Anthelmintic action of plant cysteine proteinases against the rodent stomach nematode, Protospirura muricola, in vitro and in vivo

Cysteine proteinases from the fruit and latex of plants, including papaya, pineapple and fig, were previously shown to have a rapid detrimental effect, in vitro, against the rodent gastrointestinal nematodes, H eligmosomoides polygyrus (which is found in the anterior small intestine) and Trichuris miti,is (which resides in the caecum). Proteinases in the crude latex of papaya also showed anthelmintic efficacy against both nematodes in vivo. In this paper, we describe the in vitro and in vivo effects of these plant extracts against the rodent nematode, Protospirua muricola, which is found in the stomach. As in earlier work, all the plant cysteine proteinases examined, with the exception of actinidain from the juice of kiwi fruit, caused rapid loss of motility and digestion of the cuticle, leading to death of the nematode in vitro. In vivo, in contrast to the efficacy against H. polygyrus and T. muris, papaya latex only showed efficacy against P. muricola adult female worms when the stomach acidity had been neutralized prior to administration of papaya latex. Therefore, collectively, our studies have demonstrated that, with the appropriate formulation, plant cysteine proteinases have efficacy against nematodes residing throughout the rodent gastrointestinal tract

The Importance of Commercial Law in the Legal Architecture of Post-Conflict New States

In the era of international relations ushered in by the end of the Cold War, nation-building has become all the rage. In a burst of Wilsonian optimism, Western countries have sought to recreate failed states in their own image, fashioning new governmental institutions from the ashes of violent conflict or civil collapse. These projects became possible in a fresh environment of international consensus that has prevailed since the middle of the 1990s. Developing improved legal institutions has been considered a particularly important component of any state-building project and has been a primary focus of almost all such efforts. A new label has been created to describe exercises in developing legal institutions, with the general rubric describing them alternately as “rule of law” or “legal and judicial reform” projects. The aim of these exercises is to fashion the legal system of the target country along principles found in the legal systems of developed Western states, that is, to promote judicial independence, legal transparency, civil rights, and market freedoms. This, it is said, will promote economic development, political stability, and reconciliation. To date, these efforts have been driven by legions of international experts employed by multilateral and bilateral development institutions, from the World Bank and the United States Agency for International Development (USAID) to a myriad array of U.N. agencies and private contractors. When nation-building is conducted in a post-conflict context, it is easier of course to find a willing client state counterpart with whom to cooperate. If the international community decides to intervene in a failed or new state, then its role is inevitably far more comprehensive than for a project in an otherwise developing economy. It may come into the country after a war or after foreign military intervention. As in Iraq or Afghanistan, the country’s new rulers may be hand-picked by the international community. Similarly, compliance with a state-building agenda, including practical application of the lessons of neo-institutional economics, may be a condition of holding office. U.N. agencies may have formal powers in international law (as in Bosnia and Kosovo), and the level of post-war reconstruction funds and tangible foreign military presence might give the international community formidable lobbying powers. These projects have been pursued in the context of peace operations and the construction of new states, and some significant attempts to re-craft commercial law have taken place. In order to discuss the relative merits of past attempts at legal reform in post-conflict “new” states, it is necessary to understand more generally the relationship between economic development and the rule of law. The overarching theme of this Essay is that state-building in general, and development of an effective commercial law in particular, is a science in its infancy and is one about which we know remarkably little. Vastly more needs to be learned and committed in resources. Until that happens, the exercise of trying to create effective commercial law, and thus promote economic development in new states, will be a tricky and elusive goal

In vitro and in vivo anthelmintic efficacy of plant cysteine proteinases against the rodent gastrointestinal nematode, Trichuris muris

We examined the mechanism of action and compared the anthelmintic efficacy of cysteine proteinases from papaya, pineapple, fig, kiwi fruit and Egyptian milkweed in vitro using the rodent gastrointestinal nematode Heligmosomoides polygyrus. Within a 2 h incubation period, all the cysteine proteinases, with the exception of the kiwi fruit extract, caused marked damage to the cuticle of H. polygyrus adult male and female worms, reflected in the loss of surface cuticular layers. Efficacy was comparable for both sexes of worms, was dependent on the presence of cysteine and was completely inhibited by the cysteine proteinase inhibitor, E-64. LD50 values indicated that the purified proteinases were more efficacious than the proteinases in the crude latex, with purified ficin, papain, chymopapain, Egyptian milkweed latex extract and pineapple fruit extract, containing fruit bromelain, having the most potent effect. The mechanism of action of these plant enzymes (i.e. an attack on the protective cuticle of the worm) suggests that resistance would be slow to develop in the field. The efficacy and mode of action make plant cysteine proteinases potential candidates for a novel class of anthelmintics urgently required for the treatment of humans and domestic livestock

The astacin metalloprotease moulting enzyme NAS-36 is required for normal cuticle ecdysis in free-living and parasitic nematodes

Nematodes represent one of the most abundant and species-rich groups of animals on the planet, with parasitic species causing chronic, debilitating infections in both livestock and humans worldwide. The prevalence and success of the nematodes is a direct consequence of the exceptionally protective properties of their cuticle. The synthesis of this cuticle is a complex multi-step process, which is repeated 4 times from hatchling to adult and has been investigated in detail in the free-living nematode, Caenorhabditis elegans. This process is known as moulting and involves numerous enzymes in the synthesis and degradation of the collagenous matrix. The nas-36 and nas-37 genes in C. elegans encode functionally conserved enzymes of the astacin metalloprotease family which, when mutated, result in a phenotype associated with the late-stage moulting defects, namely the inability to remove the preceding cuticle. Extensive genome searches in the gastrointestinal nematode of sheep, Haemonchus contortus, and in the filarial nematode of humans, Brugia malayi, identified NAS-36 but not NAS-37 homologues. Significantly, the nas-36 gene from B. malayi could successfully complement the moult defects associated with C. elegans nas-36, nas-37 and nas-36/nas-37 double mutants, suggesting a conserved function for NAS-36 between these diverse nematode species. This conservation between species was further indicated when the recombinant enzymes demonstrated a similar range of inhibitable metalloprotease activities

Collagen processing and cuticle formation is catalysed by the astacin metalloprotease DPY-31 in free-living and parasitic nematodes

The exoskeleton or cuticle performs many key roles in the development and survival of all nematodes. This structure is predominantly collagenous in nature and requires numerous enzymes to properly fold, modify, process and cross-link these essential structural proteins. The cuticle structure and its collagen components are conserved throughout the nematode phylum but differ from the collagenous matrices found in vertebrates. This structure, its formation and the enzymology of nematode cuticle collagen biogenesis have been elucidated in the free-living nematode Caenorhabditis elegans. The dpy-31 gene in C. elegans encodes a procollagen C-terminal processing enzyme of the astacin metalloprotease or bone morphogenetic protein class that, when mutated, results in a temperature-sensitive lethal phenotype associated with cuticle defects. In this study, orthologues of this essential gene have been identified in the phylogenetically diverse parasitic nematodes Haemonchus contortus and Brugia malayi. The DPY-31 protein is expressed in the gut and secretory system of C. elegans, a location also confirmed when a B. malayi transcriptional dpy-31 promoter-reporter gene fusion was expressed in C. elegans. Functional conservation between the nematode enzymes was supported by the fact that heterologous expression of the H. contortus dpy-31 orthologue in a C. elegans dpy-31 mutant resulted in the full rescue of the mutant body form. This interspecies conservation was further established when the recombinant nematode enzymes were found to have a similar range of inhibitable protease activities. In addition, the recombinant DPY-31 enzymes from both H. contortus and B. malayi were shown to efficiently process the C. elegans cuticle collagen SQT-3 at the correct C-terminal procollagen processing site

None of your business: the case for a paradigm shift in teaching family business in UK business schools

Objectives: This conceptual paper argues that a new paradigm is needed for UK Business Schools which embraces an oft neglected, yet economically vital, stakeholder group, namely family business.Prior Work: Builds on discussions in the extent literature about failures of Business Schools to address modern needs.Approach: A stakeholder approach, building on nominal stakeholder theory to justify a change to the teaching paradigm in business schools.Results: Not applicable.Implications: Business Schools in the UK need to begin to engage with family businesses through embracing the next generation from families in business. Policy needs to be developed that will support the next generation in a positive way by teaching about the family in business. Value: Stimulate discussion about key stakeholder and prompt review of neglect of this key area of business study in UK

VALUE OF SPEED CAPABILITIES IN YOUTH SPEED CLIMBING AT HIGH SPORTS LEVEL

Current research on speed climbing at the senior level shows that speed capabilities are a significant factor determining climbing time. The main purpose of our research was to evaluate the level of speed capabilities among young speed climbers and to examine the relationship between the level of speed capabilities and the results achieved during an international competition. The subjects of the research were girls and boys in the following age categories: Female Youth A (age=16.6), Female Youth B (age=14.5 years), Male Youth A (age=16.87 years) and Male Youth B (age=14.8 years). Measurements of somatic features were included: body height, body weight, percentage of fat tissue and BMI. Speed capabilities were measured with Wingate Test. The significance test of differences showed no significant differentiation within climbing times between the groups of girls and the groups of boys. A strong correlation between climbing time and relative peak power was noticed in the Female Youth B group. The correlation between peak power and climbing time was lower in the other groups. Research showed that in speed climbing, as career progresses, it is importance of other factors rather than speed capabilities that may increase. It can be assumed that with an increase in training experience, motor skills become more essential.

PREDICTING PERFORMANCE IN SPEED CLIMBING: ACCURACY OF THE FORCE-VELOCITY TEST ON A CYCLE ERGOMETER

The present study examined the validity of the force-velocity (F-V) mechanical parameters of the lower limbs as a predictors of the competitive performance in junior male speed climbing. The second aim was to evaluate F-V characteristics in competitive speed climbers in the junior male category. Ten junior male speed climbers (age: 18±0.5 years; BH: 174.7±4.5 cm; BW: 66.4±6.6 kg; with mean best climbing time from the competition BCT: 7.29±0.66 s) were participants in the research. All they were participants in the Youth European Cup in speed climbing. F-V characteristics were measured using a cycle ergometer test according to the Vandewalle’s protocol. To evaluate of the validity between BCT (criterion) and mechanical parameters (practical measures) from F-V test a standard error of the estimate (expressed as a raw and standardized typical error, TE) and correlation coefficients (rx,y) were used. Moreover, the validity of BCT as a potentially predictor of final competition rank (as a criterion for BCT) was evaluated. Additionally the mean value and standard deviation were calculated for all measured variables. Validity of the BCT as a competition place predictor was largely overestimated (TE=0.73 and rx,y=0.81, p p≤0.05). Accuracy of the BCT prediction for somatic and mechanical variables were very largely error biased. The standardized values of TE for these variables were: 1.93÷7.25. The rx,y were in the range of -0.18 to -0.46. The level of the mechanical variables from the F-V cycle ergometer as a predictors of the BCT in speed climbing may be largely error biased. Application of the cycle ergometer F-V test of prediction BCT values in speed climbing may have low practical value. Moreover, BCT variable may be a poor predictor of the final competition result. Coaches should take these suggestions into account during preparations to speed climbing competitions.