Comparative genomics and host resistance against infectious diseases.

The large size and complexity of the human genome have limited the identification and functional characterization of components of the innate immune system that play a critical role in front-line defense against invading microorganisms. However, advances in genome analysis (including the development of comprehensive sets of informative genetic markers, improved physical mapping methods, and novel techniques for transcript identification) have reduced the obstacles to discovery of novel host resistance genes. Study of the genomic organization and content of widely divergent vertebrate species has shown a remarkable degree of evolutionary conservation and enables meaningful cross-species comparison and analysis of newly discovered genes. Application of comparative genomics to host resistance will rapidly expand our understanding of human immune defense by facilitating the translation of knowledge acquired through the study of model organisms. We review the rationale and resources for comparative genomic analysis and describe three examples of host resistance genes successfully identified by this approach

Clinical and laboratory indices of severe renal lesions in children with febrile urinary tract infection

Aim To evaluate the predictive value of various clinical and laboratory parameters on the identification of acute extensive and/or multifocal renal involvement in children with febrile urinary tract infections (UTI). Methods The medical records of 148 children (median age: 2.4 months, range: 11 days-24 months), who were admitted during a 3-year period with a first episode of febrile UTI, were analysed. Acute dimercaptosuccinic acid scintigraphy (DMSA), 1clinical and laboratory parameters were evaluated. Results Seventy six children (51%) had abnormal findings on the acute DMSA. Of them, 20 had DMSA grade 2, while 56 had grade 3 and 4. Patients with a DMSA grade 3 and 4 were more likely to have shivering (OR 3.4), white blood count (WBC) ≥ 18 000/μL (OR 2.4), absolute neutrophil count (ANC) ≥ 9300/μL (OR 4.4), C-reactive protein (CRP) ≥ 50 mg/L (OR 2.7) and procalcitonin (PCT) ≥ 1.64 ng/mL (OR diagnostic). There was a significant difference of WBC (p = 0.004), ANC, CRP and PCT levels (p < 0.001) between children with normal and grade 2 aDMSA versus those with aDMSA grade 3 and 4. Conclusions Shivering and elevated inflammatory markers increase the risk of acute extensive and/or multifocal kidney involvement in children with febrile UTI. Procalcitonin seems to be an excellent marker of the severity of acute parenchymal involvement. ©2014 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd

Cellular ras gene activity is required for full neoplastic transformation by polyomavirus.

To investigate the role of ras gene activity in cellular transformation by polyomavirus, murine C3H10T1/2 cells were rendered ras deficient by transfection with an antisense ras gene construct. Ras deficiency resulted in a partial suppression of the polyomavirus-induced transformed phenotype. The production of viral middle T antigen and its association with pp60c-src, increased membrane-associated protein kinase C activity, and morphological transformation were unaffected by the downregulation of c-ras gene expression. On the other hand, stimulated proliferation, focus formation on confluent monolayers of normal cells, and colony formation in soft agar were all greatly reduced in cells containing reduced p21ras levels. It is concluded that ras gene activity is needed for full cell transformation by polyomavirus

Distinct 3d structural patterns of Lamin A/C expression in hodgkin and reed-sternberg cells

Classical Hodgkin’s lymphoma (cHL) is a B-Cell lymphoma comprised of mononuclear Hodgkin cells (H) and bi-to multi-nucleated Reed-Sternberg (RS) cells. Previous studies revealed that H and RS cells express lamin A/C, a component of the lamina of the nuclear matrix. Since no information was available about the three-dimensional (3D) expression patterns of lamin A/C in H and RS cells, we analyzed the 3D spatial organization of lamin in such cells, using 3D fluorescent microscopy. H and RS cells from cHL derived cell lines stained positive for lamin A/C, in contrast to peripheral blood lymphocytes (PBLs), in which the lamin A/C protein was not detected or weak, although its presence could be transiently increased with lymphocyte activation by lipopolysaccharide (LPS). Most importantly, in H and RS cells, the regular homogeneous and spherically shaped lamin A/C pattern, identified in activated lymphocytes, was absent. Instead, in H and RS cells, lamin staining showed internal lamin A/C structures, subdividing the nuclei into two or more smaller compartments. Analysis of pre-treatment cHL patients’ samples replicated the lamin patterns identified in cHL cell lines. We conclude that the investigation of lamin A/C protein could be a useful tool for understanding nuclear remodeling in cHL