bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are managers open to involvement in employee retirement? The influence of manager psycho-social characteristics, decision-making environment and older employee situational factors
Authors: DAVIES ELEANOR M. M. , VAN DER HEIJDEN BEATRICE I. J. M. , STEPHENSON JOHN 
Published: March 2017

ABSTRACTThe changing retirement landscape calls on employers to develop practices that respond to individuals’ retirement needs. Line managers are a key stakeholder in managing retirement and this study focuses on how they respond to employee retirement scenarios. This empirical work examines manager openness to involvement in retirement, focusing on three sets of explanatory variables: manager psycho-social characteristics (experience of managing older workers, intention to work past 65), their decision-making environment (influence, discretion and decision-making support) and older employee situational factors (performance, ease of replacement, retirement affect and attitude to work). Data were collected from 129 managers in the United Kingdom's university sector using survey items and a factorial vignette design. The multi-level analysis found support for each category of variables in predicting manager openness to involvement in employee retirement. Managers with more experience of managing older workers were more likely to be open to involvement although managers’ own retirement intentions were not significant as a predictor. Decision-making environment variables were significant predictors of manager openness to involvement. The only older employee situational factor that was associated with manager openness to involvement was employee performance. Practically, organisations need to recognise the potential influence that managers have on employee retirement decisions and this study's findings show that managers may need training to help them understand their own role in supporting older employee retirement.
The ‘Development’ Discourse in Multilateral Trade Lawmaking
Authors: LAMP NICOLAS 
Published: March 2017

AbstractThe impact of the idea of ‘development’ in multilateral trade lawmaking is often reduced to the principle of ‘special and differential treatment’, which exempts developing countries from certain obligations imposed by the trade regime. The article shows that ‘development’ has always presented a much wider challenge to the vision of the trade regime championed by the major trading nations. The development discourse has conceived the trade regime's historical significance, the regime's aims, and the relationships among its members in ways that were often fundamentally at odds with the conception preferred by most developed countries. The article explores how the development discourse has informed lawmaking initiatives by developing countries throughout the history of the trade regime. While not all of these initiatives were successful or necessarily fruitful, they show that the pursuit of development in trade lawmaking has always been more than an effort to seek exemption from trade rules.
Social, economic and environmental impacts of organic cotton production on the livelihood of smallholder farmers in Odisha, India
Authors: Altenbuchner Christine , Vogel Stefan , Larcher Manuela 
Published: March 2017

AbstractCotton is an important source of income for smallholder farmers in India, usually grown very intensively. To counteract negative impacts of cotton cultivation in India, such as environmental degradation and financial dependency due to high input costs, organic cotton cultivation is being promoted by non-governmental organizations in the country. This study examines how the conversion to organic cotton cultivation influences the livelihood of smallholder farmers in rural India. Interviews with organic farmers were conducted in Odisha, India, complemented by expert interviews and observations in the field. Results show that farmers profit from organic agriculture, mainly due to soil improvements, through reduced exposure to toxic chemicals and lower input costs, which in turn reduces dependency on money lenders. Organic agriculture enables smallholder farmers in the study region to improve their livelihood by providing access to training and by organizing in groups. Important social impacts identified in this study were capacity building and strengthened communities, through training and institution building. However, a higher workload, due to the higher work intensity of organic farming practices, was also observed, with this impacting women more than men. Environmental conditions and gender aspects still remain challenging.
Development assistance for health: what criteria do multi- and bilateral funders use?
Authors: Ottersen Trygve , Kamath Aparna , Moon Suerie , Martinsen Lene , Røttingen John-Arne 
Published: March 2017

AbstractAfter years of unprecedented growth in development assistance for health (DAH), the system is challenged on several fronts: by the economic downturn and stagnation of DAH, by the epidemiological transition and increase in non-communicable diseases, and by the economic transition and rise of the middle-income countries. This raises questions about which countries should receive DAH and how much, and, fundamentally, what criteria that promote fair and effective allocation. Yet, no broad comparative assessment exists of the criteria used today. We reviewed the allocation criteria stated by five multilateral and nine bilateral funders of DAH. We found that several funders had only limited information about concrete criteria publicly available. Moreover, many funders not devoted to health lacked specific criteria for DAH or criteria directly related to health, and no funder had criteria directly related to inequality. National income per capita was emphasised by many funders, but the associated eligibility thresholds varied considerably. These findings and the broad overview of criteria can assist funders in critically examining and revising the criteria they use, and inform the wider debate about what the optimal criteria are.
Molecular insights of Gas6/TAM in cancer development and therapy
Authors: Wu Guiling , Ma Zhiqiang , Hu Wei , Wang Dongjin , Gong Bing , Fan Chongxi , Jiang Shuai , Li Tian , Gao Jianyuan , Yang Yang 
Published: March 2017

AbstractSince growth arrest-specific gene 6 (Gas6) was discovered in 1988, numerous studies have highlighted the role of the Gas6 protein and its receptors Tyro3, Axl and Mer (collectively referred to as TAM), in proliferation, apoptosis, efferocytosis, leukocyte migration, sequestration and platelet aggregation. Gas6 has a critical role in the development of multiple types of cancers, including pancreatic, prostate, oral, ovarian and renal cancers. Acute myelocytic leukaemia (AML) is a Gas6-dependent cancer, and Gas6 expression predicts poor prognosis in AML. Interestingly, Gas6 also has a role in establishing tumour dormancy in the bone marrow microenvironment and in suppressing intestinal tumorigenesis. Numerous studies regarding cancer therapy have targeted Gas6 and TAM receptors with good results. However, some findings have suggested that Gas6 is associated with the development of resistance to cancer therapies. Concerning these significant effects of Gas6 in numerous cancers, we discuss the roles of Gas6 in cancer development in this review. First, we introduce basic knowledge on Gas6 and TAM receptors. Next, we describe and discuss the involvement of Gas6 and TAM receptors in cancers from different organ systems. Finally, we highlight the progress in therapies targeting Gas6 and TAM receptors. This review presents the significant roles of Gas6 in cancers from different systems and may contribute to the continued promotion of Gas6 as a therapeutic target.
Solute carrier family 12 member 5 promotes tumor invasion/metastasis of bladder urothelial carcinoma by enhancing NF-κB/MMP-7 signaling pathway
Authors: Liu J Y , Dai Y B , Li X , Cao K , Xie D , Tong Z T , Long Z , Xiao H , Chen M K , Ye Y L , Liu B , Tan J , Tang J , Xu Z Z , Gan Y , Zhou Y H , Deng F , He L Y 
Published: March 2017

AbstractSolute carrier family 12 member 5 (SLC12A5), an integral membrane KCl cotransporter, which maintains chloride homeostasis in neurons, is aberrantly expressed and involved in the tumorigenesis of certain cancers. However, the clinical significance and biological role of SLC12A5 in human bladder urothelial carcinoma (BUC) remains unclear. In this study, the expression of SLC12A5 was examined in clinical specimens of primary BUC and in BUC cell lines using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry (IHC). The prognostic value of SLC12A5 expression and its correlation with the clinicopathological features of patients with BUC were analyzed statistically. A series of in vitro and in vivo assays were performed to elucidate the effect of SLC12A5 in BUC and its underlying mechanisms. The present results showed that SLC12A5 expression was significantly increased in BUC tissues. SLC12A5 expression significantly correlated with the tumor node metastasis (TNM) stage. Kaplan–Meier survival curves showed that high SLC12A5 expression was associated with poor survival in patients with BUC. Multivariate analysis indicated that SLC12A5 expression was an independent prognostic marker for the survival of patients. Downregulation of SLC12A5 inhibited the migratory and invasive abilities of BUC cells in vitro, and knocking down SLC12A5 diminished BUC metastasis in vivo. Moreover, we identified that SLC12A5 promoted the migration and invasion of BUC by enhancing MMP-7 expression via NF-κB-dependent transcription. Taken together, our findings indicated that SLC12A5 might function as a tumor metastasis promoting factor in the development and progression of BUC by regulating the NF-κB/MMP-7 signaling pathway. Thus, SLC12A5 might be a prognostic marker as well as a therapeutic target for BUC.
Inhibition of autophagy prevents irradiation-induced neural stem and progenitor cell death in the juvenile mouse brain
Authors: Wang Yafeng , Zhou Kai , Li Tao , Xu Yiran , Xie Cuicui , Sun Yanyan , Zhang Yaodong , Rodriguez Juan , Blomgren Klas , Zhu Changlian 
Published: March 2017

AbstractRadiotherapy is an effective tool in the treatment of malignant brain tumors. However, damage to brain stem and progenitor cells constitutes a major problem and is associated with long-term side effects. Autophagy has been shown to be involved in cell death, and the purpose of this study was to evaluate the effect of autophagy inhibition on neural stem and progenitor cell death in the juvenile brain. Ten-day-old selective Atg7 knockout (KO) mice and wild-type (WT) littermates were subjected to a single 6Gy dose of whole-brain irradiation. Cell death and proliferation as well as microglia activation and inflammation were evaluated in the dentate gyrus of the hippocampus and in the cerebellum at 6 h after irradiation. We found that cell death was reduced in Atg7 KO compared with WT mice at 6 h after irradiation. The number of activated microglia increased significantly in both the dentate gyrus and the cerebellum of WT mice after irradiation, but the increase was lower in the Atg7 KO mice. The levels of proinflammatory cytokines and chemokines decreased, especially in the cerebellum, in the Atg7 KO group. These results suggest that autophagy might be a potential target for preventing radiotherapy-induced neural stem and progenitor cell death and its associated long-term side effects.
NPAS2 promotes cell survival of hepatocellular carcinoma by transactivating CDC25A
Authors: Yuan Peng , Li Jibin , Zhou Feng , Huang Qichao , Zhang Jiansheng , Guo Xu , Lyu Zhuomin , Zhang Hongxin , Xing Jinliang 
Published: March 2017

AbstractEmerging evidences show that disruption of the circadian rhythm is associated with tumor initiation and progression. Neuronal PAS domain protein 2 (NPAS2), one of the core circadian molecules, has been proved to be a potential prognostic biomarker in colorectal and breast cancers. However, to date, the potential functional roles and molecular mechanisms by which NPAS2 affects cancer cell survival are greatly unclear, especially in hepatocellular carcinoma (HCC). We first investigated the expression of NPAS2 and its clinical significance in HCC. We then systematically explored the role of NPAS2 in HCC cell survival both in vitro and in vivo and the underlying mechanism. NPAS2 was frequently upregulated in HCC, which significantly facilitated cell survival both in vitro and in vivo mainly by promoting cell proliferation and inhibiting mitochondria-dependent intrinsic apoptosis, and thus contributed to poor prognosis of HCC patients. Mechanistically, the survival-promoting role of NPAS2 was mediated by transcriptional upregulation of the CDC25A phosphatase and subsequent dephosphorylation of CDK2/4/6 and Bcl-2, which induced cell proliferation and inhibited cell apoptosis in HCC, respectively. Moreover, BMAL1, another core clock transcription factor, was identified to heterodimerize with NPAS2 to bind to the E-box element in the promoter of CDC25A and be associated with the NPAS2-mediated tumor cell survival in HCC. Our findings demonstrate that NPAS2 has a critical role in HCC cell survival and tumor growth, which is mainly mediated by transcriptional upregulation of CDC25A. Thereby, NPAS2 may serve as a potential therapeutic target in HCC patients.
Hydrogen sulfide promotes autophagy of hepatocellular carcinoma cells through the PI3K/Akt/mTOR signaling pathway
Authors: Wang Shanshan S , Chen Yuhan H , Chen Ning , Wang Lijun J , Chen Dexi X , Weng Honglei L , Dooley Steven , Ding Huiguo G 
Published: March 2017

AbstractHydrogen sulfide (H2S), in its gaseous form, plays an important role in tumor carcinogenesis. This study investigated the effects of H2S on the cell biological functions of hepatocellular carcinoma (HCC). HCC cell lines, HepG2 and HLE, were treated with NaHS, a donor of H2S, and rapamycin, a classic autophagy inducer, for different lengths of time. Western blotting, immunofluorescence, transmission electron microscopy (TEM), scratch assay, CCK-8 and flow cytometric analysis were carried out to examine the effects of H2S on HCC autophagy, cell behavior and PI3K/Akt/mTOR signaling. Treatment with NaHS upregulated expression of LC3-II and Atg5, two autophagy-related proteins, in HepG2 and HLE cells. TEM revealed increased numbers of intracellular double-membrane vesicles in those cells treated with NaHS. Like rapamycin, NaHS also significantly inhibited expression of p-PI3K, p-Akt and mTOR proteins in HCC cells. Interestingly, the expression of LC3-II was further increased when the cells were treated with NaHS together with rapamycin. In addition, NaHS inhibited HCC cell migration, proliferation and cell division. These findings show that H2S can induce HCC cell apoptosis. The biological function of the gasotransmitter H2S in HCC cells was enhanced by the addition of rapamycin. Hydrogen sulfide influences multiple biological functions of HCC cells through inhibiting the PI3K/Akt/mTOR signaling pathway.
Upregulation of miR-665 promotes apoptosis and colitis in inflammatory bowel disease by repressing the endoplasmic reticulum stress components XBP1 and ORMDL3
Authors: Li Manying , Zhang Shenghong , Qiu Yun , He Yao , Chen Baili , Mao Ren , Cui Yi , Zeng Zhirong , Chen Minhu 
Published: March 2017

AbstractMicroRNAs are critical post-transcriptional regulators of gene expression and key mediators of pathophysiology of inflammatory bowel disease (IBD). This study is aimed to study the role of miR-665 in the progression of IBD. Real-time PCR analysis was used to determine miR-665 expression in 89 freshly isolated IBD samples and dextran sulfate sodium (DSS)-induced colonic mucosal tissues. The role of miR-665 in inducing apoptosis and colitis were examined by Annexin V, TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) staining, colony formation in vitro and DSS-induced colitis mice model in vivo. Moreover, luciferase reporter assay, western blot analysis and microribonucleoprotein immunoprecipitation were performed to determine that miR-665 directly repressed XBP1 (X-box-binding protein-1) and ORMDL3 expression. Herein, our results revealed that miR-665 was markedly upregulated in active colitis. Gain-of-function and loss-of-function studies showed that ectopic expression of miR-665 promoted apoptosis under different inflammatory stimuli. Importantly, delivery of miR-665 mimic promoted, while injection of antagomiR-665 markedly impaired DSS-induced colitis in vivo. Mechanistically, we demonstrated that miR-665 induced apoptosis by inhibiting XBP1 and ORMDL3. Taken together, our findings reveal a new regulatory mechanism for ER stress signaling and suggest that miR-665 might be a potential target in IBD therapy.
BRE modulates granulosa cell death to affect ovarian follicle development and atresia in the mouse
Authors: Yeung Cheung Kwan , Wang Guang , Yao Yao , Liang Jianxin , Tenny Chung Cheuk Yiu , Chuai Manli , Lee Kenneth Ka Ho , Yang Xuesong 
Published: March 2017

AbstractThe BRE (brain and reproductive expression) gene, highly expressed in nervous and reproductive system organs, plays an important role in modulating DNA damage repair under stress response and pathological conditions. Folliculogenesis, a process that ovarian follicle develops into maturation, is closely associated with the interaction between somatic granulosa cell and oocyte. However, the regulatory role of BRE in follicular development remains undetermined. In this context, we found that BRE is normally expressed in the oocytes and granulosa cells from the primordial follicle stage. There was a reduction in follicles number of BRE mutant (BRE−/−) mice. It was attributed to increase the follicular atresia in ovaries, as a result of retarded follicular development. We established that cell proliferation was inhibited, while apoptosis was markedly increased in the granulosa cells in the absence of BRE. In addition, expressions of γ-H2AX (marker for showing DNA double-strand breaks) and DNA damage-relevant genes are both upregulated in BRE−/− mice. In sum, these results suggest that the absence of BRE, deficiency in DNA damage repair, causes increased apoptosis in granulosa cells, which in turn induces follicular atresia in BRE−/− mice.
Kaiso depletion attenuates the growth and survival of triple negative breast cancer cells
Authors: Bassey-Archibong Blessing I , Rayner Lyndsay G A , Hercules Shawn M , Aarts Craig W , Dvorkin-Gheva Anna , Bramson Jonathan L , Hassell John A , Daniel Juliet M 
Published: March 2017

AbstractTriple negative breast cancers (TNBC) are highly aggressive and lack specific targeted therapies. Recent studies have reported high expression of the transcription factor Kaiso in triple negative tumors, and this correlates with their increased aggressiveness. However, little is known about the clinical relevance of Kaiso in the growth and survival of TNBCs. Herein, we report that Kaiso depletion attenuates TNBC cell proliferation, and delays tumor onset in mice xenografted with the aggressive MDA-231 breast tumor cells. We further demonstrate that Kaiso depletion attenuates the survival of TNBC cells and increases their propensity for apoptotic-mediated cell death. Notably, Kaiso depletion downregulates BRCA1 expression in TNBC cells expressing mutant-p53 and we found that high Kaiso and BRCA1 expression correlates with a poor overall survival in breast cancer patients. Collectively, our findings reveal a role for Kaiso in the proliferation and survival of TNBC cells, and suggest a relevant role for Kaiso in the prognosis and treatment of TNBCs.
Plant cysteine oxidases are dioxygenases that directly enable arginyl transferase-catalysed arginylation of N-end rule targets
Authors: White Mark D. , Klecker Maria , Hopkinson Richard J. , Weits Daan A. , Mueller Carolin , Naumann Christin , O’Neill Rebecca , Wickens James , Yang Jiayu , Brooks-Bartlett Jonathan C. , Garman Elspeth F. , Grossmann Tom N. , Dissmeyer Nico , Flashman Emily 
Published: March 2017

AbstractCrop yield loss due to flooding is a threat to food security. Submergence-induced hypoxia in plants results in stabilization of group VII ETHYLENE RESPONSE FACTORs (ERF-VIIs), which aid survival under these adverse conditions. ERF-VII stability is controlled by the N-end rule pathway, which proposes that ERF-VII N-terminal cysteine oxidation in normoxia enables arginylation followed by proteasomal degradation. The PLANT CYSTEINE OXIDASEs (PCOs) have been identified as catalysts of this oxidation. ERF-VII stabilization in hypoxia presumably arises from reduced PCO activity. We directly demonstrate that PCO dioxygenase activity produces Cys-sulfinic acid at the N terminus of an ERF-VII peptide, which then undergoes efficient arginylation by an arginyl transferase (ATE1). This provides molecular evidence of N-terminal Cys-sulfinic acid formation and arginylation by N-end rule pathway components, and a substrate of ATE1 in plants. The PCOs and ATE1 may be viable intervention targets to stabilize N-end rule substrates, including ERF-VIIs, to enhance submergence tolerance in agriculture.
Pharmacokinetic-Pharmacodynamic modelling of intracellular Mycobacterium tuberculosis growth and kill rates is predictive of clinical treatment duration
Authors: Aljayyoussi Ghaith , Jenkins Victoria A. , Sharma Raman , Ardrey Alison , Donnellan Samantha , Ward Stephen A. , Biagini Giancarlo A. 
Published: March 2017

AbstractTuberculosis (TB) treatment is long and complex, typically involving a combination of drugs taken for 6 months. Improved drug regimens to shorten and simplify treatment are urgently required, however a major challenge to TB drug development is the lack of predictive pre-clinical tools. To address this deficiency, we have adopted a new high-content imaging-based approach capable of defining the killing kinetics of first line anti-TB drugs against intracellular Mycobacterium tuberculosis (Mtb) residing inside macrophages. Through use of this pharmacokinetic-pharmacodynamic (PK-PD) approach we demonstrate that the killing dynamics of the intracellular Mtb sub-population is critical to predicting clinical TB treatment duration. Integrated modelling of intracellular Mtb killing alongside conventional extracellular Mtb killing data, generates the biphasic responses typical of those described clinically. Our model supports the hypothesis that the use of higher doses of rifampicin (35 mg/kg) will significantly reduce treatment duration. Our described PK-PD approach offers a much needed decision making tool for the identification and prioritisation of new therapies which have the potential to reduce TB treatment duration.
Reinterpretation of oceanic 230Th profiles based on decadal export productivity (2003–2010)
Authors: Luo Yiming 
Published: March 2017

AbstractUnderstanding 230Th distributions in the global ocean is important to support and guide the use of this important radioactive nuclide in multiple aspects of oceanographic research, and this issue is now revisited. Based on estimates of export productivity (EP) over 2003–2010 and assuming 230Th scavenging at equilibrium at seven Pacific stations where linear 230Th profiles are found, an empirical equilibrium-state 230Th-scavenging versus EP correlation is established. This correlation demonstrates the relationship between 230Th-scavenging intensity and EP in the absence of advection. With this correlation, other 230Th profiles from global oceans are reinterpreted. My findings provide alternative explanations of signals carried by 230Th distributions with regard to advection, by a reassessment of the 230Th deficits in deep waters. Such an equilibrium-state 230Th-scavenging versus EP correlation provides a basis for convenient parameterization for use in 3D modeling studies of the 230Th distributions.