Pathogenic Roles of CD14, Galectin-3, and OX40 during Experimental Cerebral Malaria in Mice

An in-depth knowledge of the host molecules and biological pathways that contribute towards the pathogenesis of cerebral malaria would help guide the development of novel prognostics and therapeutics. Genome-wide transcriptional profiling of the brain tissue during experimental cerebral malaria (ECM ) caused by Plasmodium berghei ANKA parasites in mice, a well established surrogate of human cerebral malaria, has been useful in predicting the functional classes of genes involved and pathways altered during the course of disease. To further understand the contribution of individual genes to the pathogenesis of ECM, we examined the biological relevance of three molecules – CD14, galectin-3, and OX40 that were previously shown to be overexpressed during ECM. We find that CD14 plays a predominant role in the induction of ECM and regulation of parasite density; deletion of the CD14 gene not only prevented the onset of disease in a majority of susceptible mice (only 21% of CD14-deficient compared to 80% of wildtype mice developed ECM, p<0.0004) but also had an ameliorating effect on parasitemia (a 2 fold reduction during the cerebral phase). Furthermore, deletion of the galectin-3 gene in susceptible C57BL/6 mice resulted in partial protection from ECM (47% of galectin-3-deficient versus 93% of wildtype mice developed ECM, p<0.0073). Subsequent adherence assays suggest that galectin-3 induced pathogenesis of ECM is not mediated by the recognition and binding of galectin-3 to P. berghei ANKA parasites. A previous study of ECM has demonstrated that brain infiltrating T cells are strongly activated and are CD44+CD62L− differentiated memory T cells [1]. We find that OX40, a marker of both T cell activation and memory, is selectively upregulated in the brain during ECM and its distribution among CD4+ and CD8+ T cells accumulated in the brain vasculature is approximately equal

A conclusion of my study in "the transformation problem"

The spotlight is increasingly on the human resource management (HRM) strategies of Indian-owned multinational enterprises (MNEs), including those that operate within the country\u27s fast-growing business process offshoring (BPO) sector. Brewster et al. (2007: 206) argue that there exists a \u27need for a broader geographical base to our understanding of\u27 international human resource management. One of the important reasons for studying HRM strategies in diverse geographical locations is to examine the trajectories of policies in new multinational companies in emerging economies to assess if they mirror Western-derived models such as the life cycle schemes of Adler and Ghadar (1990) or Heenan and Perlmutter (1979). Until relatively recently (e.g. Kumar et al., 2009; Sauvant et al., 2010), there has been little discussion about how distinctive the HRM practices of Indian multinationals are and whether they are exportable or imitable. Cappelli et al. (2010: 4-5) claim there is a concept of an \u27India Way\u27 that encapsulates a national business philosophy, constructed on four pillars, including HRM dimensions such as holistic engagement with employees, improvisation and adaptability ( jugaad in Hindi), creation of innovative value propositions and recognition of businesses\u27 wider societal role. This book also claims international transferability of some practices, such as establishing a sense of social mission and employee engagement (Cappelli et al., 2010: 197-207)

​Neither Western not Indian:HRM policy in an Indian multinational

The spotlight is increasingly on the human resource management (HRM) strategies of Indian-owned multinational enterprises (MNEs), including those that operate within the country\u27s fast-growing business process offshoring (BPO) sector. Brewster et al. (2007: 206) argue that there exists a \u27need for a broader geographical base to our understanding of\u27 international human resource management. One of the important reasons for studying HRM strategies in diverse geographical locations is to examine the trajectories of policies in new multinational companies in emerging economies to assess if they mirror Western-derived models such as the life cycle schemes of Adler and Ghadar (1990) or Heenan and Perlmutter (1979). Until relatively recently (e.g. Kumar et al., 2009; Sauvant et al., 2010), there has been little discussion about how distinctive the HRM practices of Indian multinationals are and whether they are exportable or imitable. Cappelli et al. (2010: 4-5) claim there is a concept of an \u27India Way\u27 that encapsulates a national business philosophy, constructed on four pillars, including HRM dimensions such as holistic engagement with employees, improvisation and adaptability ( jugaad in Hindi), creation of innovative value propositions and recognition of businesses\u27 wider societal role. This book also claims international transferability of some practices, such as establishing a sense of social mission and employee engagement (Cappelli et al., 2010: 197-207)

The fast-halo assay for the detection of DNA damage

The need for express screening of the DNA damaging potential of chemicals has progressively increased over the past 20 years due to the wide number of new synthetic molecules to be evaluated, as well as the adoption of more stringent chemical regulations such as the EU REACH and risk reduction politics. In this regard, DNA diffusion assays such as the microelectrophoretic comet assay paved the way for rapid genotoxicity testing. A more significant simplification and speeding up of the experimental processes was achieved with the fast halo assay (FHA) described in the present chapter. FHA operates at the single cell level and relies on radial dispersion of the fragments of damaged DNA from intact nuclear DNA. The fragmented DNA is separated by diffusion in an alkaline solvent and is stained, visualized, and finally quantified using computer-assisted image analysis programs. This permits the rapid assessment of the extent of DNA breakage caused by different types of DNA lesions. FHA has proven to be sensitive, reliable, and flexible. This is currently one of the simplest, cheapest, and quickest assays for studying DNA damage and repair in living cells. It does not need expensive reagents or electrophoretic equipment and requires only 40 min to prepare samples for computer-based quantification. This technique can be particularly useful in rapid genotoxicity assessments and in high-throughput genotoxicity screenings