19 research outputs found

    Cooperation between Apoptotic and Viable Metacyclics Enhances the Pathogenesis of Leishmaniasis

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    Mimicking mammalian apoptotic cells by exposing phosphatidylserine (PS) is a strategy used by virus and parasitic protozoa to escape host protective inflammatory responses. With Leishmania amazonensis (La), apoptotic mimicry is a prerogative of the intramacrophagic amastigote form of the parasite and is modulated by the host. Now we show that differently from what happens with amastigotes, promastigotes exposing PS are non-viable, non-infective cells, undergoing apoptotic death. As part of the normal metacyclogenic process occurring in axenic cultures and in the gut of sand fly vectors, a sub-population of metacyclic promastigotes exposes PS. Apoptotic death of the purified PS-positive (PSPOS) sub-population was confirmed by TUNEL staining and DNA laddering. Transmission electron microscopy revealed morphological alterations in PSPOS metacyclics such as DNA condensation, cytoplasm degradation and mitochondrion and kinetoplast destruction, both in in vitro cultures and in sand fly guts. TUNELPOS promastigotes were detected only in the anterior midgut to foregut boundary of infected sand flies. Interestingly, caspase inhibitors modulated parasite death and PS exposure, when added to parasite cultures in a specific time window. Efficient in vitro macrophage infections and in vivo lesions only occur when PSPOS and PS-negative (PSNEG) parasites were simultaneously added to the cell culture or inoculated in the mammalian host. The viable PSNEG promastigote was the infective form, as shown by following the fate of fluorescently labeled parasites, while the PSPOS apoptotic sub-population inhibited host macrophage inflammatory response. PS exposure and macrophage inhibition by a subpopulation of promastigotes is a different mechanism than the one previously described with amastigotes, where the entire population exposes PS. Both mechanisms co-exist and play a role in the transmission and development of the disease in case of infection by La. Since both processes confer selective advantages to the infective microorganism they justify the occurrence of apoptotic features in a unicellular pathogen

    Public dataset for evaluating Port Scan and Slowloris attacks

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    Dataset used in the paper: Using Quadratic Discriminant Analysis by Intrusion Detection Systems for Port Scan and Slowloris Attack Classificatio

    Neuronal Assemblies Evidence Distributed Interactions within a Tactile Discrimination Task in Rats

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    Accumulating evidence suggests that neural interactions are distributed and relate to animal behavior, but many open questions remain. The neural assembly hypothesis, formulated by Hebb, states that synchronously active single neurons may transiently organize into functional neural circuits—neuronal assemblies (NAs)—and that would constitute the fundamental unit of information processing in the brain. However, the formation, vanishing, and temporal evolution of NAs are not fully understood. In particular, characterizing NAs in multiple brain regions over the course of behavioral tasks is relevant to assess the highly distributed nature of brain processing. In the context of NA characterization, active tactile discrimination tasks with rats are elucidative because they engage several cortical areas in the processing of information that are otherwise masked in passive or anesthetized scenarios. In this work, we investigate the dynamic formation of NAs within and among four different cortical regions in long-range fronto-parieto-occipital networks (primary somatosensory, primary visual, prefrontal, and posterior parietal cortices), simultaneously recorded from seven rats engaged in an active tactile discrimination task. Our results first confirm that task-related neuronal firing rate dynamics in all four regions is significantly modulated. Notably, a support vector machine decoder reveals that neural populations contain more information about the tactile stimulus than the majority of single neurons alone. Then, over the course of the task, we identify the emergence and vanishing of NAs whose participating neurons are shown to contain more information about animal behavior than randomly chosen neurons. Taken together, our results further support the role of multiple and distributed neurons as the functional unit of information processing in the brain (NA hypothesis) and their link to active animal behavior

    Non-N-methyl-d-aspartate glutamate receptors in the lateral hypothalamus modulate cardiac baroreflex responses in conscious rats

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    P>In the present study, we investigated the effects of inhibition of the lateral hypothalamus (LH) neurotransmission with bilateral microinjection of CoCl(2), a non-selective blocker of neurotransmission, on modulation of cardiac baroreflex responses in conscious rats as well as the involvement of LH glutamatergic neurotransmission in this modulation. Reflex bradycardiac and tachycardiac responses to blood pressure increases (following i.v. infusion of phenylephrine) or decreases (following i.v. infusion of sodium nitroprusside) were investigated in conscious male Wistar rats. Responses were evaluated before and after microinjection of 1 nmol/100 nL CoCl(2), 2 nmol/100 nL 1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzoquinoxaline-7-sulphonamide (NBQX; a selective non-N-methyl-d-aspartate (NMDA) glutamate receptor antagonist) or different doses (2, 4 or 8 nmol/100 nL) of the selective NMDA glutamate receptor antagonist LY235959. Microinjection of CoCl(2) into the LH had no effect on the tachycardiac baroreflex response, but did evoke a decrease in the reflex bradycardia caused by increases in blood pressure. Microinjection of NBQX into the LH had a similar effect on reflex bradycardia as CoCl(2), but had no effect on the tachycardiac response. Microinjection of increasing doses of LY235959 into the LH had no effect on the cardiac baroreflex response. In conclusion, the data suggest that the LH has a tonic facilitatory influence on the parasympathetic component of the baroreflex. The results also indicate that this facilitatory influence is mediated by local LH glutamatergic neurotransmission through non-NMDA glutamatergic receptors.FAPESPCNPq[870307/1997-5]CNPq[306381/2003-6]CNPq[505394/2003-0]Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP[06/57670-4

    Optimized camellia sinensis var. sinensis, ilex paraguariensis, and aspalathus linearis blend presents high antioxidant and antiproliferative activities in a beverage model

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    A statistical optimization study was conducted to obtain a tea containing fermented rooibos (Aspalathus linearis), white tea (Camellia sinensis var. sinensis), and roasted mate (Ilex paraguariensis). An optimal combination of these species was proposed. This optimized tea inhibited 64% the lipoperoxidation in vitro and presented a high phenolic content, especially kaempferol, (+)-catechin, (−)-epicatechin, rutin, (−)-epigallocatechin, and (−)-epicatechin-2-O-gallate. Indeed, the antioxidant effect was confirmed by decreasing 30% the reactive oxygen species generation in human hepatoma carcinoma cells (HepG2, 100 and 240 µg/mL). In the cell viability assay, the GI50 for human colorectal adenocarcinoma epithelial cells (Caco-2) was about 547 µg/mL and 481 µg/mL for HepG2. The pasteurization process (65 °C/30 min) did not affect the total phenolic content and antioxidant activity of the optimized tea formulation. The sensory test indicated an acceptability index of 78%, showing that the analytical approach adopted was feasible to develop a phenolic-rich beverage254348358CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ303188/2016-2; #302763/2014-7; #140092/2017-
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