Laser microdissection microscopy in parasitology: microscopes meet thermocyclers

The new methods of laser microdissection microscopy have received wide acceptance in biology and have been applied in a small number of parasitology investigations. Here, the techniques and applications of laser microdissection microscopy are reviewed with suggestions of how the systems might be used to explore applied questions in parasite molecular biology and host-parasite interactions.

Inhibition of interferon signaling by the New York 99 strain and Kunjin subtype of West Nile virus involves blockage of STAT1 and STAT2 activation by nonstructural proteins

The interferon (IFN) response is the first line of defense against viral infections, and the majority of viruses have developed different strategies to counteract IFN responses in order to ensure their survival in an infected host. In this study, the abilities to inhibit IFN signaling of two closely related West Nile viruses, the New York 99 strain (NY99) and Kunjin virus (KUN), strain MRM61C, were analyzed using reporter plasmid assays, as well as immunofluorescence and Western blot analyses. We have demonstrated that infections with both NY99 and KUN, as well as transient or stable transfections with their replicon RNAs, inhibited the signaling of both alpha/beta IFN (IFN-alpha/beta) and gamma IFN (IFN-gamma) by blocking the phosphorylation of STAT1 and its translocation to the nucleus. In addition, the phosphorylation of STAT2 and its translocation to the nucleus were also blocked by KUN, NY99, and their replicons in response to treatment with IFN-alpha. IFN-alpha signaling and STAT2 translocation to the nucleus was inhibited when the KUN nonstructural proteins NS2A, NS2B, NS3, NS4A, and NS4B, but not NS1 and NS5, were expressed individually from the pcDNA3 vector. The results clearly demonstrate that both NY99 and KUN inhibit IFN signaling by preventing STAT1 and STAT2 phosphorylation and identify nonstructural proteins. responsible for this inhibition.

Patterns of gene expression in the frontal cortex discriminate alcoholic from non-alcoholic individuals

Alcohol dependence is characterized by tolerance, physical dependence, and craving. The neuroadaptations underlying these effects of chronic alcohol abuse are likely due to altered gene expression. Previous gene expression studies using human post-mortem brain demonstrated that several gene families were altered by alcohol abuse. However, most of these changes in gene expression were small. It is not clear if gene expression profiles have sufficient power to discriminate control from alcoholic individuals and how consistent gene expression changes are when a relatively large sample size is examined. In the present study, microarray analysis (similar to 47 000 elements) was performed on the superior frontal cortex of 27 individual human cases ( 14 well characterized alcoholics and 13 matched controls). A partial least squares statistical procedure was applied to identify genes with altered expression levels in alcoholics. We found that genes involved in myelination, ubiquitination, apoptosis, cell adhesion, neurogenesis, and neural disease showed altered expression levels. Importantly, genes involved in neurodegenerative diseases such as Alzheimer's disease were significantly altered suggesting a link between alcoholism and other neurodegenerative conditions. A total of 27 genes identified in this study were previously shown to be changed by alcohol abuse in previous studies of human post-mortem brain. These results revealed a consistent re-programming of gene expression in alcohol abusers that reliably discriminates alcoholic from non-alcoholic individuals.

International human resource management:review and critique

The research agenda for the field of international human resource management (IHRM) is clear. For a better understanding and to benefit substantially, management scholars must study IHRM in context (Jackson, S.E. and Schuler, R.S. 1995. Understanding human resource management in the context of organizations and their environment. Annual Review of Psychology, 46: 237–264; Geringer, J.M., Frayne, C.A. and Milliman, J.F. 2002. In search of 'best practices' in international human resource management: research design and methodology. Human Resource Management, forthcoming). IHRM should be studied within the context of changing economic and business conditions. The dynamics of both the local/regional and international/global business context in which the firm operates should be given serious consideration. Further, it could be beneficial to study IHRM within the context of the industry and the firm's strategy and its other functional areas and operations. In taking these perspectives, one needs to use multiple levels of analysis when studying IHRM: the external social, political, cultural and economic environment; the industry, the firm, the sub-unit, the group, and the individual. Research in contextual isolation is misleading: it fails to advance understanding in any significant way (Adler, N.J. and Ghadar, E. 1990. Strategic human resource management: a global perspective. Human Resource Management in International Comparison. Berlin: de Gruyter; Locke, R. and Thelen, K. 1995. Apples and oranges revisited: contextualized comparisons and the study of comparative labor politics. Politics & Society, 23, 337–367). In this paper, we attempt to review the existing state of academic work in IHRM and illustrate how it incorporates the content and how it might be expanded to do so.

The application of contact mechanics to the numerical simulation of particulate material

Particulate solids are complex redundant systems which consist of discrete particles. The interactions between the particles are complex and have been the subject of many theoretical and experimental investigations. Invetigations of particulate material have been restricted by the lack of quantitative information on the mechanisms occurring within an assembly. Laboratory experimentation is limited as information on the internal behaviour can only be inferred from measurements on the assembly boundary, or the use of intrusive measuring devices. In addition comparisons between test data are uncertain due to the difficulty in reproducing exact replicas of physical systems. Nevertheless, theoretical and technological advances require more detailed material information. However, numerical simulation affords access to information on every particle and hence the micro-mechanical behaviour within an assembly, and can replicate desired systems. To use a computer program to numerically simulate material behaviour accurately it is necessary to incorporte realistic interaction laws. This research programme used the finite difference simulation program `BALL', developed by Cundall (1971), which employed linear spring force-displacement laws. It was thus necessary to incorporate more realistic interaction laws. Therefore, this research programme was primarily concerned with the implementation of the normal force-displacement law of Hertz (1882) and the tangential force-displacement laws of Mindlin and Deresiewicz (1953). Within this thesis the contact mechanics theories employed in the program are developed and the adaptations which were necessary to incorporate these laws are detailed. Verification of the new contact force-displacement laws was achieved by simulating a quasi-static oblique contact and single particle oblique impact. Applications of the program to the simulation of large assemblies of particles is given, and the problems in undertaking quasi-static shear tests along with the results from two successful shear tests are described.

The functional organisation of the fronto-temporal language system:evidence from syntactic and semantic ambiguity

Spoken language comprehension is known to involve a large left-dominant network of fronto-temporal brain regions, but there is still little consensus about how the syntactic and semantic aspects of language are processed within this network. In an fMRI study, volunteers heard spoken sentences that contained either syntactic or semantic ambiguities as well as carefully matched low-ambiguity sentences. Results showed ambiguity-related responses in the posterior left inferior frontal gyrus (pLIFG) and posterior left middle temporal regions. The pLIFG activations were present for both syntactic and semantic ambiguities suggesting that this region is not specialised for processing either semantic or syntactic information, but instead performs cognitive operations that are required to resolve different types of ambiguity irrespective of their linguistic nature, for example by selecting between possible interpretations or reinterpreting misparsed sentences. Syntactic ambiguities also produced activation in the posterior middle temporal gyrus. These data confirm the functional relationship between these two brain regions and their importance in constructing grammatical representations of spoken language.

International human resource management

Over the last two decades, international human resource management (IHRM) has evolved into an important field of research, teaching and practice. Until recently the focus of IHRM was on how to best manage human resources (HRs) in the multinational enterprise; however, IHRM has now evolved to incorporate two more perspectives, cross-cultural HRM and comparative HRM. Significant developments are taking place in the corporate world which have serious implications for IHRM. These include globalization, increasing foreign direct investments into emerging markets, growing intensity of cross-border alliances, growth of multinationals from emerging markets (such as China and India), increasing movement of people around the globe and an increasing trend in business process outsourcing to new economies. This emerging global economic scenario is creating immense opportunities for IHRM students and researchers. International Human Resource Management brings together articles which highlight the historical evolution of IHRM, discuss the contemporary issues and make projections for further developments in the field. The articles have been selected and arranged into sections in a way to help the reader better understand the developments in the field from different perspectives.