Mutant p53 Aggregates into Prion-like Amyloid Oligomers and Fibrils: IMPLICATIONS FOR CANCER

Over 50% of all human cancers lose p53 function. To evaluate the role of aggregation in cancer, we asked whether wild-type (WT) p53 and the hot-spot mutant R248Q could aggregate as amyloids under physiological conditions and whether the mutant could seed aggregation of the wild-type form. The central domains (p53C) of both constructs aggregated into a mixture of oligomers and fibrils. R248Q had a greater tendency to aggregate than WT p53. Full-length p53 aggregated into amyloid-like species that bound thioflavin T. The amyloid nature of the aggregates was demonstrated using x-ray diffraction, electron microscopy, FTIR, dynamic light scattering, cell viabilility assay, and anti-amyloid immunoassay. The x-ray diffraction pattern of the fibrillar aggregates was consistent with the typical conformation of cross β-sheet amyloid fibers with reflexions of 4.7 Å and 10 Å. A seed of R248Q p53C amyloid oligomers and fibrils accelerated the aggregation of WT p53C, a behavior typical of a prion. The R248Q mutant co-localized with amyloid-like species in a breast cancer sample, which further supported its prion-like effect. A tumor cell line containing mutant p53 also revealed massive aggregation of p53 in the nucleus. We conclude that aggregation of p53 into a mixture of oligomers and fibrils sequestrates the native protein into an inactive conformation that is typical of a prionoid. This prion-like behavior of oncogenic p53 mutants provides an explanation for the negative dominance effect and may serve as a potential target for cancer therapy.     

Feeding ecology of fishes: an overview of worldwide publications

The impact of human activity is evident in the depletion of fish populations worldwide. This being the case, there is an urgent need to discover the true biodiversity of the world before the loss rate exceeds its limits. Because the feeding ecology of a species is thoroughly linked to its population dynamics, knowledge of the feeding ecology contributes to the understanding of such subjects as resource partitioning, habitat preferences, prey selection, predation, evolution, competition and energy transfer within and between ecosystems. Such ecological information is of great value when developing conservation strategies and is, therefore, a key element in the protection of species and ecosystems. Our paper reviews the geographic and/or biogeographic regions where the majority of studies concerning the feeding ecology of fish have been conducted, with the goal of identifying regions and/or environments in need of further attention. In addition, we identify which journals published more papers regarding the subject. Our analysis was conducted by assessing studies indexed on the ISI Web of Science database. We detected a lack of data concerning several aspects of the feeding of fish, such as: threatened species; freshwater habitats especially within the Neotropical, Ethiopian and Oriental realms; species rich developing countries; and, when considering marine fish, the Eastern Indo-Pacific region. Considering the calculated weight for each journal, Ecology of Freshwater Fish, Neotropical Ichthyology and Environmental Biology of Fishes were the most important ones. If we ignore these gaps in our knowledge we run the risk of losing a huge amount of information without knowing it ever existed, especially in the fast changing world we face today.     

Convergent adaptations: bitter manioc cultivation systems in fertile anthropogenic dark earths and floodplain soils in central amazonia

SHIFTING CULTIVATION IN THE HUMID TROPICS IS INCREDIBLY DIVERSE, YET RESEARCH TENDS TO FOCUS ON ONE TYPE: long-fallow shifting cultivation. While it is a typical adaptation to the highly-weathered nutrient-poor soils of the Amazonian terra firme, fertile environments in the region offer opportunities for agricultural intensification. We hypothesized that Amazonian people have developed divergent bitter manioc cultivation systems as adaptations to the properties of different soils. We compared bitter manioc cultivation in two nutrient-rich and two nutrient-poor soils, along the middle Madeira River in Central Amazonia. We interviewed 249 farmers in 6 localities, sampled their manioc fields, and carried out genetic analysis of bitter manioc landraces. While cultivation in the two richer soils at different localities was characterized by fast-maturing, low-starch manioc landraces, with shorter cropping periods and shorter fallows, the predominant manioc landraces in these soils were generally not genetically similar. Rather, predominant landraces in each of these two fertile soils have emerged from separate selective trajectories which produced landraces that converged for fast-maturing low-starch traits adapted to intensified swidden systems in fertile soils. This contrasts with the more extensive cultivation systems found in the two poorer soils at different localities, characterized by the prevalence of slow-maturing high-starch landraces, longer cropping periods and longer fallows, typical of previous studies. Farmers plant different assemblages of bitter manioc landraces in different soils and the most popular landraces were shown to exhibit significantly different yields when planted in different soils. Farmers have selected different sets of landraces with different perceived agronomic characteristics, along with different fallow lengths, as adaptations to the specific properties of each agroecological micro-environment. These findings open up new avenues for research and debate concerning the origins, evolution, history and contemporary cultivation of bitter manioc in Amazonia and beyond.     

ANALYSIS OF ANCIENT DNA FROM FOSSIL CORALLINES (CORALLINALES,RHODOPHYTA)1

The field of molecular paleontology has recently made significant contributions to anthropology and biology. Hundreds of ancient DNA studies have been published, but none has targeted fossil coralline algae. Using regions of the SSU gene, we analyzed rDNA from fossil coralline algae of varying ages and states of preservation from Spain, Papua New Guinea (PNG), and the Great Barrier Reef (GBR). Specimens from PNG, GBR, and some localities from Spain did not contain endogenous ancient DNA. Reproducible sequence data were obtained from specimens ～550 years old from near Cadiz, Spain, and from rocky‐shore deposits in Carboneras, Almeria Province of Spain (～78,000 years before present [YBP]). Based on BLAST searches and a phylogenetic analysis of sequences, an undescribed coralline alga belonging to the Melobesioideae was discovered in the Carboneras material as well as the following coralline genera: Jania, Lithophyllum, Lithothamnion, Mesophyllum, and Phymatolithon. DNA from fleshy brown and red macroalgae was also discovered in the specimens from Carboneras. The coralline algae identified using molecular techniques were in agreement with those based on morphological methods. The identified taxa are common in the present‐day southeastern Spain littoral zone. Amino acid racemization, concentration ratios, and specific concentrations failed to show a correlation between biomolecular preservation and PCR amplification success. Results suggest that molecular investigations on fossil algae, although limited by technical difficulties, are feasible. Validity of our results was established using authentication criteria and a self‐critical approach to compliance.     

Extracellular inulinases from Penicillium janczewskii, a fungus isolated from the rhizosphere of Vernonia herbacea (Asteraceae)

Extracellular inulinases from Penicillium janczewskii were obtained from the filtrate of 12 day-old cultures supplemented with inulin from Vernonia herbacea. Crude filtrates and partially-purified enzyme preparations (peaks I and II) were active on inulin, sucrose and raffinose. The apparent M(r) of the enzymes from peaks I and II were 48 and 66 kDa, respectively. The apparent K(m) (mmol l-1) values of peak I were 0.43 for inulin and 18.7 for sucrose; for peak II they were 0.87 and 18.5 for inulin and sucrose, respectively. Their temperature and pH optima were 55 degrees C and 5.0, respectively. Both peaks catalysed the hydrolysis of beta-(2,1) fructans more rapidly than beta-(2,6) fructans. Free fructose was the predominant product released from inulin, indicating that these enzymes display exo-inulinase activity. In view of these characteristics, the yield and the high specific activity towards beta-(2,1) fructans, inulinases from P. janczewskii can be utilized for the preparation of fructose syrup from inulin.     

Familial deletion in Becker type muscular dystrophy within the pXJ region

Summary A family of an isolated patient with Becker muscular dystrophy has been investigated by DNA analysis. Southern blotting and hybridization were performed with six probes (C7, pERT87.15, pERT87.1, pXJ1.1, pXJ2.3, 754) mapping in the Xp21 region. A deletion within the pXJ region was demonstrated in the proband, his mother and all three sisters. The segregation pattern for the restriction fragment length polymorphisms (RFLPs) observed with the pXJ probes as well as with pERT87.15, pERT87.1 and 754 probes indicates that the deletion is of grandpaternal origin.     

Toxicological Aspects of the Essential Oil from Cinnamodendron dinisii

The objective of this study was to determine cytotoxic activity, hemolytic activity, and to evaluate the ability of the essential oil from Cinnamodendron dinisii to induce DNA fragmentation of human lymphocytes. The essential oil was obtained by hydrodistillation. Cytotoxic activity was determined by the MTT method. Hemolytic activity was evaluated by spectrophotometric quantification of hemoglobin released by erythrocytes. Damage to lymphocyte DNA molecules was assessed by the Comet assay. The essential oil under study showed high cytotoxic activity on Vero cells (CC₅₀ = 35.72 μg/mL) and induced hemolysis in both hematocrits, besides leading to the oxidation of hemoglobin released. The genotoxic activity of C. dinisii essential oil was also observed, which induced concentration‐dependent DNA fragmentation of human lymphocytes and, at 50 μL/mL, it was more active than the positive control. The essential oil from C. dinisii has a toxic action, suggesting a special attention in the application of this oil to health‐promoting activities; however, among its components, there are molecules with potential for future application in anticancer therapies.