Montevideo, Uruguay
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Okada D.Y.,University of Sao Paulo | Delforno T.P.,University of Sao Paulo | Etchebehere C.,Instituto Clemente Estable | Varesche M.B.A.,University of Sao Paulo
International Biodeterioration and Biodegradation | Year: 2014

The microbial communities from two upflow anaerobic sludge blanket (UASB) reactors treating synthetic wastewater supplemented with linear alkylbenzene sulfonate (LAS) (RS) and laundry wastewater (RL) were analyzed by pyrosequencing of 16S rRNA genes. A higher LAS degradation rate was observed in RL (82±9%) than RS (45±16%). A high proportion of the LAS removal rate (55-90%) was observed in the PS region for both reactors, most likely due to the low concentration of co-substrates and oxygen diffusion in this region. A microbiological analysis of samples taken at 112 days of operation from the sludge blanket (SB) and the phase-separator (PS) region of both reactors confirmed these findings. The distinct microbial communities found in each reactor resulting from the different wastewaters used were related to the LAS degradation rates obtained. The microbial community from reactor RL was more capable of degrading LAS, most likely because of the presence of xenobiotics. © 2014 Elsevier Ltd.


Aebischer J.,French Institute of Health and Medical Research | Aebischer J.,Aix - Marseille University | Cassina P.,Instituto Clemente Estable | Otsmane B.,French Institute of Health and Medical Research | And 10 more authors.
Cell Death and Differentiation | Year: 2011

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that primarily affects motoneurons in the brain and spinal cord. Dominant mutations in superoxide dismutase-1 (SOD1) cause a familial form of ALS. Mutant SOD1-damaged glial cells contribute to ALS pathogenesis by releasing neurotoxic factors, but the mechanistic basis of the motoneuron-specific elimination is poorly understood. Here, we describe a motoneuron-selective death pathway triggered by activation of lymphotoxin-Β receptor (LT-ΒR) by LIGHT, and operating by a novel signaling scheme. We show that astrocytes expressing mutant SOD1 mediate the selective death of motoneurons through the proinflammatory cytokine interferon-γ (IFNγ), which activates the LIGHT-LT-ΒR death pathway. The expression of LIGHT and LT-ΒR by motoneurons in vivo correlates with the preferential expression of IFNγ by motoneurons and astrocytes at disease onset and symptomatic stage in ALS mice. Importantly, the genetic ablation of Light in an ALS mouse model retards progression, but not onset, of the disease and increases lifespan. We propose that IFNγ contributes to a cross-talk between motoneurons and astrocytes causing the selective loss of some motoneurons following activation of the LIGHT-induced death pathway. © 2011 Macmillan Publishers Limited All rights reserved.


Infante I.,Instituto Clemente Estable | Morel M.A.,Instituto Clemente Estable | Ubalde M.C.,Instituto Clemente Estable | Martinez-Rosales C.,Instituto Clemente Estable | And 3 more authors.
World Journal of Microbiology and Biotechnology | Year: 2010

Wool is a natural animal fiber commonly used in fabrics, but requires physical and chemical processing treatment for such applications. With the aim of developing new woollen textile products using environmentally friendly treatments, proteolytic bacteria were isolated from raw wool samples of Merino sheep and screened for wool-degrading activity. Two isolates were identified as Bacillus megaterium L4 and Bacillus thuringiensis L11 by 16S rRNA gene sequence analysis. Both isolates grew on a minimal medium using wool-fiber or wool-fabric as sole carbon and nitrogen sources. Bacterial growth was correlated with extracellular protease activity, and maximal protease production was in early stationary phase. The exoprotease produced by L11 was found to be a thermo-tolerant metalloprotease stabilized by calcium or magnesium, and had optimum activity at pH 7. 0 and temperature at 40°C. During bacterial growth the wool-fiber lost weight, but it did not show changes in diameter. When wool-fabric was used instead of wool-fiber weight loss and non-shrinking was found. These are encouraging results for textile processing that should be useful for development of new textile products by direct microbial processing. A potential alternative that could be suggested from our study would be to treat wool with wool-degrading microorganisms in order to develop environmentally friendly processes. © Springer Science+Business Media B.V. 2009.


Mansilla S.F.,CONICET | Soria G.,CONICET | Soria G.,National University of Cordoba | Vallerga M.B.,CONICET | And 4 more authors.
Nucleic Acids Research | Year: 2013

Although many genotoxic treatments upregulate the cyclin kinase inhibitor p21, agents such as UV irradiation trigger p21 degradation. This suggests that p21 blocks a process relevant for the cellular response to UV. Here, we show that forced p21 stabilization after UV strongly impairs damaged-DNA replication, which is associated with permanent deficiencies in the recruitment of DNA polymerases from the Y family involved in translesion DNA synthesis), with the accumulation of DNA damage markers and increased genomic instability. Remarkably, such noxious effects disappear when disrupting the proliferating cell nuclear antigen (PCNA) interacting motif of stable p21, thus suggesting that the release of PCNA from p21 interaction is sufficient to allow the recruitment to PCNA of partners (such as Y polymerases) relevant for the UV response. Expression of degradable p21 only transiently delays early replication events and Y polymerase recruitment after UV irradiation. These temporary defects disappear in a manner that correlates with p21 degradation with no detectable consequences on later replication events or genomic stability. Together, our findings suggest that the biological role of UV-triggered p21 degradation is to prevent replication defects by facilitating the tolerance of UV-induced DNA lesions. © The Author(s) 2013. Published by Oxford University Press.


Olivera-Bravo S.,Instituto Clemente Estable | Barbeito L.,Institute Pasteur Montevideo
FEBS Letters | Year: 2015

Astrocytes are crucial for postnatal development of neuronal networks, axon myelination and neurovascular structures. Defects in astrocyte generation or maturation are associated with severe neurological developmental disorders. Glutaric acidemia type I (GAI), an inherited neurometabolic disorder characterized by accumulation of glutaric (GA) and 3-hydroxyglutaric acids, shows a paradigmatic postnatal neuropathology characterized by massive degeneration of neurons in the striatum. While the disorder is caused by genetic mutations on glutaryl-CoA dehydrogenase, the neurological defects usually start months after birth. Pathogenesis of GAI has remained largely unknown, and specifically, it is unclear how accumulation of GAI metabolites may result in neurodegeneration. Recent evidence supports a GAI model involving primary defective astrocyte maturation leading to a co-morbid spectrum of neurologic symptoms similar to those of patients. Astrocytes are vulnerable to GAI metabolites, but instead of dying, they follow long-lasting phenotypic changes leading to striatal neuron degeneration as well as defective myelination and blood brain barrier maturation. Here, we summarized recent findings on the pathogenic role of GA-damaged astrocytes in GAI and discuss if astrocyte dysfunction may be a target of therapeutic interventions. © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


Olivera-Bravo S.,Instituto Clemente Estable | Fernandez A.,University of the Republic of Uruguay | Sarlabos M.N.,Instituto Clemente Estable | Rosillo J.C.,University of the Republic of Uruguay | And 5 more authors.
PLoS ONE | Year: 2011

Background: We have investigated whether an acute metabolic damage to astrocytes during the neonatal period may critically disrupt subsequent brain development, leading to neurodevelopmental disorders. Astrocytes are vulnerable to glutaric acid (GA), a dicarboxylic acid that accumulates in millimolar concentrations in Glutaric Acidemia I (GA-I), an inherited neurometabolic childhood disease characterized by degeneration of striatal neurons. While GA induces astrocyte mitochondrial dysfunction, oxidative stress and subsequent increased proliferation, it is presently unknown whether such astrocytic dysfunction is sufficient to trigger striatal neuronal loss. Methodology/Principal Findings: A single intracerebroventricular dose of GA was administered to rat pups at postnatal day 0 (P0) to induce an acute, transient rise of GA levels in the central nervous system (CNS). GA administration potently elicited proliferation of astrocytes expressing S100β followed by GFAP astrocytosis and nitrotyrosine staining lasting until P45. Remarkably, GA did not induce acute neuronal loss assessed by FluoroJade C and NeuN cell count. Instead, neuronal death appeared several days after GA treatment and progressively increased until P45, suggesting a delayed onset of striatal degeneration. The axonal bundles perforating the striatum were disorganized following GA administration. In cell cultures, GA did not affect survival of either striatal astrocytes or neurons, even at high concentrations. However, astrocytes activated by a short exposure to GA caused neuronal death through the production of soluble factors. Iron porphyrin antioxidants prevented GA-induced astrocyte proliferation and striatal degeneration in vivo, as well as astrocyte-mediated neuronal loss in vitro. Conclusions/Significance: Taken together, these results indicate that a transient metabolic insult with GA induces long lasting phenotypic changes in astrocytes that cause them to promote striatal neuronal death. Pharmacological protection of astrocytes with antioxidants during encephalopatic crisis may prevent astrocyte dysfunction and the ineluctable progression of disease in children with GA-I. © 2011 Olivera-Bravo et al.


PubMed | Instituto Clemente Estable and Institute Pasteur Montevideo
Type: Journal Article | Journal: FEBS letters | Year: 2015

Astrocytes are crucial for postnatal development of neuronal networks, axon myelination and neurovascular structures. Defects in astrocyte generation or maturation are associated with severe neurological developmental disorders. Glutaric acidemia type I (GAI), an inherited neurometabolic disorder characterized by accumulation of glutaric (GA) and 3-hydroxyglutaric acids, shows a paradigmatic postnatal neuropathology characterized by massive degeneration of neurons in the striatum. While the disorder is caused by genetic mutations on glutaryl-CoA dehydrogenase, the neurological defects usually start months after birth. Pathogenesis of GAI has remained largely unknown, and specifically, it is unclear how accumulation of GAI metabolites may result in neurodegeneration. Recent evidence supports a GAI model involving primary defective astrocyte maturation leading to a co-morbid spectrum of neurologic symptoms similar to those of patients. Astrocytes are vulnerable to GAI metabolites, but instead of dying, they follow long-lasting phenotypic changes leading to striatal neuron degeneration as well as defective myelination and blood brain barrier maturation. Here, we summarized recent findings on the pathogenic role of GA-damaged astrocytes in GAI and discuss if astrocyte dysfunction may be a target of therapeutic interventions.


PubMed | Instituto Clemente Estable
Type: | Journal: Frontiers in behavioral neuroscience | Year: 2010

Social behavior diversity is correlated with distinctively distributed patterns of a conserved brain network, which depend on the action of neuroendocrine messengers that integrate extrinsic and intrinsic cues. Arginine vasotocin (AVT) is a key integrator underlying differences in behavior across vertebrate taxa. Weakly electric fish use their electric organ discharges (EODs) as social behavioral displays. We examined the effect of AVT on EOD rate in two species of Gymnotiformes with different social strategies: Gymnotus omarorum, territorial and highly aggressive, and Brachyhypopomus gauderio, gregarious and aggressive only between breeding males. AVT induced a long-lasting and progressive increase of EOD rate in isolated B. gauderio, partially blocked by the V1a AVT receptor antagonist (Manning compound, MC), and had no effects in G. omarorum. AVT also induced a long-lasting increase in the firing rate (prevented by MC) of the isolated medullary pacemaker nucleus (PN) of B. gauderio when tested in an in vitro preparation, indicating that the PN is the direct effector of AVT actions. AVT is involved in the seasonal, social context-dependent nocturnal increase of EOD rate that has been recently described in B. gauderio to play a role in mate selection. AVT produced the additional nocturnal increase of EOD rate in non-breeding males, whereas MC blocked it in breeding males. Also, AVT induced a larger EOD rate increase in reproductive dyads than in agonistic encounters. We demonstrated interspecific, seasonal, and context-dependent actions of AVT on the PN that contribute to the understanding of the mechanisms the brain uses to shape sociality.


NAAG is one of the neuropeptides found in highest concentrations in the CNS. The presence of micromolar concentrations of NAAG in human CSF was demonstrated by using two different and complementary analytical approaches: 1) isocratic separation of endogenous NAAG by reverse-phase high performance liquid chromatography (HPLC) with dual wavelength detection and 2) derivatization of endogenous NAAG with acidic methanol and subsequent HPLC analysis of the derivative NAAG-trimethyl ester. The NAAG concentration was between 0.44mol/l and 7.16mol/l (mean of 2.19 1.53mol/l) in CSF samples from forty neuropsychiatric patients. Endogenous NAAG or [(3)H]NAAG added to CSF samples were not significantly degraded when the CSF was incubated at 37C during one hour, suggesting that the peptide is a highly stable metabolite in the subarachnoid space. In addition, evidence is provided that NAAG does not present a concentration gradient along the lower subarachnoid space.


PubMed | Instituto Clemente Estable
Type: Journal Article | Journal: PloS one | Year: 2011

We have investigated whether an acute metabolic damage to astrocytes during the neonatal period may critically disrupt subsequent brain development, leading to neurodevelopmental disorders. Astrocytes are vulnerable to glutaric acid (GA), a dicarboxylic acid that accumulates in millimolar concentrations in Glutaric Acidemia I (GA-I), an inherited neurometabolic childhood disease characterized by degeneration of striatal neurons. While GA induces astrocyte mitochondrial dysfunction, oxidative stress and subsequent increased proliferation, it is presently unknown whether such astrocytic dysfunction is sufficient to trigger striatal neuronal loss.A single intracerebroventricular dose of GA was administered to rat pups at postnatal day 0 (P0) to induce an acute, transient rise of GA levels in the central nervous system (CNS). GA administration potently elicited proliferation of astrocytes expressing S100 followed by GFAP astrocytosis and nitrotyrosine staining lasting until P45. Remarkably, GA did not induce acute neuronal loss assessed by FluoroJade C and NeuN cell count. Instead, neuronal death appeared several days after GA treatment and progressively increased until P45, suggesting a delayed onset of striatal degeneration. The axonal bundles perforating the striatum were disorganized following GA administration. In cell cultures, GA did not affect survival of either striatal astrocytes or neurons, even at high concentrations. However, astrocytes activated by a short exposure to GA caused neuronal death through the production of soluble factors. Iron porphyrin antioxidants prevented GA-induced astrocyte proliferation and striatal degeneration in vivo, as well as astrocyte-mediated neuronal loss in vitro.Taken together, these results indicate that a transient metabolic insult with GA induces long lasting phenotypic changes in astrocytes that cause them to promote striatal neuronal death. Pharmacological protection of astrocytes with antioxidants during encephalopatic crisis may prevent astrocyte dysfunction and the ineluctable progression of disease in children with GA-I.

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