bluuebunny/crossref_metadata_2025_split huggingface dataset:
3-deoxysilybin exerts anti-inflammatory effects by suppressing NF-κB activation in lipopolysaccharide-stimulated RAW264.7 macrophages
Authors: Cho Byoung Ok , So Yangkang , Jin Chang Hyun , Nam Bo Mi , Yee Sung-Tae , Jeong Il Yun 
Published: August 2014

Abstract
3-deoxysilybin (3-DS), also known as (–)-isosilandrin A, is a natural flavonoid of Silybum marianum. This study was designed to investigate the anti-inflammatory effect and the underlying molecular mechanisms of 3-DS in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. 3-DS dose-dependently inhibited the production of NO and the expression of iNOS in LPS-stimulated RAW264.7 macrophages. 3-DS also inhibited the production of pro-inflammatory cytokines (MCP-1, TNF-α, IL-6, and IL-1β) in LPS-stimulated RAW264.7 macrophages. Moreover, 3-DS decreased the NF-κB DNA binding activity in LPS-stimulated RAW264.7 macrophages. Furthermore, 3-DS suppressed NF-κB activation by inhibiting the degradation of IκBα and nuclear translocation of p65 subunit of NF-κB in LPS-stimulated RAW264.7 macrophages. Taken together, the present study suggests for the first time that 3-DS may exhibit an anti-inflammatory effect through the suppression of NF-κB transcriptional activation in LPS-stimulated RAW264.7 macrophages.
HIV-1 Nef and KSHV oncogene K1 synergistically promote angiogenesis by inducing cellular miR-718 to regulate the PTEN/AKT/mTOR signaling pathway
Authors: Xue Min , Yao Shuihong , Hu Minmin , Li Wan , Hao Tingting , Zhou Feng , Zhu Xiaofei , Lu Hongmei , Qin Di , Yan Qin , Zhu Jianzhong , Gao Shou-Jiang , Lu Chun 
Published: August 2014

Abstract
Kaposi's sarcoma (KS) is an AIDS-defining cancer with aberrant neovascularization caused by KS-associated herpesvirus (KSHV). Although the interaction between HIV-1 and KSHV plays a pivotal role in promoting the aggressive manifestations of KS, the pathogenesis underlying AIDS-KS remains largely unknown. Here we examined HIV-1 Nef protein promotion of KSHV oncoprotein K1-induced angiogenesis. We showed that both internalized and ectopic expression of Nef in endothelial cells synergized with K1 to facilitate vascular tube formation and cell proliferation, and enhance angiogenesis in a chicken CAM model. In vivo experiments further indicated that Nef accelerated K1-induced angiogenesis and tumorigenesis in athymic nu/nu mice. Mechanistic studies revealed that Nef and K1 synergistically activated PI3K/AKT/mTOR signaling by downregulating PTEN. Furthermore, Nef and K1 induced cellular miR-718, which inhibited PTEN expression by directly targeting a seed sequence in the 3′ UTR of its mRNA. Inhibition of miR-718 expression increased PTEN synthesis and suppressed the synergistic effect of Nef- and K1-induced angiogenesis and tumorigenesis. These results indicate that, by targeting PTEN, miR-718 mediates Nef- and K1-induced angiogenesis via activation of AKT/mTOR signaling. Our results demonstrate an essential role of miR-718/AKT/mTOR axis in AIDS-KS and thus may represent an attractive therapeutic target.
Extensive remodeling of DC function by rapid maturation-induced transcriptional silencing
Authors: Seguín-Estévez Queralt , Dunand-Sauthier Isabelle , Lemeille Sylvain , Iseli Christian , Ibberson Mark , Ioannidis Vassilios , Schmid Christoph D. , Rousseau Philippe , Barras Emmanuèle , Geinoz Antoine , Xenarios Ioannis , Acha-Orbea Hans , Reith Walter 
Published: August 2014

AbstractThe activation, or maturation, of dendritic cells (DCs) is crucial for the initiation of adaptive T-cell mediated immune responses. Research on the molecular mechanisms implicated in DC maturation has focused primarily on inducible gene-expression events promoting the acquisition of new functions, such as cytokine production and enhanced T-cell-stimulatory capacity. In contrast, mechanisms that modulate DC function by inducing widespread gene-silencing remain poorly understood. Yet the termination of key functions is known to be critical for the function of activated DCs. Genome-wide analysis of activation-induced histone deacetylation, combined with genome-wide quantification of activation-induced silencing of nascent transcription, led us to identify a novel inducible transcriptional-repression pathway that makes major contributions to the DC-maturation process. This silencing response is a rapid primary event distinct from repression mechanisms known to operate at later stages of DC maturation. The repressed genes function in pivotal processes—including antigen-presentation, extracellular signal detection, intracellular signal transduction and lipid-mediator biosynthesis—underscoring the central contribution of the silencing mechanism to rapid reshaping of DC function. Interestingly, promoters of the repressed genes exhibit a surprisingly high frequency of PU.1-occupied sites, suggesting a novel role for this lineage-specific transcription factor in marking genes poised for inducible repression.
Herbicides as Weed Control Agents: State of the Art: I. Weed Control Research and Safener Technology: The Path to Modern Agriculture
Authors: Kraehmer Hansjoerg , Laber Bernd , Rosinger Chris , Schulz Arno 
Published: August 2014

Abstract
The purpose of modern industrial herbicides is to control weeds. The species of weeds that plague crops today are a consequence of the historical past, being related to the history of the evolution of crops and farming practices. Chemical weed control began over a century ago with inorganic compounds and transitioned to the age of organic herbicides. Targeted herbicide research has created a steady stream of successful products. However, safeners have proven to be more difficult to find. Once found, the mode of action of the safener must be determined, partly to help in the discovery of further compounds within the same class. However, mounting regulatory and economic pressure has changed the industry completely, making it harder to find a successful herbicide. Herbicide resistance has also become a major problem, increasing the difficulty of controlling weeds. As a result, the development of new molecules has become a rare event today.
Gender barriers in Chilean mining: a strategic management
Authors: Salinas Paulina , Romaní Gianni 
Published: August 2014

Purpose
Given Chile's high projected deficit of skilled labor in its mining industry, the purpose of this paper is to explore the gender barriers present that hinder women from entering the sector.

Design/methodology/approach
To do this, a descriptive and interpretative study was undertaken and in‐depth interviews were conducted with 70 male and female workers belonging to the operating areas in the mining companies located in northern Chile. The data were transcribed and analyzed through a qualitative approach using discourse analysis by thematic categories.

Findings
The results show that gender barriers are related to: self‐discrimination of workers themselves, family demands, and male dominance in the field.

Originality/value
These results are relevant for strategic planning in the mining industry. They allow us to redirect policies to incorporate women in the sector in order to counteract the aforementioned deficits. The practical implications of this study for the mining sector in general include the incorporation of, for male employees, awareness workshops focussing on the importance of the inclusion of women in mining and aspects that favor this process and, for female employees, leadership and empowerment workshops. These initiatives will help to generate a more satisfying work environment that promotes better human resource management and productivity of the sector.
Business failure: incidence of stakeholders’ behavior
Authors: Maria Priego Alba , Manzaneque Lizano Montserrat , Merino Madrid Elena 
Published: August 2014

Purpose
The purpose of this paper is to analyze the potential impact of stakeholders’ behavior on business failure, through its influence on the generation and distribution of value added.

Design/methodology/approach
Using a sample of 2,277 Spanish SMEs – half of which were businesses that failed during the years 2006‐2009 – the authors conducted an empirical study on a number of variables representing the participation of stakeholders in the generation and distribution of value added. This was undertaken in order to discern differential behavior between the variables and prove their usefulness in predicting business failure. For this purpose, a mean difference analysis between failed and non‐failed businesses and a multivariate logistic regression model were applied.

Findings
The results obtained show that the stakeholders’ behavior in relation to their participation in the generation and distribution of value added, affects the likelihood of business failure.

Originality/value
This paper provides empirical evidence of the influence of stakeholders’ behavior on the likelihood of business failure, through their participation in the generation and distribution of value added. The results are useful for creating management strategies because they offer advice on the implementation of business management models based on the stakeholder approach, and on the appropriate involvement of all those who make up the conglomerate in the generation and distribution of value added. They also emphasize the value of recording information related to the Value‐Added Statement in order to explain a firm's level of dependence on its stakeholders and assess the firm's risk of insolvency.
Predators, energetics and fitness drive neonatal reproductive failure in red squirrels
Authors: Studd Emily K. , Boutin Stan , McAdam Andrew G. , Krebs Charles J. , Humphries Murray M. 
Published: August 2014

SummaryNeonatal reproductive failure should occur when energetic costs of parental investment outweigh fitness benefits. However, little is known about the drivers of neonatal reproductive failure in free‐ranging species experiencing continuous natural variation in predator abundance and in the energetic and fitness costs and benefits associated with parental investment.Long‐term comprehensive studies are required to better understand how biotic, abiotic and life‐history conditions interact to drive occurrences of reproductive failure in the wild.Using 24 years (1987–2011) of reproductive data from a northern boreal population of North American red squirrels in south‐western Yukon, we examined the effects of predator abundance, energetics (resource availability, ambient temperature and litter size) and fitness benefits (probability of overwinter juvenile survival and maternal age) on occurrences of neonatal reproductive failure (494/2670 reproductive attempts; 18·5%).Neonatal reproductive failure was driven by a combination of predator abundance, and the energetic and fitness costs and benefits of parental investment. The abundance of mustelids and maternal age was positively related to the occurrence of neonatal reproductive failure. High energy costs associated with a combination of low resource availability and cold ambient temperatures or large litters, corresponded to increased occurrences of neonatal reproductive failure. However, the strength of these relationships was influenced by variation in juvenile overwinter survival (i.e. fitness benefits).We provide evidence that predation pressure is an important driver of neonatal reproductive failure. In addition, we found a trade‐off occurs between resource‐dependent energetic and fitness costs and benefits of raising the current litter to independence.
Growth and enterotoxin production of Staphylococcus aureus in Iranian ultra‐filtered white cheese
Authors: Mohammadi Khosrow , Hanifian Shahram 
Published: August 2014

This study aimed to investigate the growth and enterotoxin production of Staphylococcus aureus during the ripening and storage of Iranian ultra‐filtered white cheese (IUFWC). According to the results, the addition of starter culture had significant inhibitory effects on the growth and enterotoxin production of S. aureus. Moreover, prolong survival and enterotoxin production were observed in the samples with the highest inoculum (5 log CFU/g) of S. aureus. It was concluded that proper activity of the starter culture together with the refrigeration storage of IUFWC was the key element in inhibiting the growth and enterotoxin production of S. aureus.
Association of Toll‐like Receptor 4 Gene polymorphisms with susceptibility to type 2 diabetes mellitus in the Chinese population Toll样受体4基因多态性与中国人群2型糖尿病易感性的关联研究
Authors: Peng Danfeng , Jiang Feng , Zhang Rong , Tang Shanshan , Chen Miao , Yan Jing , Sun Xue , Luo Yi , Hu Cheng , Jia Weiping 
Published: August 2014

AbstractBackgroundToll‐like receptor 4 (TLR4) plays an important role in innate immunity. Activation of innate immune response and subsequent chronic low‐grade inflammation are thought to be involved in the pathogenesis of type 2 diabetes. In this study, we aimed to investigate the association of TLR4 variants with type 2 diabetes in the Chinese population.MethodsSeven tag single nucleotide polymorphisms (SNPs) of TLR4 based on HapMap Chinese data were genotyped in the Shanghai Chinese, including 3404 type 2 diabetes patients and 3401 controls. The controls were extensively phenotyped for the traits related to glucose metabolism and insulin secretion.ResultsIn total participants, we identified that rs10759932 and rs1927911 were associated with type 2 diabetes (odds ratio 1.106, P = 0.009 for rs10759532, odds ratio 1.092, P = 0.013 for rs1927911). rs11536889 showed a trend association with type 2 diabetes (odds ratio 0.957, P = 0.057). This SNP was also associated with 2‐h plasma glucose (P = 0.033) and high‐density lipoprotein‐cholesterol (P = 0.031). In female participants, rs10759932, rs1927911 and rs11536889 were associated with type 2 diabetes (odds ratio 1.176, P = 0.002 for rs10759932, odds ratio 1.136, P = 0.009 for rs1927911, odds ratio 0.882, P = 0.024 for rs11536889). Besides, rs11536889 was significantly associated with 2‐h plasma glucose (P = 0.050) and HOMA‐B (P = 0.046) with adjusting for age and body mass index in female normal subjects.ConclusionsWe conclude that genetic variants of TLR4 are associated with type 2 diabetes in the Chinese population, especially in female subjects.
A randomized, open‐label, multicentre, phase 2/3 study to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia
Authors: Awan Farrukh T. , Hillmen Peter , Hellmann Andrzej , Robak Tadeusz , Hughes Steven G. , Trone Denise , Shannon Megan , Flinn Ian W. , Byrd John C. ,   the LUCID trial investigators
Published: August 2014

SummaryLumiliximab is a chimeric monoclonal antibody that targets CD23 on the surface of chronic lymphocytic leukaemia (CLL) B‐cells. Early phase clinical studies with lumiliximab alone and in combination with fludarabine, cyclophosphamide and rituximab (FCR) established its potential efficacy and tolerability. The 152CL201 trial [Lumiliximab with fludarabine, cyclophosphamide and rituximab (FCR) versus FCR alone in subjects with relapsed CLL; LUCID] was a phase 2/3, randomized (1:1), open‐label, multicentre study of lumiliximab in combination with FCR versus FCR alone in patients with relapsed CLL. Six hundred and twenty‐seven patients were randomized to either arm. Overall the combination of lumiliximab with FCR was not significantly better than FCR alone (overall response rate 71% vs. 72%, complete response rate 16% vs. 15%, median progression‐free survival 24.6 vs. 23.9 months respectively, for FCR with and without lumiliximab). There was a slightly increased incidence of adverse events with lumiliximab but these increases did not appear to lead to differences in eventual outcomes. An interim analysis failed to show sufficient efficacy of the combination of lumiliximab with FCR. The study was therefore stopped early for lack of efficacy. Despite the eventual outcome, the LUCID trial is one of the largest studies that provides valuable insight into the efficacy and tolerability of FCR as a therapeutic option for patients with relapsed CLL.
Storage and secretion of naturally occurring von Willebrand factor A domain variants
Authors: Groeneveld Dafna J. , Wang Jiong‐Wei , Mourik Marjon J. , Dirven Richard J. , Valentijn Karine M. , Voorberg Jan , Reitsma Pieter H. , Eikenboom Jeroen 
Published: August 2014

SummaryVon Willebrand disease (VWD) is a bleeding disorder characterized by reduced plasma von Willebrand factor (VWF) levels or functionally abnormal VWF. Low VWF plasma levels in VWD patients are the result of mutations in the VWF gene that lead to decreased synthesis, impaired secretion, increased clearance or a combination thereof. However, expression studies of variants located in the A domains of VWF are limited. We therefore characterized the biosynthesis of VWF mutations, located in the VWF A1–A3 domains, that were found in families diagnosed with VWD. Human Embryonic Kidney 293 (HEK293) cells were transiently transfected with plasmids encoding full‐length wild‐type VWF or mutant VWF. Six mutations in the A1–A3 domains were expressed. We found that all mutants, except one, showed impaired formation of elongated pseudo‐Weibel‐Palade bodies (WPB). In addition, two mutations also showed reduced numbers of pseudo‐WPB, even in the heterozygous state, and increased endoplasmic reticulum retention, which is in accordance with the impaired regulated secretion seen in patients. Regulated secretion upon stimulation of transfected cells reproduced the in vivo situation, indicating that HEK293 cells expressing VWF variants found in patients with VWD can be used to properly assess defects in regulated secretion.
Enhanced allergic airway disease in old mice is associated with a Th17 response
Authors: Brandenberger C. , Li N. , Jackson‐Humbles D. N. , Rockwell C. E. , Wagner J. G. , Harkema J. R. 
Published: August 2014

SummaryBackgroundThe prevalence of asthma in the elderly is increasing and associated with higher mortality than in children or young adults. However, the effects of age on the development and character of allergic asthma have been understudied. It has been suggested that mixed Th2/Th17 responses cause more severe forms of asthma, but the role of Th17 response in allergic airway disease and aging is not well understood.ObjectiveTo investigate age‐dependent characteristics and Th17 immune response in allergic airway disease in a murine house dust mite (HDM)‐allergen model.MethodsTwelve‐week‐old and 15‐month‐old male BALB/c mice were sensitized and challenged with HDM. Bronchoalveolar lavage fluid (BALF), airway inflammation and hyperresponsiveness (AHR), serum immunoglobulin and splenic T cells were assessed. Age‐related T cell activation was analyzed in a co‐culture with bone marrow‐derived dendritic cells (BMDC) and splenic CD4+T cells from young and old mice.ResultsFeatures of allergic airway disease such as mucous cell hyperplasia, infiltration of airway eosinophils and lymphocytes, Th2 cytokine expression and serum IgG1 levels were greater in old compared to young mice. In contrast to the more marked inflammatory/immune responses to HDM in old mice, AHR was greater in young HDM‐treated mice. Only the old mice developed airway neutrophil infiltration and a Th17 immune response upon HDM exposure, with increases in BALF cytokines IL‐17A and KC, and Th17 cytokine producing T cells in the spleen. Stimulation of CD4+T cells and BMDC co‐cultures with HDM, resulted in an enhanced Th17 cytokine response in cells isolated from old mice.Conclusions and Clinical RelevanceOur findings in mice suggest that the severity and character of allergic airway disease are age dependent, with a bias towards a Th17 immune response with aging. Elderly, asthmatics may be prone to develop severe allergic airway inflammation with a mixed Th2/Th17 immune response.
The value of preoperative 18F‐FDG PET/CT for the assessing contralateral neck in head and neck cancer patients with unilateral node metastasis (N1‐3)
Authors: Joo Y.‐H. , Yoo I.‐R. , Cho K.‐J. , Park J.‐O. , Nam I.‐C. , Kim C.‐S. , Kim S.‐Y. , Kim M.‐S. 
Published: August 2014

ObjectivesThe purpose of this study was to determine whether preoperative 18F‐FDG PET/CT is useful in assessing contralateral lymph node metastasis in the neck.DesignA retrospective review of medical records was performed.SettingPatients treated at a single institute.ParticipantsOne hundred and fifty‐seven patients whose pathology results were positive for unilateral node metastasis (N1‐3) involvement and underwent preoperative 18F‐FDG PET/CT for head and neck squamous cell carcinoma (HNSCC) were reviewed.Main outcome measuresPrognostic factors and nodal SUVmax were studied to identify the risk of contralateral disease.ResultsThirty‐six (22.9%) patients had contralateral cervical lymph node metastases. The 18F‐FDG PET/CT had a sensitivity of 80% and a specificity of 96% in identifying the contralateral cervical lymph node metastases on a level‐by‐level basis. The median SUVmax values of the ipsilateral and contralateral lymph nodes were 3.99 ± 3.36 (range, 0–20.4) and 2.94 ± 2.04 (range, 0–8.7), respectively (P = 0.001). There was a significant difference in the median SUVmax of contralateral nodes between the benign and malignant cervical lymph nodes (2.31 ± 0.62 versus 3.28 ± 2.43, P = 0.014). The cut‐off value of contralateral median SUVmax in the context of contralateral cervical metastasis was 2.5 with the sensitivity of 75% and the specificity of 94%. A median contralateral lymph node SUVmax ≥ 2.5 was associated with 5‐year disease‐specific survival (P = 0.038).Conclusion18F‐FDG PET/CT median SUVmax cut‐off values of contralateral lymph nodes ≥2.5 were associated with contralateral cervical lymph node metastases and 5‐year disease‐specific survival in HNSCC patients with unilateral metastases.
ENERGY SECURITY IN THE ASIA‐PACIFIC REGION
Authors: Intriligator Michael D. 
Published: August 2014

AbstractThe nations of the Asia‐Pacific Region, including its three sub‐regions of Northeast Asia, Southeast Asia, and South Asia, face major potential dangers in securing the energy needed for their economies. This paper focuses on these dangers and discusses the future prospects for these vulnerable nations, including their need for closer cooperation. (JEL Q32, Q34, Q40)