Repertoire, Genealogy and Genomic Organization of Cruzipain and Homologous Genes in Trypanosoma cruzi, T. cruzi-Like and Other Trypanosome Species

Trypanosoma cruzi, the agent of Chagas disease, is a complex of genetically diverse isolates highly phylogenetically related to T. cruzi-like species, Trypanosoma cruzi marinkellei and Trypanosoma dionisii, all sharing morphology of blood and culture forms and development within cells. However, they differ in hosts, vectors and pathogenicity: T. cruzi is a human pathogen infective to virtually all mammals whilst the other two species are non-pathogenic and bat restricted. Previous studies suggest that variations in expression levels and genetic diversity of cruzipain, the major isoform of cathepsin L-like (CATL) enzymes of T. cruzi, correlate with levels of cellular invasion, differentiation, virulence and pathogenicity of distinct strains. In this study, we compared 80 sequences of genes encoding cruzipain from 25 T. cruzi isolates representative of all discrete typing units (DTUs TcI-TcVI) and the new genotype Tcbat and 10 sequences of homologous genes from other species. The catalytic domain repertoires diverged according to DTUs and trypanosome species. Relatively homogeneous sequences are found within and among isolates of the same DTU except TcV and TcVI, which displayed sequences unique or identical to those of TcII and TcIII, supporting their origin from the hybridization between these two DTUs. In network genealogies, sequences from T. cruzi clustered tightly together and closer to T. c. marinkellei than to T. dionisii and largely differed from homologues of T. rangeli and T. b. brucei. Here, analysis of isolates representative of the overall biological and genetic diversity of T. cruzi and closest T. cruzi-like species evidenced DTU- and species-specific polymorphisms corroborating phylogenetic relationships inferred with other genes. Comparison of both phylogenetically close and distant trypanosomes is valuable to understand host-parasite interactions, virulence and pathogenicity. Our findings corroborate cruzipain as valuable target for drugs, vaccine, diagnostic and genotyping approaches

The role of tenascin-C in tissue injury and tumorigenesis

The extracellular matrix molecule tenascin-C is highly expressed during embryonic development, tissue repair and in pathological situations such as chronic inflammation and cancer. Tenascin-C interacts with several other extracellular matrix molecules and cell-surface receptors, thus affecting tissue architecture, tissue resilience and cell responses. Tenascin-C modulates cell migration, proliferation and cellular signaling through induction of pro-inflammatory cytokines and oncogenic signaling molecules amongst other mechanisms. Given the causal role of inflammation in cancer progression, common mechanisms might be controlled by tenascin-C during both events. Drugs targeting the expression or function of tenascin-C or the tenascin-C protein itself are currently being developed and some drugs have already reached advanced clinical trials. This generates hope that increased knowledge about tenascin-C will further improve management of diseases with high tenascin-C expression such as chronic inflammation, heart failure, artheriosclerosis and cancer

Plasma and cellular fibronectin: distinct and independent functions during tissue repair

Fibronectin (FN) is a ubiquitous extracellular matrix (ECM) glycoprotein that plays vital roles during tissue repair. The plasma form of FN circulates in the blood, and upon tissue injury, is incorporated into fibrin clots to exert effects on platelet function and to mediate hemostasis. Cellular FN is then synthesized and assembled by cells as they migrate into the clot to reconstitute damaged tissue. The assembly of FN into a complex three-dimensional matrix during physiological repair plays a key role not only as a structural scaffold, but also as a regulator of cell function during this stage of tissue repair. FN fibrillogenesis is a complex, stepwise process that is strictly regulated by a multitude of factors. During fibrosis, there is excessive deposition of ECM, of which FN is one of the major components. Aberrant FN-matrix assembly is a major contributing factor to the switch from normal tissue repair to misregulated fibrosis. Understanding the mechanisms involved in FN assembly and how these interplay with cellular, fibrotic and immune responses may reveal targets for the future development of therapies to regulate aberrant tissue-repair processes

Cationic Host Defence Peptides:Potential as Antiviral Therapeutics

There is a pressing need to develop new antiviral treatments; of the 60 drugs currently available, half are aimed at HIV-1 and the remainder target only a further six viruses. This demand has led to the emergence of possible peptide therapies, with 15 currently in clinical trials. Advancements in understanding the antiviral potential of naturally occurring host defence peptides highlights the potential of a whole new class of molecules to be considered as antiviral therapeutics. Cationic host defence peptides, such as defensins and cathelicidins, are important components of innate immunity with antimicrobial and immunomodulatory capabilities. In recent years they have also been shown to be natural, broad-spectrum antivirals against both enveloped and non-enveloped viruses, including HIV-1, influenza virus, respiratory syncytial virus and herpes simplex virus. Here we review the antiviral properties of several families of these host peptides and their potential to inform the design of novel therapeutics

A study of two sitting positions in frail, elderly, non-mobile and totally dependent residents of aged care facilities

Objectives: To determine the effect of two 'sitting-out' positions among frail, elderly, non-mobile and totally dependent aged care residents. Methods: Ten frail elderly women older than 75 years undertook evaluation. Oxygen saturation, blood pressure and heart rate were measured in reclined ( 75 degrees from horizontal) sitting to determine the change in these parameters induced by position. Results: There was a significant increase in oxygen saturation (P = 0.000) systolic (P = 0.000) and diastolic blood pressure (P = 0.034) and heart rate (P = 0.000) when subjects were moved from the reclined sitting position to upright sitting. The recordings were sustained during the measuring periods independent of position. There was no evidence of postural hypotension induced in the upright sitting position. Conclusions: Results indicate the superiority of the upright sitting position for potential tissue oxygenation. Adopting the upright sitting position may enable participation in functional activities, thereby improving quality of life