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.     

Use of statistical tools in the study of the conditions of predation of Duddingtonia flagrans versus Panagrellus sp

The objective of the present work was to study the conditions of predation of Duddingtonia flagrans conidia versus Panagrellus sp using response surface methodology. Conidia of D. flagrans (AC001) isolate were transferred into water-agar (WA) culture media at different pHs and different concentrations defined according to Central Composite Design (CCD). Five different concentrations of D. flagrans conidia: (1292, 500, 1000, 1500 and 1707) were used. For 2%WA media were used the following pHs were used: 6.29, 6.5, 7.0, 7.5 and 7.71. The response of the design corresponded to the number of larvae (transformed to square root scale) observed at the end of the experiment (10 days). At the tenth day, the non predated larvae were recovered in the Petri dishes. The results showed that 2%WA media at pH 7.0 contributed to improve the predatory activity of conidia of D. flagrans, and therefore this tool may be used in future studies under laboratory and natural conditions.     

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.     

Performance of LBSap Vaccine after Intradermal Challenge with L. infantum and Saliva of Lu. longipalpis: Immunogenicity and Parasitological Evaluation

In the last decade, the search for new vaccines against canine visceral leishmaniasis has intensified. However, the pattern related to immune protection during long periods after experimental infection in vaccine trials is still not fully understood. Herein, we investigated the immunogenicity and parasitological levels after intradermal challenge with Leishmania infantum plus salivary gland extract in dogs immunized with a vaccine composed of L. braziliensis antigens plus saponin as an adjuvant (LBSap vaccine). The LBSap vaccine elicited higher levels of total anti-Leishmania IgG as well as both IgG1 and IgG2. Furthermore, dogs vaccinated had increased levels of lymphocytes, particularly circulating B cells (CD21⁺) and both CD4⁺ and CD8⁺ T lymphocytes. LBSap also elicited an intense in vitro cell proliferation associated with higher levels of CD4⁺ T lymphocytes specific for vaccine soluble antigen and soluble lysate of L. infantum antigen even 885 days after experimental challenge. Furthermore, LBSap vaccinated dogs presented high IFN-γ and low IL-10 and TGF-β1 expression in spleen with significant reduction of parasite load in this tissue. Overall, our results validate the potential of LBSap vaccine to protect against L. infantum experimental infection and strongly support further evaluation of efficiency of LBSap against CVL in natural infection conditions.     

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.     

miR-17-5p Regulates Endocytic Trafficking through Targeting TBC1D2/Armus

miRNA cluster miR-17-92 is known as oncomir-1 due to its potent oncogenic function. miR-17-92 is a polycistronic cluster that encodes 6 miRNAs, and can both facilitate and inhibit cell proliferation. Known targets of miRNAs encoded by this cluster are largely regulators of cell cycle progression and apoptosis. Here, we show that miRNAs encoded by this cluster and sharing the seed sequence of miR-17 exert their influence on one of the most essential cellular processes – endocytic trafficking. By mRNA expression analysis we identified that regulation of endocytic trafficking by miR-17 can potentially be achieved by targeting of a number of trafficking regulators. We have thoroughly validated TBC1D2/Armus, a GAP of Rab7 GTPase, as a novel target of miR-17. Our study reveals regulation of endocytic trafficking as a novel function of miR-17, which might act cooperatively with other functions of miR-17 and related miRNAs in health and disease.     

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.     

Effects of food quality on growth and biochemical composition of a calanoid copepod,Argyrodiaptomus furcatus,and its importance as a natural food source for larvae of two tropical fishes

Growth, reproduction and biochemical composition were analyzed for the copepod Argyrodiaptomus furcatus fed on the alga Ankistrodesmus gracilis grown in different media. The ingestion of this copepod by larvae of two species of tropical fishes was also evaluated. The mean peak density of the copepod population was 1369 individuals l^–1 for all four diets used, and the highest was 1387 individuals l^–1 on diet ARV (algae + ration + vitamins). A small copepod, A. furcatus tends to have a short life span. The smallest females did not attain maturity in the shortest time on all diets used. Food quality may play a major role in the dynamics of the biochemical composition of this copepod. Argyrodiaptomus furcatus was a more important food item for larvae of tambaqui (Colossoma macropomum) than of pacu (Piaractus mesopotamicus). However, it made up a large part of the gut contents of larvae of both species.