bluuebunny/crossref_metadata_2025 huggingface dataset:
A consideration of recovery of prolongation costs in a construction context
Authors: Champion Ronan
Published: October 2011

Purpose

The purpose of this paper is to review the principles for valuation and proof of contractor's claims for additional site overheads arising from delays to completion of construction projects.

Design/methodology/approach

An overview of prolongation costs and established principles for recovery is provided. Aspects of recent decisions are analysed critically with respect to proof of delay claims, site overheads and claims for winter working losses. Findings are compared with the established principles.

Findings

Some statements in the judgment in Costain v. Haswell [2010] TCLR 1 with respect to requirements for proof of delay claims and for recovery of site overheads depart from established principles. Other elements of the judgment confirm existing principles. The need to distinguish between time‐ and volume‐related costs emerges as critical in valuation of delay‐related losses.

Practical implications

The need for a claimant to establish proof of delays to completion, and proof of loss, particularly in professional negligence claims, is emphasised. The consequences of failing to establish proof are noted as extending potentially to loss of the entire claim.

Originality/value

The paper will help construction practitioners, academics and lawyers understand the potentially far‐reaching impact of the principles advocated in recent case law.
New homes and consumer rights: England and Australia compared
Authors: Britton Philip , Bailey Julian
Published: October 2011

Purpose

The purpose of this paper is to contrast consumer laws in England and Australia in relation to residential building projects, and considers how the laws of England may be improved in light of the Australian laws.

Design/methodology/approach

The paper reviews consumer laws in both England and Australia, and examines the measures that are in place (or not) to protect consumers who engage builders or purchase a home that contains latent defects.

Findings

After comparing the laws of the two countries, the conclusion is made that English law could be improved by imposing regulations on builders, including by mandating the use of written contracts for building work which are required to contain particular terms, requiring builders to be licensed and insured, and by introducing a consumer‐friendly form of dispute resolution for home building disputes.

Practical implications

The paper recommends that there be law reform in England.

Originality/value

The paper provides (so far as the authors are aware) the first comparison of English and Australian consumer laws in relation to residential building work.
Business and social entrepreneurs in the UK: gender, context and commitment
Authors: Levie Jonathan , Hart Mark
Published: October 2011

Purpose

The purpose of this paper is to investigate what sort of people become social entrepreneurs, and in what way they differ from business entrepreneurs. More importantly, to investigate in what socio‐economic context entrepreneurial individuals are more likely to become social than business entrepreneurs. These questions are important for policy because there has been a shift from direct to indirect delivery of many public services in the UK, requiring a professional approach to social enterprise.

Design/methodology/approach

Evidence is presented from the Global Entrepreneurship Monitor (GEM) UK survey based upon a representative sample of around 21,000 adults aged between 16 and 64 years interviewed in 2009. The authors use logistic multivariate regression techniques to identify differences between business and social entrepreneurs in demographic characteristics, effort, aspiration, use of resources, industry choice, deprivation, and organisational structure.

Findings

The results show that the odds of an early‐stage entrepreneur being a social rather than a business entrepreneur are reduced if they are from an ethnic minority, if they work ten hours or more per week on the venture, and if they have a family business background; while they are increased if they have higher levels of education and if they are a settled in‐migrant to their area. While women social entrepreneurs are more likely than business entrepreneurs to be women, this is due to gender‐based differences in time commitment to the venture. In addition, the more deprived the community they live in, the more likely women entrepreneurs are to be social than business entrepreneurs. However, this does not hold in the most deprived areas where we argue civic society is weakest and therefore not conducive to support any form of entrepreneurial endeavour based on community engagement.

Originality/value

The paper's findings suggest that women may be motivated to become social entrepreneurs by a desire to improve the socio‐economic environment of the community in which they live and see social enterprise creation as an appropriate vehicle with which to address local problems.
Motherhood and entrepreneurship: gender role identity as a resource
Authors: Leung Aegean
Published: October 2011

Purpose

The purpose of this paper is to consider gender role identity as an informal institution shaping female entrepreneurship, and to illuminate the dual effects of institutions as constraining and enabling forces.

Design/methodology/approach

The paper examines the context of female entrepreneurship in Japan, and highlights the importance of “motherhood” for Japanese women. Outlining the institutional context of gender role and female entrepreneurship, and using two case studies of Japanese female entrepreneurs as illustrative examples, the paper explores how gender role identity can be viewed as a core element driving female entrepreneurship. Drawing on institutional theory and the “role as resource” perspective, a set of propositions are advanced on linkages between gender role identity and female entrepreneurship.

Findings

The findings suggest that a strong identification with their family roles, in particular the role as a mother, lead Japanese women onto the entrepreneurial path. A strong gender role identity is also reflected in the identity of the ventures, the products and services provided by these ventures, and their organizational structure and practices.

Research limitations/implications

This study represents an initial attempt to explore how female entrepreneurs can leverage their gender role identity in creating a unique configuration for their ventures that represents a fit to their identity as mothers.

Originality/value

Instead of viewing gender role identity one‐sidedly as a constraint, the case‐study‐based conceptual arguments advanced are employed to develop a more balanced perspective on motherhood as being an enabling factor in female entrepreneurship.
Seismic vulnerability of the health infrastructure in the Himalayan township of Mussoorie, Uttarakhand, India
Authors: Rautela Piyoosh , Chandra Joshi Girish , Bhaisora Bhupendra
Published: October 2011

Purpose

The purpose of this paper is to attempt to assess the seismic vulnerability of the built environment in the Himalayan township of Mussoorie in the state of Uttarakhand (India), paying specific attention to hospitals. Also an attempt is made to assess the magnitude of minimum economic losses, so as to design and undertake measures for reducing human misery in the event of a major disaster.

Design/methodology/approach

Seismic vulnerability of the building stock is evaluated using FEMA technique rapid visual screening and the likely earthquake induced damage is depicted as a function of the damage grades of the European Macroseismic Scale (EMS‐98). In total, 3,344 buildings, including 14 hospitals, are surveyed. In the field the structures are mapped using IKONOS satellite imagery while the collected data are analysed under geographic information system environment.

Findings

It was found that 18 percent of surveyed structures fall in high probability of Grade 5 damage and very high probability of Grade 4 damage class. This is estimated to result in economic loss of US$52.47 million. Almost, 80 percent of the hospitals of Mussoorie are thus likely to be non‐functional in the post‐earthquake phase due to varying degrees of structural and non‐structural damage.

Research limitations/implications

The study does not account for the cost of demolition or ground clearance cost for reconstruction, or losses likely to be incurred by public infrastructure. Thus, it is implied that retrofitting and replacement of vulnerable healthcare infrastructure should be facilitated on a priority basis along with development of suitable plans for mitigating losses in an earthquake event.

Practical implications

The study brings forth the importance of corrective actions (retrofitting/replacement) and detailed vulnerability assessment of all lifeline structures on priority basis.

Social implications

The results are intended to reduce seismic vulnerability and human toll in the event of any earthquake in the area.

Originality/value

The work is based upon the original data generated by the authors through rigorous fieldwork in the area and the results are totally based on these.
Climate change risks and opportunities in hospital adaptation
Authors: Loosemore Martin , Carthey Jane , Chandra Venny , Mirti Chand Anumitra
Published: October 2011

Purpose

The future of healthcare delivery will depend in part on the adaptive capacity of hospital infrastructure required to respond to the predicted physical and health‐related impacts of climate change. The purpose of this paper is to assess the vulnerabilities and opportunities of existing hospital facilities faced with climate‐related extreme weather events and to identify adaptive strategies that will enable existing hospital facilities to assist rather than hinder healthcare continuity and quality during these events.

Design/methodology/approach

Four major hospitals in Australia and New Zealand, significantly exposed to climate change‐associated extreme weather event risks, were selected as case studies. A risk management workshop was conducted for each case study using the risk and opportunity management system methodology.

Findings

The preliminary findings identified several key objectives associated with responding to the impact of extreme weather events on healthcare infrastructure. Assuming the overall aim of ensuring continuity of service delivery, the common objectives are: guaranteeing the availability of essential (building) services; maintaining the physical integrity of the hospital; supporting effective inter‐agency communication; and providing access to and from the hospital for staff and patients.

Research limitations/implications

Given Australia's relatively high exposure to climate extremes, the social, economic and health benefits of developing hospital adaptation strategies to mitigate risks and maximize opportunities in responding are significant.

Practical implications

The outcomes of this research will contribute to a growing evidence base of design and facilities management adaptation strategies for hospitals susceptible to increasing risks of extreme weather events.

Originality/value

The paper presents the first assessment of climate vulnerabilities and opportunities for hospital facilities in Australia and New Zealand.
Disaster risk reduction for health facilities in the Western Pacific Region
Authors: Sam A. Geroy Lester , Pesigan Arturo M.
Published: October 2011

Purpose

The purpose of this paper is to present a qualitative report on the implementation of activities aimed at reducing disaster risks through safer health facilities in the Western Pacific region.

Design/methodology/approach

In response to the Global Campaign on Hospitals Safe from Disasters 2008‐2009, the World Health Organization, with support from the European Commission, provided tools that enabled government, communities and institutions to reduce the risks of their hospitals and health facilities from disasters due to natural hazards. Target countries included Cambodia, Lao PDR, the Philippines and Viet Nam. Different activities were implemented based on country needs, contexts and capacities.

Findings

Hospital assessments revealed gaps in infrastructure, essential emergency equipment and functional capacity. Enhancing preparedness and resilience of health facilities is a vital component to ensure risk mitigation and disaster response in communities.

Research limitations/implications

The report calls for further studies on specific gaps in health sector capacity, deficiencies in health infrastructure and economic analysis.

Practical implications

The health sector should implement disaster risk reduction and preparedness strategies through the support of local and national governments.

Originality/value

This is the first report on risk reduction initiatives in the health sector in developing countries in the region. Written at the regional perspective, it engages national and local governments, health policy makers and health facility administrators in the public and private sectors.
Today becomes tomorrow
Authors: Tilbury Daniella , Ryan Alexandra
Published: October 2011

Purpose

The present preoccupations of businesses and business educators include the increasing global debt, rising unemployment and expanding carbon footprints, and the societal and governmental pressures to minimise the impact of these challenges. Meanwhile, the urge towards technical fixes and problem solving is shaping the way that business is done today and constraining business practices for tomorrow. The repercussions for business education are serious and systemic, as these responses neglect the need to critically question, innovate and rethink business futures, through our educational processes. The purpose of this paper is to provide context and orientation to this special issue collection which showcases current thinking and practice in higher education aimed at addressing this predicament and finding new responses.

Design/methodology/approach

This paper offers a critical review of developments geared towards more sustainable and responsible forms of business education and practice. It takes an inclusive view of “sustainability” that embraces issues such as poverty and inequality, environmental degradation, human rights and access to resources. The concept reaches beyond the practice of “corporate social responsibility” to take into account the complex challenge of reorienting business practice to improve development processes and life chances worldwide, in the context of the inevitable limits to planetary resources.

Findings

The paper considers the influences of international movements in ushering in a vision of learning for sustainability in business education. It discusses challenges that have come to light through recent initiatives and in literature on curriculum innovation in this area. The paper calls for a re‐envisioning of business practice, education and learning which goes beyond remedies for current symptoms of unsustainable development and unmasks the need to reconnect business with people and planet.

Originality/value

This paper foregrounds lessons learned from several areas of thought and practice that have bearing on the communities of practice for business education. It frames and situates the contributions presented in this collection, exploring upcoming agendas in this critically important field.
Criticality by stealth: embedding tools for sustainability in the business curriculum
Authors: Redding Peter , Cato Molly Scott
Published: October 2011

Purpose

The purpose of this paper is to provide a case study which illustrates how specific skills can be embedded within an undergraduate business module thereby promoting wider criticality and an ethos of sustainability.

Design/methodology/approach

The paper analyses a pragmatic approach to redesigning a third‐year undergraduate module on twenty‐first century business topics such as globalisation and sustainability in which students acquire subject‐specific knowledge as well as the tools necessary for challenging current approaches. The redesign was guided by a series of emergent paradigms within the pedagogical literature, including student‐centred learning, emphasis on skills development and elements of the critical management perspective. “Questioning perceived wisdom” became the subtext for a series of activities linked to continuous assessment. Action research provided a basis for curricular development, and resulted in lectures with multiple viewpoints and a variety of weekly tasks including analyses of in‐class debates, surveys, and online discussions in small groups. The new structure also sought to address instrumental attitudes and student engagement. Rich qualitative and quantitative data were generated from the surveys, discussion groups, exam scripts and student feedback.

Findings

Data show that students responded well to those activities which implicitly reinforced the skills of “questioning” and judgement based on evidence. The increased engagement may be due to incentivisation of the chosen assessment structure and/or the heuristic nature of the varied activities.

Originality/value

This paper invites practitioners to shift away from “teaching” sustainability or criticality as an intellectual topic, and rather to concentrate more on creating those experiential opportunities where the student can develop the skills to question current dogma, whether neo‐liberalism or even environmental fundamentalism.
Responsibility and integrity in the curriculum
Authors: Robinson Simon , Dowson Paul
Published: October 2011

Purpose

The purpose of this paper is to examine the meaning of responsibility and how it might be integrated into the business school and university curriculum.

Design/methodology/approach

The paper analyses responsibility in terms of interactive modes, involving imputability (critical agency connecting culture and meaning, through reflection on purpose, values and practice), accountability (involving capacity to give an account and to handle plural accountability), and moral liability (involving responsibility for people, environment and practice, requiring shared and negotiated responsibility). This is related to employability and integrity, and then to practice in the curriculum.

Findings

The paper argues that the theory and practice of responsibility is able to integrate cognate concepts, different disciplines, different skills and dispositions and plural roles. The paper then argues that responsibility is most effectively engaged through a pedagogy of reflective practice and critical conversation, focused in personal, professional, civil, corporate and global responsibility, and provides a practical example.

Originality/value

The paper is original in the breadth of its view of responsibility, the stress on responsibility as focused in plurality and identity, and in the attempt to develop an integrated approach to teaching that focuses on responsibility.
PEST‐domain‐enriched tyrosine phosphatase and glucocorticoids as regulators of anaphylaxis in mice
Authors: Obiri D. D. , Flink N. , Maier J. V. , Neeb A. , Maddalo D. , Thiele W. , Menon A. , Stassen M. , Kulkarni R. A. , Garabedian M. J. , Barrios A. M. , Cato A. C. B.
Published: October 2011

To cite this article: Obiri DD, Flink N, Maier JV, Neeb A, Maddalo D, Thiele W, Menon A, Stassen M, Kulkarni RA, Garabedian MJ, Barrios AM, Cato ACB. PEST‐domain‐enriched tyrosine phosphatase and glucocorticoids as regulators of anaphylaxis in mice. Allergy 2012; 67: 175–182.

Background:  PEST‐domain‐enriched tyrosine phosphatase (PEP) is a protein tyrosine phosphatase exclusively expressed in hematopoietic cells. It is a potent negative regulator of T‐cell receptor signalling that acts on receptor‐coupled protein tyrosine kinases. PEST‐domain‐enriched tyrosine phosphatase is also expressed in mast cell and is positively regulated by glucocorticoids, but its function is unknown. In this communication, the function of PEP is analysed in mast cells.

Methods:  Signal transduction cascades following IgE receptor cross‐linking were compared in bone marrow‐derived mast cells (BMMC) from PEP−/− and PEP+/+ mice. Furthermore, antigen‐induced passive systemic anaphylaxis (PSA) was analysed in PEP+/+ and PEP−/− mice.

Results:  Bone marrow‐derived mast cells from PEP−/− mice showed impaired PLCγ1 phosphorylation and Ca2+ mobilization. Additionally, mice deficient in PEP showed impaired mast cell degranulation and were less susceptible to PSA. Treatment of wild‐type BMMC or mice with an Au(I)–phosphine complex that selectively inhibits PEP activity produced defects in Ca2+ signalling pathway and reduced anaphylaxis similar to that caused by the deletion of the PEP gene. Glucocorticoid that negatively regulates a wide range of mast cell action increased PEP expression and only partially inhibited anaphylaxis. However, glucocorticoid potently inhibited anaphylaxis when combined with the PEP inhibitor.

Conclusions:  PEST‐domain‐enriched tyrosine phosphatase is an important positive regulator of anaphylaxis. Pharmacological inhibition of its activity together with glucocorticoid administration provide an effective rescue for PSA in mice.
Negative screening colonoscopy after a positive guaiac faecal occult blood test: not a contraindication to continued screening
Authors: Carrera A. , McClements P. L. , Watling C. , Libby G. , Weller D. , Brewster D. H. , Carey F. A. , Fraser C. G. , Steele R. J. C.
Published: October 2011

Aim  In guaiac faecal occult blood test (gFOBT) screening at least 50% of positive individuals will have a colonoscopy negative for colorectal neoplasia. The question of continuing screening in this group has not been addressed.

Method  Data on participants aged 50–69 years with a positive gFOBT result and a negative colonoscopy were followed through the biennial screening pilot conducted between 2000 and 2007 in Scotland.

Results  In the first screening round, 1527 colonoscopies were negative for neoplasia. 1300 were re‐invited in the second round, 905 accepted, and 157 had a positive gFOBT result, giving a positivity rate of 17.4%. Colonoscopy revealed 20 subjects with adenoma and six with invasive cancer. In the third screening round 1031 were invited for a third time and 730 accepted: 55 had a positive gFOBT test, giving a positivity rate of 7.5%. In this group, six colonoscopies revealed adenomas but there were no cancers diagnosed. In the third screening round, 108 individuals had had two positive gFOBT results and two subsequent negative colonoscopies. Eighty‐four were invited for a third gFOBT, 66 accepted and 19 (25.6%) had a positive result none of whom had an adenoma or carcinoma.

Conclusion  These data indicate that a negative colonoscopy following a positive gFOBT is not a contraindication for further screening, although this is likely to have a low yield of neoplastic pathology after two negative colonoscopies.
Adaptive responses to alloxan‐induced mild oxidative stress ameliorate certain tauopathy phenotypes
Authors: Yoshiike Yuji , Yamashita Shunji , Mizoroki Tatsuya , Maeda Sumihiro , Murayama Miyuki , Kimura Tetsuya , Sahara Naruhiko , Soeda Yoshiyuki , Takashima Akihiko
Published: October 2011

Oxidative stress is considered to promote aging and age‐related disorders such as tauopathy. Although recent reports suggest that oxidative stress under certain conditions possesses anti‐aging properties, no such conditions have been reported to ameliorate protein‐misfolding diseases. Here, we used neuronal and murine models that overexpress human tau to demonstrate that mild oxidative stress generated by alloxan suppresses several phenotypes of tauopathy. Alloxan treatment reduced HSP90 levels and promoted proteasomal degradation of tau, c‐Jun N‐amino terminal kinase, and histone deacetylase (HDAC) 6. Moreover, reduced soluble tau (phosphorylated tau) levels suppressed the formation of insoluble tau in tau transgenic mice, while reduced HDAC6 levels contributed to microtubule stability by increasing tubulin acetylation. Age‐dependent decreases in HDAC2 and phospho‐tau levels correlated with spatial memory enhancement in alloxan‐injected tau mice. These results suggest that mild oxidative stress, through adaptive stress responses, operates counteractively against some of the tauopathy phenotypes.
Dysregulated expression of miR‐146a contributes to age‐related dysfunction of macrophages
Authors: Jiang Minghong , Xiang Yang , Wang Dongsheng , Gao Jing , Liu Dan , Liu Yanxin , Liu Shilian , Zheng Dexian
Published: October 2011

Age‐associated immune dysfunction, characterized by increased systemic levels of cytokines, manifests as an increased susceptibility to infections. Thus, understanding these negative regulators of the immune response has paved the way to delineating signaling pathways that impact immune senescence. In the present study, we found that miR‐146a, which negatively regulated the expression of IL‐1β and IL‐6, was highly expressed in aged mice. However, there was a lack of response to the stimulation of lipopolysaccharide (LPS) and proinflammatory cytokines in macrophages of aged mice. As a result, the negative feedback regulation loop with miR‐146a involving down‐regulation of inflammation factors was interrupted in aged mice. Aberrant NF‐κB binding to the miR‐146a promoter was demonstrated to be associated with the abnormal expression of miR‐146a in aged mice. The DNA methyltransferase inhibitor (5‐aza‐2‐deoxycytidine) and the histone deacetylase inhibitor [trichostatin A (TSA)] both significantly up‐regulated miR‐146a transcriptional activation by altering the DNA‐binding activity of NF‐κB in macrophages isolated from aged mice, which suggests that DNA methylation and histone acetylation are involved in the suppression of age‐dependent miR‐146a expression. Additionally, high levels of histone deacetylase (HDACs) expressions contributed to the inhibition of miR‐146a expression in LPS‐stimulated macrophages from aged mice in vitro. While the suppression of HDACs activities by TSA could improve LPS‐induced inflammatory responses owing to up‐regulation of miR‐146a expression in macrophages from aged mice. These data indicate that the dysregulated expression of miR‐146a results in the age‐associated dysfunction of macrophages, and miR‐146a may be a good target for the treatment of age‐related inflammatory diseases.
Effects of long‐term use of antiretroviral therapy on the prevalence of oral Epstein–Barr virus
Authors: Amornthatree Korntip , Sriplung Hutcha , Mitarnun Winyou , Nittayananta Wipawee
Published: October 2011

J Oral Pathol Med (2012) 41: 249–254

Background:  The objectives of this study were to determine (i) the prevalence of oral Epstein–Barr virus (EBV) in HIV‐infected subjects compared to non‐HIV controls and (ii) the effects of long‐term use of antiretroviral therapy (ART) on the prevalence of oral EBV.

Methods:  A cross‐sectional study was performed in HIV‐infected subjects with and without ART, and non‐HIV individuals. DNA in saliva samples was extracted and used as a template to detect EBV BamH1W and EBNA1 by quantitative polymerase chain reaction. Student t‐test and ANOVA test were performed to determine the prevalence rates among groups.

Results:  Forty‐nine HIV‐infected subjects: 37 on ART (age range 23–54 year, mean 37 year), 12 not on ART (age range 20–40 year, mean 31 year), and 20 non‐HIV controls (age range 19–53 year, mean 31 year) were enrolled. The numbers of EBV BamH1W in saliva were found to be significantly higher in HIV‐infected subjects than non‐HIV controls (80% vs. 20%, mean = 12 118 vs. 134 copies/105 cells, P < 0.001). HIV‐infected subjects who were on ART had significantly lower numbers of EBV BamH1W than those who were not (mean = 4102 vs. 138 613 copies/105 cells, P = 0.011). The numbers were significantly lower in those who received long‐term ART compared with short‐term (mean = 1401 vs. 11 124 copies/105 cells, P = 0.034). No significant difference was observed between the groups when using EBNA1 primers.

Conclusions:  Prevalence of oral EBV was significantly higher in HIV‐infected subjects than non‐HIV‐controls. The numbers of the virus were significantly decreased by ART. Long‐term use of ART did not increase oral EBV.
A Comparison of the Efficacy of Newly Developed Reversible Inhibitors of Acetylcholinesterase with Commonly Used Pyridostigmine as Pharmacological Pre‐Treatment of Soman‐Poisoned Mice
Authors: Kassa Jiri , Musilek Kamil , Koomlova Marketa , Bajgar Jiri
Published: October 2011

Abstract:  The ability of three newly developed reversible inhibitors of acetylcholinesterase (AChE) (K298, K344 and K474) and currently available carbamate pyridostigmine to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman‐poisoned mice was compared. Neither pyridostigmine nor new reversible inhibitors of AChE were able to increase the LD50 value of soman. Thus, the pharmacological pre‐treatment with pyridostigmine or newly synthesized inhibitors of AChE was not able to protect mice against soman‐induced lethal acute toxicity. The pharmacological pre‐treatment with pyridostigmine alone or with K474 was able to slightly increase the efficacy of antidotal treatment (the oxime HI‐6 in combination with atropine) of soman‐poisoned mice, but the increase in the efficacy of antidotal treatment was not significant. The other newly developed reversible inhibitors of AChF (K298, K344) were completely ineffective. These findings demonstrate that pharmacological pre‐treatment of soman‐poisoned mice with tested reversible inhibitors of AChF is not promising.
Inhibition of coding region determinant binding protein sensitizes melanoma cells to chemotherapeutic agents
Authors: Craig Evisabel A. , Spiegelman Vladimir S.
Published: October 2011

We previously reported that malignant melanomas express high levels of the mRNA binding protein coding region determinant binding protein (CRD‐BP). This molecule is important for the activation of anti‐apoptotic pathways, a mechanism often linked to insensitivity to therapeutics. However, it is not known whether CRD‐BP plays a role in the resistance of melanomas to anti‐cancer treatment. Here we demonstrate that knockdown of CRD‐BP with a specific sh‐RNA enhances the effect of dacarbazine, temozolomide, vinblastine, and etoposide on both primary and metastatic melanoma cell lines. CRD‐BP down‐regulation contributes to cell sensitization by increasing apoptosis and diminishing melanoma cell growth in response to chemotherapeutic agents. Furthermore, inhibition of CRD‐BP decreases microphthalmia‐associated transcription factor (MITF) expression and reintroduction of MITF partially compensates for the absence of CRD‐BP. These findings suggest that high expression of CRD‐BP in melanoma cells confers resistance to chemotherapy and that these CRD‐BP responses are mediated, at least in part, by MITF.
The Dent Stage of Maize Kernels Is the Most Conducive for Fumonisin Biosynthesis under Field Conditions
Authors: Picot Adeline , Barreau Christian , Pinson-Gadais Laï¿½titia , Piraux Franï¿½ois , Caron Daniel , Lannou Christian , Richard-Forget Florence
Published: October 2011

The fungal pathogen
Fusarium verticillioides
infects maize ears and produces fumonisins, known for their adverse effects on human and animal health. Basic questions remain unanswered regarding the kernel stage(s) associated with fumonisin biosynthesis and the kernel components involved in fumonisin regulation during
F. verticillioides
-maize interaction under field conditions. In this 2-year field study, the time course of
F. verticillioides
growth and fumonisin accumulation in developing maize kernels, along with the variations in kernel pH and amylopectin content, were monitored using relevant and accurate analytical tools. In all experiments, the most significant increase in fumonisin accumulation or in fumonisin productivity (i.e., fumonisin production per unit of fungus) was shown to occur within a very short period of time, between 22/32 and 42 days after inoculation and corresponding to the dent stage. This stage was also characterized by acidification in the kernel pH and a maximum level of amylopectin content. Our data clearly support published results based on
in vitro
experiments suggesting that the physiological stages of the maize kernel play a major role in regulating fumonisin production. Here we have validated this result for
in planta
and field conditions, and we demonstrate that under such conditions the dent stage is the most conducive for fumonisin accumulation.
Wastewater Utilization for Poly-β-Hydroxybutyrate Production by the Cyanobacterium Aulosira fertilissima in a Recirculatory Aquaculture System
Authors: Samantaray Shilalipi , Nayak Jitendra Kumar , Mallick Nirupama
Published: October 2011

Intensive aquaculture releases large quantities of nutrients into aquatic bodies, which can lead to eutrophication. The objective of this study was the development of a biological recirculatory wastewater treatment system with a diazotrophic cyanobacterium,
Aulosira fertilissima
, and simultaneous production of valuable product in the form of poly-β-hydroxybutyrate (PHB). To investigate this possible synergy, batch scale tests were conducted under a recirculatory aquaculture system in fiber-reinforced plastic tanks enhanced by several manageable parameters (e.g., sedimentation, inoculum size, depth, turbulence, and light intensity), an adequate combination of which showed better productivity. The dissolved-oxygen level increased in the range of 3.2 to 6.9 mg liter
−1
during the culture period. Nutrients such as ammonia, nitrite, and phosphate decreased to as low as zero within 15 days of incubation, indicating the system's bioremediation capability while yielding valuable cyanobacterial biomass for PHB production. Maximum PHB accumulation in
A. fertilissima
was found in sedimented fish pond discharge at 20-cm culture depth with stirring and an initial inoculum size of 80 mg dry cell weight (dcw) liter
−1
. Under optimized conditions, the PHB yield was boosted to 92, 89, and 80 g m
−2
, respectively for the summer, rainy, and winter seasons. Extrapolation of the result showed that a hectare of
A. fertilissima
cultivation in fish pond discharge would give an annual harvest of ∼17 tons dry biomass, consisting of 14 tons of PHB with material properties comparable to those of the bacterial polymer, with simultaneous treatment of 32,640 m
3
water discharge.
Evaluation of Subsampling-Based Normalization Strategies for Tagged High-Throughput Sequencing Data Sets from Gut Microbiomes
Authors: Aguirre de Cárcer Daniel , Denman Stuart E. , McSweeney Chris , Morrison Mark
Published: October 2011

Several subsampling-based normalization strategies were applied to different high-throughput sequencing data sets originating from human and murine gut environments. Their effects on the data sets' characteristics and normalization efficiencies, as measured by several β-diversity metrics, were compared. For both data sets, subsampling to the median rather than the minimum number appeared to improve the analysis.
Characterization of the Poly-β-1,6-
N
-Acetylglucosamine Polysaccharide Component of Burkholderia Biofilms
Authors: Yakandawala Nandadeva , Gawande Purushottam V. , LoVetri Karen , Cardona Silvia T. , Romeo Tony , Nitz Mark , Madhyastha Srinivasa
Published: October 2011

We demonstrated the production of poly-β-1,6-
N
-acetylglucosamine (PNAG) polysaccharide in the biofilms of
Burkholderia multivorans
,
Burkholderia vietnamiensis
,
Burkholderia ambifaria
,
Burkholderia cepacia
, and
Burkholderia cenocepacia
using an immunoblot assay for PNAG. These results were confirmed by further studies, which showed that the PNAG hydrolase, dispersin B, eliminated immunoreactivity of extracts from the species that were tested (
B. cenocepacia
and
B. multivorans
). Dispersin B also inhibited biofilm formation and dispersed preformed biofilms of
Burkholderia
species. These results imply a role for PNAG in the maintenance of
Burkholderia
biofilm integrity. While PNAG was present in biofilms of all of the wild-type test organisms, a Δ
pgaBC
mutant of
B. multivorans
(Mu5) produced no detectable PNAG, indicating that these genes are needed for
Burkholderia
PNAG formation. Furthermore, restoration of PNAG production in PNAG negative
E. coli
TRXWMGΔC (Δ
pgaC
) by complementation with
B. multivorans pgaBCD
confirmed the involvement of these genes in
Burkholderia
PNAG production. While the confocal scanning laser microscopy of untreated wild-type
B. multivorans
showed thick, multilayered biofilm, Mu5 and dispersin B-treated wild-type biofilms were thin, poorly developed, and disrupted, confirming the involvement of PNAG in
B. multivorans
biofilm formation. Thus, PNAG appears to be an important component of
Burkholderia
biofilms, potentially contributing to its resistance to multiple antibiotics and persistence during chronic infections, including cystic fibrosis-associated infection.
In Vitro
Fermentation of Sugar Beet Arabino-Oligosaccharides by Fecal Microbiota Obtained from Patients with Ulcerative Colitis To Selectively Stimulate the Growth of Bifidobacterium spp. and Lactobacillus spp
Authors: Vigsn�s Louise Kristine , Holck Jesper , Meyer Anne S. , Licht Tine Rask
Published: October 2011

The potential prebiotic properties of arabino-oligosaccharides (AOS) derived from sugar beet pulp was studied using mixed cultures of human fecal bacteria from patients with ulcerative colitis (UC), in remission or with active disease, and in healthy controls. These results were compared to those for fructo-oligosaccharides (FOS), which are known to have a prebiotic effect. Fermentation studies were carried out using a small-scale static batch system, and changes in the fecal microbial communities and metabolites were monitored after 24 h by quantitative real-time PCR and short-chain fatty acid analysis. With a few minor exceptions, AOS affected the communities similarly to what was seen for FOS. Quantitative real-time PCR revealed that
Bifidobacterium
spp. and
Lactobacillus
spp. were selectively increased after fermentation of AOS or FOS by fecal microbiota derived from UC patients. The stimulation of growth of
Lactobacillus
spp. and
Bifidobacterium
spp. was accompanied by a high production of acetate and hence a decrease of pH. The fermentation of AOS may help improve the inflammatory conditions in UC patients through stimulation of bacteria eliciting anti-inflammatory responses and through production of acetate. AOS may therefore represent a new prebiotic candidate for reduction of the risk of flare-ups in UC patients. However, human trials are needed to confirm a health-promoting effect.
Quantitative PCR Enumeration of Total/Toxic Planktothrix rubescens and Total Cyanobacteria in Preserved DNA Isolated from Lake Sediments
Authors: Savichtcheva Olga , Debroas Didier , Kurmayer Rainer , Villar Clement , Jenny Jean Philippe , Arnaud Fabien , Perga Marie Elodie , Domaizon Isabelle
Published: October 2011

The variability of spatial distribution and the determinism of cyanobacterial blooms, as well as their impact at the lake scale, are still not understood, partly due to the lack of long-term climatic and environmental monitoring data. The paucity of these data can be alleviated by the use of proxy data from high-resolution sampling of sediments. Coupling paleolimnological and molecular tools and using biomarkers such as preserved DNA are promising approaches, although they have not been performed often enough so far. In our study, a quantitative PCR (qPCR) technique was applied to enumerate total cyanobacterial and total and toxic
Planktothrix
communities in preserved DNA derived from sediments of three lakes located in the French Alps (Lake Geneva, Lake Bourget, and Lake Annecy), containing a wide range of cyanobacterial species. Preserved DNA from lake sediments was analyzed to assess its quality, quantity, and integrity, with further application for qPCR. We applied the qPCR assay to enumerate the total cyanobacterial community, and multiplex qPCR assays were applied to quantify total and microcystin-producing
Planktothrix
populations in a single reaction tube. These methods were optimized, calibrated, and applied to sediment samples, and the specificity and reproducibility of qPCR enumeration were tested. Accurate estimation of potential inhibition within sediment samples was performed to assess the sensitivity of such enumeration by qPCR. Some precautions needed for interpreting qPCR results in the context of paleolimnological approaches are discussed. We concluded that the qPCR assay can be used successfully for the analysis of lake sediments when DNA is well preserved in order to assess the presence and dominance of cyanobacterial and
Planktothrix
communities.
Fate of Escherichia coli O26 in Corn Silage Experimentally Contaminated at Ensiling, at Silo Opening, or after Aerobic Exposure, and Protective Effect of Various Bacterial Inoculants
Authors: Dunière Lysiane , Gleizal Audrey , Chaucheyras-Durand Frédérique , Chevallier Isabelle , Thévenot-Sergentet Delphine
Published: October 2011

Shiga toxin-producing
Escherichia coli
(STEC) strains are responsible for human illness. Ruminants are recognized as a major reservoir of STEC, and animal feeds, such as silages, have been pointed out as a possible vehicle for the spread of STEC. The present study aimed to monitor the fate of pathogenic
E. coli
O26 strains in corn material experimentally inoculated (10
5
CFU/g) during ensiling, just after silo opening, and after several days of aerobic exposure. The addition of 3 bacterial inoculants,
Propionibacterium
sp.,
Lactobacillus buchneri
, and
Leuconostoc mesenteroides
(10
6
CFU/g), was evaluated for their abilities to control these pathogens. The results showed that
E. coli
O26 could not survive in corn silage 5 days postensiling, and the 3 inoculants tested did not modify the fate of pathogen survival during ensiling. In the case of direct contamination at silo opening,
E. coli
O26 could be totally eradicated from corn silage previously inoculated with
Leuconostoc mesenteroides
. The combination of proper ensiling techniques and the utilization of selected bacterial inoculants appears to represent a good strategy to guarantee nutritional qualities of cattle feed while at the same time limiting the entry of pathogenic
E. coli
into the epidemiological cycle to improve the microbial safety of the food chain.
Ruminant Rhombencephalitis-Associated Listeria monocytogenes Alleles Linked to a Multilocus Variable-Number Tandem-Repeat Analysis Complex
Authors: Balandyt� Lina , Brodard Isabelle , Frey Joachim , Oevermann Anna , Abril Carlos
Published: October 2011

Listeria monocytogenes
is among the most important food-borne pathogens and is well adapted to persist in the environment. To gain insight into the genetic relatedness and potential virulence of
L. monocytogenes
strains causing central nervous system (CNS) infections, we used multilocus variable-number tandem-repeat analysis (MLVA) to subtype 183
L. monocytogenes
isolates, most from ruminant rhombencephalitis and some from human patients, food, and the environment. Allelic-profile-based comparisons grouped
L. monocytogenes
strains mainly into three clonal complexes and linked single-locus variants (SLVs). Clonal complex A essentially consisted of isolates from human and ruminant brain samples. All but one rhombencephalitis isolate from cattle were located in clonal complex A. In contrast, food and environmental isolates mainly clustered into clonal complex C, and none was classified as clonal complex A. Isolates of the two main clonal complexes (A and C) obtained by MLVA were analyzed by PCR for the presence of 11 virulence-associated genes (
prfA
,
actA
,
inlA
,
inlB
,
inlC
,
inlD
,
inlE
,
inlF
,
inlG
,
inlJ
, and
inlC2H
). Virulence gene analysis revealed significant differences in the
actA
,
inlF
,
inlG
, and
inlJ
allelic profiles between clinical isolates (complex A) and nonclinical isolates (complex C). The association of particular alleles of
actA
,
inlF
, and newly described alleles of
inlJ
with isolates from CNS infections (particularly rhombencephalitis) suggests that these virulence genes participate in neurovirulence of
L. monocytogenes
. The overall absence of
inlG
in clinical complex A and its presence in complex C isolates suggests that the InlG protein is more relevant for the survival of
L. monocytogenes
in the environment.
Axl2 Integrates Polarity Establishment, Maintenance, and Environmental Stress Response in the Filamentous Fungus Ashbya gossypii
Authors: Anker Jonathan F. , Gladfelter Amy S.
Published: October 2011

In budding yeast, new sites of polarity are chosen with each cell cycle and polarization is transient. In filamentous fungi, sites of polarity persist for extended periods of growth and new polarity sites can be established while existing sites are maintained. How the polarity establishment machinery functions in these distinct growth forms found in fungi is still not well understood. We have examined the function of Axl2, a transmembrane bud site selection protein discovered in
Saccharomyces cerevisiae
, in the filamentous fungus
Ashbya gossypii
.
A. gossypii
does not divide by budding and instead exhibits persistent highly polarized growth, and multiple axes of polarity coexist in one cell.
A. gossypii
axl2
Δ
(Ag
axl2
Δ
) cells have wavy hyphae, bulbous tips, and a high frequency of branch initiations that fail to elongate, indicative of a polarity maintenance defect. Mutant colonies also have significantly lower radial growth and hyphal tip elongation speeds than wild-type colonies, and Ag
axl2
Δ
hyphae have depolarized actin patches. Consistent with a function in polarity, AgAxl2 localizes to hyphal tips, branches, and septin rings. Unlike
S. cerevisiae
Axl2, AgAxl2 contains a Mid2 homology domain and may function to sense or respond to environmental stress. In support of this idea, hyphae lacking AgAxl2 also display hypersensitivity to heat, osmotic, and cell wall stresses. Axl2 serves to integrate polarity establishment, polarity maintenance, and environmental stress response for optimal polarized growth in
A. gossypii.
Serine-Rich Repeat Proteins and Pili Promote Streptococcus agalactiae Colonization of the Vaginal Tract
Authors: Sheen Tamsin R. , Jimenez Alyssa , Wang Nai-Yu , Banerjee Anirban , van Sorge Nina M. , Doran Kelly S.
Published: October 2011

Streptococcus agalactiae(group B streptococcus [GBS]) is a Gram-positive bacterium found in the female rectovaginal tract and is capable of producing severe disease in susceptible hosts, including newborns and pregnant women. The vaginal tract is considered a major reservoir for GBS, and maternal vaginal colonization poses a significant risk to the newborn; however, little is known about the specific bacterial factors that promote GBS colonization and persistence in the female reproductive tract. We have developedin vitromodels of GBS interaction with the human female cervicovaginal tract using human vaginal and cervical epithelial cell lines. Analysis of isogenic mutant GBS strains deficient in cell surface organelles such as pili and serine-rich repeat (Srr) proteins shows that these factors contribute to host cell attachment. As Srr proteins are heavily glycosylated, we confirmed that carbohydrate moieties contribute to the effective interaction of Srr-1 with vaginal epithelial cells. Antibody inhibition assays identified keratin 4 as a possible host receptor for Srr-1. Our findings were further substantiated in anin vivomouse model of GBS vaginal colonization, where mice inoculated with an Srr-1-deficient mutant exhibited decreased GBS vaginal persistence compared to those inoculated with the wild-type (WT) parental strain. Furthermore, competition experiments in mice showed that WT GBS exhibited a significant survival advantage over the ΔpilAor Δsrr-1mutant in the vaginal tract. Our results suggest that these GBS surface proteins contribute to vaginal colonization and may offer new insights into the mechanisms of vaginal niche establishment.