Unplanned land clearing of Colombian rainforests: Spreading like disease?

Deforestation often occurs as temporal waves and in localized fronts termed 'deforestation hotspots' driven by economic pulses and population pressure. Of particular concern for conservation planning are 'biodiversity hotspots' where high concentrations of endemic species undergo rapid loss and fragmentation of habitat. We investigate the deforestation process in Caqueta, a biodiversity hotspot and major colonization front of the Colombian Amazon using multi-temporal satellite imagery of the periods 1989-1996-1999-2002. The probabilities of deforestation and regeneration were modeled against soil fertility, accessibility and neighborhood terms, using logistic regression analysis. Deforestation and regeneration patterns and rates were highly variable across the colonization front. The regional average annual deforestation rate was 2.6%, but varied locally between -1.8% (regeneration) and 5.3%, with maximum rates in landscapes with 40-60% forest cover and highest edge densities, showing an analogous pattern to the spread of disease. Soil fertility and forest and secondary vegetation neighbors showed positive and significant relationships with the probability of deforestation. For forest regeneration, soil fertility had a significant negative effect while the other parameters were marginally significant. The logistic regression models across all periods showed a high level of discrimination power for both deforestation and forest regeneration, with ROC values > 0.80. We document the effect of policies and institutional changes on the land clearing process, such as the failed peace process between government and guerillas in 1999-2002, which redirected the spread of deforestation and increased forest regeneration. The implications for conservation in biologically rich areas, such as Caqueta are discussed. (c) 2005 Elsevier B.V All rights reserved.

Secondary prevention of renal and cardiovascular disease: Results of a renal and cardiovascular treatment program in an Australian aboriginal community

Australian Aborigines are experiencing an epidemic of renal and cardiovascular disease. In late 1995 we introduced a treatment program into the Tiwi community, which has a three- to fivefold increase in death rates and a recent annual incidence of treated ESRD of 2760 per million. Eligible for treatment were people with hypertension, diabetics with micro or overt albuminuria, and all people with overt albuminuria. Treatment centered around use of perindopril (Coversyl, Servier), with other agents added to reach BP goals; attempts to control glucose and lipid levels; and health education. Thirty percent of the adult population, or 267 people, were enrolled, with a mean follow up of 3.39 yr. Clinical parameters were followed every 6 mo, and rates of terminal endpoints were compared with those of 327 historical controls matched for baseline disease severity, followed in the pretreatment program era. There was a dramatic reduction in BP in the treatment group, which was sustained through 3 yr of treatment. Albuminuria and GFR stabilized or improved. Rates of natural deaths were reduced by an estimated 50% (P = 0.012); renal deaths were reduced by 57% (P = 0.038); and nonrenal deaths by 46% (P = 0.085). Survival benefit was suggested at all levels of overt albuminuria, and regardless of diabetes status, baseline BP, or prior administration of angiotensin converting enzyme inhibitors (ACEI). No significant benefit was apparent among people without overt albuminuria, nor among those with GFR less than 60 ml/min. An estimated 13 renal deaths and 10 nonrenal deaths were prevented, with the number-needed-to-treat to avoid one terminal event of only 11.6. Falling deaths and renal failure in the whole community support these estimates. The program was extremely cost-effective. Programs like this should be introduced to all high-risk communities as a matter of urgency.

L-arginine-dependent nitric oxide production of a murine macrophage-like RAW 264.7 cell line stimulated with Porphyromonas gingivalis lipopolysaccharide

The aim of this study was to determine nitric oxide (NO) production of a murine macrophage cell line (RAW 264.7 cells) when stimulated with Porphyromonas gingivalis lipopolysaccharides (Pg-LPS). RAW264.7 cells were incubated with i) various concentrations of Pg-LPS or Salmonella typhosa LPS (St-LPS), ii) Pg-LPS with or without L-arginine and/or N-G-monomethyl-L-arginine (NMMA), an arginine analog or iii) Pg-LPS and interferon-gamma (IFN-gamma) with or without anti-IFN-gamma antibodies or interleukin-10 (IL-10). Tissue culture supernatants were assayed for NO levels after 24 h in culture. NO was not observed in tissue culture supernatants of RAW 264.7 cells following stimulation with Pg-LPS, but was observed after stimulation with St-LPS. Exogenous L-arginine restored the ability of Pg-LPS to induce NO production; however, the increase in NO levels of cells stimulated with Pg-LPS with exogenous L-arginine was abolished by NMMA. IFN-gamma induced independent NO production by Pg-LPS-stimulated macrophages and this stimulatory effect of IFN-gamma could be completely suppressed by anti-IFN-gamma antibodies and IL-10. These results suggest that Pg-LPS is able to stimulate NO production in the RAW264.7 macrophage cell model in an L-arginine-dependent mechanism which is itself independent of the action of IFN-gamma.

Cognitive disorders and neurogenesis deficits in Huntington's disease mice are rescued by fluoxetine

Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeat encoding an extended polyglutamine tract in the huntingtin protein. Affected individuals display progressive motor, cognitive and psychiatric symptoms (including depression), leading to terminal decline. Given that transgenic HD mice have decreased hippocampal cell proliferation and that a deficit in neurogenesis has been postulated as an underlying cause of depression, we hypothesized that decreased hippocampal neurogenesis contributes to depressive symptoms and cognitive decline in HD. Fluoxetine, a serotonin-reuptake inhibitor commonly prescribed for the treatment of depression, is known to increase neurogenesis in the dentate gyrus of wild-type mouse hippocampus. Here we show that hippocampal-dependent cognitive and depressive-like behavioural symptoms occur in HD mice, and that the administration of fluoxetine produces a marked improvement in these deficits. Furthermore, fluoxetine was found to rescue deficits of neurogenesis and volume loss in the dentate gyrus of HD mice.

Zebrafish as a model for caveolin-associated muscle disease; caveolin-3 is required for myofibril organization and muscle cell patterning

Caveolae are an abundant feature of many animal cells. However, the exact function of caveolae remains unclear. We have used the zebrafish, Danio rerio, as a system to understand caveolae function focusing on the muscle-specific caveolar protein, caveolin-3 (Cav3). We have identified caveolin-1 (alpha and beta), caveolin-2 and Cav3 in the zebrafish. Zebrafish Cav3 has 72% identity to human CAV3, and the amino acids altered in human muscle diseases are conserved in the zebrafish protein. During embryonic development, cav3 expression is apparent by early segmentation stages in the first differentiating muscle precursors, the adaxial cells and slightly later in the notochord. cav3 expression appears in the somites during mid-segmentation stages and then later in the pectoral fins and facial muscles. Cav3 and caveolae are located along the entire sarcolemma of late stage embryonic muscle fibers, whereas beta-dystroglycan is restricted to the muscle fiber ends. Down-regulation of Cav3 expression causes gross muscle abnormalities and uncoordinated movement. Ultrastructural analysis of isolated muscle fibers reveals defects in myoblast fusion and disorganized myofibril and membrane systems. Expression of the zebrafish equivalent to a human muscular dystrophy mutant, CAV3P104L, causes severe disruption of muscle differentiation. In addition, knockdown of Cav3 resulted in a dramatic up-regulation of eng1a expression resulting in an increase in the number of muscle pioneer-like cells adjacent to the notochord. These studies provide new insights into the role of Cav3 in muscle development and demonstrate its requirement for correct intracellular organization and myoblast fusion.

Basal-like breast carcinomas: clinical outcome and response to chemotherapy

Background: Grade-III invasive ductal carcinomas of no special type (IDCs-NST) constitute a heterogeneous group of tumours with different clinical behaviour and response to chemotherapy. As many as 25% of all grade-III IDCs-NST are known to harbour a basal-like phenotype, as defined by gene expression profiling or immunohistochemistry for basal cytokeratins. Patients with basal-like breast carcinomas (BLBC) are reported to have a shorter disease-free and overall survival. Material and methods: A retrospective analysis of 49 patients with BLBC (as defined by basal cytokeratin expression) and 49 controls matched for age, nodal status and grade was carried out. Histological features, immunohistochemical findings for oestrogen receptor (ER), progesterone receptor (PgR) and HER2, and clinical outcome and survival after adjuvant chemotherapy were compared between the two groups. Results: It was more likely for patients with BLBCs to be found negative for ER (p < 0.0001), PgR (p < 0.0001) and HER2 (p < 0.01) than controls. Patients with BLBCs were found to have a significantly higher recurrence rate (p < 0.05) and were associated with significantly shorter disease-free and overall survival (both p, 0.05). In the group of patients who received anthracycline-based adjuvant chemotherapy (BLBC group, n = 47; controls, n = 49), both disease-free and overall survival were found to be significantly shorter in the BLBC group (p < 0.05). Conclusions: BLBCs are a distinct clinical and pathological entity, characterised by high nuclear grade, lack of hormone receptors and HER2 expression and a more aggressive clinical course. Standard adjuvant chemotherapy seems to be less effective in these tumours and new therapeutic approaches are indicated.

Hepatitis B surface antigen vector delivers protective cytotoxic T-lymphocyte responses to disease-relevant foreign epitopes

Although hepatitis B surface antigen (HBsAg) per se is highly immunogenic, its use as a vector for the delivery of foreign cytotoxic T-lymphocyte (CTL) epitopes has met with little success because of constraints on HBsAg stability and secretion imposed by the insertion of foreign sequence into critical hydrophobic/amphipathic regions. Using a strategy entailing deletion of DNA encoding HBsAg-specific CTL epitopes and replacement with DNA encoding foreign CTL epitopes, we have derived chimeric HBsAg DNA immunogens which elicited effector and memory CTL responses in vitro, and pathogen- and tumor-protective responses in vivo, when the chimeric HBsAg DNAs were used to immunize mice. We further show that HBsAg DNA recombinant for both respiratory syncytial virus and human papillomavirus CTL epitopes elicited simultaneous responses to both pathogens. These data demonstrate the efficacy of HBsAg DNA as a vector for the delivery of disease-relevant protective CTL responses. They also suggest the applicability of the approach of deriving chimeric HBsAg DNA immunogens simultaneously encoding protective CTL epitopes for multiple diseases. The DNAs we tested formed chimeric HBsAg virus-like particles (VLPs). Thus, our results have implications for the development of vaccination strategies using either chimeric HBsAg DNA or VLP vaccines. HBsAg is the globally administered vaccine for hepatitis B virus infection, inviting its usage as a vector for the delivery of immunogens from other diseases.

Bacterial community structure associated with white band disease in the elkhorn coral Acropora palmata determined using culture-independent 16S rRNA techniques

Culture-independent molecular (16S ribosomal RNA) techniques showed distinct differences in bacterial communities associated with white band disease (WBD) Type I and healthy elkhorn coral Acropora palmata. Differences were apparent at all levels, with a greater diversity present in tissues of diseased colonies. The bacterial community associated with remote, non-diseased coral was distinct from the apparently healthy tissues of infected corals several cm from the disease lesion. This demonstrates a whole-organism effect from what appears to be a localised disease lesion, an effect that has also been recently demonstrated in white plague-like disease in star coral Montastraea annularis. The pattern of bacterial community structure changes was similar to that recently demonstrated for white plague-like disease and black band disease. Some of the changes are likely to be explained by the colonisation of dead and degrading tissues by a micro-heterotroph community adapted to the decomposition of coral tissues. However, specific ribosomal types that are absent from healthy tissues appear consistently in all samples of each of the diseases. These ribotypes are closely related members of a group of alpha-proteobacteria that cause disease, notably juvenile oyster disease, in other marine organisms. It is clearly important that members of this group are isolated for challenge experiments to determine their role in the diseases.

Sequence variation in the Newcastle disease virus genome

Full-length genome sequences of five virulent and five avirulent strains of Newcastle disease virus isolated between 1998 and 2002 in Victoria and New South Wales, Australia were determined. Comparisons between these strains revealed that coding sequence variability in the haemagglutinin-neuraminidase (HN), matrix (M) and phosphoprotein (P) gene sequences appeared to be more variable than in the fusion (F), nucleocapsid (N) and RNA dependent-RNA replicase (L) genes. Sequence analysis of a number of other isolates made during the recent virulent NDV outbreaks, also identified the presence of a number of variants with altered F gene cleavage sites, which resulted in altered biological properties of those viruses. Quasispecies analysis of a number of field isolates indicated the presence of virulent virus in one particular isolate. Gene sequence analysis of the progenitor virus isolated in 1998 showed very little sequence variation when compared to that of a progenitor-like virus isolated in 2001 demonstrating that in the field. viral genome sequence variation appears to be biologically restricted to that of a consensus sequence. (c) 2005 Elsevier B.V. All rights reserved.

The v-MFG test: Investigating maternal, offspring and maternal-fetal genetic incompatibility effects on disease and viability

The MFG test is a family-based association test that detects genetic effects contributing to disease in offspring, including offspring allelic effects, maternal allelic effects and MFG incompatibility effects. Like many other family-based association tests, it assumes that the offspring survival and the offspring-parent genotypes are conditionally independent provided the offspring is affected. However, when the putative disease-increasing locus can affect another competing phenotype, for example, offspring viability, the conditional independence assumption fails and these tests could lead to incorrect conclusions regarding the role of the gene in disease. We propose the v-MFG test to adjust for the genetic effects on one phenotype, e.g., viability, when testing the effects of that locus on another phenotype, e.g., disease. Using genotype data from nuclear families containing parents and at least one affected offspring, the v-MFG test models the distribution of family genotypes conditional on offspring phenotypes. It simultaneously estimates genetic effects on two phenotypes, viability and disease. Simulations show that the v-MFG test produces accurate genetic effect estimates on disease as well as on viability under several different scenarios. It generates accurate type-I error rates and provides adequate power with moderate sample sizes to detect genetic effects on disease risk when viability is reduced. We demonstrate the v-MFG test with HLA-DRB1 data from study participants with rheumatoid arthritis (RA) and their parents, we show that the v-MFG test successfully detects an MFG incompatibility effect on RA while simultaneously adjusting for a possible viability loss.

Ultraviolet absorbance of the mucus of a tropical damselfish: Effects of ontogeny, captivity and disease

The ultraviolet (UV) absorbance of the mucus of a Great Barrier Reef damselfish Pomacentrus amboinensis was investigated with regard to ontogeny and time spent in captivity. The UV absorbance of P. amboinensis mucus increased with fish size and decreased with time spent in captivity. The wavelength of maximum absorbance of the mucus did not change with fish size, but shifted towards shorter wavelengths with increasing time spent in captivity. The UV absorbance of the mucus of fish with 'fin rot' was compared to that of similar healthy individuals, and a significant decrease in UV absorbance of unhealthy fish mucus was detected; no wavelength shifting occurred. Pomacentrus amboinensis appears to sequester mycosporine-like amino acids from the diet in order to protect epithelial tissues from UV damage, and decreases in UV absorbance in captive fish were probably due to insufficient dietary availability.

Viruses: agents of coral disease?

The potential role of viruses in coral disease has only recently begun to receive attention. Here we describe our attempts to determine whether viruses are present in thermally stressed corals Pavona danai, Acropora formosa and Stylophora pistillata and zoanthids Zoanthus sp., and their zooxanthellae. Heat-shocked P. danai, A. formosa and Zoanthus sp. all produced numerous virus-like particles (VLPs) that were evident in the animal tissue, zooxanthellae and the surrounding seawater; VLPs were also seen around heat-shocked freshly isolated zooxanthellae (FIZ) from P. danai and S. pistillata. The most commonly seen VLPs were tail-less, hexagonal and about 40 to 50 nm in diameter, though a diverse range of other VLP morphotypes (e.g. rounded, rod-shaped, droplet-shaped, filamentous) were also present around corals. When VLPs around heat-shocked FIZ from S. pistillata were added to non-stressed FIZ from this coral, they resulted in cell lysis, suggesting that an infectious agent was present; however, analysis with transmission electron microscopy provided no clear evidence of viral infection. The release of diverse VLPs was again apparent when flow cytometry was used to enumerate release by heat-stressed A. formosa nubbins. Our data support the infection of reef corals by viruses, though we cannot yet determine the precise origin (i.e. coral, zooxanthellae and/or surface microbes) of the VLPs seen. Furthermore, genome sequence data are required to establish the presence of viruses unequivocally.