Potential link between the Sphingosine-1-Phosphate (S1P) system and defective alveolar macrophage phagocytic function in Chronic Obstructive Pulmonary Disease (COPD)

We previously reported that alveolar macrophages from patients with chronic obstructive pulmonary disease (COPD) are defective in their ability to phagocytose apoptotic cells, with a similar defect in response to cigarette smoke. The exact mechanisms for this defect are unknown. Sphingolipids including ceramide, sphingosine and sphingosine-1-phosphate (S1P) are involved in diverse cellular processes and we hypothesised that a comprehensive analysis of this system in alveolar macrophages in COPD may help to delineate the reasons for defective phagocytic function.We compared mRNA expression of sphingosine kinases (SPHK1/2), S1P receptors (S1PR1-5) and S1P-degrading enzymes (SGPP1, SGPP2, SGPL1) in bronchoalveolar lavage-derived alveolar macrophages from 10 healthy controls, 7 healthy smokers and 20 COPD patients (10 current- and 10 ex-smokers) using Real-Time PCR. Phagocytosis of apoptotic cells was investigated using flow cytometry. Functional associations were assessed between sphingosine signalling system components and alveolar macrophage phagocytic ability in COPD. To elucidate functional effects of increased S1PR5 on macrophage phagocytic ability, we performed the phagocytosis assay in the presence of varying concentrations of suramin, an antagonist of S1PR3 and S1PR5. The effects of cigarette smoking on the S1P system were investigated using a THP-1 macrophage cell line model.We found significant increases in SPHK1/2 (3.4- and 2.1-fold increases respectively), S1PR2 and 5 (4.3- and 14.6-fold increases respectively), and SGPL1 (4.5-fold increase) in COPD vs. controls. S1PR5 and SGPL1 expression was unaffected by smoking status, suggesting a COPD "disease effect" rather than smoke effect per se. Significant associations were noted between S1PR5 and both lung function and phagocytosis. Cigarette smoke extract significantly increased mRNA expression of SPHK1, SPHK2, S1PR2 and S1PR5 by THP-1 macrophages, confirming the results in patient-derived macrophages. Antagonising SIPR5 significantly improved phagocytosis.Our results suggest a potential link between the S1P signalling system and defective macrophage phagocytic function in COPD and advise therapeutic targets.Jameel Barnawi, Hai Tran, Hubertus Jersmann, Stuart Pitson, Eugene Roscioli, Greg Hodge, Robyn Meech, Rainer Haberberger, Sandra Hodg

Improve Teachers' Ability in Compiling Classroom Action Research Through Workshop Activities

This action research aims to improve the ability of teachers in compiling Classroom Action Research. The subjects of this study were 11 madrasah teachers under the guidance of researchers, namely at MIS Al-Wathoniyah Cantilan. The research was conducted in two cycles where each cycle went through the planning, implementation, observation and reflection stages. Data collection techniques using observation techniques and document study. The collected data were analyzed qualitatively descriptive with the type of percentage. The results showed that teacher activity from 70% in the first cycle increased to 88.89% in the second cycle and the quality of the lesson plans from an average of 77.60 in the first cycle increased to 86.00 in the second cycle. There has been an increase in the quality of PTK by 8.4 points from cycle I to cycle II. Thus it can be concluded that the mentored teachers' abilities in preparing CAR can be improved through workshops. &nbsp

TDMA scheduling for data gathering in wireless sensor networks

We consider wireless sensor networks where a number of unconstrained nodes (Access Points) with unlimited power source can be deployed together with constrained and limited energy sensor nodes. The presence of unconstrained nodes promotes the use of centralized TDMA scheduling mechanisms that can potentially reduce the delay and save power by eliminating collisions. In this paper we propose two scheduling schemes: Interleaved and Non-interleaved scheduling, that allocate time slots to nodes in a spatial way to enable the follow of data from sensors to the Access Point (Sink). We investigate the performance of these schemes in terms of energy and latency. Through simulation we show that interleaved scheduling reduces average end-to-end delay by a factor of 5.25 for a 60 nodes network and by 3.07 for a 400 nodes network compared to non-interleaved scheduling. In addition, interleaved scheduling consumes on average less energy (42.6 mJ) per packet than non-interleaved which consumes about 138 mJ when network size is 400 nodes

A time & energy efficient topology discovery and scheduling protocol for wireless sensor networks

TDMA-based MAC protocols are considered an energy efficient solution to prolong wireless sensor network lifetime. The topology learning and collection process, together with the used scheduling scheme, are essential parts in the design of such MAC protocols. Previous MAC and multihop scheduling protocols rely completely on CSMA to exchange topology scheduling information. However, for large or dense sensor networks, CSMA may lengthen the time it takes to reach a state in which enough information has been collected to build a highly conflict free multihop schedule. In addition, due to the nature of CSMA, collisions may occur during packet transmission. These factors cause energy waste in an environment where energy resources are scarce. In this paper, we propose PROGRESSIVE, a time and energy efficient topology discovery and multihop scheduling protocol that progressively schedules nodes as their topology information becomes available at the sink. The proposed protocol controls the time during which CSMA is used for control message transmission, and hence, energy consumption is reduced. Simulation results show that PROGRESSIVE is able to schedule a large number of nodes in less time and energy compared to DRAND

Cigarette smoke inhibits efferocytosis via deregulation of sphingosine kinase signaling: reversal with exogenous S1P and the S1P analogue FTY720

Alveolar macrophages from chronic obstructive pulmonary disease patients and cigarette smokers are deficient in their ability to phagocytose apoptotic bronchial epithelial cells (efferocytosis). We hypothesized that the defect is mediated via inhibition of sphingosine kinases and/or their subcellular mislocalization in response to cigarette smoke and can be normalized with exogenous sphingosine-1-phosphate or FTY720 (fingolimod), a modulator of sphingosine-1-phosphate signaling, which has been shown to be clinically useful in multiple sclerosis. Measurement of sphingosine kinase 1/2 activities by [(32)P]-labeled sphingosine-1-phosphate revealed a 30% reduction of sphingosine kinase 1 (P < 0.05) and a nonsignificant decrease of sphingosine kinase 2 in THP-1 macrophages after 1 h cigarette smoke extract exposure. By confocal analysis macrophage sphingosine kinase 1 protein was normally localized to the plasma membrane and cytoplasm and sphingosine kinase 2 to the nucleus and cytoplasm but absent at the cell surface. Cigarette smoke extract exposure (24 h) led to a retraction of sphingosine kinase 1 from the plasma membrane and sphingosine kinase 1/2 clumping in the Golgi domain. Selective inhibition of sphingosine kinase 2 with 25 µM ABC294640 led to 36% inhibition of efferocytosis (P < 0.05); 10 µM sphingosine kinase inhibitor/5C (sphingosine kinase 1-selective inhibitor) induced a nonsignificant inhibition of efferocytosis, but its combination with ABC294640 led to 56% inhibition (P < 0.01 vs. control and < 0.05 vs. single inhibitors). Cigarette smoke-inhibited efferocytosis was significantly (P < 0.05) reversed to near-control levels in the presence of 10-100 nM exogenous sphingosine-1-phosphate or FTY720, and FTY720 reduced cigarette smoke-induced clumping of sphingosine kinase 1/2 in the Golgi domain. These data strongly support a role of sphingosine kinase 1/2 in efferocytosis and as novel therapeutic targets in chronic obstructive pulmonary disease.Hai B. Tran, Jameel Barnawi, Miranda Ween, Rhys Hamon, Eugene Roscioli, Greg Hodge, Paul N. Reynolds, Stuart M. Pitson, Lorena T. Davies, Rainer Haberberger and Sandra Hodg