5-Lipoxygenase Deficiency Impairs Innate and Adaptive Immune Responses during Fungal Infection

5-lipoxygenase-derived products have been implicated in both the inhibition and promotion of chronic infection. Here, we sought to investigate the roles of endogenous 5-lipoxygenase products and exogenous leukotrienes during Histoplasma capsulatum infection in vivo and in vitro. 5-LO deficiency led to increased lung CFU, decreased nitric oxide production and a deficient primary immune response during active fungal infection. Moreover, H. capsulatum-infected 5-LO-/- mice showed an intense influx of neutrophils and an impaired ability to generate and recruit effector T cells to the lung. The fungal susceptibility of 5-LO-/- mice correlated with a lower rate of macrophage ingestion of IgG-H. capsulatum relative to WT macrophages. Conversely, exogenous LTB4 and LTC4 restored macrophage phagocytosis in 5-LO deficient mice. Our results demonstrate that leukotrienes are required to control chronic fungal infection by amplifying both the innate and adaptive immune response during histoplasmosis.

Serum amyloid A is a growth factor for 3T3-L1 adipocytes, inhibits differentiation and promotes insulin resistance

BACKGROUND/OBJECTIVES: Serum amyloid A (SAA) is an acute-phase protein that has been recently correlated with obesity and insulin resistance. Therefore, we first examined whether human recombinant SAA (rSAA) could affect the proliferation, differentiation and metabolism of 3T3-L1 preadipocytes. DESIGN: Preadipocytes were treated with rSAA and analyzed for changes in viability and [H-3-methyl]-thymidine incorporation as well as cell cycle perturbations using flow cytometry analysis. The mRNA expression profiles of adipogenic factors during the differentiation protocol were also analyzed using real-time PCR. After differentiation, 2-deoxy-[1,2-H-3]-glucose uptake and glycerol release were evaluated. RESULTS: rSAA treatment caused a 2.6-fold increase in cell proliferation, which was consistent with the results from flow cytometry showing that rSAA treatment augmented the percentage of cells in the S phase (60.9 +/- 0.54%) compared with the control cells (39.8 +/- 2.2%, ***P<0.001). The rSAA-induced cell proliferation was mediated by the ERK1/2 signaling pathway, which was assessed by pretreatment with the inhibitor PD98059. However, the exposure of 3T3-L1 cells to rSAA during the differentiation process resulted in attenuated adipogenesis and decreased expression of adipogenesis-related factors. During the first 72 h of differentiation, rSAA inhibited the differentiation process by altering the mRNA expression kinetics of adipogenic transcription factors and proteins, such as PPAR gamma 2 (peroxisome proliferator-activated receptor gamma 2), C/EBP beta (CCAAT/enhancer-binding protein beta) and GLUT4. rSAA prevented the intracellular accumulation of lipids and, in fully differentiated cells, increased lipolysis and prevented 2-deoxy-[1,2-H-3]-glucose uptake, which favors insulin resistance. Additionally, rSAA stimulated the secretion of proinflammatory cytokines interleukin 6 and tumor necrosis factor alpha, and upregulated SAA3 mRNA expression during adipogenesis. CONCLUSIONS: We showed that rSAA enhanced proliferation and inhibited differentiation in 3T3-L1 preadipocytes and altered insulin sensitivity in differentiated cells. These results highlight the complex role of SAA in the adipogenic process and support a direct link between obesity and its co-morbidities such as type II diabetes.

Speed Neuro-fuzzy Estimator Applied To Sensorless Induction Motor Control

This work proposes the development of an Adaptive Neuro-fuzzy Inference System (ANFIS) estimator applied to speed control in a three-phase induction motor sensorless drive. Usually, ANFIS is used to replace the traditional PI controller in induction motor drives. The evaluation of the estimation capability of the ANFIS in a sensorless drive is one of the contributions of this work. The ANFIS speed estimator is validated in a magnetizing flux oriented control scheme, consisting in one more contribution. As an open-loop estimator, it is applied to moderate performance drives and it is not the proposal of this work to solve the low and zero speed estimation problems. Simulations to evaluate the performance of the estimator considering the vector drive system were done from the Matlab/Simulink(R) software. To determine the benefits of the proposed model, a practical system was implemented using a voltage source inverter (VSI) to drive the motor and the vector control including the ANFIS estimator, which is carried out by the Real Time Toolbox from Matlab/Simulink(R) software and a data acquisition card from National Instruments.

Frequency and precision of feedback and the adaptive process of learning a dual motor task

This work investigated the effects of frequency and precision of feedback on the learning of a dual-motor task. One hundred and twenty adults were randomly assigned to six groups of different knowledge of results (KR), frequency (100%, 66% or 33%) and precision (specific or general) levels. In the stabilization phase, participants performed the dual task (combination of linear positioning and manual force control) with the provision of KR. Ten non-KR adaptation trials were performed for the same task, but with the introduction of an electromagnetic opposite traction force. The analysis showed a significant main effect for frequency of KR. The participants who received KR in 66% of the stabilization trials showed superior adaptation performance than those who received 100% or 33%. This finding reinforces that there is an optimal level of information, neither too high nor too low, for motor learning to be effective.