Low-resolution structural studies of human Stanniocalcin-1

Background  

Stanniocalcins (STCs) represent small glycoprotein hormones, found in all vertebrates, which have been functionally implicated in Calcium homeostasis. However, recent data from mammalian systems indicated that they may be also involved in embryogenesis, tumorigenesis and in the context of the latter especially in angiogenesis. Human STC1 is a 247 amino acids protein with a predicted molecular mass of 27 kDa, but preliminary data suggested its di- or multimerization. The latter in conjunction with alternative splicing and/or post-translational modification gives rise to forms described as STC₅₀ and "big STC", which molecular weights range from 56 to 135 kDa.     

Gangliosides Are Important for the Preservation of the Structure and Organization of RBL-2H3 Mast Cells

Gangliosides are known to be important in many biological processes. However, details concerning the exact function of these glycosphingolipids in cell physiology are poorly understood. In this study, the role of gangliosides present on the surface of rodent mast cells in maintaining cell structure was examined using RBL-2H3 mast cells and two mutant cell lines (E5 and D1) deficient in the gangliosides, GM₁ and the α-galactosyl derivatives of the ganglioside GD_1b. The two deficient cell lines were morphologically different from each other as well as from the parental RBL-2H3 cells. Actin filaments in RBL-2H3 and E5 cells were under the plasma membrane following the spindle shape of the cells, whereas in D1 cells, they were concentrated in large membrane ruffles. Microtubules in RBL-2H3 and E5 cells radiated from the centrosome and were organized into long, straight bundles. The bundles in D1 cells were thicker and organized circumferentially under the plasma membrane. The endoplasmic reticulum, the Golgi complex, and the secretory granule matrix were also altered in the mutant cell lines. These results suggest that the mast cell–specific α-galactosyl derivatives of ganglioside GD_1b and GM₁ are important in maintaining normal cell morphology. (J Histochem Cytochem 58:83–93, 2010)     

Temporal lags in observed and dark diversity in the Anthropocene

Understanding biodiversity changes in the Anthropocene (e.g. due to climate and land‐use change) is an urgent ecological issue. This important task is challenging because global change effects and species responses are dependent on the spatial scales considered. Furthermore, responses are often not immediate. However, both scale and time delay issues can be tackled when, at each study site, we consider dynamics in both observed and dark diversity. Dark diversity includes those species in the region that can potentially establish and thrive in the local sites’ conditions but are currently locally absent. Effectively, dark diversity connects biodiversity at the study site to the regional scales and defines the site‐specific species pool (observed and dark diversity together). With dark diversity, it is possible to decompose species gains and losses into two space‐related components: one associated with local dynamics (species moving from observed to dark diversity and vice versa) and another related to gains and losses of site‐specific species pool (species moving to and from the pool after regional immigration, regional extinction or change in local ecological conditions). Extinction debt and immigration credit are useful to understand dynamics in observed diversity, but delays might happen in species pool changes as well. In this opinion piece we suggest that considering both observed and dark diversity and their temporal dynamics provides a deeper understanding of biodiversity changes. Considering both observed and dark diversity creates opportunities to improve conservation by allowing to identify species that are likely to go regionally extinct as well as foreseeing which of the species that newly arrive to the region are more likely to colonize local sites. Finally, by considering temporal lags and species gains and losses in observed and dark diversity, we combine phenomena at both spatial and temporal scales, providing a novel tool to examine biodiversity change in the Anthropocene.     

Targeted association analysis identified japonica rice varieties achieving Na+/K+ homeostasis without the allelic make-up of the salt tolerant indica variety Nona Bokra

During the last decade, a large number of QTLs and candidate genes for rice tolerance to salinity have been reported. Using 124 SNP and 52 SSR markers, we targeted 14 QTLs and 65 candidate genes for association mapping within the European Rice Core collection (ERCC) comprising 180 japonica accessions. Significant differences in phenotypic response to salinity were observed. Nineteen distinct loci significantly associated with one or more phenotypic response traits were detected. Linkage disequilibrium between these loci was extremely low, indicating a random distribution of favourable alleles in the ERCC. Analysis of the function of these loci indicated that all major tolerance mechanisms were present in the ERCC although the useful level of expression of the different mechanisms was scattered among different accessions. Under moderate salinity stress some accessions achieved the same level of control of Na(+) concentration and Na(+)/K(+) equilibrium as the indica reference variety for salinity tolerance Nona Bokra, although without sharing the same alleles at several loci associated with Na(+) concentration. This suggests (a) differences between indica and japonica subspecies in the effect of QTLs and genes involved in salinity tolerance and (b) further potential for the improvement of tolerance to salinity above the tolerance level of Nona Bokra, provided the underlying mechanisms are complementary at the whole plant level. No accession carried all favourable alleles, or showed the best phenotypic responses for all traits measured. At least nine accessions were needed to assemble the favourable alleles and all the best phenotypic responses. An effective strategy for the accumulation of the favourable alleles would be marker-assisted population improvement.     

Amyloid-β induced toxicity involves ganglioside expression and is sensitive to GM1 neuroprotective action

The effect of Aβ25-35 peptide, in its fibrillar and non-fibrillar forms, on ganglioside expression in organotypic hippocampal slice cultures was investigated. Gangliosides were endogenously labeled with D-[1-C¹⁴] galactose and results showed that Aβ25-35 affected ganglioside expression, depending on the peptide aggregation state, that is, fibrillar Aβ25-35 caused an increase in GM3 labeling and a reduction in GD1b labeling, whereas the non-fibrillar form was able to enhance GM1 expression. Interestingly, GM1 exhibited a neuroprotective effect in this organotypic model, since pre-treatment of the hippocampal slices with GM1 10 μM was able to prevent the toxicity triggered by the fibrillar Aβ25-35, when measured by propidium iodide uptake protocol. With the purpose of further investigating a possible mechanism of action, we analyzed the effect of GM1 treatment (1, 6, 12 and 24 h) upon the Aβ-induced alterations on GSK3β dephosphorylation/activation state. Results demonstrated an important effect after 24-h incubation, with GM1 preventing the Aβ-induced dephosphorylation (activation) of GSK3β, a signaling pathway involved in apoptosis triggering and neuronal death in models of Alzheimer’s disease. Taken together, present results provide a new and important support for ganglioside participation in development of Alzheimer’s disease experimental models and suggest a protective role for GM1 in Aβ-induced toxicity. This may be useful for designing new therapeutic strategies for Alzheimer’s treatment.     

Modulation of ERG Genes Expression in Clinical Isolates of Candida tropicalis Susceptible and Resistant to Fluconazole and Itraconazole

Mycopathologia - Candida tropicalis is a non-albicans Candida specie that causes candidosis in several countries, including Brazil. However, little is known about the mechanisms of drug resistance...     

RNAi pathways in parasitic protists and worms

Tropical diseases caused by parasitic worms and protists are of major public health concern affecting millions of people worldwide. New therapeutic and diagnostic tools would be of great help in dealing with the public health and economic impact of these diseases. RNA interference (RNAi) pathways utilize small non-coding RNAs to regulate gene expression in a sequence-specific manner. In recent years, a wealth of data about the mechanisms and biological functions of RNAi pathways in distinct groups of eukaryotes has been described. Often, RNAi pathways have unique features that are restricted to groups of eukaryotes. The focus of this review will be on RNAi pathways in specific groups of parasitic eukaryotes that include Trypanosoma cruzi, Plasmodium and Schistosoma mansoni. These parasites are the causative agents of Chagas disease, Malaria, and Schistosomiasis, respectively, all of which are tropical diseases that would greatly benefit from the development of new diagnostic and therapeutic tools. In this context, we will describe specific features of RNAi pathways in each of these parasitic eukaryotic groups and discuss how they could be exploited for the treatment of tropical diseases.