Cathepsin L1, the major protease involved in liver fluke (Fasciola hepatica) virulence.

The secretion and activation of the major cathepsin L1 cysteine protease involved in the virulence of the helminth pathogen Fasciola hepatica was investigated. Only the fully processed and active mature enzyme can be detected in medium in which adult F. hepatica are cultured. However, immunocytochemical studies revealed that the inactive procathepsin L1 is packaged in secretory vesicles of epithelial cells that line the parasite gut. These observations suggest that processing and activation of procathepsin L1 occurs following secretion from these cells into the acidic gut lumen. Expression of the 37-kDa procathepsin L1 in Pichia pastoris showed that an intermolecular processing event within a conserved GXNXFXD motif in the propeptide generates an active 30-kDa intermediate form. Further activation of the enzyme was initiated by decreasing the pH to 5.0 and involved the progressive processing of the 37 and 30-kDa forms to other intermediates and finally to a fully mature 24.5 kDa cathepsin L with an additional 1 or 2 amino acids. An active site mutant procathepsin L, constructed by replacing the Cys26 with Gly26, failed to autoprocess. However, [Gly26]procathepsin L was processed by exogenous wild-type cathepsin L to a mature enzyme plus 10 amino acids attached to the N terminus. This exogenous processing occurred without the formation of a 30-kDa intermediate form. The results indicate that activation of procathepsin L1 by removal of the propeptide can occur by different pathways, and that this takes place within the parasite gut where the protease functions in food digestion and from where it is liberated as an active enzyme for additional extracorporeal roles.

De la cooperativa agroalimentaria a la "learning netchain". Hacia un planteamiento teorico interorganizativo e interpersonal

Se propone un planteamiento teórico/conceptual para determinar si las relaciones interorganizativas e interpersonales de la netchain de las cooperativas agroalimentarias evolucionan hacia una learning netchain. Las propuestas del trabajo muestran que el mayor grado de asociacionismo y la mayor cooperación/colaboración vertical a lo largo de la cadena están positivamente relacionados con la posición horizontal de la empresa focal más cercana del consumidor final. Esto requiere una planificación y una resolución de problemas de manera conjunta, lo que está positivamente relacionado con el mayor flujo y diversidad de la información/conocimiento obtenido y diseminado a lo largo de la netchain. Al mismo tiempo se necesita desarrollar un contexto social en el que fluya la información/conocimiento y las nuevas ideas de manera informal y esto se logra con redes personales y, principalmente, profesionales y con redes internas y, principalmente, externas. Todo esto permitirá una mayor satisfacción de los socios de la cooperativa agroalimentaria y de sus distribuidores y una mayor intensidad en I+D, convirtiéndose la netchain de la cooperativa agroalimentaria, así, en una learning netchain.

Orientación al mercado y tipología de las cooperativas agroalimentarias en base a la competitividad. Caso-estudio de las citrícolas españolas

La globalización ha recrudecido más si cabe la competencia en los mercados y las empresas deben afianzar y mejorar su posición competitiva para asegurar la supervivencia. Para ello resulta vital, entre otras cuestiones, velar por los intereses de los inversores al tiempo que cuidan de sus clientes. Las cooperativas sufren una coyuntura semejante respecto a sus socios y el mercado, es decir respecto a sus clientes internos (socios) y externos (mercado). El enfoque de las actividades y la estrategia de la cooperativa frente a esta dualidad determina su grado de orientación al mercado.Los estudios relacionados con la orientación al mercado en cooperativas son escasos en comparación con otras formas empresariales y han estado normalmente centrados en la figura de las cooperativas de segundo grado y circunscritos a sectores muy específicos.El sector citrícola español es uno de los más dinámicos y desarrollados del panorama productivo agrario. Su extensa experiencia comercial tanto a nivel doméstico como internacional confiere un carácter diferenciador a las entidades que operan en este subsector. Este trabajo analiza la posición de las cooperativas citrícolas españolas en relación a la orientación al mercado así como los factores de gestión y estrategia que están relacionadoscon ella. Para ello se utiliza una escala MARKOR, validada en estudios anteriores, sobre una muestra de 45 cooperativas.Se establece además una tipología de cooperativas citrícolas en base a los factores de competitividad que permiten ahondar en el conocimiento que existe sobre esta cuestión en entidades de economía social. Los resultados ponen de manifiesto un elevado grado de relación entre la innovación, el perfil del empresario y el conocimiento del entorno en relación con el grado de orientación al mercado.

The influence of gender in the direction of Spanish cooperative societies on profitability and indebtedness: an empirical analysis

In this paper the claim for the market for a new business management to ensure the presence of women in decision -making to respond to new social needs addressed. Thus, this paper analyzes the influence of gender diversity of the directors on the profitability and the level of debt for a sample of 5,199 Spanish cooperatives. Unlike capitalist societies, these organizations have a number of peculiarities in their government, and that the partners are themselves major time, agents and customers. The study focuses on the Spanish context, where there is an open debate on the importance of women's business management, as in other countries, driven by the proliferation of legislation on gender equality, being, in addition, Spain, the pioneer in having specific legislation on Social Economy. The results show that cooperatives with greater female representation in theirs Boards have higher profitability. On the other hand, those Boards with a higher percentage of women show a lower level of indebtedness.

Applying an Agility/Discipline Assessment for a Small Software Organisation

The adoption of agile software development methodologies may appear to be a rather straightforward process yielding instantly improved software in less time and increasingly satisfied customers. This paper will show that such a notion is a misunderstanding and can be harmful to small software development organisations. A more reasonable approach involves a careful risk assessment and framework for introducing agile practices to address specific risks. A case study with a small software development organisation is provided to show the assessment in practice and the resulting risk mitigation strategies for process improvement.

Questionnaire Survey of Physical activITy in Genral Practictioners (PHIT GP Study)

Objectives: To assess the levels of physical activity and other health related behaviours of General Practitioners (GPs) and compare their reported levels of physical activity with those of the general population. Study Design: Cross sectional postal questionnaire survey. Methods: A questionnaire, which did not allow identification of individual respondents, was posted to all 1074 (GPs) in Northern Ireland. It included the validated International Physical Activity Questionnaire (IPAQ) and questions relating to smoking and alcohol consumption. A national survey of a representative sample of the general population of similar age (29-67 years; n = 3010) provided comparative data. Results: 735 GPs responded (68.4%). IPAQ data indicated that fewer GPs (43.4%) were “physically inactive” compared to the general population (56.2%) (p

Optimal Credit Rationing in Not-For-Profit Financial Institutions

We examine the dynamic optimization problem for not-for-profit financial institutions (NFPs) that maximize consumer surplus, not profits. We characterize the optimal dynamic policy and find that it involves credit rationing. Interest rates set by mature NFPs will typically be more favorable to customers than market rates, as any surplus is distributed in the form of interest rate subsidies, with credit rationing being required to prevent these subsidies from distorting loan volumes from their optimal levels. Rationing overcomes a fundamental problem in NFPs; it allows them to distribute the surplus without distorting the volume of activity from the efficient level.

Ubiquitin-dependent proteolysis of trihydrophobin 1 (TH1) by the human papilloma virus E6-associated protein (E6-AP).

Human Papilloma virus E6-associated protein (E6-AP), which is known as an E3 ubiquitin ligase, mediates ubiquitination and subsequent degradation of a series of cellular proteins. In this paper, we identify here trihydrophobin 1 (TH1), an integral subunit of the human negative transcription elongation factor (NELF) complex, as a novel E6-AP interaction protein and a target of E6-AP-mediated degradation. Overexpression of E6-AP results in degradation of TH1 in a dose-dependent manner, whereas knock-down of endogenous E6-AP elevates the TH1 protein level. TH1 protein turnover is substantially faster, compared to controls, in cells that overexpressed E6-AP. Wild-type E6-AP promotes the ubiquitination of TH1, while a catalytically inactive point mutant of E6-AP abolishes its ubiquitination. Furthermore, in vitro ubiquitination assay also demonstrates that TH1 can be ubiquitinated by E6-AP. The degradation is blocked by treatment with proteasome inhibitor MG132. Herein, we provide strong evidence that TH1 is a specific substrate that is targeted for degradation through E6-AP-catalyzed polyubiquitination.

William Herschel Telescope observations of distant comets

We present results from broad-band V- and R-filter observations obtained at the 4.2-m William Herschel Telescope on La Palma on 2002 July 12-14. A total of six comets were imaged, and their heliocentric distances ranged from 2.8 to 6.1 au. The comets observed were 43P/Wolf-Harrington, 129P/Shoemaker-Levy 3, 133P/Elst-Pizarro, 143P/Kowal-Mrkos, P/1998 U4 (Spahr) and P/2001 H5 (NEAT). A detailed surface brightness profile analysis indicates that three of the targeted comets (43P/Wolf-Harrington, 129P/Shoemaker-Levy 3 and P/1998 U4) were visibly active, and the remaining three comets were stellar in appearance. Further analysis shows that for the three `stellar-like' comets the possible coma contribution to the observed flux does not exceed 12.2 per cent, and in the case of comet 143P/Kowal-Mrkos the coma contribution is expected to be as low as 1 per cent, and so the resulting photometry most likely represents that of the projected nucleus surface. Effective radii for the inactive comets range from 1.02 to 4.56 km, and the effective radius upper limits for the active comets range from 1.94 to 4.15 km. We assume an albedo and phase coefficient of 0.04 and 0.035 mag deg-1, respectively, with the exception of comets 133P/Elst-Pizarro and 143P/Kowal-Mrkos for which phase coefficients were previously measured. These values are compared with previous measurements, and for comet 43P/Wolf-Harrington we find that the nucleus axial ratio a/b could be as large as 2.44. For the active comets we measured dust production levels in terms of the Af? quantity. Spectral gradients were extracted for two of the inactive comets from their measured broad-band colour indices, and compared with the rest of the comet population for which (V-R) colour and spectral gradient values exist. We find a spectral gradient for 143P/Kowal-Mrkos of 9.9 +/- 8.1 per cent/100 nm, which is very typical of Jupiter-family comets, the majority of which have reflectivity gradients in the range 0-13 per cent (100 nm)-1. The spectral gradient for comet 133P/Elst-Pizarro is amongst the bluest yet measured. We measure a (V-R) colour index value of 0.14 +/- 0.11 for the nucleus of 133P/Elst-Pizarro which is considerably lower than previous measurements. A possible explanation for this difference is considered.

Optical observations of 23 distant Jupiter Family Comets, including 36P/Whipple at multiple phase angles

We present photometry on 23 Jupiter Family Comets (JFCs) observed at large heliocentric distance, primarily using the 2.5-m Isaac Newton Telescope (INT). Snapshot images were taken of 17 comets, of which five were not detected, three were active and nine were unresolved and apparently inactive. These include 103P/Hartley 2, the target of the NASA Deep Impact extended mission, EPOXI. For six comets we obtained time-series photometry and use this to constrain the shape and rotation period of these nuclei. The data are not of sufficient quantity or quality to measure precise rotation periods, but the time-series do allow us to measure accurate effective radii and surface colours. Of the comets observed over an extended period, 40P/Väisälä 1, 47P/Ashbrook-Jackson and P/2004 H2 (Larsen) showed faint activity which limited the study of the nucleus. Light curves for 94P/Russell 4 and 121P/Shoemaker-Holt 2 reveal rotation periods of around 33 and 10h, respectively, although in both cases these are not unique solutions. 94P was observed to have a large range in magnitudes implying that it is one of the most elongated nuclei known, with an axial ratio a/b >= 3. 36P/Whipple was observed at five different epochs, with the INT and ESO's 3.6-m NTT, primarily in an attempt to confirm the preliminary short rotation period apparent in the first data set. The combined data set shows that the rotation period is actually longer than 24h. A measurement of the phase function of 36P's nucleus gives a relatively steep ß = 0.060 +/- 0.019. Finally, we discuss the distribution of surface colours observed in JFC nuclei, and show that it is possible to trace the evolution of colours from the Kuiper Belt Object (KBO) population to the JFC population by applying a `dereddening' function to the KBO colour distribution.

New ways to break an old bond: the bacterial carbon-phosphorus hydrolases and their role in biogeochemical phosphorus cycling

Phosphonates are organophosphorus molecules that contain the highly stable C-P bond, rather than the more common, and more labile, C-O-P phosphate ester bond. They have ancient origins but their biosynthesis is widespread among more primitive organisms and their importance in the contemporary biosphere is increasingly recognized; for example phosphonate-P is believed to play a particularly significant role in the productivity of the oceans. The microbial degradation of phosphonates was originally thought to occur only under conditions of phosphate limitation, mediated exclusively by the poorly characterized C-P lyase multienzyme system, under Pho regulon control. However, more recent studies have demonstrated the Pho-independent mineralization by environmental bacteria of three of the most widely distributed biogenic phosphonates: 2-aminoethylphosphonic acid (ciliatine), phosphonoacetic acid, and 2-amino-3-phosphonopropionic acid (phosphonoalanine). The three phosphonohydrolases responsible have unique specificities and are members of separate enzyme superfamilies; their expression is regulated by distinct members of the LysR family of bacterial transcriptional regulators, for each of which the phosphonate substrate of the respective degradative operon serves as coinducer. Previously no organophosphorus compound was known to induce the enzymes required for its own degradation. Whole-genome and metagenome sequence analysis indicates that the genes encoding these newly described C-P hydrolases are distributed widely among prokaryotes. As they are able to function under conditions in which C-P lyases are inactive, the three enzymes may play a hitherto-unrecognized role in phosphonate breakdown in the environment and hence make a significant contribution to global biogeochemical P-cycling.

Catalytic role of gold in gold-based catalysts: A density functional theory study on the CO oxidation on gold

Gold-based catalysts have been of intense interests in recent years, being regarded as a new generation of catalysts due to their unusually high catalytic performance. For example, CO oxidation on Au/TiO2 has been found to occur at a temperature as low as 200 K. Despite extensive studies in the field, the microscopic mechanism of CO oxidation on Au-based catalysts remains controversial. Aiming to provide insight into the catalytic roles of Au, we have performed extensive density functional theory calculations for the elementary steps in CO oxidation on Au surfaces. O atom adsorption, CO adsorption, O-2 dissociation, and CO oxidation on a series of Au surfaces, including flat surfaces, defects and small clusters, have been investigated in detail. Many transition states involved are located, and the lowest energy pathways are determined. We find the following: (i) the most stable site for O atom on Au is the bridge site of step edge, not a kink site; (ii) O-2 dissociation on Au (O-2-->20(ad)) is hindered by high barriers with the lowest barrier being 0.93 eV on a step edge; (iii) CO can react with atomic O with a substantially lower barrier, 0.25 eV, on Au steps where CO can adsorb; (iv) CO can react with molecular O-2 on Au steps with a low barrier of 0.46 eV, which features an unsymmetrical four-center intermediate state (O-O-CO); and (v) O-2 can adsorb on the interface of Au/TiO2 with a reasonable chemisorption energy. On the basis of our calculations, we suggest that (i) O-2 dissociation on Au surfaces including particles cannot occur at low temperatures; (ii) CO oxidation on Au/inactive-materials occurs on Au steps via a two-step mechanism: CO+O-2-->CO2+O, and CO+O-->CO2; and (iii) CO oxidation on Au/active-materials also follows the two-step mechanism with reactions occurring at the interface.

Disposable, stable media for reproducible surface-enhanced Raman spectroscopy

Large numbers of identical and stable SE(R)RS [surface-enhanced (resonance) Raman]-active media, which are convenient to handle and manipulate but sufficiently inexpensive that they can be used once and then discarded, have been prepared by isolating nanoparticles from Ag and Au sols in hydrophilic polymer gels. The preparation simply involves mixing a suitable polymer with the sol to give a viscous suspension that can be coated onto a substrate and dried to form a hard translucent film. The films remain inactive until they are treated with aqueous analyte solution, which causes the film to swell and brings the analyte into contact with the active metal particles. The swollen films give strong SERS spectra which are effectively identical to those obtained from simple sols. The advantage of this method is that the dried polymers can be stored indefinitely before use and that they give a high degree of spectral reproducibility.

Credit and community: working class debt in the UK since 1880

This book examines credit in working class communities since 1880, focusing on forms of borrowing that were dependent on personal relationships and social networks. It provides an extended historical discussion of credit unions, legal and illegal moneylenders (loan sharks), and looks at the concept of ‘financial exclusion’. Initially, the book focuses on the history of tallymen, check traders, and their eventual movement into moneylending following the loss of their more affluent customers, due to increased spending power and an increasingly liberalized credit market. They also faced growing competition from mail order companies operating through networks of female agents, whose success owed much to the reciprocal cultural and economic conventions that lay at the heart of traditional working class credit relationships. Discussion of these forms of credit is related to theoretical debates about cultural aspects of credit exchange that ensured the continuing success of such forms of lending, despite persistent controversies about their use. The book contrasts commercial forms of credit with formal and informal co-operative alternatives, such as the mutuality clubs operated by co-operative retailers and credit unions. It charts the impact of post-war immigration upon credit patterns, particularly in relation to the migrant (Irish and Caribbean) origins of many credit unions and explains the relative lack of success of the credit union movement. The book contributes to anti-debt debates by exploring the historical difficulties of developing legislation in relation to the millions of borrowers who have patronized what has come to be termed the sub-prime sector.

An empirical study of green supply chain management practices amongst UK manufacturers

Purpose: The purpose of this paper is to examine the extent and nature of greening the supply chain (SC) in the UK manufacturing sector; and the factors that influence the breadth and depth of this activity.

Design/methodology/approach: Based on the findings from a sample of manufacturing organisations drawn from the membership of The Chartered Institute for Purchasing and Supply. Data are collected using a questionnaire, piloted and pre-tested before distribution with responses from 60 manufacturing companies.

Findings: On average manufacturers perceive the greatest pressure to improve environmental performance through legislation and internal drivers (IDs). The least influential pressures are related to societal drivers and SC pressures from individual customers. Green supply chain management (GSCM) practices amongst this “average” group of UK manufacturing organisations are focusing on internal, higher risk, descriptive activities, rather than proactive, external engagement processes. Environmental attitude (EA) is a key predictor of GSCM activity and those organisations that have a progressive attitude are also operationally very active. EA shows some relationship to legislative drivers but other factors are also influential. Operational activity may also be moderated by organisational contingencies such as risk, size, and nationality.

Research limitations/implications: The main limitation to this paper is the relatively small manufacturing sample.

Practical implications: This paper presents a series of constructs that identify GSCM operational activities companies to benchmark themselves against. It suggests which factors are driving these operational changes and how industry contingencies may be influential.

Originality/value: This paper explores what is driving environmental behaviour amongst an “average” sample of manufacturers, what specific management practices take place and the relationships between them.

Keywords: Manufacturing industries, Environmental management, Supply chain management, Sustainable development, United Kingdom
Paper type: Research paper