Indomethacin treatment reduces microglia activation and increases numbers of neuroblasts in the subventricular zone and ischaemic striatum after focal ischaemia

Neuroblasts from the subventricular zone (SVZ) migrate to striatum following stroke, but most of them die in the ischaemic milieu and this can be related to exacerbated microglial activation. Here, we explored the effects of the non-steroidal anti-inflammatory indomethacin on microglial activation, neuronal preservation and neuroblast migration following experimental striatal stroke in adult rats. Animals were submitted to endothelin-1 (ET-1)-induced focal striatal ischaemia and were treated with indomethacin or sterile saline (i.p.) for 7 days, being perfused after 8 or 14 days. Immunohistochemistry was performed to assess neuronal loss (anti-NeuN), microglial activation (anti-Iba1, ED1) and migrating neuroblasts (anti-DCX) by counting NeuN, ED1 and DCX-positive cells in the ischaemic striatum or SVZ. Indomethacin treatment reduced microglia activation and the number of ED1⁺ cells in both 8 and 14 days post injury as compared with controls. There was an increase in the number of DCX⁺ cells in both SVZ and striatum at the same survival times. Moreover, there was a decrease in the number of NeuN⁺ cells in indomethacin-treated animals as compared with the control group at 8 days but not after 14 days post injury. Our results suggest that indomethacin treatment modulates microglia activation, contributing to increased neuroblast proliferation in the SVZ and migration to the ischaemic striatum following stroke.     

Morphology and Phylogeny of Calyptospora paranaidji n. sp. (Eimeriorina: Calyptosporidae), an Apicomplexan Parasite of the Hepatic Tissue of Cichla piquiti Kullander & Ferreira, 2006, From a Reservoir in the Brazilian Amazon Region

The coccidians of the family Calyptosporidae are parasites of the tissue and organs of fish and aquatic invertebrates, in particular in the tropical region. In contrast with other apicomplexans of the suborder Eimeriorina, the diversity and ecology of the species of the genus Calyptospora have been poorly investigated, resulting in a lacuna that restricts the understanding of the distribution and prevalence of this group of eukaryote microparasites in the Amazon region. In the present study, the integrated comparative analysis of morphological characteristics, histological and structural traits, and the sequences of a fragment of the 18S rRNA gene, provides support for the identification of a new species of Calyptospora, found parasitizing the hepatic tissue of the piscivorous blue peacock bass, Cichla piquiti, captured in the reservoir of the Estreito hydroelectric dam on the middle Tocantins River in northern Brazil. This new species was named Calyptospora paranaidji n. sp.     

Insulin Accelerates Seedling Growth of Canavalia ensiformis (Jack bean)

Insulin is a 6 kDa peptide hormone that activates several metabolic processes and cellular growth. Germination studies showed that insulin, vanadyl sulphate (an insulin mimetic compound), tyrphostin (an inhibitor of insulin receptor kinase activity), pinitol (a chiro inositol analogue) and glucose were able to accelerate Canavalia ensiformis (Jack bean) seedling radicle and epicotyl development. Immunofluorescence microscopy analysis showed that proteins binding to insulin, insulin receptor and phosphoserine antibodies are localized in an internal layer of the C. ensiformis seed coat. These results and others previously reported from our laboratory suggest that insulin, insulin receptor and phosphoserine proteins could be components of signalling pathways akin to those present in animals.     

Rational confederation of genes and diseases: NGS interpretation via GeneCards,MalaCards and VarElect

Background

A key challenge in the realm of human disease research is next generation sequencing (NGS) interpretation, whereby identified filtered variant-harboring genes are associated with a patient’s disease phenotypes. This necessitates bioinformatics tools linked to comprehensive knowledgebases. The GeneCards suite databases, which include GeneCards (human genes), MalaCards (human diseases) and PathCards (human pathways) together with additional tools, are presented with the focus on MalaCards utility for NGS interpretation as well as for large scale bioinformatic analyses.

Results

VarElect, our NGS interpretation tool, leverages the broad information in the GeneCards suite databases. MalaCards algorithms unify disease-related terms and annotations from 69 sources. Further, MalaCards defines hierarchical relatedness—aliases, disease families, a related diseases network, categories and ontological classifications. GeneCards and MalaCards delineate and share a multi-tiered, scored gene-disease network, with stringency levels, including the definition of elite status—high quality gene-disease pairs, coming from manually curated trustworthy sources, that includes 4500 genes for 8000 diseases. This unique resource is key to NGS interpretation by VarElect. VarElect, a comprehensive search tool that helps infer both direct and indirect links between genes and user-supplied disease/phenotype terms, is robustly strengthened by the information found in MalaCards. The indirect mode benefits from GeneCards’ diverse gene-to-gene relationships, including SuperPaths—integrated biological pathways from 12 information sources. We are currently adding an important information layer in the form of “disease SuperPaths”, generated from the gene-disease matrix by an algorithm similar to that previously employed for biological pathway unification. This allows the discovery of novel gene-disease and disease–disease relationships. The advent of whole genome sequencing necessitates capacities to go beyond protein coding genes. GeneCards is highly useful in this respect, as it also addresses 101,976 non-protein-coding RNA genes. In a more recent development, we are currently adding an inclusive map of regulatory elements and their inferred target genes, generated by integration from 4 resources.

Conclusions

MalaCards provides a rich big-data scaffold for in silico biomedical discovery within the gene-disease universe. VarElect, which depends significantly on both GeneCards and MalaCards power, is a potent tool for supporting the interpretation of wet-lab experiments, notably NGS analyses of disease. The GeneCards suite has thus transcended its 2-decade role in biomedical research, maturing into a key player in clinical investigation.

     

Lanfrediella amphicirrus gen. nov. sp. nov. Nematotaeniidae (Cestoda: Cyclophyllidea), a tapeworm parasite of Rhinella marina (Linnaeus, 1758) (Amphibia: Bufonidae)

The family Nematotaeniidae, tapeworms commonly found in the small intestines of amphibians and reptiles, includes 27 recognised species distributed among four genera: Bitegmen Jones, Cylindrotaenia Jewell, Distoichometra Dickey and Nematotaenia Lühe. The taxonomy of these cestodes is poorly defined, due in part to the difficulties of observing many anatomical traits. This study presents and describes a new genus and species of nematotaeniid parasite found in cane toads (Rhinella marina) from eastern Brazilian Amazonia. The cestodes were collected during the necropsy of 20 hosts captured in the urban area of Belém, Pará. The specimens were fixed and processed for light microscopy, scanning electron microscopy (SEM) and three-dimensional (3D) reconstruction. Samples were also collected for molecular analyses. The specimens presented a cylindrical body, two testes and paruterine organs. However, they could not be allocated to any of the four existing nematotaeniid genera due to the presence of two each of dorsal compact medullary testes, cirri, cirrus pouches, genital pores, ovaries and vitelline glands per mature segment. Lanfrediella amphicirrus gen. nov. sp. nov. is the first nematotaeniid studied using Historesin analysis, SEM and 3D reconstruction, and it is the second taxon for which molecular data have been deposited in GenBank.     

Action of sisal (Agave sisalana, Perrine) extract in the in vitro development of sheep and goat gastrointestinal nematodes

Active compounds from Agave sisalana with antiparasitic action against gastrointestinal nematodes (GINs) could be an alternative to diversify the range of parasite management methods in the livestock sector. The objective of this study was to evaluate the in vitro action of A. sisalana extract on the development of sheep and goat GINs. The extract, obtained from shredded sisal leaves, was utilized at various concentrations in the egg hatch test (EHT), larval development test (LDT), larval feeding inhibition test (LFIT) and adult motility test (AMT). The LC(50) and LC(95) in the EHT were 6.90 and 24.79 mg/mL, in the LDT were 0.041 and 0.067 mg/mL and in the LFIT were 0.053 and 0.24 mg/mL, respectively, showing a dose-dependent relationship. The development and feeding inhibition on L(1) were both 100% at a dose of 0.12 mg/mL. In the AMT there was 100% inhibition at 75 mg/mL after 24h of exposure. The extract of A. sisalana therefore demonstrated significant action on L(1) at 0.12 mg/mL. So, if part of the A. sisalana extract passes through the animal's gastrointestinal system, this material can have a significant effect on the parasites in the feces. This is an interesting approach because it can drastically reduce the pasture contamination as well as the infection of herds.     

Sesquiterpenes and a phenylpropanoid from Cordia trichotoma

Two new secondary metabolites, the phenylpropanoid 3-(2',4',5'-trimethoxyphenyl)propanoic acid (1) and the sesquiterpene (+)-1beta,4beta,6alpha-trihydroxyeudesmane (2) were isolated from the heartwood of Cordia trichotoma Vell., along with the known sesquiterpenes (-)-1beta,4beta,7alpha-trihydroxyeudesmane (3) and (+)-1beta,4beta,11-trihydroxyoppositane (4). Their structures were elucidated by means of spectroscopic data interpretation, mainly 1D and 2D NMR and mass spectrometry.