A novel alternate secretory pathway for the export of Plasmodium proteins into the host erythrocyte

The malarial parasite dramatically alters its host cell by exporting and targeting proteins to specific locations within the erythrocyte. Little is known about the mechanisms by which the parasite is able to carry out this extraparasite transport. The fungal metabolite brefeldin A (BFA) has been used to study the secretory pathway in eukaryotes. BFA treatment of infected erythrocytes inhibits protein export and results in the accumulation of exported Plasmodium proteins into a compartment that is at the parasite periphery. Parasite proteins that are normally localized to the erythrocyte membrane, to nonmembrane bound inclusions in the erythrocyte cytoplasm, or to the parasitophorous vacuolar membrane accumulate in this BFA-induced compartment. A single BFA-induced compartment is detected per parasite and the various exported proteins colocalize to this compartment regardless of their final destinations. Parasite membrane proteins do not accumulate in this novel compartment, but accumulate in the endoplasmic reticulum (ER), suggesting that the parasite has two secretory pathways. This alternate secretory pathway is established immediately after merozoite invasion and at least some dense granule proteins also use the alternate pathway. The BFA-induced compartment exhibits properties that are similar to the ER, but it is clearly distinct from the ER. We propose to call this new organelle the secondary ER of apicomplexa. This ER-like organelle is an early, if not the first, step in the export of Plasmodium proteins into the host erythrocyte.

Cellular mechanisms of β-amyloid production and secretion

The major constituent of senile plaques in Alzheimer’s disease is a 42-aa peptide, referred to as β-amyloid (Aβ). Aβ is generated from a family of differentially spliced, type-1 transmembrane domain (TM)-containing proteins, called APP, by endoproteolytic processing. The major, relatively ubiquitous pathway of APP metabolism in cell culture involves cleavage by α-secretase, which cleaves within the Aβ sequence, thus precluding Aβ formation and deposition. An alternate secretory pathway, enriched in neurons and brain, leads to cleavage of APP at the N terminus of the Aβ peptide by β-secretase, thus generating a cell-associated β-C-terminal fragment (β-CTF). A pathogenic mutation at codons 670/671 in APP (APP “Swedish”) leads to enhanced cleavage at the β-secretase scissile bond and increased Aβ formation. An inhibitor of vacuolar ATPases, bafilomycin, selectively inhibits the action of β-secretase in cell culture, suggesting a requirement for an acidic intracellular compartment for effective β-secretase cleavage of APP. β-CTF is cleaved in the TM domain by γ-secretase(s), generating both Aβ 1–40 (90%) and Aβ 1–42 (10%). Pathogenic mutations in APP at codon 717 (APP “London”) lead to an increased proportion of Aβ 1–42 being produced and secreted. Missense mutations in PS-1, localized to chromosome 14, are pathogenic in the majority of familial Alzheimer’s pedigrees. These mutations also lead to increased production of Aβ 1–42 over Aβ 1–40. Knockout of PS-1 in transgenic animals leads to significant inhibition of production of both Aβ 1–40 and Aβ 1–42 in primary cultures, indicating that PS-1 expression is important for γ-secretase cleavages. Peptide aldehyde inhibitors that block Aβ production by inhibiting γ-secretase cleavage of β-CTF have been discovered.

Open business intelligence: on the importance of data quality awareness in user-friendly data mining

Citizens demand more and more data for making decisions in their daily life. Therefore, mechanisms that allow citizens to understand and analyze linked open data (LOD) in a user-friendly manner are highly required. To this aim, the concept of Open Business Intelligence (OpenBI) is introduced in this position paper. OpenBI facilitates non-expert users to (i) analyze and visualize LOD, thus generating actionable information by means of reporting, OLAP analysis, dashboards or data mining; and to (ii) share the new acquired information as LOD to be reused by anyone. One of the most challenging issues of OpenBI is related to data mining, since non-experts (as citizens) need guidance during preprocessing and application of mining algorithms due to the complexity of the mining process and the low quality of the data sources. This is even worst when dealing with LOD, not only because of the different kind of links among data, but also because of its high dimensionality. As a consequence, in this position paper we advocate that data mining for OpenBI requires data quality-aware mechanisms for guiding non-expert users in obtaining and sharing the most reliable knowledge from the available LOD.

The business of fashion in the nineteenth and twentieth centuries

Fashion is a complex social and cultural phenomenon with strong economic implications. Historical analysis reveals that the mechanisms of creating and spreading fashion have not remained constant, but have varied according to social structures, forms of producing and distributing apparel and social media, while the level of influence of fashion on society has increased in line with economic development. This special issue of Investigaciones de Historia Económica-Economic History Research is dedicated to fashion as an economic phenomenon in the contemporary period. The four articles which make it up show the plurality of the subject areas, sources and methodological approaches in the current research on this topic.

Business communication in interactions between mainland Chinese and western firms through Hong Kong Chinese intermediaries

Purpose-The paper aims to analyse the nature of business communication and its influence on relationships development between Hong Kong Chinese intermediaries sourcing from Mainland Chinese sellers involved in manufacturing for sale to Western buyer firms. Design/methodology/approach-A case study-driven methodology with purposeful sampling is applied to yield maximum variation in the sampling to elicit underlying tendencies and generative mechanisms that exist within and across the multiple cases of relationships. Findings-The paper finds that Mainland Chinese sellers and Hong Kong Chinese intermediaries tend not to have the close ties that might be expected. Mainland Chinese sellers constrained their use of social information, requiring Hong Kong Chinese intermediaries to use commercial information transfers to evaluate the trustworthiness of their Mainland Chinese partners. An ingroup/outgroup bias exacerbates the modesty bias of the Mainland Chinese and also hinders learning through the transfer of technical information within these Chinese interactions. On the other hand, Western buyers tend not to prefer social information interactions with their Hong Kong Chinese intermediaries, requiring these intermediaries to emphasise commercial information interactions to evaluate the trustworthiness of their Western buyers. Research limitations/implications-This research uses a restricted sample of case study respondents. Representative sampling across multiple contexts will assist in testing the generality of the findings. Practical implications-For the West to source increasingly attractive manufactures from Mainland China, Hong Kong intermediaries will remain fundamentally important even though this creates further interactions. The aggregate of these multiple exchange arrangements is less problematic than would be the case if Western business were to deal directly with the Mainland Chinese. Originality/value-This article sheds light on the nature of business communication interactions in a group of relationships between Hong Kong Chinese intermediaries and Mainland sellers, and buyers from the West. Implications for relationships development among the Chinese and Western actors are identified with propositions framed to guide further investigation.

Local skirmishes in the contruction of (global) digital business communication technologies

This paper applies Latour’s 1992 translation map as a device to explore the development of and recent conflict between two data standards for the exchange of business information – EDIFACT and XBRL. Our research is focussed in France, where EDIFACT is well established and XBRL is just emerging. The alliances supporting both standards are local and global. The French/European EDIFACT is promulgated through the United Nations while a consortium of national jurisdictions and companies has coalesced around the US initiated XBRL International (XII). We suggest cultural differences pose a barrier to co-operation between the two networks. Competing data standards create the risk of switching costs. The different technical characteristics of the standards are identified as raising implications for regulators and users. A key concern is the lack of co-ordination of data standard production and the mechanisms regulatory agencies use to choose platforms for electronic data submission.

Human resource management, employee attitudes and business performance in Post Office Ltd

Whilst a consistent link between the adoption of human resource management (HRM) practices by organisations and their performance has been confirmed by numerous studies, there is a need for greater understanding of why such effects occur. Recently, the attention of researchers has shifted towards understanding the so-called ‘black box’ linking HRM and business performance. This study focuses on this area of research by testing processes through which HRM may affect performance, in particular the process of HR implementation, mediation mechanisms, and fit with internal and external boundary conditions. This research was based on a sample of 136 Post Office branches in the UK and investigated the role of HR implementation, employee attitudes and competitive environment. The study revealed that HR implementation, a climate for service, job satisfaction and effective organisational commitment predicted independent measures of economic and service performance in branches. Employee attitudes moderated the relationship between implemented HRM and service performance, and both job satisfaction and commitment were found to mediate relationships between a climate for service and service performance. Finally, relative levels of competition faced by branches moderated the relationship between employee attitudes and sales. The findings demonstrate how the process of HR implementation, interactions with employee attitudes and moderation by external competition all influence the impact of HR systems on service and economic performance outcomes. These results illustrate the need for greater attention to processes of internal and external fit within HRM research in order to develop theory relating to why HR systems affect performance.

An investigation into the synaptic conditions and celluar mechanisms underlying cerebellar synaptic plasticity

The direction of synaptic plasticity at the connection between parallel fibres (PFs) and Purkinje cells can be modified by PF stimulation alone. Strong activation (Hartell, 1996) or high frequency stimulation (Schreurs and Alkon, 1993) of PFs induced a long-term depression (LTD) of PF-mediated excitatory postsynaptic currents. Brief raised frequency molecular layer stimulation produced a cAMP-dependent long-temi potentiation (LTP) of field potential (FP) responses (Salin et al., 1998). Thin slices of cerebellar vermis were prepared from 14-21 day old male Wistar rats decapitated under Halothane anaesthesia. FP's were recorded from the Purkinje cell layer in response to alternate 0.2Hz activation of stimulating electrodes placed in the molecular layer. In the presence of picrotoxin, FPs displayed two tetrodotoxin-sensitive, negative-going components termed N1 and N2. EPs were graded responses with paired pulse facilitation and were selectively blocked by 101AM 6-cyano-7-nitroquinoxaline-2,3-dicne (CNQX) an antagonist at iy,-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-type ionotropic glutamate receptors (AMPAR) suggesting that they were primarily PE-mediated. The effects of raised stimulus intensity (RS) and/or increased frequency (IF) activation of the molecular layer on FP responses were examined. In sagittai and transverse slices combined RS and IF molecular layer activation induced a LTD of the N2 component of FP responses. RSIF stimulation produced fewer incidences of LTD in sagittal slices when an inhibitor of nitric oxide synthase (NOS), guanylate cyclase (GC), protein kinase G (PKG) or the GABAB receptor antagonist CGP62349 was included into the perfusion medium. Application of a nitric oxide (NO) donor, a cyclic guanosine monophosphate (cGMP) analogue or a phosphodiesterase (PDE) type V inhibitor to prevent cGMP breakdown paired with IF stimulation produced an acute depression, Raised frequency (RF) molecular layer stimulation produced a slowly emerging LTD of N2 in sagittal slices that was largely blocked in the presence of NOS, cGMP or PKG inhibitors. In transverse slices RE stimulation produced a LTP of the N2 component that was prevented by an inhibitor of protein kinase A or NOS. Inhibition of cGMP-signalling frequently revealed an underlying potentiation suggesting that cGMP activity might mask the effects of cAMP. In sagittal slices RE stimulation resulted in a potentiation of FPs when the cAMP-specific PDE type IV inhibitor rolipram was incorporated into the perfusion medium. In summary, raised levels of PE stimulation can alter the synaptic efficacy at PF-Purkinje cell synapses. The results provide support for a role of NO/cGMP/PKG signalling in the induction of LTD in the cerebellar cortex and suggest that activation of GABAa receptors might also be important. The level of cyclic nucleotide-specific PDE activities may be crucial in determining the level of cGMP and CAMP activity and hence the direction of synaptic plasticity.

How do public private partnerships influence business school performance in English-speaking Caribbean?

This thesis addresses the question of how business schoolsestablished as public privatepartnerships (PPPs) within a regional university in the English-speaking Caribbean survived for over twenty-one years and achieved legitimacy in their environment. The aim of the study was to examine how public and private sector actors contributed to the evolution of the PPPs. A social network perspective provided a broad relational focus from which to explore the phenomenon and engage disciplinary and middle-rangetheories to develop explanations. Legitimacy theory provided an appropriate performance dimension from which to assess PPP success. An embedded multiple-case research design, with three case sites analysed at three levels including the country and university environment, the PPP as a firm and the subgroup level constituted the methodological framing of the research process. The analysis techniques included four methods but relied primarily on discourse and social network analysis of interview data from 40 respondents across the three sites. A staged analysis of the evolution of the firm provided the ‘time and effects’ antecedents which formed the basis for sense-making to arrive at explanations of the public-private relationship-influenced change. A conceptual model guided the study and explanations from the cross-case analysis were used to refine the process model and develop a dynamic framework and set of theoretical propositions that would underpin explanations of PPP success and legitimacy in matched contexts through analytical generalisation. The study found that PPP success was based on different models of collaboration and partner resource contribution that arose from a confluence of variables including the development of shared purpose, private voluntary control in corporate governance mechanisms and boundary spanning leadership. The study contributes a contextual theory that explains how PPPs work and a research agenda of ‘corporate governance as inspiration’ from a sociological perspective of ‘liquid modernity’. Recommendations for policy and management practice were developed.

Business-driven social change:a systematic review of the evidence

How can companies help change people's behaviour in order to benefit society? Organizations have the resources and market influence to effect positive change. Through product labeling, supply chain management, cause marketing, corporate philanthropy, employee volunteerism and NGO (non-government organization) partnerships, companies are helping society get active, eat healthy foods, dispose of products properly, use less energy and generally live more sustainable lives. This report reveals the three conditions necessary for changing people's behaviour that create benefits for society. The report also includes 19 mechanisms companies can use to motivate people to change and to create the capabilities and opportunities for change.

KM governance:the mechanisms for guiding and controlling KM program

Purpose: To establish and sustain their KM programs organizations need to establish mechanisms to ensure their governance. KM programs require business integration, senior management involvement and decision making authority. The present research investigates the KM governance mechanisms organizations use to guide and control their KM programs. The research seeks to contribute to a better understanding of the governance of KM and to support organizations in the development of their KM programs. Methodology: The study employs multiple case research methodology to analyze the KM governance arrangements of twelve international organizations and identify patterns in their governance configurations. Findings: The analysis identifies a range of structural, process and relational mechanisms that are critical for governing an organizational KM program. Different patterns among the KM governance mechanisms are identified which lead to the development of generic KM governance typologies. Research implications: The development of the KM governance framework allows future research to systematically investigate the KM governance phenomenon. As the present study is based on a configurational analysis future research should particularly target the performance implications of different KM governance configurations. Practical implications: The research provides insights into the diversity of KM governance mechanisms and their impact on a KM program. The KM governance framework can assist managers in reviewing their present and prospective KM programs and thereby support benchmarking or re-organization efforts. Originality: Building on prior research that has focused on individual KM governance aspects, the present study adopts a comprehensive perspective integrating structural, process and relational governance mechanisms.

Alternative mechanisms guiding salespersons’ ambidextrous product selling

Ambidextrous product-selling strategies, in which companies’ salespeople concurrently pursue the sale of existing and new products, are hard to implement. Previous studies have addressed this issue for relatively simple consumer settings with the manager in close proximity to the salespersons and focusing on different levels of control and autonomy to resolve this issue. However, little is known about how field salespeople can be influenced to pursue such dual goals proactively for more complex business-to-business products. In this study, the authors distinguish between salespeople’s proactive selling behaviour for new and existing products, and study the impact of two alternative mechanisms: a situational mechanism (i.e. perceived manager product-selling ambidexterity) and a structural mechanism (i.e. salesperson organizational identification). Using a time-lagged, multisource data set from a large ambidextrous company, the authors demonstrate that both mechanisms contribute to salespeople’s proactive selling of new and existing products, but also act as each other’s substitutes. The results suggest two most likely strategies for salespeople to obtain overall sales targets: focusing on existing product selling; or acting ambidextrously. The latter approach offers the benefits of better achieving ambidextrous company sales goals and of greater performance stability, and is thus preferred.

Web designers, social e-value creation and e-business planning:understanding resistance from conflicting demands

This chapter investigates the conflicting demands faced by web designers in the development of social e-atmospherics that aim to encourage e-value creation, thus strengthening and prolonging market planning strategies. While recent studies have shown that significant shifts are occurring concerning the importance of users’ generated content by way of social e-communication tools (e.g. blogs), these trends are also creating expectations that social and cultural cues ought to become a greater part of e-atmospherics and e-business strategies. Yet, there is growing evidence that organizations are resisting such efforts, fearing that they will lose control of their e-marketing strategy. This chapter contributes to the theory and literature on online cross-cultural understanding and the impact website designers (meso-level) can have on improving the sustainability of e-business planning, departing from recent studies that focus mainly on firms’ e-business plans (macro-level) or final consumers (micro-level). A second contribution is made with respect to online behavior regarding the advancement of technologies that facilitate the development and shaping of new social e-atmospherics that affect users’ behavior and long term e-business strategies through the avoidance of traditional, formal decision making processes and marketing strategy mechanisms implemented by firms. These issues have been highlighted in the literature on the co-production and co-creation of value, which few organizations have thus far integrated in their strategic and pragmatic e-business plans. Drawing upon fifteen online interviews with web designers in the USA, as key non-institutional actors at the meso-level who are developing what future websites will be like, this chapter analyzes ways in which identifying points of resistance and conflicting demands can lead to engagement with the debate over the online co-creation of value and more sustainable future e-business planning. A number of points of resistance to the inclusion of more e-social atmospherics are identified, and the implications for web designers’ roles and web design planning are discussed along with the limitations of the study and potential future research for e-business studies.

Internal communication and prosocial service behaviors of front-line employees:investigating mediating mechanisms

This paper contributes to the prosocial service behavior (PSB) literature by developing and testing a conceptual framework to investigate the mediating mechanisms underlying the relationships between internal communication and PSBs. Data collected from front-line employees (FLEs) in a UK based service organization was used to test our conceptual framework. Our findings demonstrate that FLE perceptions of internal communication practices influence their role stress and organizational commitment, which, in turn, influence their PSBs. The results highlight the significance of studying role stress and organizational commitment as mediators in the relationship between internal communication and PSBs. The limitations of the study are then sketched, and suggestions for future research are also provided.