A Global Perspective on the Population Structure and Reproductive System of Phyllosticta citricarpa.

The citrus pathogen Phyllosticta citricarpa was first described 117 years ago in Australia; subsequently, from the summer rainfall citrus-growing regions in China, Africa, and South America; and, recently, the United States. Limited information is available on the pathogen's population structure, mode of reproduction, and introduction pathways, which were investigated by genotyping 383 isolates representing 12 populations from South Africa, the United States, Australia, China, and Brazil. Populations were genotyped using seven published and eight newly developed polymorphic simple-sequence repeat markers. The Chinese and Australian populations had the highest genetic diversities, whereas populations from Brazil, the United States, and South Africa exhibited characteristics of founder populations. The U.S. population was clonal. Based on principal coordinate and minimum spanning network analyses, the Chinese populations were distinct from the other populations. Population differentiation and clustering analyses revealed high connectivity and possibly linked introduction pathways between South Africa, Australia, and Brazil. With the exception of the clonal U.S. populations that only contained one mating type, all the other populations contained both mating types in a ratio that did not deviate significantly from 1:1. Although most populations exhibited sexual reproduction, linkage disequilibrium analyses indicated that asexual reproduction is important in the pathogen's life cycle.

Cancer/testis antigens for therapeutic use.

Since van der Bruggen and colleagues first identified specific human tumour-associated antigens of the MAGE family, numerous potential immunotherapeutic targets have been discovered, often belonging to the so-called cancer/ testis gene family. Several members of this group have been described as immunogenic and have been utilised in clinical trials. In a search for interesting targets within this family, our laboratory has focussed its works for a number of years on two novel cancer/testis antigens called T21 and HAGE. In this article, we will focus our discussion on their levels of expression in a wide variety of both normal and cancer tissues, their possible role in tumour cell development and proliferation, and their immunogenic potential.

Timing of Fungicide Applications for Control of Husk Spot Caused by Pseudocercospora macadamiae in Macadamia.

Pseudocercospora macadamiae is an important pathogen of macadamia in Australia, causing a disease known as husk spot. Growers strive to control the disease with a number of carbendazim and copper treatments. The aim of this study was to consider the macadamia fruit developmental stage at which fungicide application is most effective against husk spot, and whether application of copper-only applications at full-size fruit developmental stage toward the end of the season contributed to effective disease control. Fungicides were applied to macadamia trees at four developmental stages in three orchards in two subsequent production seasons. The effects of the treatments on disease incidence and severity were quantified using area under disease progress curve (AUDPC) and logistic regression models. Although disease incidence varied between cultivars, incidence and severity on cv. A16 showed consistent differences between the treatments. Most significant reduction in husk spot incidence occurred when spraying commenced at match-head sized-fruit developmental stage. All treatments significantly reduced husk spot incidence and severity compared with the untreated controls, and a significant positive linear relationship (R2 = 73%) between AUDPC and severity showed that timing of the first fungicide application is important for effective disease control. Application of fungicide at full-size fruit stage reduced disease incidence but had no impact on premature fruit drop.

Cytoplasmic PML promotes TGF-ß-associated epithelial-mesenchymal transition and invasion in prostate cancer.

Epithelial-mesenchymal transition (EMT) is a key event that is involved in the invasion and dissemination of cancer cells. Although typically considered as having tumour-suppressive properties, transforming growth factor (TGF)-ß signalling is altered during cancer and has been associated with the invasion of cancer cells and metastasis. In this study, we report a previously unknown role for the cytoplasmic promyelocytic leukaemia (cPML) tumour suppressor in TGF-ß signalling-induced regulation of prostate cancer-associated EMT and invasion. We demonstrate that cPML promotes a mesenchymal phenotype and increases the invasiveness of prostate cancer cells. This event is associated with activation of TGF-ß canonical signalling pathway through the induction of Sma and Mad related family 2 and 3 (SMAD2 and SMAD3) phosphorylation. Furthermore, the cytoplasmic localization of promyelocytic leukaemia (PML) is mediated by its nuclear export in a chromosomal maintenance 1 (CRM1)-dependent manner. This was clinically tested in prostate cancer tissue and shown that cytoplasmic PML and CRM1 co-expression correlates with reduced disease-specific survival. In summary, we provide evidence of dysfunctional TGF-ß signalling occurring at an early stage in prostate cancer. We show that this disease pathway is mediated by cPML and CRM1 and results in a more aggressive cancer cell phenotype. We propose that the targeting of this pathway could be therapeutically exploited for clinical benefit.

Spatial and temporal heterogeneity in metallic elements in industrialized aquatic bird habitats.

This study examined the potential for exposure of migratory aquatic birds to contaminants in highly industrialized habitats at Baltimore Harbor, Maryland. Seven nearshore, benthic sites were sampled every 3 or 6 months from June 1987 to December 1988. Twenty metallic elements were measured in composites (i.e. annelids, amphipods, and isopods were pooled), clams, and sediments. Elevated concentrations were widespread throughout the sites, depending on the element. Most concentrations in composites were lowest at sites innermost and outside the harbor. Higher concentrations in composites were not related to season. Most concentrations were higher in composites than in sediments or clams, but they varied by element for clams and sediments. The largest flock of wintering waterfowl frequented the site exhibiting the highest concentrations of most elements ( [Formula: see text] ). Average concentrations of known toxic elements were probably not harmful to aquatic birds or their prey, but the highest detected concentrations of eight elements warrant caution. At least eight other elements exceeded background concentrations, but toxicity to birds or their prey are unknown.

Effects of the mosquito larvicide GB-1111 on bird eggs.

Golden Bear Oil (GB-1111; legal trade name for GB-1313) is a petroleum distillate used in the United States and other countries as a mosquito larvicide. As part of an evaluation of the potential effects of GB-1111 on birds, fertile eggs of mallards (Anas platyrhynchos) and bobwhite (Colinus virginianus) were incubated in the laboratory, and treated on day 4 of incubation with external applications equivalent to either 0, 1/3, 1, 3 or 10 times the maximum rate (X) of 47 l/ha (5 gal/A) of field application of GB-1111. Hatching success was significantly reduced in mallards treated at 3 and 10 times the maximum field application, with a calculated approximate LD50 of 1.9 times the maximum field application. Most mortality occurred within a week of treatment. Hepatic P450-associated monooxygenase activity (ethoxyresorufin-O-dealkylase; EROD) was negatively related to dose. In the 3X group there was a significant increase in the concentration of hepatic reduced glutathione (GSH) but a decrease in protein-bound thiols (PBSH). Hatching success of bobwhite was marginally reduced at the highest level of treatment (10X). Other effects at this level in bobwhite included a significant increase in incidence of abnormal embryos or hatchlings, lower body and liver weights, and a two-fold increase in hepatic microsomal EROD activity in hatchlings. The recommended maximum rate of field application of GB-1111 is unlikely to impair the survival or development of bobwhite embryos but is potentially toxic to mallard embryos under conditions of larvicide drift or spray overlap.

The helicase HAGE prevents interferon-α-induced PML expression in ABCB5+ malignant melanoma-initiating cells by promoting the expression of SOCS1.

The tumour suppressor PML (promyelocytic leukaemia protein) regulates several cellular pathways involving cell growth, apoptosis, differentiation and senescence. PML also has an important role in the regulation of stem cell proliferation and differentiation. Here, we show the involvement of the helicase HAGE in the transcriptional repression of PML expression in ABCB5+ malignant melanoma-initiating cells (ABCB5+ MMICs), a population of cancer stem cells which are responsible for melanoma growth, progression and resistance to drug-based therapy. HAGE prevents PML gene expression by inhibiting the activation of the JAK-STAT (janus kinase-signal transducers and activators of transcription) pathway in a mechanism which implicates the suppressor of cytokine signalling 1 (SOCS1). Knockdown of HAGE led to a significant decrease in SOCS1 protein expression, activation of the JAK-STAT signalling cascade and a consequent increase of PML expression. To confirm that the reduction in SOCS1 expression was dependent on the HAGE helicase activity, we showed that SOCS1, effectively silenced by small interfering RNA, could be rescued by re-introduction of HAGE into cells lacking HAGE. Furthermore, we provide a mechanism by which HAGE promotes SOCS1 mRNA unwinding and protein expression in vitro. Finally, using a stem cell proliferation assay and tumour xenotransplantation assay in non-obese diabetic/severe combined immunodeficiency mice, we show that HAGE promotes MMICs-dependent tumour initiation and tumour growth by preventing the anti-proliferative effects of interferon-α (IFNα). Our results suggest that the helicase HAGE has a key role in the resistance of ABCB5+ MMICs to IFNα treatment and that cancer therapies targeting HAGE may have broad implications for the treatment of malignant melanoma.

Serum biomarker profiling in cancer studies: a question of standardisation?

Companion animals are exposed to similar environmental conditions and carcinogens as humans. In some animal cancers, there also appears to be the same genetic changes associated as in humans. However, little work has been carried out in cancer biomarker identification in animals. The recent dramatic advances in molecular medicine, genomics, proteomics and translational research will allow biomarker identification, which may provide the best strategies for veterinarians and clinicians to combat disease by early diagnosis and administration of effective treatments. Proteomics may have important applications in cancer diagnosis, prognosis and predictive clinical outcome that could directly change clinical practice by affecting critical elemen-ts of care and management. This review summarizes the advances in proteomics that has propelled us to this exciting age of clinical proteomics, and highlights the future work that is required for this to become a reality. In this review, we will discuss the available proteomic technologies and their limitations, and highlight the key areas of research and how they have been used to discover cancer biomarkers. The principles described here are equally applicable to human and animal disease, but implementation of 'omic' technologies requires stringent guidelines for collection of clinical material, the application of analytical techniques and interpretation of the data.

Expressed MHC class II genes in sea otters (Enhydra lutris) from geographically disparate populations.

The major histocompatibility complex (MHC) is central to maintaining the immunologic vigor of individuals and populations. Classical MHC class II genes were targeted for partial sequencing in sea otters (Enhydra lutris) from populations in California, Washington, and Alaska. Sequences derived from sea otter peripheral blood leukocyte mRNAs were similar to those classified as DQA, DQB, DRA, and DRB in other species. Comparisons of the derived amino acid compositions supported the classification of these as functional molecules from at least one DQA, DQB, and DRA locus and at least two DRB loci. While limited in scope, phylogenetic analysis of the DRB peptide-binding region suggested the possible existence of distinct clades demarcated by geographic region. These preliminary findings support the need for additional MHC gene sequencing and expansion to a comprehensive study targeting additional otters.