bluuebunny/crossref_metadata_2025 huggingface dataset:
An analysis of the perceived effects of economic and monetary union on hotels in the north of Portugal
Authors: Pinto Cardoso Carla , Vaughan Roger , Edwards Jonathan
Published: September 2010

Purpose

The purpose of this paper is to reflect on the perceived implications of economic and monetary union (EMU) as a driver for changes in the hotel business environment and, consequently, on Portuguese competitiveness, in terms of the conceptual framework and methodology adopted and showing the way how it may contribute to help managers and decision makers to effectively manage their competitive strategies.

Design/methodology/approach

The paper adopted and adapted Porter's models (Diamond, Five Forces and Value Chain) as the basis for analysing the implications of EMU upon the hotel business environment (at national, industry and operational level). Those implications are the ones perceived by the stakeholders in that sector: public authorities, trade associations and hoteliers.

Findings

The findings indicated that EMU not only changed the hotel business environment at a national level, but also changed the competitive and operational environment. Nonetheless, as this study found, the hotel stakeholders had relatively different hopes and fears concerning EMU.

Practical implications

The paper offers a conceptual framework sufficiently versatile (regarding the context of the study) which can be used by decision makers or managers as a tool to understand their business environment and, consequently, to cope with potential challenges.

Originality/value

Two of the innovative features of this study are: the triangulation of perspectives on the implications of EMU on hotels and the use of a combination of Porter's models as a suitable tool for studying the implications of EMU in the services sector. This can be useful to service decision makers and managers that seek to cope with the business environment challenges.
Douro Valley Tourism Plan
Authors: Fazenda Nuno , Nunes da Silva Fernando , Costa Carlos
Published: September 2010

Purpose

The purpose of this paper is to demonstrate through a case study, how a tourist destination plan can contribute to the management of the destination, via the development of sustainable, coherent, integrated and efficient tourism actions.

Design/methodology/approach

The methodology incorporates a literature review on tourism planning and a case study, where the models and tools presented are applied to the Douro Valley region.

Findings

The Douro Valley Tourism Plan (DVTP) is based on an integrated and global perspective (by taking into consideration all the elements of the tourism system) and has been designed with the close and active involvement of the stakeholders. The goal is to ensure that all future actions will be pursued through a high commitment from the community and institutions of the region.

Practical implications

Aware of the interest that the Portuguese Government has in the region, as well as the financial resources that can be deployed, attracting private investment and promotion can be facilitated. These tasks, essential to the development of the region, are more easily facilitated as the DVTP gives a positive sign to the markets (investors and travel operators) and consequently to potential tourists.

Originality/value

The paper reports on the Douro Valley as the first destination in the World that has been assessed by the World Centre of Excellence for Destinations. The System for Measuring Excellence on Destinations, helping destinations to achieve sustainable development objectives, constitutes a tool for a better implementation of the “Douro Valley Tourism Plan” and so is an excellent example for other destinations.
Sustainability control and management of Porto Belo Island, Santa Catarina State, Brazil
Authors: van de Meene Ruschmann Doris , Carla Sagi Luciana
Published: September 2010

Purpose

The purpose of this paper is to illustrate the structure and results of a project between university and enterprise aimed at managing and controlling sustainable and competitive tourism in a fragile area: an island. The project started in 1996 and was completed in 2009. It helped the island to preserve its environment and to structure equipment and services adequate to market needs – with quality and responsibility. It also helped young professionals to develop their skills toward market needs, creating not only standards of highly professional behaviour, but also ethical values of respect, comprehension and hospitality.

Design/methodology/approach

To understand the market needs, the use of equipment and services of the island by visitors and the visitors' profiles, personal interviews were conducted. The approach to visitors happened when leaving the island as it was agreed that only when visitors have had the experience were they able to comment. In addition to this paper, an observation of visitors was also developed, in order to check if their behaviour was compatible with their answers in formal interviews. The sustainability of the island was analyzed and evaluated through specific reports that defined indicators and qualitative criteria for the evaluation process.

Findings

The results presented are favourable since it is clear that the negative impacts on the environment were minimized, the island became a good business, the local community was involved, the trainees learnt in practice, and the visitors were very satisfied with the results of the project.

Research limitations/implications

The paper is limited to understand two aspects of sustainability: management and market. To achieve more sustainability for the island very important complementary studies need to be considered: the characterization of local flora and fauna, both terrestrial and marine; landscape studies and research about the business impact on the life of the local community.

Originality/value

The paper is a case study that compiles 14 years of successful experience using methods, techniques and instruments to manage and control sustainability in a place that combines a fragile environment, tourism, recreation and business. This case is a reference for similar environments in Brazil.
How can tourist destinations become more competitive
Authors: Costa Jorge , Salazar Ana , Montenegro Mónica , Gomes João
Published: September 2010

Purpose

The purpose of this paper is to review the question: What have we learned about how tourist destinations may become more competitive and the tools to achieve this aim?

Design/methodology/approach

The paper considers the contribution made by each theme issue article to an overall understanding of tourism destinations' competitiveness and how this can be achieved and improved by using a series of strategic and operational tools.

Findings

The paper presents examples of key tools for improving destinations' competitiveness, how they were applied in industry contexts and recommendations for future use.

Practical implications

The paper summarizes the strategies and actions undertaken by organizations and destinations to improve competitiveness and comments on the practical implications.

Originality/value

The paper takes further the ideas put forward in the editorial and provides a concise analysis of how companies and destinations may improve their competitiveness by taken a sustainable and holistic approach to tourism development.
Achieving food security in China: past three decades and beyond
Authors: Zhou Zhangyue
Published: September 2010

Purpose

The paper aims to review and assess China's food security practice over the past three decades with a view of drawing implications for further improving its food security in the future.

Design/methodology/approach

A normative food security framework is used to assess China's food security achievements and examine any remaining and emerging issues in its pursuit for food security.

Findings

China has done well in achieving grain security in the past three decades. However, it cannot be concluded that China has achieved its food security according to the normative food security framework. This is because there are serious problems in the aspects of food safety and quality, environmental sustainability, and social stability. To achieve long‐term food security, China has to tackle the wide spread issues of unsafe foods and foods of dubious quality, environmental pollution and degradation, and the establishment of a social security system.

Originality/value

Examining China's food security practice over the past three decades can generate experiences and lessons valuable not only for China, but also for other developing countries in their efforts to achieving national food security. Issues are identified to which the Chinese government needs to pay attention in order to improve China's food security in the future.
The role of the state in making a national market
Authors: Zhou Wubiao
Published: September 2010

Purpose

The paper aims to examine Karl Polanyi's view of market evolution in the context of the emergence of a national grain market in China's transition economy.

Design/methodology/approach

The dataset used includes information about inter‐provincial grain trade on China's grain market from November 1999 to October 2000. A priori blockmodelling method is used for hypothesis testing.

Findings

This paper finds that a partially integrated national grain market had emerged at the beginning of the twenty‐first century in China in spite of local protectionism. Additionally, the emergence of this market is found to be partly a result of the reform‐oriented state's attempt to create national wholesale grain markets.

Originality/value

The findings of the paper might have implications for market development in both China and other transition economies.
Health and growth: causality through education
Authors: Huang Rui , Fulginiti Lilyan E. , Wesley F. Peterson E.
Published: September 2010

Purpose

The paper aims to theoretically and empirically investigate the impact on human capital investment decisions and income growth of lowered life expectancy as a result of HIV/AIDS and other diseases.

Design/methodology/approach

The theoretical model is a three‐period overlapping generations model where individuals go through three stages in their lives, namely, young, adult, and old. The model extends existing theoretical models by allowing the probability of premature death to differ for individuals at different life stages, and by allowing for stochastic technological advances. The empirical investigation focuses on the effect of HIV/AIDS on life expectancy and on the role of health in educational investments and growth. Potential endogeneity is addressed by using various strategies, such as controlling for country‐specific time‐invariant unobservables and by using the male‐circumcision rate as an instrumental variable for HIV/AIDS prevalence.

Findings

The paper shows theoretically that an increased probability of premature death leads to less investment in human capital, and consequently slower growth. Empirically, the paper finds that HIV/AIDS has resulted in a substantial decline in life expectancy in African countries and these falling life expectancies are indeed associated with lower educational attainment and slower economic growth world wide.

Originality/value

The theoretical and empirical findings reveal a causal link flowing from health to growth, which has been largely overlooked by the existing literature. The main implication is that health investments that decrease the incidence of diseases like HIV/AIDS resulting in increases in life expectancy through their complementarity with human capital investments lead to long run growth.
The diminishing influences of agricultural output changes on general price changes in China
Authors: Liu Xiaoyun , Luo Wanchun , Mao Xuefeng , Wang Xiuqing , Xin Xian
Published: September 2010

Purpose

The paper aims to assess the impact of agricultural output changes on the general price level over time with China as an example.

Design/methodology/approach

A simple numerical global general equilibrium (GE) model of two regions (China and the rest of the world) and three commodities (agriculture, manufacturing goods, and services) is used to assess the impacts of agricultural output changes on the overall economy price changes. The numerical GE model of this paper consists of production, final consumption, and market clear conditions. The results are generated with the GE model calibrated to aggregated China's input‐output tables of 1987, 1997, and 2005.

Findings

The results suggest that China witnessed a declining influence of agricultural output changes on general price changes. The contribution of given agricultural output change on the general price change in 2005 was merely less than 60 percent of that in 1987, which in turn implies that macro policies targeting to curb general inflation via boosting agricultural output will be less effective as those of 20 years ago.

Practical implications

China's policy makers should rely less and less on promoting agricultural output policies to fight against general inflation and should resort to non‐agricultural policies.

Originality/value

The paper argues that the influence of agriculture on the China's general price indices has been weakening along with China's economic development with a numerical GE model calibrated to aggregated China's input‐output tables of 1987, 1997, and 2005.
Anthropological and clinical implications for the structural diversity of the Helicobacter pylori CagA oncoprotein
Authors: Hatakeyama Masanori
Published: September 2010

Helicobacter pylori CagA is the first bacterial oncoprotein to be identified in relation to human cancer. CagA is delivered into gastric epithelial cells through a bacterial type IV secretion system and localizes to the plasma membrane, where it undergoes tyrosine phosphorylation by host cell kinases. Membrane‐localized CagA then mimics mammalian scaffold proteins and perturbs a number of host signaling pathways in both tyrosine phosphorylation‐dependent and ‐independent manners, thereby promoting transformation of gastric epithelial cells. Helicobacter pylori CagA is noted for structural diversity in its C‐terminal region, with which CagA interacts with numerous host cell proteins. This CagA polymorphism is primarily due to differential combination and alignment of the four distinct EPIYA segments and the two different CagA‐multimerization sequences in making the C‐terminal region. The structural diversity substantially influences the pathophysiological action of CagA. This review focuses on the molecular basis for the structural polymorphism that determines the degrees of virulence and oncogenic potential of individual CagA. The pylogeographic distribution of differential CagA isoforms is also discussed in the context of human migration history, which may underlie large geographical variations in the incidence of gastric cancer in different parts of the world. (Cancer Sci 2011; 102: 36–43)
BPR0C261 is a novel orally active antitumor agent with antimitotic and anti‐angiogenic activities
Authors: Hu Chih‐Bo , Chen Ching‐Ping , Yeh Teng‐Kuang , Song Jen‐Shin , Chang Chi‐Yen , Chuu Jiunn‐Jye , Tung Fei‐Feng , Ho Pei‐Yin , Chen Tung‐Wei , Lin Chi‐Hung , Wang Min‐Hsien , Chang Kai‐Yen , Huang Chen‐Lung , Lin Heng‐Liang , Li Wen‐Tai , Hwang Der‐Ren , Chern Jyh‐Haur , Hwang Ling‐Ling , Chang Jang‐Yang , Chao Yu‐Sheng , Chen Chiung‐Tong
Published: September 2010

BPR0C261 is a synthetic small molecule compound cytotoxic against human cancer cells and active prolonging the lifespan of leukemia mice. In the present study, we further investigated the mechanisms of its anticancer action and found that BPR0C261 inhibited microtubule polymerization through interacting with the colchicine binding sites on tubulins, disrupted microtubule arrangement and caused cell cycle arrest at G2/M phase in cancer cells. BPR0C261 also inhibited the clonogenic growths of cancer cells and showed cytotoxicity against human cervical cancer cells of multidrug‐resistant phenotype. In addition, BPR0C261 concentration‐dependently inhibited the proliferation and migration of HUVECs and disrupted the endothelial capillary‐like tube formations in HUVEC and rat aorta ring cultures. Given orally, BPR0C261 inhibited angiogenesis in s.c. implanted Matrigel plugs in mice. Notably, its IC50 values against the endothelial cell growths were approximately 10‐fold lower than those against the cancer cells. It was found orally absorbable in mice and showed a good oral bioavailability (43%) in dogs. BPR0C261 permeated through the human intestinal Caco‐2 cell monolayer, suggesting oral availability in humans. Orally absorbed BPR0C261 distributed readily into the s.c. xenografted tumors in nude mice in which the tumor tissue levels of BPR0C261 were found oral dose‐dependent. BPR0C261 showed in vivo activities against human colorectal, gastric, and nasopharyngeal tumors in nude mice. Most interestingly, the combination of BPR0C261 plus cisplatin synergistically prolonged the lifespans of mice inoculated with murine leukemia cells. Thus, BPR0C261 is a novel orally active tubulin‐binding antitumor agent with antimitotic, apoptosis‐inducing, and vasculature disrupting activities. (Cancer Sci 2011; 102: 182–191)
Differentiation of bone marrow‐derived mesenchymal stem cells into hepatocyte‐like cells in an alginate scaffold
Authors: Lin N. , Lin J. , Bo L. , Weidong P. , Chen S. , Xu R.
Published: September 2010

Objectives:  Alginate scaffolds are the most frequently investigated biomaterials in tissue engineering. Tissue engineering techniques that generate liver tissue have become important for treatment of a number of liver diseases and recent studies indicate that bone marrow‐derived stem cells (BMSCs) can differentiate into hepatocyte‐like cells. The goal of the study described here, was to examine in vitro hepatic differentiation potential of BMSCs cultured in an alginate scaffold.

Materials and methods:  To investigate the potential of BMSCs to differentiate into hepatocyte‐like cells, we cultured BMSCs in alginate scaffolds in the presence of specific growth factors including hepatocyte growth factor, epidermal growth factor and fibroblast growth factor‐4.

Results:  We can demonstrate that alginate scaffolds are compatible for growth of BMSCs and when cultured in alginate scaffolds for several days they display several liver‐specific markers and functions. Specifically, they expressed genes encoding alpha‐foetoprotein, albumin (ALB), connexin 32 and CYP7A1. In addition, these BMSCs produced both ALB and urea, expressed cytokeratin‐18 (CK‐18) and were capable of glycogen storage. Percentage of CK‐18 positive cells, a marker of hepatocytes, was 56.7%.

Conclusions:  Our three‐dimensional alginate scaffolds were highly biocompatible with BMSCs. Furthermore, culturing induced their differentiation into hepatocyte‐like cells. Therefore, BMSCs cultured in alginate scaffolds may be applicable for hepatic tissue engineering.
Culture and in vitro hepatogenic differentiation of placenta‐derived stem cells, using placental extract as an alternative to serum
Authors: Shin K. S. , Lee H. J. , Jung J. , Cha D. H. , Kim G. J.
Published: September 2010

Objectives:  Translational research using adult stem cells derived from various tissues has been highlighted in cell‐based therapy. However, there are many limitations to using conventional culture systems of adult stem cells for clinically applicability, including limited combinations of cytokines and use of nutrients derived from animals. Here, we have investigated the effects of placental extract (PE) for culture of placenta‐derived stem cells (PDSCs) as well as their potential for hepatogenic differentiation.

Materials and methods:  Placental extract, extracted using water‐soluble methods, was used as a supplement for culture of PDSCs. Cell viability was determined using the MTT assay, and cytokine assay was performed using Luminex assay kit. Gene expression, indocyanine green (ICG) up‐take, PAS (Periodic Acid‐Schiff) staining and urea production were also analysed.

Results:  The placental extract contained several types of cytokine and chemokine essential for maintenance and differentiation of stem cells. Expression of stemness markers in PDSCs cultured with PE is no different from that of PDSCs cultured with foetal bovine serum (FBS). After hepatogenic differentiation, expression patterns for hepatocyte‐specific markers in PDSCs cultured with PE were consistent and potential for hepatogenic differentiation of PDSCs cultured with PE was similar to that of PDSCs cultured with FBS, as shown by PAS staining and urea production assays.

Conclusions:  Our findings revealed that placental extract could be used as a new component for culture of adult stem cells, as well as for development of human‐based medium, in translational research for regenerative medicine.
The role of inhibitor of DNA‐binding (Id1) in hyperproliferation of keratinocytes: the pathological basis for middle ear cholesteatoma from chronic otitis media
Authors: Hamajima Y. , Komori M. , Preciado D. A. , Choo D. I. , Moribe K. , Murakami S. , Ondrey F. G. , Lin J.
Published: September 2010

Objectives:  A hallmark of cholesteatoma is hyperproliferation of keratinocytes with abundant production of keratins in the middle ear under chronic inflammatory conditions. However, little is known about the driving force of cellular proliferation and keratin production of cholesteatomal matrix. The purpose of this study was to investigate the cellular proliferation and keratin production of keratinocytes under the influence of Id1, a candidate transcription factor to cell proliferation.

Materials and methods:  Keratinocytes were transfected with Id1 and the responses of keratinocytes to Id1 were studied by using cellular and molecular biologic methods.

Results:  Id1 positively contributed to the cell cycle progression and negatively to the p16Ink4a downregulation via the nuclear factor‐kappa B (NF‐κB)/cyclin D1 pathway. Id1 significantly increased the promoter activity of NF‐κB which, in turn, up‐regulated the expression of cyclin D1 and keratin 10 in keratinocytes. Specific NF‐κB inhibitors (pyrrolidine dithiocarbamate, PDTC), or dominant‐negative inhibitor (I kappa B alpha mutant, IκBαM) abrogated the Id1‐induced cell proliferation and keratin 10 production whereas p65, a subunit of the NF‐κB heterodimer and an enhancer of the NF‐κB activity, strengthened the Id1‐induced cell proliferation and keratin 10 production.

Conclusions:  Id1 contributed to hyperproliferation of keratinocytes via enhancement of cell cycle progression, removal of cell cycle inhibition, and simultaneously increased keratin production.
Chloroform extract from Moricandia arvensis inhibits growth of B16‐F0 melanoma cells and promotes differentiation in vitro
Authors: Skandrani I. , Pinon A. , Simon A. , Ghedira K. , Chekir‐Ghedira L.
Published: September 2010

Objectives:  Poor therapeutic results have been reported for treatment of malignant melanoma; therefore in this study we have investigated inhibitory capacity of ethyl acetate, chloroform (Chl) and methanol extracts from Moricandia arvensis on mouse melanoma (B16‐F0) and human keratinocyte (HaCaT) cell proliferation. Influence of Chl extract on percentage distribution in cell cycle phases and melanogenesis was also studied.

Material and methods:  Cell viability was determined at various periods using the MTT assay, and flow cytometry was used to analyse effects of Chl extract on progression through the cell cycle and apoptosis. In addition, amounts of melanin and tyrosinase were measured spectrophotometrically at 475 nm.

Results:  Chl extract exhibited significant anti‐proliferative activity after incubation with the two types of tumour skin cells. Morphological changes in B16‐F0 cells, accompanied by increase of tyrosinase activity, and of melanin synthesis were observed, which are markers of differentiation of malignant melanoma cells. Furthermore, cell cycle analysis revealed that B16‐F0 cells treated with Chl extract were arrested predominantly in G1 phase.

Conclusion:  Chl extract had the ability to reverse malignant melanoma cells from proliferative to differentiated state, thus providing a new perspective in developing novel strategies for prevention and treatment of malignant melanoma, possibly through consumption of the extract in an appropriate cancer prevention diet. Moreover, there is scope for the extract being introduced into cosmetic products as a natural tanning agent.
Combination of photodynamic therapy with aspirin in human‐derived lung adenocarcinoma cells affects proteasome activity and induces apoptosis
Authors: Chiaviello A. , Paciello I. , Postiglione I. , Crescenzi E. , Palumbo G.
Published: September 2010

Objectives:  Photodynamic treatment (PDT) of human lung carcinoma cells A549 (p53+/+) and H1299 (p53−/−) induces fast but transient stalling of proteasome activity. We have explored the possibility of prolonging this effect by combining PDT with drugs capable of sustaining the stall, and promote apoptosis of surviving cells. We show that aspirin can be used to accomplish this.

Materials and methods:  Cells were irradiated at doses ranging from 0.54 to 1.10 J cm−2, and subsequently were incubated with aspirin at either high (10 and 5 mm) or low concentration (2.5 and 1.5 mm). Photofrin concentration and incubation time were constant (2.5 μg/ml and 16 h). Under these conditions, we analysed cell viability, colony‐forming efficiency, cycle profile, expression patterns of specific proteins and ubiquitination state, after individual or combined administration.

Results:  Treatment with either PDT or aspirin, rapidly induced proteasome malfunction and accumulation of cells in G2M, but did not induce apoptosis. However, when aspirin was added to cells (even at low concentrations) after PDT, the proteasome block was sustained. Moreover, significant cytotoxic effects, including apoptosis, were observed along with cytostatic effects (G2M accumulation/decreased colony formation).

Conclusions:  Combination of PDT and low‐toxicity drugs (such as aspirin) resulted in protracted inhibition of proteasome activity and induced apoptosis even in apoptosis‐resistant cancer cells.
17β‐oestradiol acts as a negative modulator of insulin‐induced lactotroph cell proliferation through oestrogen receptor alpha, via nitric oxide/guanylyl cyclase/cGMP
Authors: Gutiérrez S. , Petiti J. P. , Sosa L. d V. , Fozzatti L. , De Paul A. L. , Masini‐Repiso A. M. , Torres A. I.
Published: September 2010

Objectives:  17β‐oestradiol interacts with growth factors to modulate lactotroph cell population. However, contribution of isoforms of the oestrogen receptor in these activities is not fully understood. In the present study, we have established participation of α and β oestrogen receptors in effects of 17β‐oestradiol on lactotroph proliferation induced by insulin and shown involvement of the NO/sGC/cGMP pathway.

Materials and methods:  Cell cultures were prepared from anterior pituitaries of female rats to evaluate lactotroph cell proliferation using bromodeoxyuridine (BrdUrd) detection, protein expression by western blotting and cGMP by enzyme immunoassay.

Results:  In serum‐free conditions, 17β‐oestradiol and α and β oestrogen receptor agonists (PPT and DPN) failed to increase numbers of lactotroph cells undergoing mitosis. Co‐incubation of 17β‐oestradiol/insulin and PPT/insulin significantly decreased lactotroph mitogenic activity promoted by insulin alone. Both ICI 182780 and NOS inhibitors (L‐NMMA and L‐NAME) induced reversal of the anti‐proliferative effect promoted by 17β‐oestradiol/insulin and PPT/insulin. Moreover, 17β‐oestradiol, PPT and insulin increased sGC α1 protein expression and inhibited β1, whereas co‐incubation of 17β‐oestradiol/insulin or PPT/insulin induced increases of the two isoforms α1 and β1. 17β‐oestradiol and insulin reduced cGMP production, while 17β‐oestradiol/insulin co‐incubation increased this cyclic nucleotide.

Conclusions:  Our results suggest that 17β‐oestradiol is capable of arresting lactotroph proliferation induced by insulin through ER α with participation of the signalling NO/sGC/cGMP pathway.
Proteomic analysis of 3T3‐L1 preadipocytes having a higher cell proliferation rate after treatment with low‐molecular‐weight silk fibroin peptides
Authors: Huang G. , Li G. , Chen H. , He Y. , Yao Q. , Chen K.
Published: September 2010

Objectives:  Previous studies have reported that fibroin peptides can be used in a new strategy for development of anti‐diabetic peptide drugs. In this study, we separated silk fibroin hydrolysates (SFH) containing silk fibroin peptides into four components according to their molecular weight and tested the effects of these together with three synthetic silk fibroin hexapeptides GAGAGS, GAGAGY, GAGAGA on cell proliferation of 3T3‐L1 preadipocytes. The aim of this study was to investigate protein expression profiles of 3T3‐L1 preadipocytes and those treated with SFH component Fraction I and the synthetic silk fibroin hexapeptide GAGAGS to be able to elucidate difference in protein expression between the 3T3‐L1 preadipocytes and those treated with fibroin peptides Fraction I and GAGAGS.

Materials and methods:  SFH was separated by dialysis. MTT assays were performed to test effects of SFH components and synthetic silk fibroin hexapeptides on 3T3‐L1 preadipocyte proliferation. We generated proteome maps using two‐dimensional gel electrophoresis and analysed them by peptide mass fingerprinting.

Results:  GAGAGS and peptide mixtures, Fraction I and Fraction II, had significant effect in promoting 3T3‐L1 preadipocyte proliferation. In the proteomic analysis, 73 protein spots were successfully identified, including 15 which were differentially expressed.

Conclusions:  Our results show that some silk fibroin peptides of low molecular weight SFH and hexapeptide GAGAGS affected 3T3‐L1 preadipocyte proliferation.
Transcriptionally active nuclei are selective in mature multinucleated osteoclasts
Authors: Youn Min‐Young , Takada Ichiro , Imai Yuuki , Yasuda Hisataka , Kato Shigeaki
Published: September 2010

Multinucleation is indispensable for the bone‐resorbing activity of mature osteoclasts. Although multinucleation is evident in mature osteoclasts and certain other cell types, putative regulatory networks among nuclei remain poorly characterized. To address this issue, transcriptional activity of each nucleus in a multinucleated osteoclast was assessed by detecting the distributions of nuclear proteins by immunocytochemistry and primary transcripts by RNA FISH. Patterns of epigenetic histone markers governing transcription as well as localization of tested nuclear receptor proteins appeared indistinguishable among nuclei in differentiated Raw264 cells and mouse mature osteoclasts. However, RNAPII‐Ser5P/2P and NFATc1 proteins were selectively distributed in certain nuclei in the same cell. Similarly, the distributions of primary transcripts for osteoclast‐specific genes (Nfatc1, Ctsk and Acp5) as well as a housekeeping gene (beta‐tubulin) were limited in certain nuclei within individual cells. By fusing two Raw264 cell lines that stably expressed ZsGreen‐NLS and DsRed‐NLS proteins, transmission of nuclear proteins across all of the nuclei in a cell could be observed, presumably through the shared cytoplasm. Taken together, we conclude that although nuclear proteins are diffusible among nuclei, only certain nuclei within a multinucleated osteoclast are transcriptionally active.
Structural insights into the enzyme catalysis from comparison of three forms of dissimilatory sulphite reductase from Desulfovibrio gigas
Authors: Hsieh Yin‐Cheng , Liu Ming‐Yih , Wang Vincent C.‐C. , Chiang Yen‐Lung , Liu En‐Huang , Wu Wen‐guey , Chan Sunney I. , Chen Chun‐Jung
Published: September 2010

The crystal structures of two active forms of dissimilatory sulphite reductase (Dsr) from Desulfovibrio gigas, Dsr‐I and Dsr‐II, are compared at 1.76 and 2.05 Å resolution respectively. The dimeric α2β2γ2 structure of Dsr‐I contains eight [4Fe–4S] clusters, two saddle‐shaped sirohaems and two flat sirohydrochlorins. In Dsr‐II, the [4Fe–4S] cluster associated with the sirohaem in Dsr‐I is replaced by a [3Fe–4S] cluster. Electron paramagnetic resonance (EPR) of the active Dsr‐I and Dsr‐II confirm the co‐factor structures, whereas EPR of a third but inactive form, Dsr‐III, suggests that the sirohaem has been demetallated in addition to its associated [4Fe–4S] cluster replaced by a [3Fe–4S] centre. In Dsr‐I and Dsr‐II, the sirohydrochlorin is located in a putative substrate channel connected to the sirohaem. The γ‐subunit C‐terminus is inserted into a positively charged channel formed between the α‐ and β‐subunits, with its conserved terminal Cysγ104 side‐chain covalently linked to the CHA atom of the sirohaem in Dsr‐I. In Dsr‐II, the thioether bond is broken, and the Cysγ104 side‐chain moves closer to the bound sulphite at the sirohaem pocket. These different forms of Dsr offer structural insights into a mechanism of sulphite reduction that can lead to S3O62−, S2O32− and S2−.
Charged residues in the cytoplasmic loop of MotA are required for stator assembly into the bacterial flagellar motor
Authors: Morimoto Yusuke V. , Nakamura Shuichi , Kami‐ike Nobunori , Namba Keiichi , Minamino Tohru
Published: September 2010

MotA and MotB form a transmembrane proton channel that acts as the stator of the bacterial flagellar motor to couple proton flow with torque generation. The C‐terminal periplasmic domain of MotB plays a role in anchoring the stators to the motor. However, it remains unclear where their initial binding sites are. Here, we constructed Salmonella strains expressing GFP‐MotB and MotA‐mCherry and investigated their subcellular localization by fluorescence microscopy. Neither the D33N and D33A mutations in MotB, which abolish the proton flow, nor depletion of proton motive force affected the assembly of GFP‐MotB into the motor, indicating that the proton translocation activity is not required for stator assembly. Overexpression of MotA markedly inhibited wild‐type motility, and it was due to the reduction in the number of functional stators. Consistently, MotA‐mCherry was observed to colocalize with GFP‐FliG even in the absence of MotB. These results suggest that MotA alone can be installed into the motor. The R90E and E98K mutations in the cytoplasmic loop of MotA (MotAC), which has been shown to abolish the interaction with FliG, significantly affected stator assembly, suggesting that the electrostatic interaction of MotAC with FliG is required for the efficient assembly of the stators around the rotor.
Conserved components, but distinct mechanisms for the placement and assembly of the cell division machinery in unicellular and filamentous ascomycetes
Authors: Seiler Stephan , Justa‐Schuch Daniela
Published: September 2010

Cytokinesis is essential for cell proliferation, yet its molecular description is challenging, because > 100 conserved proteins must be spatially and temporally co‐ordinated. Despite the high importance of a tight co‐ordination of cytokinesis with chromosome and organelle segregation, the mechanism for determining the cell division plane is one of the least conserved aspects of cytokinesis in eukaryotic cells. Budding and fission yeast have developed fundamentally distinct mechanisms to ensure proper nuclear segregation. The extent to which these pathways are conserved in multicellular fungi remains unknown. Recent progress indicates common components, but different mechanisms that are required for proper selection of the septation site in the different groups of Ascomycota. Cortical cues are used in yeast‐ and filament‐forming species of the Saccharomycotina clade that are established at the incipient bud site or the hyphal tip respectively. In contrast, septum formation in the filament‐forming Pezizomycotina species Aspergillus nidulans and Neurospora crassa seems more closely related to the fission yeast programme in that they may combine mitotic signals with a cell end‐based marker system and Rho GTPase signalling. Thus, significant differences in the use and connection of conserved signalling modules become apparent that reflect the phylogenetic relationship of the analysed models.
Helicobacter pylori HP0518 affects flagellin glycosylation to alter bacterial motility
Authors: Asakura Hiroshi , Churin Yuri , Bauer Bianca , Boettcher Jan Peter , Bartfeld Sina , Hashii Noritaka , Kawasaki Nana , Mollenkopf Hans J. , Jungblut Peter R. , Brinkmann Volker , Meyer Thomas F.
Published: September 2010

Helicobacter pylori is a human gastric pathogen associated with gastric and duodenal ulcers as well as gastric cancer. Mounting evidence suggests this pathogen's motility is prerequisite for successful colonization of human gastric tissues. Here, we isolated an H. pylori G27 HP0518 mutant exhibiting altered motility in comparison to its parental strain. We show that the mutant's modulated motility is linked to increased levels of O‐linked glycosylation on flagellin A (FlaA) protein. Recombinant HP0518 protein decreased glycosylation levels of H. pylori flagellin in vitro, indicating that HP0518 functions in deglycosylation of FlaA protein. Furthermore, mass spectrometric analysis revealed increased glycosylation of HP0518 FlaA was due to a change in pseudaminic acid (Pse) levels on FlaA; HP0518 mutant‐derived flagellin contained approximately threefold more Pse than the parental strain. Further phenotypic and molecular characterization demonstrated that the hyper‐motile HP0518 mutant exhibits superior colonization capabilities and subsequently triggers enhanced CagA phosphorylation and NF‐κB activation in AGS cells. Our study shows that HP0518 is involved in the deglycosylation of flagellin, thereby regulating pathogen motility. These findings corroborate the prominent function of H. pylori flagella in pathogen–host cell interactions and modulation of host cell responses, likely influencing the pathogenesis process.
Bacillus subtilis MreB paralogues have different filament architectures and lead to shape remodelling of a heterologous cell system
Authors: Defeu Soufo Hervé Joël , Graumann Peter L.
Published: September 2010

Like many bacteria, Bacillus subtilis cells contain three actin‐like MreB proteins. We show that the three paralogues, MreB, Mbl and MreBH, have different filament architectures in a heterologous cell system, and form straight filaments, helices or ring structures, different from the regular helical arrangement in B. subtilis cells. However, when coexpressed, they colocalize into a single filamentous helical structure, showing that the paralogues influence each other's filament architecture. Ring‐like MreBH structures can be converted into MreB‐like helical filaments by a single point mutation affecting subunit contacts, showing that MreB paralogues feature flexible filament arrangements. Time‐lapse and FRAP experiments show that filaments can extend as well as shrink at both ends, and also show internal rearrangement, suggesting that filaments consist of overlapping bundles of shorter filaments that continuously turn over. Upon induction in Escherichia coli cells, B. subtilis MreB (BsMreB) filaments push the cells into strikingly altered cell morphology, showing that MreB filaments can change cell shape. E. coli cells with a weakened cell wall were ruptured upon induction of BsMreB filaments, suggesting that the bacterial actin orthologue may exert force against the cell membrane and envelope, and thus possibly plays an additional mechanical role in bacteria.
Report: Cutaneous disorders in uremic patients on hemodialysis: an Egyptian case‐controlled study
Authors: Attia Enas A. S. , Hassan Samah I. , Youssef Nagwa M.
Published: September 2010

Background  We studied the prevalence of mucocutaneous disorders in uremic adults and children on hemodialysis (HD) vs. controls, in Egypt.

Methods  A total of 206 Egyptians with uremia (163 adults and 43 children) undergoing HD, and 199 healthy controls (161 adults and 38 children), were examined for mucocutaneous abnormalities.

Results  Specific cutaneous diseases associated with renal insufficiency were found in five adults, including acquired perforating dermatosis and pseudo‐porphyria. Non‐specific abnormalities included xerosis (54%), pallor (42.2%), nail changes (34.9%), hair changes (34%), pruritus (32%), hyper‐pigmentation (22.2%), coated tongue (14.1%), ecchymosis (1.5%), and gingival hypertrophy (1.5%). Disorders found significantly more often in uremics than controls included pallor, nail changes, hair changes, pruritus, hyper‐pigmentation and coated tongue in adults (P < 0.05), and nail changes, hair changes, and hyper‐pigmentation in children (P < 0.05). The prevalence of each mucocutaneous abnormality was similar in uremic adults and children except for pallor [more common in adults (P = 0.001)], and hyper‐pigmentation [more common in children (P = 0.003)]. A greater number of hepatitis C virus‐positive than ‐negative adult uremics had hyper‐pigmentation (P < 0.05), and more diabetic uremics had pruritus than did non‐diabetics (P < 0.05).

Conclusion  Mucocutaneous disorders occur in adults and children with uremia, some of which are specific associations with the underlying renal disease. Occurrence of some of the non‐specific abnormalities, such as xerosis, ecchymosis, and gingival hypertrophy, may be coincidental or associated with factors other than renal insufficiency.
Review: Ultraviolet radiation and skin cancer
Authors: Narayanan Deevya L. , Saladi Rao N. , Fox Joshua L.
Published: September 2010

Skin cancer is the most common type of cancer in fair‐skinned populations in many parts of the world. The incidence, morbidity and mortality rates of skin cancers are increasing and, therefore, pose a significant public health concern. Ultraviolet radiation (UVR) is the major etiologic agent in the development of skin cancers. UVR causes DNA damage and genetic mutations, which subsequently lead to skin cancer. A clearer understanding of UVR is crucial in the prevention of skin cancer. This article reviews UVR, its damaging effects on the skin and its relationship to UV immunosuppression and skin cancer. Several factors influence the amount of UVR reaching the earth’s surface, including ozone depletion, UV light elevation, latitude, altitude, and weather conditions. The current treatment modalities utilizing UVR (i.e. phototherapy) can also predispose to skin cancers. Unnecessary exposure to the sun and artificial UVR (tanning lamps) are important personal attributable risks. This article aims to provide a comprehensive overview of skin cancer with an emphasis on carefully evaluated statistics, the epidemiology of UVR‐induced skin cancers, incidence rates, risk factors, and preventative behaviors & strategies, including personal behavioral modifications and public educational initiatives.
Review: Aquatic Sports Dematoses. Part 2 – In the Water: Saltwater Dermatoses
Authors: Tlougan Brook E. , Podjasek Joshua O. , Adams Brian B.
Published: September 2010

The second part of this three‐part series on water‐related dermatoses will discuss dermatologic conditions seen in athletes exposed to saltwater. The vast majority of the following dermatoses result from contact with organisms that inhabit saltwater, including bacteria, cnidarians, and echinoderms. This review also will include other dermatoses affecting saltwater athletes and should serve as a guide for dermatologists, sports medicine physicians, and other medical practitioners in recognition and treatment of these dermatoses.
Clinicopathologic challenge: Erythematous and edematous eruption of the face
Authors: Oon Hazel H. , Lim Kar Seng , Chong Wei‐Sheng , Tan Suat Hoon
Published: September 2010

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Pharmacology and therapeutics: Neutrophil elastase promotes proliferation of HaCaT cell line and transwell psoriasis organ culture model
Authors: Yang Xichuan , Yan Heng , Zhai Zhifang , Hao Fei , Ye Qingyi , Zhong Baiyu
Published: September 2010

Background  Neutrophil elastase (NE) plays an important role in psoriasis. In this study we observed the effect of NE on the proliferation of HaCaT cells and transwell psoriasis organ culture model and investigated the mechanism.

Methods  HaCaT cells were treated with various concentrations NE (0, 0.1, 1, 10, 100 IU/l). In addition, the cells were co‐stimulated with 10 IU/l NE and 1 g/l sivelestat. Then, HaCaT cells proliferation and DNA synthesis were determined using methyl thiazolyl tetrazolium (MTT) and tritiated thymidine (3H‐TdR) assay respectively. Cell cycle distribution was measured using fluorescence activated cell sorting (FACS). Subsequently, we established cultured transwell psoriasis organ model in vitro. Then, the cultured transwell psoriasis organ model was treated with 10 IU/l NE. Immunohistochemistry was employed to detect the expression levels of Ki67 and p53 in the cultured transwell psoriasis organ model.

Results  MTT and 3H‐TdR incorporation assay suggested NE could remarkably promote the proliferation and DNA synthesis of HaCaT cell in a dose‐dependent manner. After NE treatment (10 IU/l) for 24 h, the cell fraction of HaCaT cell in G2 + S phase was increased significantly, whereas the cell fraction in G1 phase was reduced remarkably. Immunohistochemistry results revealed enhanced expression of both Ki67 and p53 genes in cultured transwell psoriasis organ model after NE treatment.

Conclusions  NE significantly promotes the proliferation of HaCaT cell. Meanwhile, it also up‐regulates the expression levels of Ki67 and p53 in psoriasis lesion tissue, which plays an important role in the pathogenesis of psoriasis lesion.
Clinical trial: Reliability and validity of the Arabic version of “dermatitis family impact” questionnaire in children with atopic dermatitis
Authors: Al Robaee Ahmad A.
Published: September 2010

The aim of this study was to develop an Arabic version of the original English version of Dermatitis Family Impact (DFI) questionnaire and to evaluate its reliability and validity among Saudi families having children with atopic dermatitis (AD). Participants were 379 families of affected pediatric patients with AD diagnosed by consultant dermatologists in addition to a control group of 124 parents, who denied the presence of any dermatologic disorders in their children. To develop an Arabic version of the DFI, rigorous international guidelines for translation‐back‐translation were followed. In addition, reliability and validity were evaluated by calculating Cronbach’s alpha and correlation coefficients. Construct validity was assessed by comparing individual items and total scores among various case severity groups and controls. Cronbach’s alpha (=0.90) was acceptable. The inter‐item, item‐total score and item‐severity correlations ranged from moderate to high and were statistically significant (∼0.60, P‐values <0.001). The distribution of item responses evaluated by the ceiling and floor effects showed appropriate proportions and a good discrimination between cases and controls and between severity groups. The DFI scale scores (Mean ± SD) were 3.0 ± 1.50 for control, 9.6 ± 2.88 for mild, 14.67 ± 2.27 for moderate and 18.14 ± 2.0 for severe cases (P < 0.001). The results of this study showed that our translated Arabic version of the DFI is an efficient tool in terms of its reliability and validity for the measurement of the disease impact in families with AD.