Evidence from bioinformatics, expression and inhibition studies of phosphoinositide-3 kinase signalling in Giardia intestinalis

Background  

Giardia intestinalis is a parasitic protozoan and major cause of diarrhoeal disease. Disease transmission is dependent on the ability of the parasite to differentiate back and forth between an intestine-colonising trophozoite and an environmentally-resistant infective cyst. Our current understanding of the intracellular signalling mechanisms that regulate parasite replication and differentiation is limited, yet such information could suggest new methods of disease control. Phosphoinositide-3 kinase (PI3K) signalling pathways have a central involvement in many vital eukaryotic processes, such as regulation of cell growth, intracellular membrane trafficking and cell motility. Here we present evidence for the existence of functional PI3K intracellular signalling pathways in G. intestinalis.     

Immunopharmacology: a new frontier

Immunopharmacology is a hybrid science which has been founded upon the principles, theory, and technical developments of both immunology and pharmacology, but which has a unique identity incorporating both basic and applied areas of research. Basic immunopharmacological research is concerned with the underlying mechanisms by which endogenous and synthetic chemicals interact with the cells of the immune system. Important areas of research include the actions of chemicals such as lymphokines, cytokines, complement, kinins, autacoids, drugs, and even neuropeptides on immune function. Applied immunopharmacology is concerned with the development and testing of new immunomodulatory drugs which will be of benefit to clinical medicine but also as basic research tools. In the past, the two fields of immunology and pharmacology have contributed to each other in many significant ways. Immunology has contributed to pharmacological research by the development of antibodies which are frequently used today as specific probes for the quantitative and qualitative analysis of many different classes of chemicals of interest. Pharmacology has contributed to the field of immunology by providing basic pharmacological information on subjects such as the mediators of hypersensitivity reactions and inflammation. In the future, the truly hybrid field of immunopharmacology promises to have an expanding role in clinical medicine and basic research. This prediction is based on the observation that recombinant lymphokines and newly discovered immunomodulatory substances have begun to enter the clinic in ever increasing numbers. Future immunopharmacological research will include the study of the pharmacology of these lymphokines but also the rational development of new drugs that act as antagonists or agonists for the endogenous lymphokines that normally regulate the immune response.(ABSTRACT TRUNCATED AT 250 WORDS)     

On the ordering of N-alkane and N-alcohol solutes in phospholipid bilayer model membrane systems

²H-NMR measurements of the ordering of several n-alkane and one n-alcohol solutes in lipid bilayers formed from dimyristoyl lecithin (DML) are reported. The results are consistent with orientation of the solutes between the lipid chains, the n-alkanes having a preference for the bilayer interior, while the n-octanol is anchored at the bilayer surface. Solubility of the short chain n-alkanes, n-hexane and n-octane as an ordered component in the L_α phase is more limited than that of n-dodecane. The NMR data are supported by low angle X-ray diffraction results which confirm that n-octanol has a more dramatic influence on bilayer area than the n-alkanes.     

Maternal prenatal depressive symptoms predict infant NR3C1 1F and BDNF IV DNA methylation

Prenatal maternal psychological distress increases risk for adverse infant outcomes. However, the biological mechanisms underlying this association remain unclear. Prenatal stress can impact fetal epigenetic regulation that could underlie changes in infant stress responses. It has been suggested that maternal glucocorticoids may mediate this epigenetic effect. We examined this hypothesis by determining the impact of maternal cortisol and depressive symptoms during pregnancy on infant NR3C1 and BDNF DNA methylation. Fifty-seven pregnant women were recruited during the second or third trimester. Participants self-reported depressive symptoms and salivary cortisol samples were collected diurnally and in response to a stressor. Buccal swabs for DNA extraction and DNA methylation analysis were collected from each infant at 2 months of age, and mothers were assessed for postnatal depressive symptoms. Prenatal depressive symptoms significantly predicted increased NR3C1 1F DNA methylation in male infants (β = 2.147, P = 0.044). Prenatal depressive symptoms also significantly predicted decreased BDNF IV DNA methylation in both male and female infants (β = −3.244, P = 0.013). No measure of maternal cortisol during pregnancy predicted infant NR3C1 1F or BDNF promoter IV DNA methylation. Our findings highlight the susceptibility of males to changes in NR3C1 DNA methylation and present novel evidence for altered BDNF IV DNA methylation in response to maternal depression during pregnancy. The lack of association between maternal cortisol and infant DNA methylation suggests that effects of maternal depression may not be mediated directly by glucocorticoids. Future studies should consider other potential mediating mechanisms in the link between maternal mood and infant outcomes.