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1.
Internet resource in English, Portuguese | LIS -Health Information Locator | ID: lis-48227

ABSTRACT

A Iniciativa Brasileira de Reprodutibilidade é uma iniciativa multicêntrica para estimar a reprodutibilidade da ciência biomédica brasileira. Financiada pelo Instituto Serrapilheira, nossa meta é reproduzir uma amostra de 60 a 80 experimentos de artigos brasileiros, inicialmente em 3 técnicas diferentes: ensaio de viabilidade celular por MTT, PCR quantitativo - RT-PCR e labirinto elevado em cruz). O sitio web traz informação sobre publicações, atividades, parcerias, eventos e outros projetos do grupo


Subject(s)
Reproducibility of Results , Biomedical Research
2.
Mem Inst Oswaldo Cruz ; 115: e200328, 2020.
Article in English | MEDLINE | ID: mdl-33111750

ABSTRACT

Scientists have increasingly recognised that low methodological and analytical rigour combined with publish-or-perish incentives can make the published scientific literature unreliable. As a response to this, large-scale systematic replications of the literature have emerged as a way to assess the problem empirically. The Brazilian Reproducibility Initiative is one such effort, aimed at estimating the reproducibility of Brazilian biomedical research. Its goal is to perform multicentre replications of a quasi-random sample of at least 60 experiments from Brazilian articles published over a 20-year period, using a set of common laboratory methods. In this article, we describe the challenges of managing a multicentre project with collaborating teams across the country, as well as its successes and failures over the first two years. We end with a brief discussion of the Initiative's current status and its possible future contributions after the project is concluded in 2021.


Subject(s)
Biomedical Research/trends , Research Design , Brazil , Reproducibility of Results
3.
Mem. Inst. Oswaldo Cruz ; 115: e200328, 2020. tab, graf
Article in English | LILACS, Sec. Est. Saúde SP | ID: biblio-1135233

ABSTRACT

Scientists have increasingly recognised that low methodological and analytical rigour combined with publish-or-perish incentives can make the published scientific literature unreliable. As a response to this, large-scale systematic replications of the literature have emerged as a way to assess the problem empirically. The Brazilian Reproducibility Initiative is one such effort, aimed at estimating the reproducibility of Brazilian biomedical research. Its goal is to perform multicentre replications of a quasi-random sample of at least 60 experiments from Brazilian articles published over a 20-year period, using a set of common laboratory methods. In this article, we describe the challenges of managing a multicentre project with collaborating teams across the country, as well as its successes and failures over the first two years. We end with a brief discussion of the Initiative's current status and its possible future contributions after the project is concluded in 2021.


Subject(s)
Research Design , Biomedical Research/trends , Brazil , Reproducibility of Results
4.
Physiol Behav ; 123: 55-61, 2014 Jan 17.
Article in English | MEDLINE | ID: mdl-24096193

ABSTRACT

Cognitive dysfunction is found in patients with brain tumors and there is a need to determine whether it can be replicated in an experimental model. In the present study, the object recognition (OR) paradigm was used to investigate cognitive performance in nude mice, which represent one of the most important animal models available to study human tumors in vivo. Mice with orthotopic xenografts of the human U87MG glioblastoma cell line were trained at 9, 14, and 18days (D9, D14, and D18, respectively) after implantation of 5×10(5) cells. At D9, the mice showed normal behavior when tested 90min or 24h after training and compared to control nude mice. Animals at D14 were still able to discriminate between familiar and novel objects, but exhibited a lower performance than animals at D9. Total impairment in the OR memory was observed when animals were evaluated on D18. These alterations were detected earlier than any other clinical symptoms, which were observed only 22-24days after tumor implantation. There was a significant correlation between the discrimination index (d2) and time after tumor implantation as well as between d2 and tumor volume. These data indicate that the OR task is a robust test to identify early behavior alterations caused by glioblastoma in nude mice. In addition, these results suggest that OR task can be a reliable tool to test the efficacy of new therapies against these tumors.


Subject(s)
Brain Neoplasms/complications , Glioblastoma/complications , Memory Disorders/etiology , Recognition, Psychology/physiology , Animals , Brain Neoplasms/pathology , Disease Models, Animal , Glioblastoma/pathology , Hippocampus/pathology , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Statistics as Topic , Time Factors , Transplantation, Heterologous/methods
5.
Psychopharmacology (Berl) ; 218(3): 461-70, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21556803

ABSTRACT

RATIONALE: D -Serine is an endogenous co-agonist of the N-methyl-D: -aspartate (NMDA) receptor and has been suggested to improve cognitive deficits in schizophrenia. OBJECTIVES: The present study investigates the effects of treatment with D -serine in mice on tasks that require recognition learning and working memory, two cognitive domains that are impaired in schizophrenia. METHODS: We studied the effects of various regimens of systemic administration of D -serine (50 mg/kg/day) on BALB/c mice performing object recognition, T-maze alternation, and open-field exploration tasks. For the object recognition task, we also contrasted the effects of D -serine and D -cycloserine and investigated whether D -serine could reverse alterations induced by subchronic injections of the NMDA antagonist MK-801. D -Serine levels after injections were measured by high-performance liquid chromatography. RESULTS: In the object recognition task, pre-training treatment with D -serine or D -cycloserine significantly enhanced recognition memory 24 h after training. A single administration of D -serine 30 min (but not 6 h) after training produced similar enhancement, suggesting an effect on memory consolidation. Daily treatment with D: -serine enhanced both object recognition and T-maze performance over multiple days and improved short-term memory in MK-801-treated mice. D -Serine treatment did not alter open-field exploration. Behavioral effects were accompanied by increased levels of D -serine in the hippocampus of treated animals. CONCLUSIONS: Our results show that treatment with D -serine can improve performance in tasks related to recognition learning and working memory, suggesting that this agent can be useful for the treatment of disorders involving declines in these cognitive domains.


Subject(s)
Memory, Short-Term/drug effects , Recognition, Psychology/drug effects , Serine/pharmacology , Animals , Behavior, Animal/drug effects , Chromatography, High Pressure Liquid , Cycloserine/pharmacology , Dizocilpine Maleate/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Hippocampus/metabolism , Male , Maze Learning/drug effects , Mice , Mice, Inbred BALB C , Receptors, N-Methyl-D-Aspartate/agonists , Receptors, N-Methyl-D-Aspartate/metabolism , Time Factors
6.
J Neurochem ; 117(3): 538-53, 2011 May.
Article in English | MEDLINE | ID: mdl-21352228

ABSTRACT

In Alzheimer's disease, the amyloid-ß peptide (Aß) interacts with distinct proteins at the cell surface to interfere with synaptic communication. Recent data have implicated the prion protein (PrP(C)) as a putative receptor for Aß. We show here that Aß oligomers signal in cells in a PrP(C)-dependent manner, as might be expected if Aß oligomers use PrP(C) as a receptor. Immunofluorescence, flow cytometry and cell surface protein biotinylation experiments indicated that treatment with Aß oligomers, but not monomers, increased the localization of PrP(C) at the cell surface in cell lines. These results were reproduced in hippocampal neuronal cultures by labeling cell surface PrP(C). In order to understand possible mechanisms involved with this effect of Aß oligomers, we used live cell confocal and total internal reflection microscopy in cell lines. Aß oligomers inhibited the constitutive endocytosis of PrP(C), but we also found that after Aß oligomer-treatment PrP(C) formed more clusters at the cell surface, suggesting the possibility of multiple effects of Aß oligomers. Our experiments show for the first time that Aß oligomers signal in a PrP(C)-dependent way and that they can affect PrP(C) trafficking, increasing its localization at the cell surface.


Subject(s)
Amyloid beta-Peptides/pharmacology , Cell Membrane/metabolism , Neurons/drug effects , Peptide Fragments/pharmacology , PrPC Proteins/metabolism , Analysis of Variance , Animals , Biotinylation/methods , Cell Membrane/drug effects , Cells, Cultured , Embryo, Mammalian , Flow Cytometry/methods , Green Fluorescent Proteins/genetics , Hippocampus/cytology , Humans , Mice , Microscopy, Confocal/methods , Mitogen-Activated Protein Kinase 3/metabolism , Neurons/cytology , Protein Transport/drug effects , Time Factors , Transfection , rab5 GTP-Binding Proteins/metabolism
7.
Neurotox Res ; 18(2): 112-23, 2010 Aug.
Article in English | MEDLINE | ID: mdl-19949915

ABSTRACT

2,4-Dinitrophenol (DNP) is classically known as a mitochondrial uncoupler and, at high concentrations, is toxic to a variety of cells. However, it has recently been shown that, at subtoxic concentrations, DNP protects neurons against a variety of insults and promotes neuronal differentiation and neuritogenesis. The molecular and cellular mechanisms underlying the beneficial neuroactive properties of DNP are still largely unknown. We have now used DNA microarray analysis to investigate changes in gene expression in rat hippocampal neurons in culture treated with low micromolar concentrations of DNP. Under conditions that did not affect neuronal viability, high-energy phosphate levels or mitochondrial oxygen consumption, DNP induced up-regulation of 275 genes and down-regulation of 231 genes. Significantly, several up-regulated genes were linked to intracellular cAMP signaling, known to be involved in neurite outgrowth, synaptic plasticity, and neuronal survival. Differential expression of specific genes was validated by quantitative RT-PCR using independent samples. Results shed light on molecular mechanisms underlying neuroprotection by DNP and point to possible targets for development of novel therapeutics for neurodegenerative disorders.


Subject(s)
2,4-Dinitrophenol/pharmacology , Cyclic AMP/genetics , Hippocampus/metabolism , Neuroprotective Agents/pharmacology , Signal Transduction/genetics , Up-Regulation/drug effects , Adenosine Diphosphate/metabolism , Adenosine Triphosphate/metabolism , Animals , Cell Culture Techniques , Cell Survival/drug effects , Dose-Response Relationship, Drug , Down-Regulation/drug effects , Gene Expression Profiling/methods , Hippocampus/drug effects , Oligonucleotide Array Sequence Analysis/methods , Oxygen Consumption/drug effects , Rats , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects
8.
Curr Alzheimer Res ; 4(3): 263-71, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17627483

ABSTRACT

One of the earliest manifestations of Alzheimer's disease (AD) is the characteristic inability of affected individuals to form new memories. Memory impairment appears to significantly predate the death of nerve cells, implying that neuronal dysfunction is responsible for the pathophysiology of early stage AD. Mounting evidence now indicates that soluble oligomers of the amyloid-beta peptide (Abeta) are the main neurotoxins that lead to early neuronal dysfunction and memory deficits in AD. Cyclic AMP (cAMP) is a central component of intracellular signaling pathways that regulate a wide range of biological functions, including memory. Among other actions, cAMP triggers the phosphorylation and activation of the cAMP responsive element binding protein (CREB), a transcription factor that regulates the expression of genes that are important for long-term memory. Here, we discuss recent evidence suggesting that cAMP enhancing compounds may find applications as neurocognitive enhancers in AD and in other neurological disorders, as well as possible roles of cAMP in the regulation of neuronal regeneration. In particular, we review recent results showing that low concentrations of 2,4-dinitrophenol (DNP) upregulate neuronal cAMP and tau levels, promote neurite outgrowth and neuronal differentiation and block the oligomerization and neurotoxicity of Abeta. Possible implications of these findings in the development of novel therapeutic approaches in AD are discussed.


Subject(s)
2,4-Dinitrophenol/therapeutic use , Alzheimer Disease/drug therapy , Amyloid beta-Peptides/chemistry , Amyloid beta-Peptides/metabolism , 2,4-Dinitrophenol/pharmacology , Amyloid Precursor Protein Secretases , Animals , Cyclic AMP/metabolism , Cyclic AMP Response Element-Binding Protein/metabolism , Gene Expression Regulation/drug effects , Humans , tau Proteins/metabolism
9.
FASEB J ; 19(12): 1627-36, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16195371

ABSTRACT

Neurite outgrowth is a critical event in neuronal development, formation, and remodeling of synapses, response to injury, and regeneration. We examined the effects of 2,4-dinitrophenol (DNP), a recently described blocker of the aggregation and neurotoxicity of the beta-amyloid peptide, on neurite elongation of central neurons. Morphometric analysis of rat embryo hippocampal and cortical neuronal cultures showed that neurite outgrowth was stimulated by DNP. This effect was accompanied by increases in the neuronal levels of the microtubule-associated protein tau and of cyclic adenosine 3',5' monophosphate (cAMP). DNP also promoted cAMP accumulation, increased tau level, neurite outgrowth, and neuronal differentiation in the mouse neuroblastoma cell line N2A. We show that DNP-induced differentiation requires activation of the extracellular signal-regulated kinase (ERK). The finding that DNP promotes neuritogenesis and neuronal differentiation suggests that, in addition to its anti-amyloidogenic actions, it may be a useful lead compound in the development of novel therapeutic approaches targeting neurite dystrophy and synaptic dysfunction in neurodegenerative pathologies such as Alzheimer's disease.


Subject(s)
2,4-Dinitrophenol/pharmacology , Amyloid/chemistry , Neurites/pathology , Neurons/metabolism , Amyloid beta-Peptides/chemistry , Animals , Blotting, Western , Cell Differentiation , Cell Line , Cell Line, Tumor , Cerebral Cortex/pathology , Cyclic AMP/metabolism , Dose-Response Relationship, Drug , Extracellular Signal-Regulated MAP Kinases/metabolism , Hippocampus/cytology , Hippocampus/embryology , MAP Kinase Signaling System , Mice , Microscopy, Fluorescence , Neurodegenerative Diseases/pathology , Oxygen/metabolism , Oxygen Consumption , Peptide Fragments/chemistry , Rats , Reactive Oxygen Species , Time Factors , Uncoupling Agents/pharmacology , tau Proteins/chemistry
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