, MDA, and TAS values were compared at the beginning and the end of the follow-up. Results Best-corrected visual acuity did not change during the follow-up, irrespective of supplementation. However, the retinopathy stage showed a retardation of progression in the subgroup with supplementation, but worsened in the subgroup with no antioxidant supplementation. Furthermore, the antioxidant supplementation group maintained its antioxidant plasma status levels, which was related to decreased oxidative plasma activity. Conclusions Oral antioxidant supplementation could be a useful adjunctive long-term therapy in the treatment of nonproliferative DR.
An Efficient Catalytic Chromium‐Mediated Iodocyclopropanation Reaction: Stereoselective Synthesis of Iodocyclopropanecarboxamides
Authors: Concellón José M. , Rodríguez‐Solla Humberto , Blanco Elena G. , García‐Granda Santiago , Díaz and M. Rosario 
Published: December 2010

AbstractA catalytic chromium‐mediated novel synthesis of iodocyclopropanecarboxamides is reported. This reaction can be carried out on aromatic (E)‐ or (Z)‐α,β‐unsaturated amides in which the CC double bond is di‐ or trisubstituted. This process takes place with total stereospecificity and the new CI stereogenic center is generated with high stereoselectivity. Some synthetic applications of the obtained iodocyclopropanecarboxamides are also reported. The structures of the iodocyclopropanes and derivatives were established by X‐ray analysis.