Epithelial transport and deamidation of gliadin peptides:a role for coeliac disease patient immunoglobulin A

In coeliac disease, the intake of dietary gluten induces small-bowel mucosal damage and the production of immunoglobulin (Ig)A class autoantibodies against transglutaminase 2 (TG2). We examined the effect of coeliac patient IgA on the apical-to-basal passage of gluten-derived gliadin peptides p31-43 and p57-68 in intestinal epithelial cells. We demonstrate that coeliac IgA enhances the passage of gliadin peptides, which could be abolished by inhibition of TG2 enzymatic activity. Moreover, we also found that both the apical and the basal cell culture media containing the immunogenic gliadin peptides were able to induce the proliferation of deamidation-dependent coeliac patient-derived T cells even in the absence of exogenous TG2. Our results suggest that coeliac patient IgA could play a role in the transepithelial passage of gliadin peptides, a process during which they might be deamidated.

Role of hexose transport in control of glycolytic flux in Saccharomyces cerevisiae

The yeast Saccharomyces cerevisiae predominantly ferments glucose to ethanol at high external glucose concentrations, irrespective of the presence of oxygen. In contrast, at low external glucose concentrations and in the presence of oxygen, as in a glucose-limited chemostat, no ethanol is produced. The importance of the external glucose concentration suggests a central role for the affinity and maximal transport rates of yeast's glucose transporters in the control of ethanol production. Here we present a series of strains producing functional chimeras between the hexose transporters Hxt1 and Hxt7, each of which lias distinct glucose transport characteristics. The strains display a range of decreasing glycolytic rates resulting in a proportional decrease in ethanol production. Using these strains, we show for the first time that at high glucose levels, the glucose uptake capacity of wild-type S. cerevisiae does not control glycolytic flux during exponential batch growth. In contrast, our chimeric Hxt transporters control the rate of glycolysis to a high degree. Strains whose glucose uptake is mediated by these chimeric transporters will undoubtedly provide a powerful tool with which to examine in detail the mechanism underlying the switch between fermentation and respiration in S. cerevisiae and will provide new tools for the control of industrial fermentations.

Purchasing green transport and logistics services:implications for small business

Considering its strong environmental impact, logistics plays a critical role in green supply chain management. It provides strategic links in the supply chain and is an essential function in the delivery of green products to the consumer. There is a general consensus on the fact that more environmentally sustainable companies may be achieved only if transport and logistics activities also become greener. To achieve this objective, buyer companies need to incorporate green considerations in the purchasing of transport and logistics services. This appears particularly challenging for small and medium sized enterprises (SMEs) because of their traditional lack of managerial, organisational and financial resources that often result in failure to adopt an environmental perspective. In the extant literature, green purchasing has received increased attention over the past decade and the strategic importance of introducing green aspects into purchasing practices has been recognised. However, little has been written in relation to purchasing green transport and logistics services. The aim of this paper is to explore practices in the buying of green transport and logistics services and to derive implications for small buyer companies. The paper analyses how general environmental company ambitions and environmental purchasing practices are reflected when green transport and logistics services are purchased in three different European countries (Italy, Ireland and Sweden) using a multiple case study research approach. The results of the paper indicate that while the case companies show a relatively high concern for green issues at corporate level, a lower importance is attributed to green issues at the purchasing function level. When green concerns in the purchasing of transport and logistics services are analysed the level of importance decreases further. Thus, a conflicting attitude is evident between the overall corporate level and the purchasing of transport and logistics services specifically. This suggests that there is potential for improvement especially in the area of green collaboration in buyer and supplier relationships.

Role of community acceptance in sustainable bioenergy projects in India

Community acceptance has been identified as one of the key requirements for a sustainable bioenergy project. However less attention has been paid to this aspect from developing nations and small projects perspective. Therefore this research examines the role of community acceptance for sustainable small scale bioenergy projects in India. While addressing the aim, this work identifies influence of community over bioenergy projects, major concerns of communities regarding bioenergy projects and factors influencing perceptions of communities about bioenergy projects. The empirical research was carried out on four bioenergy companies in India as case studies. It has been identified that communities have significant influence over bioenergy projects in India. Local air pollution, inappropriate storage of by-products and credibility of developer are identified as some of the important concerns. Local energy needs, benefits to community from bioenergy companies, level of trust on company and relationship between company and the community are some of the prime factors which influence community's perception on bioenergy projects. This research sheds light on important aspects related to community acceptance of bioenergy projects, and this information would help practitioners in understanding the community perceptions and take appropriate actions to satisfy them. © 2014 Elsevier Ltd.

Purchasing green transport and logistics services:implications from the environmental sustainability attitude of 3PLs

Environmental sustainability is an area of increasing importance for third party logistics (3PL) companies. As the design and implementation of services requires interaction between buyer and 3PL, the 3PLs are in a critical position to support the efforts towards greening operations of different supply chain participants. However the literature in this field reflects a gap between the perspectives of buyers and 3PLs. This chapter attempts to fill this void through an explorative case study analysis on the environmental attitude of 3PLs in order to derive implications for buyers’ behavior. The results indicate that the buyer’s role is critical in different ways in the development of green initiatives among 3PLs. An increased orientation towards longer-term contracts and joint development would likely enhance the level of green initiatives. Indirectly, the buyer has the opportunity to influence its 3PLs through interaction with employees on different levels in the company, including top management.

The role of transport and mobility in the health of older people

The world's population is ageing. Older people are healthier and more active than previous generations. Living in a hypermobile world, people want to stay connected to dispersed communities as they age. Staying connected to communities and social networks enables older people to contribute and connect with society and is associated with positive mental and physical health, facilitating independence and physical activity while reducing social isolation. Changes in physiology and cognition associated with later life mean longer journeys may have to be curtailed. A shift in focus is needed to fully explore older people, transport and health; a need to be multidisciplinary in approach and to embrace social sciences and arts and humanities. A need to embrace different types of mobilities is needed for a full understanding of ageing, transport and health, moving from literal or corporeal through virtual and potential to imaginative mobility, taking into account aspirations and emotions. Mobility in later life is more than a means of getting to destinations and includes more affective or emotive associations. Cycling and walking are facilitated not just by improving safety but through social and cultural norms. Car driving can be continued safely in later life if people make appropriate and informed decisions about when and how to stop driving; stringent testing of driver ability and skill has as yet had little effect on safety. Bus use facilitates physical activity and keeps people connected but there are concerns for the future viability of buses. The future of transport may be more community led and involve more sharing of transport modes.

Journey to work:exploring difficulties, solutions and the impact of aging

A study was conducted in the UK, as part of the New Dynamics of Ageing Working Late project, of the journey to work among 1215 older workers (age groups 45-49, 50-55, 56-60 and 60 + ). The aim was to identify problems or concerns that they might have with their commute, strategies that have been adopted to address them, and the role that employers can play to assist them. Follow-up interviews with 36 employees identified many strategies for assisting with the problems of journeys to work, ranging from car share and using public transport to flexible working and working some days from home. Further interviews with a sample of 12 mainly larger companies showed that employers feel a responsibility for their workers’ commute, with some offering schemes to assist them, such as adjusting work shift timings to facilitate easier parking. The research suggests that the journey to work presents difficulties for a significant minority of those aged over 45, including issues with cost, stress, health, fatigue and journey time. It may be possible to reduce the impact of these difficulties on employee decisions to change jobs or retire by assisting them to adopt mitigating strategies. It does not appear that the likelihood of experiencing a problem with the journey to work increases as the employee approaches retirement; therefore, any mitigating strategy is likely to help employees of all ages. These strategies have been disseminated to a wider audience through an online resource at www.workinglate.org.

A novel role for retromer in the control of epithelial cell polarity

The establishment and maintenance of epithelial cell polarity is essential throughout the development and adult life of all multicellular organisms. A key player in maintaining epithelial polarity is Crumbs (Crb), an evolutionarily conserved type-I transmembrane protein initially identified in Drosophila. Correct Crb levels and apical localization are imperative for its function. However, as is the case for many polarized proteins, the mechanisms of its trafficking and strict apical localization are poorly understood. To address these questions, we developed a liposome-based assay to identify trafficking coats and interaction partners of Crb in a native-like environment. Thereby, we demonstrated that Crb is a cargo for Retromer, a trafficking complex required for transport from endosomes to the trans-Golgi-network. The functional importance of this interaction was revealed by studies in Drosophila epithelia, which established Retromer as a novel regulator of epithelial cell polarity and verified the vast potential of this technique.

Polyol transport in yeast: studying transport proteins and manipulating osmotic responses

The Saccharomyces cerevisiae MIP channel Fps1p plays an important role in yeast osmoregulation by exporting glycerol. Glycerol accumulates in the cell as a compatible osmolyte during hyperosmotic conditions and is exported once conditions become hypotonic. A gpd1 gpd2 mutant is unable to produce glycerol and is therefore very sensitive to high concentrations of polyols in the growth medium. The sensitivity to C3, C4 and C5, but not C6 polyols, is suppressed by expression of truncated, hyperactive Fps1p. This is because the polyols can then equilibrate over the membrane and hence the concentration gradient collapses. This experiments reveals the substrate spectrum of Fps1p. The system can be used in different ways. For instance, growth assays on different polyols elucidate the substrate range of heterologous channels such as that of the rat aquaglyceroporin AQP9. In addition, the same system is used to search for novel hyperactive mutants of Fps1p, which provide additional information on the mechanism underlying channel regulation. Finally we illustrate that the gpd1 gpd2 double mutant expressing hyperactive Fps1p can be used to manipulate activation and deactivation of the HOG pathway, contributing to our understanding of the control of this osmoregulatory system.

Role of fibroblast growth factor receptor in regulation of membrane traffic

Several studies show that membrane transport mechanisms are regulated by signalling molecules. Recently, genome-wide screen analyses in C.elegans have enabled scientists to identify novel regulators in membrane trafficking and also signalling molecules which are found to couple with this machinery. Fibroblast growth factor (FGF) via binding to fibroblast growth factor receptor (FGFR) mediate signals which are essential in the development of an organism, patterning, cell migration and tissue homeostasis. Impaired FGFR-mediated signalling has been associated with various developmental, neoplastic, metabolic and neurological diseases and cancer. In this study, the potential role of FGFR-mediated signalling pathway as a regulator of membrane trafficking was investigated. The GFP-tagged yolk protein YP170-GFP trafficking was analysed in worms where 1) FGFR signalling cascade components were depleted by RNAi and 2) in mutant animals. From these results, it was found that the disruption of the genes egl-15 (FGFR), egl-17(FGF), let-756(FGF), sem-5, let-60, lin-45, mek-2, mpk-1 and plc-3 lead to abnormal localization of YP170-GFP, suggesting that signalling downstream of FGFR via activation of MAPK and PLC-γ pathway is regulating membrane transport. The route of trafficking was further investigated, to pinpoint which membrane step is regulated by worm FGFR, by analysing a number of GFP-tagged intracellular membrane markers in the intestine of Wild Type (WT) and FGFR mutant worms. FGFR mutant worms showed a significant difference in the localisation of several endosomal membrane markers, suggesting its regulatory role in early and recycling steps of endocytosis. Finally, the trafficking of transferrin in a mammalian NIH/3T3 cell line was investigated to identify the conservation of these membrane trafficking regulatory mechanisms between organisms. Results showed no significant changes in transferrin trafficking upon FGFR stimulation or inhibition.