E‐Selectin Genotypes and Risk of Type 2 Diabetes in Women

Endothelial dysfunction increases risk for type 2 diabetes. We examined whether variation in the gene for E‐selectin (SELE), a biomarker of endothelial dysfunction, was associated with levels of E‐selectin or diabetes quantitative traits (including fasting levels of insulin and hemoglobin A_1c) in 719 nondiabetic participants of the Nurses’ Health Study or with risk of diabetes in 602 incident (over 10 years of follow‐up) cases and 655 control women matched for age, race, and fasting status. Variation in three single nucleotide polymorphisms previously associated with cardiovascular disease risk and having effects on E‐selectin function, S128R, G98T, and L554F, was not significantly (p > 0.05) associated with levels of E‐selectin or diabetes quantitative traits, or with risk of incident diabetes in the primary analysis. Among women with low levels of subclinical inflammation (C‐reactive protein levels below the population median), S128R R allele carriers had a diabetes risk factor‐adjusted relative risk of incident diabetes of 1.71 (95% confidence interval, 1.04 to 2.81) relative to those with the SS genotype. Apart from an association in this subgroup, we conclude that the E‐selectin variants we examined are not important genetic risk factors for type 2 diabetes in women.     

DDR1 regulates the stabilization of cell surface E‐cadherin and E‐cadherin‐mediated cell aggregation

The stabilization of cell surface E‐cadherin is important for the maintenance of apical junction complexes and epithelial polarity. Previously, we reported that discoidin domain receptor 1 (DDR1) forms a complex with E‐cadherin at adhesive contacts; however, the regulatory role of DDR1 in the stabilization of cell surface E‐cadherin and E‐cadherin‐mediated cell behaviors remained undefined. To gain insight into these questions, we utilized two stable clones depleted for DDR1 via the small interfering RNA (siRNA) technique, and we over‐expressed DDR1 in MDCK cells. We performed Western blotting, immunofluorescence analysis, flow cytometry, and cell aggregation studies to investigate the effect of DDR1 on cell surface E‐cadherin. The results showed that both DDR1/2 and E‐cadherin use their extracellular domains to form DDR/E‐cadherin complexes. Neither the depletion nor the over‐expression of DDR1 changed the expression level of E‐cadherin in MDCK cells. Collagen disrupted the formation of E‐cadherin complexes and caused E‐cadherin to accumulate in the cytoplasm; however, over‐expression of DDR1 stabilized E‐cadherin on the cell surface and decreased its cytoplasmic accumulation. Furthermore, independently of collagen stimulation, the depletion of DDR1 resulted in a decrease in the level of cell surface E‐cadherin, which consequently caused its cytoplasmic accumulation and decreased E‐cadherin‐mediated cell aggregation. These results indicate that DDR1 can increase the stability of cell surface E‐cadherin and promote MDCK cell aggregation, which may be mediated through the formation of DDR1/E‐cadherin complexes. Overall, these findings have implications for the physiological roles of DDR1 in association with the maintenance of both the adhesion junction and epithelial polarity. J. Cell. Physiol. 224: 387–397, 2010. © 2010 Wiley‐Liss, Inc.     

India's E‐Waste Rules and Their Impact on E‐Waste Management Practices: A Case Study

India, like many other developed and developing countries, has adopted an extended producer responsibility (EPR) approach for electronic waste (e‐waste) management under its E‐waste (Management and Handling) Rules, 2011. Under these rules, producers have been made responsible for setting up collection centers of e‐waste and financing and organizing a system for environmentally sound management of e‐waste. In this article, we use the implementation of these rules in Ahmedabad in western India as a case study to conduct a critical analysis of the implementation of India's Rules. Interviews of main stakeholder groups, including a sample of regulated commercial establishments, regulatory agencies enforcing the Rules, informal actors involved in waste collection and handling, as well as publicly available information on the implementation constitute data for our case study. Our results indicate that while there has been an increase in the formal waste processing capacity after the implementation of the Rules, only 5% to 15% of the total waste generated is likely channeled through formal processing facilities. While the EPR regulation forced the producers to take action on a few relatively inexpensive aspects of the Rules, the collection and recycling system has not been made convenient for the consumers to deposit e‐waste in formal collection and recycling centers. Based on our findings, we argue that Indian EPR regulation should go beyond simple take‐back mandates and consider implementing other policy instruments such as a deposit‐refund system. An important implication for developing countries is the need for careful attention to instrument choice and design within EPR regulations.     

Cancer: leaping the E‐cadherin hurdle

Aberrant activation of the Wnt signaling pathway is a common cause of colon cancer and other tumor types, accomplishing many of the hallmarks of cancer including sustained proliferative signaling, replicative immortality, reprogrammed metabolism, angiogenesis, and invasion. Yet, the dominant mutation that leads to chronic Wnt signaling in colon cancer is quite different from the spectrum of mutations that activate Wnt signaling in other tumor types. In this issue of The EMBO Journal, Huels et al ( 2015 ) focus on the influential role E‐cadherin plays in shaping these differences.     

E‐Clic – easy climate data converter

There are an increasing number of studies that are now focussing on the influence of climate change on species’ distributions. However, access to predictive climatic datasets for future scenarios is difficult due to their specific formats and/or the need to be geographically downscaled. The TYN dataset is freely available to users and provides a synthetic format with several climatic models and IPCC future climate scenarios. Moreover, the CRU historical dataset (1901–2000) is also available which allows users to create baseline models for current climatic variables. E‐clic is a free, user‐friendly software package that offers three different ways to convert these two datasets into a spatially explicit raster format which is compatible with the most common geographic information systems and usable on different platforms.     

An extracellular Leptospira interrogans leucine‐rich repeat protein binds human E‐ and VE‐cadherins

Pathogenic Leptospira bacteria are the causative agents of leptospirosis, a zoonotic disease affecting animals and humans worldwide. These pathogenic species have the ability to rapidly cross host tissue barriers by a yet unknown mechanism. A comparative analysis of pathogens and saprophytes revealed a higher abundance of genes encoding proteins with leucine‐rich repeat (LRR) domains in the genomes of pathogens. In other bacterial pathogens, proteins with LRR domains have been shown to be involved in mediating host cell attachment and invasion. One protein from the pathogenic species Leptospira interrogans, LIC10831, has been previously analysed via X‐ray crystallography, with findings suggesting it may be an important bacterial adhesin. Herein we show that LIC10831 elicits an antibody response in infected animals, is actively secreted by the bacterium, and binds human E‐ and VE‐cadherins. These results provide biochemical and cellular evidences of LRR protein‐mediated host–pathogen interactions and identify a new multireceptor binding protein from this infectious Leptospira species.     

Structural scaffold for eIF4E binding selectivity of 4E‐BP isoforms: crystal structure of eIF4E binding region of 4E‐BP2 and its comparison with that of 4E‐BP1

To clarify the higher eukaryotic initiation factor 4E (eIF4E) binding selectivity of 4E‐binding protein 2 (4E‐BP2) than of 4E‐BP1, as determined by Trp fluorescence analysis, the crystal structure of the eIF4E binding region of 4E‐BP2 in complex with m⁷GTP‐bound human eIF4E has been determined by X‐ray diffraction analysis and compared with that of 4E‐BP1. The crystal structure revealed that the Pro47‐Ser65 moiety of 4E‐BP2 adopts a L ‐shaped conformation involving extended and α‐helical structures and extends over the N‐terminal loop and two different helix regions of eIF4E through hydrogen bonds, and electrostatic and hydrophobic interactions; these features were similarly observed for 4E‐BP1. Although the pattern of the overall interaction of 4E‐BP2 with eIF4E was similar to that of 4E‐BP1, a notable difference was observed for the 60–63 sequence in relation to the conformation and binding selectivity of the 4E‐BP isoform, i.e. Met‐Glu‐Cys‐Arg for 4E‐BP1 and Leu‐Asp‐Arg‐Arg for 4E‐BP2. In this paper, we report that the structural scaffold of the eIF4E binding preference for 4E‐BP2 over 4E‐BP1 is based on the stacking of the Arg63 planar side chain on the Trp73 indole ring of eIF4E and the construction of a compact hydrophobic space around the Trp73 indole ring by the Leu59‐Leu60 sequence of 4E‐BP2. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.     

E‐Commerce Effects on Energy Consumption: A Multi‐Year Ecosystem‐Level Assessment

This research investigates the impact of e‐commerce on energy consumption in all four sectors of the U.S. economy (commercial, industrial, residential, and transportation), using macroeconomic data from 1992 to 2015. These data capture all the development phases of e‐commerce, as well as direct and rebound effects in and across sectors. Empirical dynamic models (EDMs), a novel methodology in industrial ecology, are applied to the e‐commerce/energy relationship to accommodate for complex system behavior and state‐dependent effects. The results of these data‐driven methods suggest that e‐commerce increases energy consumption mainly through increases in the residential and commercial sectors. These findings contrast with extant research that focuses on transportation effects, which appear less prominent in this investigation. E‐commerce effects also demonstrate state dependence, varying over the magnitude of e‐commerce as a percentage of the total retail sector, particularly in commercial and transportation realms. Assuming these effects will continue in the future, the findings imply that policy makers should focus on mitigating the environmentally deteriorating effects of e‐commerce in the residential sector. However, this investigation cannot provide root causes for the uncovered e‐commerce effects. Robustness of the empirical findings, limitations of the novel EDM methodology, and respective avenues for future methodological and substantial research are discussed.     

E‐, P‐, and N‐cadherin are co‐expressed in the nasopharyngeal carcinoma cell line TW‐039

The cadherin/catenin complex plays a key role in the initiation of cell‐cell recognition, and adhesion, and the elaboration of structural and functional organization in multicellular tissues and organs. It is associated with tumor metastasis and also acts as an “invasion suppressor” of cancer cells. Nasopharyngeal carcinoma (NPC) is notorious for its highly metastatic nature. The expression of the E‐cadherin/catenin complex is down‐regulated in NPC tumor specimens. To obtain better insight into the intercellular adhesive property of NPC cells, we used immunofluorescence microscopy, immunoprecipitation, and immunoblot analysis to examine the expression of the classical cadherins and β‐catenin in a NPC cell line, TW‐039. The results demonstrate a change in the distribution of E‐cadherin from cytosolic flakes to cell‐cell contacts with increasing time in culture. Between days 1 and 5 after plating, the detergent‐insoluble fraction of E‐cadherin increased from 20% to 37% of total E‐cadherin, and that for P‐cadherin increased from 33% to 40%. By contrast, the values for β‐catenin remained unchanged (26% and 25%). Both immunofluorescence and immunoblot studies suggested that P‐cadherin may be involved in pioneer contact adhesion of TW‐039 cells. Interestingly, E‐, P‐, and N‐cadherin are co‐expressed in this cell line. Immunoprecipitation studies also showed that other members of the cadherin family may be involved in the contact adhesion of TW‐039 cells. J. Cell. Biochem. 76:161–172, 1999. © 1999 Wiley‐Liss, Inc.     

Selectin glycoprotein ligands

Lectin selectins and their counter-receptors participate in discontinuous cell-cell interactions concurrent with leukocyte tethering and rolling on endothelium, which, in consequence, leads to leukocyte penetration to lymphatic organs and generation of inflammation sites. Counter-receptors are glycoproteins in which carbohydrate units, the direct selectin ligands, are built into the polypeptide framework. In this review, the distribution, structure and function of the main ligands and counter-receptors for P-, L- and E-selectins known so far, have been discussed. The common biosynthetic pathway of sialyl-Lewis x and sulpho-sialyl-Lewis x determinants of selectin ligands has been described.     

Closing the Loop on E‐waste: A Multidisciplinary Perspective

This paper describes the challenges faced, and opportunities identified, by a multidisciplinary team of researchers developing a novel closed loop system to recover valuable metals and reduce e‐waste, focusing on mobile phones as a case study. This multidisciplinary approach is contrasted with current top‐down approaches to making the transition to the circular economy (CE). The aim of the research presented here is to develop a product service system (PSS) that facilitates the recovery of valuable functional components and metals from mobile phone circuit boards. To create a holistic solution and limit unintended consequences, in addition to technological solutions, this paper considers appropriate component lifetimes; the (often ignored) role of the citizen in the circular economy; customer interaction with the PSS; environmental life cycle assessment; and social impacts of the proposed PSS. Development of enabling technologies and materials to facilitate recovery of components and metals and to provide an emotionally durable external enclosure is described. This research also highlights the importance of understanding value in the CE from a multifaceted and interdisciplinary perspective.     

E‐cadherin determines Caveolin‐1 tumor suppression or metastasis enhancing function in melanoma cells

The role of caveolin‐1 (CAV1) in cancer is highly controversial. CAV1 suppresses genes that favor tumor development, yet also promotes focal adhesion turnover and migration of metastatic cells. How these contrasting observations relate to CAV1 function in vivo is unclear. Our previous studies implicate E‐cadherin in CAV1‐dependent tumor suppression. Here, we use murine melanoma B16F10 cells, with low levels of endogenous CAV1 and E‐cadherin, to unravel how CAV1 affects tumor growth and metastasis and to assess how co‐expression of E‐cadherin modulates CAV1 function in vivo in C57BL/6 mice. We find that overexpression of CAV1 in B16F10 (cav‐1) cells reduces subcutaneous tumor formation, but enhances metastasis relative to control cells. Furthermore, E‐cadherin expression in B16F10 (E‐cad) cells reduces subcutaneous tumor formation and lung metastasis when intravenously injected. Importantly, co‐expression of CAV1 and E‐cadherin in B16F10 (cav‐1/E‐cad) cells abolishes tumor formation, lung metastasis, increased Rac‐1 activity, and cell migration observed with B16F10 (cav‐1) cells. Finally, consistent with the notion that CAV1 participates in switching human melanomas to a more malignant phenotype, elevated levels of CAV1 expression correlated with enhanced migration and Rac‐1 activation in these cells.