Chapter Three – Host–Parasite Interactions and the Evolution of Immune Defense

Parasites and pathogens are ubiquitous and act as an important selection pressure on animals. Here, drawing primarily on our own research, mostly on insects, we illustrate how host-parasite interactions have played a role in the evolution of a range of phenomena, including animal coloration, social behavior, foraging ecology, sexual selection, and life-history tradeoffs, as well as how variation in host behavior and ecology can drive variation in parasitism risk and host allocation of resources to immunity and other antiparasite defenses. We conclude by identifying key areas for future study.

Induction of GADD45 and JNK/SAPK-dependent apoptosis following inducible expression of BRCA1

The breast cancer susceptibility gene BRCA1 encodes a protein implicated in the cellular response to DNA damage, with postulated roles in homologous recombination as well as transcriptional regulation. To identify downstream target genes, we established cell lines with tightly regulated inducible expression of BRCA1. High-density oligonucleotide arrays were used to analyze gene expression profiles at various times following BRCA1 induction. A major BRCA1 target is the DNA damage-responsive gene GADD45. Induction of BRCA1 triggers apoptosis through activation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK), a signaling pathway potentially linked to GADD45 gene family members. The p53-independent induction of GADD45 by BRCA1 and its activation of JNK/SAPK suggest a pathway for BRCA1-induced apoptosis.

The androgen receptor controls expression of the cancer-associated sTn antigen and cell adhesion through induction of ST6GalNAc1 in prostate cancer

Patterns of glycosylation are important in cancer, but the molecular mechanisms that drive changes are often poorly understood. The androgen receptor drives prostate cancer (PCa) development and progression to lethal metastatic castration-resistant disease. Here we used RNA-Seq coupled with bioinformatic analyses of androgen-receptor (AR) binding sites and clinical PCa expression array data to identify ST6GalNAc1 as a direct and rapidly activated target gene of the AR in PCa cells. ST6GalNAc1 encodes a sialytransferase that catalyses formation of the cancer-associated sialyl-Tn antigen (sTn), which we find is also induced by androgen exposure. Androgens induce expression of a novel splice variant of the ST6GalNAc1 protein in PCa cells. This splice variant encodes a shorter protein isoform that is still fully functional as a sialyltransferase and able to induce expression of the sTn-antigen. Surprisingly, given its high expression in tumours, stable expression of ST6GalNAc1 in PCa cells reduced formation of stable tumours in mice, reduced cell adhesion and induced a switch towards a more mesenchymal-like cell phenotype in vitro. ST6GalNAc1 has a dynamic expression pattern in clinical datasets, beingsignificantly up-regulated in primary prostate carcinoma but relatively down-regulated in established metastatic tissue. ST6GalNAc1 is frequently upregulated concurrently with another important glycosylation enzyme GCNT1 previously associated with prostate cancer progression and implicated in Sialyl Lewis X antigen synthesis. Together our data establishes an androgen-dependent mechanism for sTn antigen expression in PCa, and are consistent with a general role for the androgen receptor in driving important coordinate changes to the glycoproteome during PCa progression.

HDAC1 and HDAC2 independently predict mortality in hepatocellular carcinoma by a competing risk regression model in a Southeast Asian population

Histone deacetylases (HDACs) are enzymes involved in transcriptional repression. We aimed to examine the significance of HDAC1 and HDAC2 gene expression in the prediction of recurrence and survival in 156 patients with hepatocellular carcinoma (HCC) among a South East Asian population who underwent curative surgical resection in Singapore. We found that HDAC1 and HDAC2 were upregulated in the majority of HCC tissues. The presence of HDAC1 in tumor tissues was correlated with poor tumor differentiation. Notably, HDAC1 expression in adjacent non-tumor hepatic tissues was correlated with the presence of satellite nodules and multiple lesions, suggesting that HDAC1 upregulation within the field of HCC may contribute to tumor spread. Using competing risk regression analysis, we found that increased cancer-specific mortality was significantly associated with HDAC2 expression. Mortality was also increased with high HDAC1 expression. In the liver cancer cell lines, HEP3B, HEPG2, PLC5, and a colorectal cancer cell line, HCT116, the combined knockdown of HDAC1 and HDAC2 increased cell death and reduced cell proliferation as well as colony formation. In contrast, knockdown of either HDAC1 or HDAC2 alone had minimal effects on cell death and proliferation. Taken together, our study suggests that both HDAC1 and HDAC2 exert pro-survival effects in HCC cells, and the combination of isoform-specific HDAC inhibitors against both HDACs may be effective in targeting HCC to reduce mortality.

Ferroelectric Vortices and Related Configurations

This chapter discusses that the theoretical studies, using both atomistic and phenomenological approaches, have made clear predictions about the existence and behaviour of ferroelectric (FE) vortices. Effective Hamiltonians can be implemented within both Monte Carlo (MC) and molecular dynamics (MD) simulations. In contrast to the effective Hamiltonian method, which is atomistic in nature, the phase field method employs a continuum approach, in which the polarization field is the order parameter. Properties of FE nanostructures are largely governed by the existence of a depolarization field, which is much stronger than the demagnetization field in magnetic nanosystems. The topological patterns seen in rare earth manganites are often referred to as vortices and yet this claim never seems to be explicitly justified. By inspection, the form of a vortex structure is such that there is a continuous rotation in the orientation of dipole vectors around the singularity at the centre of the vortex.

Glycosylation is an Androgen-Regulated Process Essential for Prostate Cancer Cell Viability

Steroid androgen hormones play a key role in the progression and treatment of prostate cancer, with androgen deprivation therapy being the first-line treatment used to control cancer growth. Here we apply a novel search strategy to identify androgen-regulated cellular pathways that may be clinically important in prostate cancer. Using RNASeq data, we searched for genes that showed reciprocal changes in expression in response to acute androgen stimulation in culture, and androgen deprivation in patients with prostate cancer. Amongst 700 genes displaying reciprocal expression patterns we observed a significant enrichment in the cellular process glycosylation. Of 31 reciprocally-regulated glycosylation enzymes, a set of 8 (GALNT7, ST6GalNAc1, GCNT1, UAP1, PGM3, CSGALNACT1, ST6GAL1 and EDEM3) were significantly up-regulated in clinical prostate carcinoma. Androgen exposure stimulated synthesis of glycan structures downstream of this core set of regulated enzymes including sialyl-Tn (sTn), sialyl Lewis(X) (SLe(X)), O-GlcNAc and chondroitin sulphate, suggesting androgen regulation of the core set of enzymes controls key steps in glycan synthesis. Expression of each of these enzymes also contributed to prostate cancer cell viability. This study identifies glycosylation as a global target for androgen control, and suggests loss of specific glycosylation enzymes might contribute to tumour regression following androgen depletion therapy.

Radiation damping effects on L-shell photoionization cross- sections of O-like Fe xix and N-like recombination rate coefficients for Fe xx

Photoionization cross-sections out of the fine-structure levels (2S(2)2p(4) P-3(2,0,1)) of the O-like Fe ion Fe XIX have been reinvestigated. Data for photoionization out of each of these finestructure levels have been obtained, where the calculations have been performed with and without the inclusion of radiation damping on the resonance structure in order to assess the importance of this process. Recombination rate coefficients are determined using the Milne relation, for the case of an electron recombining with N-like Fe ions (Fe XX) in the ground state to form O-like Fe (Fe XIX) existing in each of the fine- structure ground-state levels. Recombination rates are presented over a temperature range similar to 4.0 less than or equal to log T-e less than or equal to 7.0, of importance to the modelling of X-ray emission plasmas.

Levels and distribution of genetic diversity of coconut (Cocos nucifera L., var. Typica form typica) from Sri Lanka assessed by microsatellite markers

The coconut variety Typica, form typica, commonly known as Sri Lanka tall coconuts is the most widely exploited and grown variety in Sri Lanka. Under the coconut bio-diversity conservation programme, several Typica populations have been collected by island-wide surveys and planted ex situ. Thirty-three coconut populations were subjected to microsatellite assay with eight coconut-specific microsatellite primer pairs in order to study the levels and distribution of genetic variation of the collected materials for formulating future collection strategies and selecting parents for the breeding programme. A total of 56 alleles were detected ranging from 3 to 10 alleles per primer pair with an average of 7 alleles per locus. Overall a very high level of genetic diversity was detected (0.999) for all the populations studied ranging from 0.526 for population Debarayaya to 0.683 for population Dickwella. Only four introduced coconut populations, i.e. Clovis, Margeret, Dickwella, Mirishena and an embryo-cultured population were clearly separated from the resulting dendrogram. A very high level of within population variation (99%) accounted for native populations suggests a common history and a restricted genetic base for native Sri Lankan tall coconuts. Categorization of alleles into different classes according to their frequency and distribution confirmed the results of the dedrogram and concluded the adequacy of single large collection from the entire target area to represent the total genetic diversity in Sri Lanka. This study discusses useful information regarding conservation and breeding of coconut in Sri Lanka.

Uptake of carbon, nitrogen and phosphorus by phytoplankton along the 20 degrees W meridian in the NE Atlantic between 57.5 degrees N and 37 degrees N

Phytoplankton biomass and rate of production were measured along a transect from 57.54 degreesN to 37.01 degreesN in the northeast Atlantic during July 1996 and at a series of stations over a 7-day period at 37 degreesN 20 degreesW. Surface nutrient concentrations ranged from 4 mu mol l(-1) NO3-, and 0.35 mu mol l(-1) PO43- at 57.54 degreesN to <10 nmol l(-1) NO3- and similar to 10 nmol l(-1) PO43- at 37.01 degreesN. The greatest phytoplankton biomass and production were measured in the vicinity of a frontal system at 50 degreesN, and there was a general decline in total phytoplankton biomass and production to the south of the transect. Production was measured in three size fractions. At the station with the highest chlorophyll concentrations (50.34 degreesN), phytoplankton cells larger than 5 mum dominated the assemblage, accounting for 72% of the chlorophyll concentration (22.9 mg m(-2)) and 51% of primary production (54.1 mmol Cm-2 d(-1)), but picophytoplankton production was also high (43%). At 57 degreesN, carbon fixation by the > 5 mum fraction accounted for 75% of the daily production of 60.75 mmol Cm-2 d(-1). At 37 degreesN, picophytoplankton was the dominant group, accounting for similar to 58% (10 mg m(-2)) of chlorophyll and similar to 64% (46 mmol Cm-2 d(-1)), of primary production. Nitrate, ammonium and phosphate uptake rates also were determined. Although high nitrate uptake rates were measured in the surface water at similar to 50 degreesN, the greatest uptake rates of both depth-integrated nitrate and ammonium were at the south of the transect. At 37 degreesN, a deep euphotic zone was present and light penetrated through the nitracline; total nitrate uptake was enhanced because of assimilation at the base of the euphotic zone. As a consequence, high values of depth-integrated f-ratio were measured in the oligotrophic waters at the south of the transect. Phosphate was predominantly incorporated into the picoplankton fraction, which included heterotrophic and autotrophic components, at all stations and a significant proportion of phosphate uptake occurred in the dark. The C:N:P assimilation ratios were variable throughout the region; phosphate uptake was generally greater than would be expected if nutrient assimilation were in proportion to the Redfield ratio. (C) 2001 Elsevier Science Ltd. All rights reserved.