A preliminary investigation into the impact of a pesticide combination on human neuronal and glial cell lines in vitro

Many pesticides are used increasingly in combinations during crop protection and their stability ensures the presence of such combinations in foodstuffs. The effects of three fungicides, pyrimethanil, cyprodinil and fludioxonil, were investigated together and separately on U251 and SH-SY5Y cells, which can be representative of human CNS glial and neuronal cells respectively. Over 48h, all three agents showed significant reductions in cellular ATP, at concentrations that were more than tenfold lower than those which significantly impaired cellular viability. The effects on energy metabolism were reflected in their marked toxic effects on mitochondrial membrane potential. In addition, evidence of oxidative stress was seen in terms of a fall in cellular thiols coupled with increases in the expression of enzymes associated with reactive species formation, such as GSH peroxidase and superoxide dismutase. The glial cell line showed significant responsiveness to the toxin challenge in terms of changes in antioxidant gene expression, although the neuronal SH-SY5Y line exhibited greater vulnerability to toxicity, which was reflected in significant increases in caspase-3 expression, which is indicative of the initiation of apoptosis. Cyprodinil was the most toxic agent individually, although oxidative stress-related enzyme gene expression increases appeared to demonstrate some degree of synergy in the presence of the combination of agents. This report suggests that the impact of some pesticides, both individually and in combinations, merits further study in terms of their impact on human cellular health.

Does the World Bank have any impact on human development in the poorest countries? Some preliminary evidence from Africa

In an attempt to better understand the impact of the World Bank on human development in poor countries, we use cross-country data on African countries for the 1990–2002 period to examine this relationship. The coefficient estimates of our parsimonious fixed-effects models indicate that while loans and grants of the Bank have had a positive impact on some relatively short-term indicators of health and education in an average African country, there is little evidence to suggest that such loans and grants have helped these countries to consolidate on the short-term gains.

Growth expectations of business owners:impact of human capital, firm characteristics and environmental transition

This paper presents an empirical study based on a survey of 399 owners of small and medium size companies in Lithuania. Applying bivariate and ordered probit estimators, we investigate why some business owners expect their firms to expand, while others do not. Our main findings provide evidence that SME owner's generic and specific human capital matter. Those with higher education and 'learning by doing' attributes, either through previous job experience or additional entrepreneurial experience, expect their businesses to expand. The expectations of growth are positively related to exporting and non-monotonically to enterprise size. In addition, we analyse the link between the perceptions of constraints to business activities and growth expectations and find that the factors, which are perceived as main business barriers, are not necessary those which are associated with reduced growth expectations. In particular, perceptions of both corruption and of inadequate tax systems seem to affect growth expectations the most.

A predictive in vitro model of the impact of drugs with anticholinergic properties on human neuronal and astrocytic systems

The link between off-target anticholinergic effects of medications and acute cognitive impairment in older adults requires urgent investigation. We aimed to determine whether a relevant in vitro model may aid the identification of anticholinergic responses to drugs and the prediction of anticholinergic risk during polypharmacy. In this preliminary study we employed a co-culture of human-derived neurons and astrocytes (NT2.N/A) derived from the NT2 cell line. NT2.N/A cells possess much of the functionality of mature neurons and astrocytes, key cholinergic phenotypic markers and muscarinic acetylcholine receptors (mAChRs). The cholinergic response of NT2 astrocytes to the mAChR agonist oxotremorine was examined using the fluorescent dye fluo-4 to quantitate increases in intracellular calcium [Ca2+]i. Inhibition of this response by drugs classified as severe (dicycloverine, amitriptyline), moderate (cyclobenzaprine) and possible (cimetidine) on the Anticholinergic Cognitive Burden (ACB) scale, was examined after exposure to individual and pairs of compounds. Individually, dicycloverine had the most significant effect regarding inhibition of the astrocytic cholinergic response to oxotremorine, followed by amitriptyline then cyclobenzaprine and cimetidine, in agreement with the ACB scale. In combination, dicycloverine with cyclobenzaprine had the most significant effect, followed by dicycloverine with amitriptyline. The order of potency of the drugs in combination frequently disagreed with predicted ACB scores derived from summation of the individual drug scores, suggesting current scales may underestimate the effect of polypharmacy. Overall, this NT2.N/A model may be appropriate for further investigation of adverse anticholinergic effects of multiple medications, in order to inform clinical choices of suitable drug use in the elderly.

Differential impact of amino acid substitutions on critical residues of the human glucagon-like peptide-1 receptor involved in peptide activity and small-molecule allosterys

The glucagon-like peptide-1 receptor (GLP-1R) is a class B G protein-coupled receptor that has a critical role in the regulation of glucose homeostasis, principally through the regulation of insulin secretion. The receptor systemis highly complex, able to be activated by both endogenous [GLP-1(1-36)NH2, GLP-1(1-37), GLP-1(7-36)NH2, GLP-1(7-37), oxyntomodulin], and exogenous (exendin-4) peptides in addition to small-molecule allosteric agonists (compound 2 [6,7-dichloro-2-methylsulfonyl-3-tertbutylaminoquinoxaline], BETP [4-(3-benzyloxy)phenyl)-2-ethylsulfinyl-6-(trifluoromethyl)pyrimidine]). Furthermore, the GLP-1R is subject to single-nucleotide polymorphic variance, resulting in amino acid changes in the receptor protein. In this study, we investigated two polymorphic variants previously reported to impact peptidemediated receptor activity (M149) and small-molecule allostery (C333). These residues were mutated to a series of alternate amino acids, and their functionality was monitored across physiologically significant signaling pathways, including cAMP, extracellular signal-regulated kinase 1 and 2 phosphorylation, and intracellular Ca2+ mobilization, in addition to peptide binding and cell-surface expression. We observed that residue 149 is highly sensitive to mutation, with almost all peptide responses significantly attenuated at mutated receptors. However, most reductions in activity were able to be restored by the small-molecule allosteric agonist compound 2. Conversely, mutation of residue 333 had little impact on peptide-mediated receptor activation, but this activity could not be modulated by compound 2 to the same extent as that observed at the wild-type receptor. These results provide insight into the importance of residues 149 and 333 in peptide function and highlight the complexities of allosteric modulation within this receptor system.

Measuring the impact of innovative human capital on small firms' propensity to innovate

The ability to identify and evaluate the competitive advantage of employees' transferable and innovative characteristics is of importance to firms and policymakers. This research extends the standard measure of human capital by developing a unique and far reaching concept of Innovative Human Capital and emphasises its effect on small firm innovation and hence growth (jobs, sales and productivity). This new Innovative Human Capital concept encapsulates four elements: education, training, willingness to change in the workplace and job satisfaction to overcome the limitations of measurements used previously. An augmented innovation production function is used to test the hypothesis that small firms who employ managers with Innovative Human Capital are more likely to innovate. There is evidence from the results that Innovative Human Capital may be more valuable to small firms (i.e. less than 50 employees) than larger-sized firms (i.e. more than 50 employees). The research expands innovation theory to include the concept of Innovative Human Capital as a competitive advantage and determinant of small firm innovation; and distinguishes Innovative Human Capital as a significant concept to consider when creating public support programmes for small firms.

Human resource management and organizational performance:evidence from the retail banking sector

Underpinned by the resource-based view (RBV), social exchange theory (SET), and a theory of intrinsic motivation (empowerment), I proposed and tested a multi-level model that simultaneously examines the intermediate linkages or mechanisms through which HPWS impact individual and organizational performance. First and underpinned by RBV, I examined at the unit level, collective human capital and competitive advantage as path-ways through which the use of HPWS influences – branch market performance. Second and-, underpinned by social exchange (perceived organizational support) and intrinsic motivation (psychological empowerment) theories, I examined cross and individual level mechanisms through which experienced HPWS may influence employee performance. I tested the propositions of this study with multisource data obtained from junior and senior customer contact employees, and managers of 37 branches of two banks in Ghana. Results of the Structural Equation Modeling (SEM) analysis revealed that (i) collective human capital partially mediated the relationship between management-rated HPWS and competitive advantage, while competitive advantage completely mediated the influence of human capital on branch market performance. Consequently, management-rated HPWS influenced branch market performance indirectly through collective human capital and competitive advantage. Additionally, results of hierarchical linear modeling (HLM) tests of the cross-level influences on the motivational implications of HPWS revealed that (i) management-rated HPWS influenced experienced HPWS; (ii) perceived organizational support (POS) and psychological empowerment fully mediated the influence of experienced HPWS on service-oriented organizational citizenship behaviour (OCB), and; (iii) service-oriented OCB mediated the influence of psychological empowerment and POS on service quality and task performance. I discuss the theoretical and practical implications of these findings.

Interocular suppression and contrast gain control in human vision

The human visual system combines contrast information from the two eyes to produce a single cyclopean representation of the external world. This task requires both summation of congruent images and inhibition of incongruent images across the eyes. These processes were explored psychophysically using narrowband sinusoidal grating stimuli. Initial experiments focussed on binocular interactions within a single detecting mechanism, using contrast discrimination and contrast matching tasks. Consistent with previous findings, dichoptic presentation produced greater masking than monocular or binocular presentation. Four computational models were compared, two of which performed well on all data sets. Suppression between mechanisms was then investigated, using orthogonal and oblique stimuli. Two distinct suppressive pathways were identified, corresponding to monocular and dichoptic presentation. Both pathways impact prior to binocular summation of signals, and differ in their strengths, tuning, and response to adaptation, consistent with recent single-cell findings in cat. Strikingly, the magnitude of dichoptic masking was found to be spatiotemporally scale invariant, whereas monocular masking was dependent on stimulus speed. Interocular suppression was further explored using a novel manipulation, whereby stimuli were presented in dichoptic antiphase. Consistent with the predictions of a computational model, this produced weaker masking than in-phase presentation. This allowed the bandwidths of suppression to be measured without the complicating factor of additive combination of mask and test. Finally, contrast vision in strabismic amblyopia was investigated. Although amblyopes are generally believed to have impaired binocular vision, binocular summation was shown to be intact when stimuli were normalized for interocular sensitivity differences. An alternative account of amblyopia was developed, in which signals in the affected eye are subject to attenuation and additive noise prior to binocular combination.

Identification of nesfatin-1 in human and murine adipose tissue:a novel depot-specific adipokine with increased levels in obesity

Nesfatin-1 is a recently identified anorexigenic peptide derived from its precursor protein, nonesterified fatty acid/nucleobindin 2 (NUCB2). Although the hypothalamus is pivotal for the maintenance of energy homeostasis, adipose tissue plays an important role in the integration of metabolic activity and energy balance by communicating with peripheral organs and the brain via adipokines. Currently no data exist on nesfatin-1 expression, regulation, and secretion in adipose tissue. We therefore investigated NUCB2/nesfatin-1 gene and protein expression in human and murine adipose tissue depots. Additionally, the effects of insulin, dexamethasone, and inflammatory cytokines and the impact of food deprivation and obesity on nesfatin-1 expression were studied by quantitative RT-PCR and Western blotting. We present data showing NUCB2 mRNA (P < 0.001), nesfatin-1 intracellular protein (P < 0.001), and secretion (P < 0.01) were significantly higher in sc adipose tissue compared with other depots. Also, nesfatin-1 protein expression was significantly increased in high-fat-fed mice (P < 0.01) and reduced under food deprivation (P < 0.01) compared with controls. Stimulation of sc adipose tissue explants with inflammatory cytokines (TNFa and IL-6), insulin, and dexamethasone resulted in a marked increase in intracellular nesfatin-1 levels. Furthermore, we present evidence that the secretion of nesfatin-1 into the culture media was dramatically increased during the differentiation of 3T3-L1 preadipocytes into adipocytes (P < 0.001) and after treatments with TNF-a, IL-6, insulin, and dexamethasone (P < 0.01). In addition, circulating nesfatin-1 levels were higher in high-fat-fed mice (P < 0.05) and showed positive correlation with body mass index in human. We report that nesfatin-1 is a novel depot specific adipokine preferentially produced by sc tissue, with obesity- and food deprivation-regulated expression.

The effect of human resource management policies on organisational performance in Greek manufacturing

This paper investigates if HRM policies have an impact on organisational performance. The research is based on a sample of 178 organisations operating in the Greek manufacturing sector. The 'universalistic model’ of HRM is adopted to conduct the investigation. The results show strong support for the model, indicating that the HRM policies of recruitment, training, promotion, incentives, benefits, involvement, and health and safety are positively related with organisational performance. The study contributes to both HRM theory and has important messages for practitioners.

Human resource management systems and organizational performance:a test of a mediating model in the Greek manufacturing context

This paper investigates the relationship between systems of HRM policies and organizational performance. The research is based on a sample of 178 organizations operating in the Greek manufacturing sector. A mediation model is tested to examine the link between HRM and organizational performance. The results of this study support the hypothesis that the relationship between the HRM systems of resourcing-development and reward-relations, and organizational performance, is mediated through the HRM outcomes of skills and attitudes. The paper not only supports the theory that HRM systems have a positive impact on organizational performance but also explains the mechanisms through which HRM systems improve organizational performance.

The effect of human resource management policies on organizational performance in Greek manufacturing firms

This article investigates if human resource management (HRM) policies have an impact on organizational performance in the Greek manufacturing context. The research is based on a sample of 178 firms. The "universalistic model" of HRM is adopted to conduct the investigation. The results show strong support for the model, indicating that the HRM policies of recruitment, training, promotion, incentives, benefits, involvement, and health and safety are positively related with organizational performance. The study both contributes to HRM theory and has important implications for practitioners. © 2007 Wiley Periodicals, Inc.

Empirical analysis of human capital development and economic growth in Europe

Recent discussion of the knowledge-based economy draws increasingly attention to the role that the creation and management of knowledge plays in economic development. Development of human capital, the principal mechanism for knowledge creation and management, becomes a central issue for policy-makers and practitioners at the regional, as well as national, level. Facing competition both within and across nations, regional policy-makers view human capital development as a key to strengthening the positions of their economies in the global market. Against this background, the aim of this study is to go some way towards answering the question of whether, and how, investment in education and vocational training at regional level provides these territorial units with comparative advantages. The study reviews literature in economics and economic geography on economic growth (Chapter 2). In growth model literature, human capital has gained increased recognition as a key production factor along with physical capital and labour. Although leaving technical progress as an exogenous factor, neoclassical Solow-Swan models have improved their estimates through the inclusion of human capital. In contrast, endogenous growth models place investment in research at centre stage in accounting for technical progress. As a result, they often focus upon research workers, who embody high-order human capital, as a key variable in their framework. An issue of discussion is how human capital facilitates economic growth: is it the level of its stock or its accumulation that influences the rate of growth? In addition, these economic models are criticised in economic geography literature for their failure to consider spatial aspects of economic development, and particularly for their lack of attention to tacit knowledge and urban environments that facilitate the exchange of such knowledge. Our empirical analysis of European regions (Chapter 3) shows that investment by individuals in human capital formation has distinct patterns. Those regions with a higher level of investment in tertiary education tend to have a larger concentration of information and communication technology (ICT) sectors (including provision of ICT services and manufacture of ICT devices and equipment) and research functions. Not surprisingly, regions with major metropolitan areas where higher education institutions are located show a high enrolment rate for tertiary education, suggesting a possible link to the demand from high-order corporate functions located there. Furthermore, the rate of human capital development (at the level of vocational type of upper secondary education) appears to have significant association with the level of entrepreneurship in emerging industries such as ICT-related services and ICT manufacturing, whereas such association is not found with traditional manufacturing industries. In general, a high level of investment by individuals in tertiary education is found in those regions that accommodate high-tech industries and high-order corporate functions such as research and development (R&D). These functions are supported through the urban infrastructure and public science base, facilitating exchange of tacit knowledge. They also enjoy a low unemployment rate. However, the existing stock of human and physical capital in those regions with a high level of urban infrastructure does not lead to a high rate of economic growth. Our empirical analysis demonstrates that the rate of economic growth is determined by the accumulation of human and physical capital, not by level of their existing stocks. We found no significant effects of scale that would favour those regions with a larger stock of human capital. The primary policy implication of our study is that, in order to facilitate economic growth, education and training need to supply human capital at a faster pace than simply replenishing it as it disappears from the labour market. Given the significant impact of high-order human capital (such as business R&D staff in our case study) as well as the increasingly fast pace of technological change that makes human capital obsolete, a concerted effort needs to be made to facilitate its continuous development.

The impact of foreign direct investment on labour productivity in the Chinese electronics industry

Foreign direct investment (FDI) may have a positive impact on labour productivity in recipient industries through direct introduction of capital, technology and management skills and indirectly through spillover effects on domestic firms. This study uses a model intended to examine the overall effects of inward FDI in the Chinese electronics industry. Official data are used for 41 sub-sectors of the industry in 1996 and 1997 having differing levels of FDI. Labour productivity is modelled as dependent on the degree of foreign presence in the industry and other variables, namely capital intensity, human capital and firm size for scale factors. The econometric results suggest that foreign presence in the industry is associated with higher labour productivity. © 2001 Elsevier Science Ltd.