REM sleep deprivation promotes a dopaminergic influence in the striatal MT2 anxiolytic-like effects

AbstractThe aim of this study was to investigate the possible anxiolytic-like effects of striatal MT2 activation, and its counteraction induced by the selective blockade of this receptor. Furthermore, we analyzed this condition under the paradigm of rapid eye movement (REM) sleep deprivation (REMSD) and the animal model of Parkinson’s disease (PD) induced by rotenone. Male Wistar rats were infused with intranigral rotenone (12μg/μL), and 7 days later were subjected to 24h of REMSD. Afterwards the rats underwent striatal micro-infusions of selective melatonin MT2 receptor agonist, 8-M-PDOT (10μg/μL) or selective melatonin MT2 receptor antagonist, 4-P-PDOT (5μg/μL) or vehicle. Subsequently, the animals were tested in the open-field (OP) and elevated plus maze (EPM) tests. Results indicated that the activation of MT2 receptors produced anxiolytic-like effects. In opposite, the MT2 blockade did not show an anxiogenic-like effect. Besides, REMSD induced anxiolytic-like effects similar to 8-M-PDOT. MT2 activation generated a prevalent locomotor increase compared to MT2 blockade in the context of REMSD. Together, these results suggest a striatal MT2 modulation associated to the REMSD-induced dopaminergic supersensitivity causing a possible dopaminergic influence in the MT2 anxiolytic-like effects in the intranigral rotenone model of PD

Pseudomonas aeruginosa toxin ExoU induces a PAF-dependent impairment of alveolar fibrin turnover secondary to enhanced activation of coagulation and increased expression of plasminogen activator inhibitor-1 in the course of mice pneumosepsis

<p>Abstract</p> <p>Background</p> <p>ExoU, a <it>Pseudomonas aeruginosa </it>cytotoxin with phospholipase A₂activity, was shown to induce vascular hyperpermeability and thrombus formation in a murine model of pneumosepsis. In this study, we investigated the toxin ability to induce alterations in pulmonary fibrinolysis and the contribution of the platelet activating factor (PAF) in the ExoU-induced overexpression of plasminogen activator inhibitor-1 (PAI-1).</p> <p>Methods</p> <p>Mice were intratracheally instilled with the ExoU producing PA103 <it>P. aeruginosa </it>or its mutant with deletion of the <it>exoU </it>gene. After 24 h, animal bronchoalveolar lavage fluids (BALF) were analyzed and lung sections were submitted to fibrin and PAI-1 immunohistochemical localization. Supernatants from A549 airway epithelial cells and THP-1 macrophage cultures infected with both bacterial strains were also analyzed at 24 h post-infection.</p> <p>Results</p> <p>In PA103-infected mice, but not in control animals or in mice infected with the bacterial mutant, extensive fibrin deposition was detected in lung parenchyma and microvasculature whereas mice BALF exhibited elevated tissue factor-dependent procoagulant activity and PAI-1 concentration. ExoU-triggered PAI-1 overexpression was confirmed by immunohistochemistry. In <it>in vitro </it>assays, PA103-infected A549 cells exhibited overexpression of PAI-1 mRNA. Increased concentration of PAI-1 protein was detected in both A549 and THP-1 culture supernatants. Mice treatment with a PAF antagonist prior to PA103 infection reduced significantly PAI-1 concentrations in mice BALF. Similarly, A549 cell treatment with an antibody against PAF receptor significantly reduced PAI-1 mRNA expression and PAI-1 concentrations in cell supernatants, respectively.</p> <p>Conclusion</p> <p>ExoU was shown to induce disturbed fibrin turnover, secondary to enhanced procoagulant and antifibrinolytic activity during <it>P. aeruginosa </it>pneumosepsis, by a PAF-dependent mechanism. Besides its possible pathophysiological relevance, <it>in vitro </it>detection of e<it>xoU </it>gene in bacterial clinical isolates warrants investigation as a predictor of outcome of patients with <it>P. aeruginosa </it>pneumonia/sepsis and as a marker to guide treatment strategies.</p

Gene expression profiling of Trypanosoma cruzi in the presence of heme points to glycosomal metabolic adaptation of epimastigotes inside the vector

Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite, Trypanosoma cruzi, and is transmitted by triatomine insects during its blood meal. Proliferative epimastigotes forms thrive inside the insects in the presence of heme (iron protoporphyrin IX), an abundant product of blood digestion, however little is known about the metabolic outcome of this signaling molecule in the parasite. Trypanosomatids exhibit unusual gene transcription employing a polycistronic transcription mechanism through trans-splicing that regulates its life cycle. Using the Deep Seq transcriptome sequencing we characterized the heme induced transcriptome of epimastigotes and determined that most of the upregulated genes were related to glucose metabolism inside the glycosomes. These results were supported by the upregulation of glycosomal isoforms of PEPCK and fumarate reductase of heme-treated parasites, implying that the fermentation process was favored. Moreover, the downregulation of mitochondrial gene enzymes in the presence of heme also supported the hypothesis that heme shifts the parasite glycosomal glucose metabolism towards aerobic fermentation. These results are examples of the environmental metabolic plasticity inside the vector supporting ATP production, promoting epimastigotes proliferation and survival

‘People lie’: overcoming obstacles to incorporate social science research to biodiversity conservation

Mesmo com o reconhecimento da importância da interdisciplinaridade na conservação da biodiversidade, ainda há resistência em incorporar a pesquisa em ciências sociais (PCS) ao pensamento e à prática conservacionista. As razões para tal resistência podem ser resumidas em três afirmações gerais ainda comumente atribuídas à PCS: 'tem pouca utilidade' e 'menos rigor metodológico' quando comparada à pesquisa em ciências naturais e, sobretudo, é pouco confiável porque 'as pessoas mentem'. Neste ensaio, desenvolvido a partir da experiência dos participantes de uma comunidade de prática, formada por profissionais de diversas áreas e setores relacionados à conservação, e das discussões geradas nesse espaço de aprendizado coletivo, abordamos as limitações e os equívocos por trás das afirmações acima. A PCS não é menos útil na conservação e nem tem menos rigor metodológico do que a pesquisa em ciências naturais, e quando as pessoas mentem para o pesquisador o problema não está na pesquisa em si, mas na relação entre sujeito e pesquisador. Argumentamos que à medida que os conservacionistas se familiarizam com a PCS e que os princípios de equidade e justiça são incorporados aos valores e objetivos da conservação, a importância e necessidade da PCS na conservação tornam-se óbvias, e a falta de confiança entre pesquisador e sujeitos deixa de ser uma preocupação significativa. Capacitar, integrar e apoiar são nossas recomendações básicas para pesquisadores, educadores, gestores e tomadores de decisão nas áreas de conservação, ensino, publicação e financiamento, para que a PCS cumpra plenamente seu papel na conservação.Despite the acknowledged importance of interdisciplinarity in biodiversity conservation, there is still resistance to incorporate social science research (SSR) to both conservationist thinking and practice. The reasons for such a resistance can be summarized in three general statements still commonly attributed to SSR, namely: it is of 'little use' and it has 'less methodological rigor' than research in the natural sciences and, above all, it is unreliable because 'people lie'. The current essay was developed based on the experience of participants of a community of practice (formed by professionals from different fields and sectors  associated with conservation), as well as on discussions held in this space of collective learning. It addresses the limitations and misconceptions behind the aforementioned statements. SSR is not less useful in conservation and not less methodologically rigorous than research conducted in the natural sciences. When researchers are lied to, the problem does not lie on the research itself, but on the subject-researcher relationship. We herein argue that as conservationists become more familiar with SSR, and as principles like equity and justice are incorporated to conservation values and goals, both the importance and need of SSR in conservation become obvious, making the lack of trust between researcher and subjects no longer a significant concern. Increasing capacity, integrating and supporting are our basic recommendations for researchers, educators, managers and decision-makers in the conservation, teaching, publishing and funding fields, so that SSR can fully fulfill its role in conservation

High prevalence of HIV-associated neurocognitive disorders (HAND) in São Paulo City, Brazil

Introduction: HIV-associated neurocognitive disorders (HAND) are the subject of many studies, some of them reporting a prevalence of up to 50 percent. Objectives: To determine the prevalence and factors associated with HIV neurocognitive disorders (HAND) in a cohort of HIV-1-infected patients in São Paulo city, Brazil. Methodology: Descriptive cross-sectional study including 106 HIV-1-infected patients, employing direct interview and neuropsychological tests, applied by trained neuro-psychologists with expertise in the tests. Other, similar assessment tools we used were Brief Neurocognitive Questionnaire, International HIV Dementia Scale, Lawton Instrumental Activities of Daily Living, Hospital Anxiety and Depression Scale, Social Support Scale for People with HIV/Aids, Assessment of Adherence to Antiretroviral Therapy Questionnaire, and a complex neuropsychological assessment. Results: We included 106 patients from May 2015 to April 2018. We found a high prevalence of HAND in our patients (45%), with 27.5% presenting asymptomatic neurological impairment (ANI) and 17.5% mild neurological dysfunction (MND); only one patient presented HIV-associated dementia (HAD) (0.9%). Women were more likely to have MND (52.9%) and the only case of HAD was also female. The high prevalence of neurocognitive disorders was independent of the immunological status, use of efavirenz, or virological control. Conclusions: This study may mirror the national and international scenarios, showing a high prevalence of HAND (45%) and the prevalence of some risk factors, in special among women

Microglial cells are involved in the susceptibility of NADPH oxidase knockout mice to 6-hydroxy-dopamine-induced neurodegeneration

We explored the impact of Nox-2 in modulating inflammatory-mediated microglial responses in the 6-hydroxydopamine (6-OHDA)-induced Parkinson’s disease (PD) model. Nox1 and Nox2 gene expression were found to increase in striatum, whereas a marked increase of Nox2 expression was observed in substantia nigra (SN) of wild-type (wt) mice after PD induction. Gp91phox-/- 6-OHDA-lesioned mice exhibited a significant reduction in the apomorphine-induced rotational behavior, when compared to wt mice. Immunolabeling assays indicated that striatal 6-OHDA injections reduced the number of dopaminergic (DA) neurons in the SN of wt mice. In gp91phox-/- 6-OHDA-lesioned mice the DA degeneration was negligible, suggesting an involvement of Nox in 6-OHDA-mediated SN degeneration. Gp91phox-/- 6-OHDA-lesioned mice treated with minocycline, a tetracycline derivative that exerts multiple anti-inflammatory effects, including microglial inhibition, exhibited increased apomorphine-induced rotational behavior and degeneration of DA neurons after 6-OHDA injections. The same treatment also increased TNF-α release and potentiated NF-κB activation in the SN of gp91phox-/--lesioned mice. Our results demonstrate for the first time that inhibition of microglial cells increases the susceptibility of gp91phox-/- 6-OHDA lesioned mice to develop PD. Blockade of microglia leads to NF-κB activation and TNF-α release into the SN of gp91phox-/- 6-OHDA lesioned mice, a likely mechanism whereby gp91phox-/- 6-OHDA lesioned mice may be more susceptible to develop PD after microglial cell inhibition. Nox2 adds an essential level of regulation to signaling pathways underlying the inflammatory response after PD inductionFAPESPCNPqApplied Neuroscience Nucleus (NAPNA, University of São Paulo

Ingesta de hierro, vitamina A y C, en mujeres

El hierro es un elemento esencial para la fisiología humana normal, ya que cumple funciones vitales. Su carencia se relaciona con anemia. El bajo consumo de hierro es una de las carencias nutricionales más importantes a nivel mundial, dado que afecta a países desarrollados y en vías en desarrollo. Argentina no es ajena a esta problemátic

Reply to "comment on 'Free-Radical Formation by the Peroxidase-Like Catalytic Activity of MFe2O4 (M = Fe, Ni, and Mn) Nanoparticles'"

Recently we have reported a qualitative, quantitative and reproducible study of the generation of free radicals as a result of the surface catalytic activity of Fe3O4, Fe2O3, MnFe2O4 and NiFe2O4 nanoparticles as a function of the Fe2+/Fe3+ oxidation state under different pHs (4.8 and 7.4) and temperatures (25 ºC and 40 ºC) condition. These results were contrasted with those obtained from the in vitro experiments in BV2 cells incubated with dextran-coated magneticnanoparticles. Based on these results we affirm that our ferrite magnetic nanoparticles catalyze the formation of free radicals and the decomposition of H2O2 by a ?peroxidase-like? activity. In a comment on this article, Meunier and A. Robert question two points: First they assert that the measured free radicals are not produced by a peroxidase reaction. Also, based on a different normalization method from those reported in our work, they also discuss that the reaction is not catalytic. Here we reply the arguments of the authors about these two points.Fil: Moreno Maldonado, Ana Carolina. Instituto de Nanociencia de Aragón; ; EspañaFil: Winkler, Elin Lilian. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: Raineri Andersen, Mariana. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: Toro Cordova, Alfonso. Universidad de Zaragoza; EspañaFil: Rodriguez, Luis Miguel. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: Troiani, Horacio Esteban. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mojica Pisciotti, Mary Luz. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vasquez Mansilla, Marcelo. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: Tobia, Dina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: Nadal, Marcela. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: Torres Molina, Teobaldo Enrique. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: de Biasi, Emilio. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: Ramos, Carlos Alberto. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: Goya, Gerardo Fabian. Universidad de Zaragoza; EspañaFil: Zysler, Roberto Daniel. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; ArgentinaFil: Lima, Enio Junior. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad Ejecutora Instituto de Nanociencia y Nanotecnología; Argentin