Hepatic mitochondrial content in malondialdehyde may be a marker of sea lamprey contact with atrazine

The atrazine attracts special attention as pollutant because of itspersistence in the aquatic environment. Although this herbicide has been studied in teleost, its toxicity in the sea lamprey, Petromyzon marinus is still poorly understood. Oxidative stress may occur if chemical pollutants contribute to block the capacity of mitochondria to generate ATP with continuous production of reactive oxygen species (ROS), disturbing the success of P. marinus seawater acclimation. So, the aim of this study was to evaluate how atrazine influences the malondialdehyde (MDA), glutathione (GSH) and glutathione disulfide (GSSG) contents of gills and liver mitochondria of juveniles from Lima river basin, Portugal during salt acclimation. Sampling occurred at the beginning of the P. marinus downstream migration. The sampled juveniles were transported alive to the laboratory and maintained in 200 l tanks with LSS 8 life support system. Two groups of 40 specimens were hold in tanks with 50 or 100 lg/l atrazine, during 30 days. The salinity was gradually increased from 0 to 35 psu,following a three step procedure during a 30 days period. The control group was maintained in freshwater without atrazine. Mitochondria obtained by centrifugation at 15000 g, 30 min, 4°C, of tissues homogenates prepared in 50 mM Tris-HCl pH 7.5 buffer were used in determination of ROS, MDA, GSH and GSSG by fluorescence. The statistical analysis were performed by ANOVA I and Duncan (p < 0.05), using SPSS 22 for Windows.The results showed that in P. marinus juveniles, no significant changes in the markers of oxidative stress and cell damages were detected in the mitochondrial gills. Nevertheless, in the animals exposed to 50 lg/l atrazine the content in glutathione and GSSG increased. A similar pattern of stress markers was detected in hepatic mitochondria. However, in the presence of atrazine, the MDA level of the mitochondria of liver increased threefold in the animals during salt acclimation. The high level of mitochondrial damages, detected in the hepatic mitochondria of macrophthalmia treated with atrazine, suggests that herbicide exposure caused metabolic failures which can disturb the adaptation of these specimens to the oceanic feeding phase. The hepatic mitochondrial MDA levels of P. marinus, may eventually detect sea lamprey contact with chlorine herbicides

Can the mitochondrial malondialdehyde content be an useful tool to distinguish ecological quality of Petromyzon marinus habitat?

The sea lamprey is an anadromous species that migrates twice during its life cycle between freshwater and seawater. Microphagous larvae generally spend 4–5 years burrowed in the substrate of rivers and streams before undergoing metamorphosis that ends with the beginning of the juvenile trophic migration. Once metamorphosis is complete, sea lamprey juvenile downstream migrants are fully tolerant to 35 PSU seawater. Pollution resulting from industrial effluents may disturb the seawater acclimatization causing oxidative damages, and ultimately may lead to a decrease of sea lamprey population. The aim of this study was to compare salt acclimation of sea lamprey juveniles captured in river basins with different levels of aquatic pollution, using mitochondrial glutathione and malondialdehyde of gills and liver as markers of physiological stress and cell damages. The results showed that juveniles from Lima basin exhibited the highest levels of mitochondrial malondialdehyde in gills, even though significant changes in the stress markers of mitochondrial gills of all animals subject to salt acclimation were not detected. In addition, an increase in the oxidative damages of hepatic mitochondria of macrophthalmia from Vouga basin suggests the occurrence of metabolic failures with the potential to disturb the capacity to adaptation to the marine environment

Diastolic tolerance to systolic pressures closely reflects systolic performance in patients with coronary heart disease

In animal experiments, elevating systolic pressures induces diastolic dysfunction and may contribute to congestion, a finding not yet translated to humans. Coronary surgery patients (63 ± 8 years) were studied with left ventricular (LV) pressure (n = 17) or pressure-volume (n = 3) catheters, immediately before cardiopulmonary bypass. Single-beat graded pressure elevations were induced by clamping the ascending aorta. Protocol was repeated after volume loading (n = 7). Consecutive patients with a wide range of systolic function were included. Peak isovolumetric LV pressure (LVP(iso)) ranged from 113 to 261 mmHg. With preserved systolic function, LVP elevations neither delayed relaxation nor increased filling pressures. With decreasing systolic function, diastolic tolerance to afterload progressively disappeared: relaxation slowed and filling pressures increased (diastolic dysfunction). In severely depressed systolic function, filling pressures increased even with minor LVP elevations, suggesting baseline load-dependent elevation of diastolic pressures. The magnitude of filling pressure elevation induced in isovolumetric heartbeats was closely and inversely related to systolic performance, evaluated by LVP(iso) (r = -0.96), and directly related to changes in the time constant of relaxation τ (r = 0.95). The maximum tolerated systolic LVP (without diastolic dysfunction) was similarly correlated with LVP(iso) (r = 0.99). Volume loading itself accelerated relaxation, but augmented afterload-induced upward shift of filling pressures (7.9 ± 3.7 vs. 3.0 ± 1.5; P < 0.01). The normal human response to even markedly increased systolic pressures is no slowing of relaxation and preservation of normal filling pressures. When cardiac function deteriorates, the LV becomes less tolerant, responding with slowed relaxation and increased filling pressures. This increase is exacerbated by volume loading

Foveated image processing for faster object detection and recognition in embedded systems using deep convolutional neural networks

Object detection and recognition algorithms using deep convolutional neural networks (CNNs) tend to be computationally intensive to implement. This presents a particular challenge for embedded systems, such as mobile robots, where the computational resources tend to be far less than for workstations. As an alternative to standard, uniformly sampled images, we propose the use of foveated image sampling here to reduce the size of images, which are faster to process in a CNN due to the reduced number of convolution operations. We evaluate object detection and recognition on the Microsoft COCO database, using foveated image sampling at different image sizes, ranging from 416×416 to 96×96 pixels, on an embedded GPU – an NVIDIA Jetson TX2 with 256 CUDA cores. The results show that it is possible to achieve a 4× speed-up in frame rates, from 3.59 FPS to 15.24 FPS, using 416×416 and 128×128 pixel images respectively. For foveated sampling, this image size reduction led to just a small decrease in recall performance in the foveal region, to 92.0% of the baseline performance with full-sized images, compared to a significant decrease to 50.1% of baseline recall performance in uniformly sampled images, demonstrating the advantage of foveated sampling

Immunophenotypic characterization of patients with American cutaneous leishmaniasis prior to and after treatment in Pernambuco, Brazil

Leishmania infections induce a specific activation of host immunological response, particularly characterized by T cell expansion. Studies indicate the importance of the balance between CD4+ and CD8+ T cells, in which the first ones would have their number reduced during the healing process. Meanwhile, CD25+ T cells have been associated with the suppression of the immune response. Since the immune response has an essential role in both healing and progression of diseases, this study aimed to identify the percentage of CD3+, CD4+, CD8+, CD16+ and CD25+ T cells in the peripheral blood of patients afflicted with American cutaneous leishmaniasis (ACL) - before and after treatment - and healthy controls. Peripheral blood was collected and transferred to cytometry tubes containing monoclonal antibodies specific for cell surface markers CD3, CD4, CD8, CD16 e CD25. The immunophenotypic and morphometric parameters of cells were determined by flow cytometry and the results demonstrated a significant increase in the number of T CD8+ cells after treatment, suggesting a cytotoxic T cell response. An increase in CD25+ T cells in patients with active ACL and after treatment was also observed, suggesting the participation of these cells in the modulation of the exacerbated effector response

Virtualization of elastic optical networks and regenerators with traffic grooming

An elastic optical network (EON) plays an important role in transport technology for virtualization of networks. A key aspect of EONs is to establish lightpaths (virtual links) with exactly the amount of spectrum that is needed and with the possibility of grooming, the process of grouping many small traffic flows into larger units, creating a super-lightpath. Grooming eliminates the need for many guard bands between lightpaths and also saves transceivers; however, it often leads to the need to perform optical–electrical–optical conversions to multiple-data-rate optical signals at intermediate nodes. The aim of this paper is to provide a mixed-integer linear programming (MILP) formulation, as well as heuristic and meta-heuristic approaches, for the design of multiple virtual optical networks (VONs) in an elastic optical substrate network with bandwidth-variable lightpaths, modulation format constraints, and virtual elastic regenerator placement. Traffic grooming is allowed inside each VON, and a distance-adaptive modulation format technique is employed to guarantee efficiency in terms of bandwidth for a physical substrate, subject to several virtual topologies. A reduced MILP formulation without grooming capability is also proposed for comparison. The complete MILP formulation jointly solves the virtual topology design, regenerator placement, and grooming problems, as well as the routing, modulation, and spectrum assignment (RMSA) problem. The reduced MILP formulation, heuristics, and meta-heuristic, on the other hand, separate the virtual topology design problem from the RMSA problem. It is shown that the grooming approach can provide good results, since it solves the problem for a complete design when compared to the approach without grooming. Furthermore, heuristic solutions for large networks are proposed, which present good performance (in terms of saving spectrum) for the design with large instances

Expression and clinical relevance of SOX9 in gastric cancer

Gastric cancer is one of the most frequent tumours and the third leading cause of cancer-related death worldwide. The investigation of new biomarkers that can predict patient outcome more accurately and allow better treatment and follow-up decisions is of crucial importance. SOX9 (sex-determining region Y (SRY)-box 9) is a regulator of cell fate decisions in embryogenesis and adulthood. Here, we sought to ascertain the relevance of SOX9 transcription factor as a prognostic marker in gastric cancer. SOX9 expression was analyzed by immunohistochemistry in 333 gastric adenocarcinoma cases, and its association with clinicopathological and follow-up data was evaluated. SOX9 nuclear expression was absent in 17% of gastric cancer cases and predicted worse disease-free survival (P = 0 03). SOX9 expression was associated with lower risk of relapse in Cox univariable analysis (HR = 0 58; 95% CI = 0 35-0.97; P = 0 04). The prognostic value of SOX9 was more pronounced in tumours with expansive growth (P = 0 01) or with venous invasion (P = 0 02). Two validation cohorts from the Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) confirmed that low SOX9 expression was significantly associated with poor patient outcome. In conclusion, we have identified SOX9 as a biomarker of disease relapse in gastric cancer patients. Further experiments are needed to elucidate its biological relevance at the cellular level.The authors wish to acknowledge the tumour and tissue bank at Hospital de São João for providing all the means to collect the human tissue samples included in this study. This work was supported by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). This work was also financed by the projects NORTE-01-0145-FEDER-000003 (DOCnet) and NORTE-07-0124-FEDER-000029 supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). BP and RB acknowledge FCT for financial support (grants SFRH/BPD/109794/2015 and SFRH/BPD/68276/2010, respectively)

SRC inhibition prevents P-cadherin mediated signaling and function in basal-like breast cancer cells

BACKGROUND: Basal-like breast cancer (BLBC) is a poor prognosis subgroup of triple-negative carcinomas that still lack specific target therapies and accurate biomarkers for treatment selection. P-cadherin is frequently overexpressed in these tumors, promoting cell invasion, stem cell activity and tumorigenesis by the activation of Src-Family kinase (SRC) signaling. Therefore, our aim was to evaluate if the treatment of BLBC cells with dasatinib, the FDA approved SRC inhibitor, would impact on P-cadherin induced tumor aggressive behavior. METHODS: P-cadherin and SRC expression was evaluated in a series of invasive Breast Cancer and contingency tables and chi-square tests were performed. Cell-cell adhesion measurements were performed by Atomic Force Microscopy, where frequency histograms and Gaussian curves were applied. 2D and 3D cell migration and invasion, proteases secretion and self-renew potential were evaluated in vitro. Student's t-tests were used to determine statistically significant differences. The cadherin/catenin complex interactions were evaluated by in situ proximity-ligation assay, and statistically significant results were determined by using Mann-Whitney test with a Bonferroni correction. In vivo xenograft mouse models were used to evaluate the impact of dasatinib on tumor growth and survival. ANOVA test was used to evaluate the differences in tumor size, considering a confidence interval of 95%. Survival curves were estimated by the Kaplan-Meier's method, using the log-rank test to assess significant differences for mice overall survival. RESULTS: Our data demonstrated that P-cadherin overexpression is significantly associated with SRC activation in breast cancer cells, which was also validated in a large series of primary tumor samples. SRC activity suppression with dasatinib significantly prevented the in vitro functional effects of P-cadherin overexpressing cells, as well as their in vivo tumorigenic and metastatic ability, by increasing mice overall survival. Mechanistically, SRC inhibition affects P-cadherin downstream signaling, rescues the E-cadherin/p120-catenin complex to the cell membrane, recovering cell-cell adhesion function. CONCLUSIONS: In conclusion our findings show that targeting P-cadherin/SRC signaling and functional activity may open novel therapeutic opportunities for highly aggressive and poor prognostic basal-like breast cancer.This work was funded by Laço Grant 2014, by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by FCT - Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia e Ensino Superior under the projects PTDC/SAU-GMG/120049/ 2010-FCOMP-01-0124-FEDER-021209, PEst-C/SAU/LA0003/2013, NORTE-01- 0145-FEDER-000029 and POCI-01-0145-FEDER-016390. FCT funded the research grants of ASR (SFRH/BPD/75705/2011), ARN (SFRH/BD/100380/2014), BS (SFRH/ BPD/104208/2014), AFV (SFRH/BPD/90303/2012), as well as JP with Programa IFCT 2013 (FCT Investigator). IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274)

Volatile constituents and behavioral change induced by Cymbopogon winterianus leaf essential oil in rodents

Cymbopogon winterianus Jowitt (‘Java citronella’) is an important essential oil yielding aromatic grass cultivated in India and Brazil and its volatile essential oils extracted from its leaves are used in perfumery, cosmetics, pharmaceuticals and flavoring industries. However, there is no report on any psychopharmacological study of C. winterianus leaf essential oil (LEO) available to date. In this study, the pharmacological effects of the LEO were investigated in animal models and its phytochemical analyses. GC-MS analysis showed a mixture of monoterpenes, as citronellal (36.19%), geraniol (32.82%) and citronellol (11.37%). LEO exhibited an inhibitory effect on the locomotor activity of mice, an antinociceptive effect by increasing the reaction time in the writhing and capsaicin tests. All doses induced a significant increase in the sleeping time of animals not having modified however, the latency. The LEO did not alter the remaining time of the animals on the rota-rod apparatus. These results suggest a possible central effect.Key words: Cymbopogon winterianus, essential oil, CNS, behavioral effects, analgesic