A New and Fast Technique to Generate Offspring after Germ Cells Transplantation in Adult Fish: The Nile Tilapia (Oreochromis niloticus) Model

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

High Content Screening of a Kinase-Focused Library Reveals Compounds Broadly-Active against Dengue Viruses

Dengue virus is a mosquito-borne flavivirus that has a large impact in global health. It is considered as one of the medically important arboviruses, and developing a preventive or therapeutic solution remains a top priority in the medical and scientific community. Drug discovery programs for potential dengue antivirals have increased dramatically over the last decade, largely in part to the introduction of high-throughput assays. In this study, we have developed an image-based dengue high-throughput/high-content assay (HT/HCA) using an innovative computer vision approach to screen a kinase-focused library for anti-dengue compounds. Using this dengue HT/HCA, we identified a group of compounds with a 4-(1-aminoethyl)-N-methylthiazol-2-amine as a common core structure that inhibits dengue viral infection in a human liver-derived cell line (Huh-7.5 cells). Compounds CND1201, CND1203 and CND1243 exhibited strong antiviral activities against all four dengue serotypes. Plaque reduction and time-of-addition assays suggests that these compounds interfere with the late stage of viral infection cycle. These findings demonstrate that our image-based dengue HT/HCA is a reliable tool that can be used to screen various chemical libraries for potential dengue antiviral candidates. © 2013 Cruz et al.

Effect of melatonin on tumor growth and angiogenesis in xenograft model of breast cancer

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Histopathological Changes by the Use of Soft Reline Materials: A Rat Model Study

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Characterization of Chemically Induced Ovarian Carcinomas in an Ethanol-Preferring Rat Model: Influence of Long-Term Melatonin Treatment

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Ginkgo Biloba Extract in an Animal Model of Parkinson's Disease: A Systematic Review

Although the exact cause of neuronal loss in Parkinson's disease is not known, evidence points to oxidative stress and the production of reactive oxygen species as the main events that occur in the substantia nigra pars compacta of the brain of parkinsonians. EGb761 is an extract of the leaves from the Ginkgo biloba tree that has been reported as an antioxidant and neuroprotective agent. The objective of this work was to perform a systematic review of the studies that analysed the effect of Ginkgo biloba extract on Parkinson's disease or Parkinsonism. This research was conducted using the following databases: Medline, PsycInfo, Cinahl, Sigle, Lilacs, Scielo, Cochrane Library, and Embase. Initially, we selected 32 articles. After a more detailed analysis, only 10 articles remained. One of the hypotheses for the positive effect of EGb761 on Parkinson's disease is the reduction or inhibition of monoamine-oxidase activity. This enzyme metabolises dopamine, inducing the formation of free radicals, which in turn damage nigrostriatal neurons. Another hypothesis is that the neuroprotective effect of EGb761 against 6-hydroxydopamine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and MPP+ toxins. As there are few studies on the effect of EGb761 on humans, this review could contribute new data to further the discussion of this issue.

Predictive Usefulness of Urinary Biomarkers for the Identification of Cyclosporine A-Induced Nephrotoxicity in a Rat Model

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Synergistic Anti-Inflammatory Activity of the Antimicrobial Peptides Human Beta-Defensin-3 (hBD-3) and Cathelicidin (LL-37) in a Three-Dimensional Co-Culture Model of Gingival Epithelial Cells and Fibroblasts

Given the spread of antibiotic resistance in bacterial pathogens, antimicrobial peptides that can also modulate the immune response may be a novel approach for effectively controlling periodontal infections. In the present study, we used a three-dimensional (3D) co-culture model of gingival epithelial cells and fibroblasts stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS) to investigate the anti-inflammatory properties of human beta-defensin-3 (hBD-3) and cathelicidin (LL-37) and to determine whether these antimicrobial peptides can act in synergy. The 3D co-culture model composed of gingival fibroblasts embedded in a collagen matrix overlaid with gingival epithelial cells had a synergistic effect with respect to the secretion of IL-6 and IL-8 in response to LPS stimulation compared to fibroblasts and epithelial cells alone. The 3D co-culture model was stimulated with non-cytotoxic concentrations of hBD-3 (10 and 20 mu M) and LL-37 (0.1 and 0.2 mu M) individually and in combination in the presence of A. actinomycetemcomitans LPS. A multiplex ELISA assay was used to quantify the secretion of 41 different cytokines. hBD-3 and LL-37 acted in synergy to reduce the secretion of GRO-alpha, G-CSF, IP-10, IL-6, and MCP-1, but only had an additive effect on reducing the secretion of IL-8 in response to A. actinomycetemcomitans LPS stimulation. The present study showed that hBD-3 acted in synergy with LL-37 to reduce the secretion of cytokines by an LPS-stimulated 3D model of gingival mucosa. This combination of antimicrobial peptides thus shows promising potential as an adjunctive therapy for treating inflammatory periodontitis.

Implications of the Adoption of BISAC for Classifying Library Collections

We analysed the written statements of libraries that have adopted the bookstore model for coherence or lack of coherence with common public library guidelines. We used a text-based Foucauldian genealogical discourse analysis to investigate the written statements used by libraries that have adopted BISAC and other aspects of the bookstore model. Libraries adopting bookstore models such as BISAC should consider the potential consequences of adopting a commercial model for a public entity. This paper has practical implications for libraries considering adopting any aspect of the bookstore model, but especially the BISAC system, as it examines the potential benefits and drawbacks of the bookstore model popular in some libraries with respect to the purposes and goals of public libraries. BISAC application in libraries seems to be part of a trend of applying commercial practices, values and terminology in libraries, perhaps not with the purpose of replacing libraries with bookstores, but with the aim for both systems to converge into a new kind of commercial entity and context. The influence of one kind of system over the other does not seem to be totally reciprocal, since the application of library practices, values and standards in bookstores has not had the same effects and resonance as has occurred in the opposite direction.

Interaction between fiscal and monetary policy in a dynamic nonlinear model

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

De novo transcriptome assembly for a non-model species, the blood-sucking bug Triatoma brasiliensis, a vector of Chagas disease

High throughput sequencing (HTS) provides new research opportunities for work on non-model organisms, such as differential expression studies between populations exposed to different environmental conditions. However, such transcriptomic studies first require the production of a reference assembly. The choice of sampling procedure, sequencing strategy and assembly workflow is crucial. To develop a reliable reference transcriptome for Triatoma brasiliensis, the major Chagas disease vector in Northeastern Brazil, different de novo assembly protocols were generated using various datasets and software. Both 454 and Illumina sequencing technologies were applied on RNA extracted from antennae and mouthparts from single or pooled individuals. The 454 library yielded 278 Mb. Fifteen Illumina libraries were constructed and yielded nearly 360 million RNA-seq single reads and 46 million RNA-seq paired-end reads for nearly 45 Gb. For the 454 reads, we used three assemblers, Newbler, CAP3 and/or MIRA and for the Illumina reads, the Trinity assembler. Ten assembly workflows were compared using these programs separately or in combination. To compare the assemblies obtained, quantitative and qualitative criteria were used, including contig length, N50, contig number and the percentage of chimeric contigs. Completeness of the assemblies was estimated using the CEGMA pipeline. The best assembly (57,657 contigs, completeness of 80 %, < 1 % chimeric contigs) was a hybrid assembly leading to recommend the use of (1) a single individual with large representation of biological tissues, (2) merging both long reads and short paired-end Illumina reads, (3) several assemblers in order to combine the specific advantages of each.

Expression of cellular components in granulomatous inflammatory response in piaractus mesopotamicus model

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Ac2-26 mimetic peptide of annexin A1 inhibits local and systemic inflammatory processes induced by bothrops moojeni venom and the lys-49 phospholipase A2 in a rat model

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Chronic VEGF Blockade Worsens Glomerular Injury in the Remnant Kidney Model

VEGF inhibition can promote renal vascular and parenchymal injury, causing proteinuria, hypertension and thrombotic microangiopathy. The mechanisms underlying these side effects are unclear. We investigated the renal effects of the administration, during 45 days, of sunitinib (Su), a VEGF receptor inhibitor, to rats with 5/6 renal ablation (Nx). Adult male Munich-Wistar rats were distributed among groups S+V, sham-operated rats receiving vehicle only; S+Su, S rats given Su, 4 mg/kg/day; Nx+V, Nx rats receiving V; and Nx+Su, Nx rats receiving Su. Su caused no change in Group S. Seven and 45 days after renal ablation, renal cortical interstitium was expanded, in association with rarefaction of peritubular capillaries. Su did not worsen hypertension, proteinuria or interstitial expansion, nor did it affect capillary rarefaction, suggesting little angiogenic activity in this model. Nx animals exhibited glomerulosclerosis (GS), which was aggravated by Su. This effect could not be explained by podocyte damage, nor could it be ascribed to tuft hypertrophy or hyperplasia. GS may have derived from organization of capillary microthrombi, frequently observed in Group Nx+Su. Treatment with Su did not reduce the fractional glomerular endothelial area, suggesting functional rather than structural cell injury. Chronic VEGF inhibition has little effect on normal rats, but can affect glomerular endothelium when renal damage is already present.