Antihypertensive Treatment Differentially Affects Vascular Sphingolipid Biology in Spontaneously Hypertensive Rats

We have previously shown that essential hypertension in humans and spontaneously hypertensive rats (SHR), is associated with increased levels of ceramide and marked alterations in sphingolipid biology. Pharmacological elevation of ceramide in isolated carotid arteries of SHR leads to vasoconstriction via a calcium-independent phospholipase A2, cyclooxygenase-1 and thromboxane synthase-dependent release of thromboxane A2. This phenomenon is almost absent in vessels from normotensive Wistar Kyoto (WKY) rats. Here we investigated whether lowering of blood pressure can reverse elevated ceramide levels and reduce ceramide-mediated contractions in SHR. Methods and Findings For this purpose SHR were treated for 4 weeks with the angiotensin II type 1 receptor antagonist losartan or the vasodilator hydralazine. Both drugs decreased blood pressure equally (SBP untreated SHR: 191±7 mmHg, losartan: 125±5 mmHg and hydralazine: 113±14 mmHg). The blood pressure lowering was associated with a 20–25% reduction in vascular ceramide levels and improved endothelial function of isolated carotid arteries in both groups. Interestingly, losartan, but not hydralazine treatment, markedly reduced sphingomyelinase-induced contractions. While both drugs lowered cyclooxygenase-1 expression, only losartan and not hydralazine, reduced the endothelial expression of calcium-independent phospholipase A2. The latter finding may explain the effect of losartan treatment on sphingomyelinase-induced vascular contraction. Conclusion In summary, this study corroborates the importance of sphingolipid biology in blood pressure control and specifically shows that blood pressure lowering reduces vascular ceramide levels in SHR and that losartan treatment, but not blood pressure lowering per se, reduces ceramide-mediated arterial contractions

Hypertension Is Associated with Marked Alterations in Sphingolipid Biology: A Potential Role for Ceramide

Background Hypertension is, amongst others, characterized by endothelial dysfunction and vascular remodeling. As sphingolipids have been implicated in both the regulation of vascular contractility and growth, we investigated whether sphingolipid biology is altered in hypertension and whether this is reflected in altered vascular function. Methods and Findings In isolated carotid arteries from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats, shifting the ceramide/S1P ratio towards ceramide dominance by administration of a sphingosine kinase inhibitor (dimethylsphingosine) or exogenous application of sphingomyelinase, induced marked endothelium-dependent contractions in SHR vessels (DMS: 1.4±0.4 and SMase: 2.1±0.1 mN/mm; n = 10), that were virtually absent in WKY vessels (DMS: 0.0±0.0 and SMase: 0.6±0.1 mN/mm; n = 9, p Conclusions Hypertension is associated with marked alterations in vascular sphingolipid biology such as elevated ceramide levels and signaling, that contribute to increased vascular tone

A Conserved Cysteine Motif Is Critical for Rice Ceramide Kinase Activity and Function

Ceramide kinase (CERK) is a key regulator of cell survival in dicotyledonous plants and animals. Much less is known about the roles of CERK and ceramides in mediating cellular processes in monocot plants. Here, we report the characterization of a ceramide kinase, OsCERK, from rice (Oryza sativa spp. Japonica cv. Nipponbare) and investigate the effects of ceramides on rice cell viability.OsCERK can complement the Arabidopsis CERK mutant acd5. Recombinant OsCERK has ceramide kinase activity with Michaelis-Menten kinetics and optimal activity at 7.0 pH and 40°C. Mg2+ activates OsCERK in a concentration-dependent manner. Importantly, a CXXXCXXC motif, conserved in all ceramide kinases and important for the activity of the human enzyme, is critical for OsCERK enzyme activity and in planta function. In a rice protoplast system, inhibition of CERK leads to cell death and the ratio of added ceramide and ceramide-1-phosphate, CERK's substrate and product, respectively, influences cell survival. Ceramide-induced rice cell death has apoptotic features and is an active process that requires both de novo protein synthesis and phosphorylation, respectively. Finally, mitochondria membrane potential loss previously associated with ceramide-induced cell death in Arabidopsis was also found in rice, but it occurred with different timing.OsCERK is a bona fide ceramide kinase with a functionally and evolutionarily conserved Cys-rich motif that plays an important role in modulating cell fate in plants. The vital function of the conserved motif in both human and rice CERKs suggests that the biochemical mechanism of CERKs is similar in animals and plants. Furthermore, ceramides induce cell death with similar features in monocot and dicot plants

Advances in modelling of biomimetic fluid flow at different scales

The biomimetic flow at different scales has been discussed at length. The need of looking into the biological surfaces and morphologies and both geometrical and physical similarities to imitate the technological products and processes has been emphasized. The complex fluid flow and heat transfer problems, the fluid-interface and the physics involved at multiscale and macro-, meso-, micro- and nano-scales have been discussed. The flow and heat transfer simulation is done by various CFD solvers including Navier-Stokes and energy equations, lattice Boltzmann method and molecular dynamics method. Combined continuum-molecular dynamics method is also reviewed

A Study factors affecting managerial and executive turnover intensions in apparel industry : Sri Lanka

Significantly, Managing Employee turnover is an essential element to the continuing growth of any Business or the Organization around the world. Before taking any actions to avoid Employee turnover, it is a must to look upon Employee Turnover intention and the reasons for such intention. In this Research study, 200 Managerial and Executive Employees were selected from the Garment Factories which are situated in the Free Trade Zone, Katunayake where most of the Garment Factories in Sri Lanka are situated in that Geographical area. It is always hard to identify the inner feeling of anyone, in the same manner, selected subject of the research also deeply goes into the inner feeling of the above said set of employees on what level of turn over intention they have on their jobs. In order to measure the above which is a critical fact, properly designed structured questionnaire was used to measure the levels and how the employees feel about each factor. Data was collected using random sampling technique and then coded. After coding process, Data analysis was completed through SPSS and Microsoft Excel. Descriptive and inferential statistics used for the study. Also it should be noted that the reason for selecting such a complex topic is to bring the real situation into light where most of the time inner feelings of the employees who are in front end of hierarchy are not considered when making policies or implementing strategies. Therefore it is very important to note that fact and give some suggestions to the top management of the Garment Factories about how the executive employees “feel” about their jobs

A Generalized preprocessing and feature extraction platform for scalp EEG signals on FPGA

Brain-computer interfaces (BCIs) require real-time feature extraction for translating input EEG signals recorded from a subject into an output command or decision. Owing to the inherent difficulties in EEG signal processing and neural decoding, many of the feature extraction algorithms are complex and computationally demanding. Presently, software does exist to perform real-time feature extraction and classification of EEG signals. However, the requirement of a personal computer is a major obstacle in bringing these technologies to the home and mobile user affording ease of use. We present the FPGA design and novel architecture of a generalized platform that provides a set of predefined features and preprocessing steps that can be configured by a user for BCI applications. The preprocessing steps include power line noise cancellation and baseline removal while the feature set includes a combination of linear and nonlinear, univariate and bivariate measures commonly utilized in BCIs. We provide a comparison of our results with software and also validate the platform by implementing a seizure detection algorithm on a standard dataset and obtained a classification accuracy of over 96%. A gradual transition of BCI systems to hardware would prove beneficial in terms of compactness, power consumption and much faster response to stimuli

GIS/GPS/GPRS and Web – based framework for fleet tracking

The paper presents the combined application of Geographical Information Systems (GIS), the Global Positioning System (GPS), the General Packet Radio Service (GPRS) and the Internet for tracking of vehicle fleets. It is one component of an enterprise solution that is designed to manage and track a large fleet. The key features of the system are an open-source GIS platform, real-time location information update, and a web-based user interface. The system consists of GPS-based vehicle tracking devices, a communications server, a web-server, a database server, and a map server. The tracking devices mounted in the vehicles collect location information in real-time via the GPS. This information is transferred continuously through GPRS to a central database. The users are able to view the current location of each of the vehicles in the fleet via a web-based application, and thereby manage the fleet. The vehicle positions and other related information are displayed on a digital map, which is made available by a map server. It is a typical example of how the advantages of ICTs may be leveraged for the efficient and effective management of a company’s resources, particularly in the face of sky-rocketing fuel costs

Loss of miR-29b following acute ischemic stroke contributes to neural cell death and infarct size

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Phosphatidic acid mediates activation of mTORC1 through the ERK signaling pathway

The mammalian target of rapamycin (mTOR) assembles into two distinct multiprotein complexes known as mTORC1 and mTORC2. Of the two complexes, mTORC1 acts to integrate a variety of positive and negative signals to downstream targets that regulate cell growth. The lipid second messenger, phosphatidic acid (PA), represents one positive input to mTORC1, and it is thought to act by binding directly to mTOR, thereby enhancing the protein kinase activity of mTORC1. Support for this model includes findings that PA binds directly to mTOR and addition of PA to the medium of cells in culture results in activation of mTORC1. In contrast, the results of the present study do not support a model in which PA activates mTORC1 through direct interaction with the protein kinase but, instead, show that the lipid promotes mTORC1 signaling through activation of the ERK pathway. Moreover, rather than acting directly on mTORC1, the results suggest that exogenous PA must be metabolized to lysophosphatidic acid (LPA), which subsequently activates the LPA receptor endothelial differentiation gene (EDG-2). Finally, in contrast to previous studies, the results of the present study demonstrate that leucine does not act through phospholipase D and PA to activate mTORC1 and, instead, show that the two mediators act through parallel upstream signaling pathways to activate mTORC1. Overall, the results demonstrate that leucine and PA signal through parallel pathways to activate mTORC1 and that PA mediates its effect through the ERK pathway, rather than through direct binding to mTOR