다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

Sphingolipids constitute a class of lipids defined by their eighteen carbon amino-alcohol backbones which are synthesized in the ER from nonsphingolipid precursors Modification of this basic structure is what gives rise to the vast family of sphingolipids that play significant roles in membrane biology and provide many bioactive metabolites that regulate cell function Despite the diversity of structure and function of sphingolipids, their creation and destruction are governed by common synthetic and catabolic pathways In this regard, sphingolipid metabolism can be imagined as an array of interconnected networks that diverge from a single common entry point and converge into a single common breakdown pathway In their simplest forms, sphingosine, phytosphingosine and dihydrosphingosine serve as the backbones upon which further complexity is achieved For example, phosphorylation of the C1 hydroxyl group yields the final breakdown products and/or the important signaling molecules sphingosine-1-phosphate, phytosphingosine-1-phosphate and dihydrosphingosine-1-phosphate, respectively On the other hand, acylation of sphingosine, phytosphingosine, or dihydrosphingosine with one of several possible acyl CoA molecules through the action of distinct ceramide synthases produces the molecules defined as ceramide, phytoceramide, or dihydroceramide Ceramide, due to the differing acyl CoAs that can be used to produce it, is technically a class of molecules rather than a single molecule and therefore may have different biological functions depending on the acyl chain it is composed of At the apex of complexity is the group of lipids known as glycosphingolipids (GSL) which contain dozens of different sphingolipid species differing by both the order and type of sugar residues attached to their headgroups Since these molecules are produced from ceramide precursors, they too may have differences in their acyl chain composition, revealing an additional layer of variation The glycosphingolipids are divided broadly into two categories: glucosphingolipids and galactosphingolipids The glucosphingolipids depend initially on the enzyme glucosylceramide synthase (GCS) which attaches glucose as the first residue to the C1 hydroxyl position Galactosphingolipids, on the other hand, are generated from galactosylceramide synthase (GalCerS), an evolutionarily dissimilar enzyme from GCS Glycosphingolipids are further divided based upon further modification by various glycosyltransferases which increases the potential variation in lipid species by several fold Far more abundant are the sphingomyelin species which are produced in parallel with glycosphingolipids, however they are defined by a phosphocholine headgroup rather than the addition of sugar residues Although sphingomyelin species all share a common headgroup, they too are produced from a variety of ceramide species and therefore can have differing acyl chains attached to their C-2 amino groups Whether or not the differing acyl chain lengths in SMs dictate unique functions or important biophysical distinctions has not yet been established Understanding the function of all the existing glycosphingolipids and sphingomyelin species will be a major undertaking in the future since the tools to study and measure these species are only beginning to be developed (see Fig 1 for an illustrated depiction of the various sphingolipid structures) The simple sphingolipids serve both as the precursors and the breakdown products of the more complex ones Importantly, in recent decades, these simple sphingolipids have gained attention for having significant signaling and regulatory roles within cells In addition, many tools have emerged to measure the levels of simple sphingolipids and therefore have become the focus of even more intense study in recent years With this thought in mind, this chapter will pay tribute to the complex sphingolipids, but focus on the regulation of simple sphingolipid metabolism

An overview of sphingolipid metabolism: from synthesis to breakdown.

Much has been made about J. L. W. Thudichum’s colorful, and one could say clairvoyant, naming of sphingosine “in commemoration of the many enigmas which it presented to the inquirer” in his 1884 treatise The Chemistry of the Brain(1) because many of the riddles of sphingolipids (as the broader field was later named)(2) remained unanswered for the following century. This changed radically over the past several decades as researchers explored, and ultimately established, what seemed at the time to be radical concepts: that sphingolipids are not just structural elements of cells but also participate in intra- and extracellular signaling; that not only the complex glycan headgroups, but also the lipid backbones, are highly specified metabolically and have selective biochemical functions; and that even the longest known function of these lipids, as structural components of the “fluid mosaic” of cell membrane lipids, is not so simple, and often involves the dynamic clustering of sphingolipids in nontraditional microdomains referred to as rafts. We still know only a fraction of their secrets, but this enlightenment has defined models for thinking about these compounds that remove them from their enigmatic “black box.”

Now, a major challenge is to keep up with the rapid growth in knowledge about the sphingolipidome, that is, the ensemble of all sphingolipids.(3) A major goal of the review is to help the reader more easily grasp the metabolic interrelationships that account for the tens of thousands of molecular subspecies (and perhaps more) that appear in nature, with a focus on mammals. The magnitude of this subject precludes the inclusion of all of the enzymes and metabolites, and the author apologizes for the omission of many interesting topics. To put this information in context, there is a brief background discussion of their structures and functions, which have been dealt with also in a recent Chemical Reviews article(4) on the chemicophysical features of sphingolipids and raft formation, and by excellent reviews on sphingolipid signaling5,6 and the biological functions of complex glycosphingolipids.7−10

Sphingolipid and Glycosphingolipid Metabolic Pathways in the Era of Sphingolipidomics

A Comprehensive Survey on Attacks, Security Issues and Blockchain Solutions for IoT and IIoT

Sphingosine 1-phosphate (S1P), an abundant lipid mediator in plasma, regulates vascular and immune cells by activating S1P receptors. In this report, we investigated the mechanisms by which high plasma S1P levels are maintained in mice. We found that plasma S1P turns over rapidly with a half-life of ≈15 minutes, suggesting the existence of a high-capacity biosynthetic source(s). Transplantation of bone marrow from wild-type to Sphk1−/−Sphk2+/− mice restored plasma S1P levels, suggesting that hematopoietic cells are capable of secreting S1P into plasma. However, plasma S1P levels were not appreciably altered in mice that were thrombocytopenic, anemic, or leukopenic. Surprisingly, reconstitution of Sphk1−/−Sphk2+/− bone marrow cells into wild-type hosts failed to reduce plasma S1P, suggesting the existence of an additional, nonhematopoietic source for plasma S1P. Adenoviral expression of Sphk1 in the liver of Sphk1−/− mice restored plasma S1P levels. In vitro, vascular endothelial cells, but not hepatocytes...

Vascular Endothelium As a Contributor of Plasma Sphingosine 1-Phosphate

Sphingosine 1-phosphate (S1P), produced by Sphks (sphingosine kinases), is a multifunctional lipid mediator that regulates immune cell trafficking and vascular development. Mammals maintain a large concentration gradient of S1P between vascular and extravascular compartments. Mechanisms by which S1P is released from cells and concentrated in the plasma are poorly understood. We recently demonstrated [Ancellin, Colmont, Su, Li, Mittereder, Chae, Stefansson, Liau and Hla (2002) J. Biol. Chem. 277, 6667–6675] that Sphk1 activity is constitutively secreted by vascular endothelial cells. In the present study, we show that among the five Sphk isoforms expressed in endothelial cells, the Sphk-1a isoform is selectively secreted in HEK-293 cells (human embryonic kidney cells) and human umbilical-vein endothelial cells. In sharp contrast, Sphk2 is not secreted. The exported Sphk-1a isoform is enzymatically active and produced sufficient S1P to induce S1P receptor internalization. Wild-type mouse plasma contains significant Sphk activity (179 pmol·min−1·g−1). In contrast, Sphk1−/− mouse plasma has undetectable Sphk activity and approx. 65% reduction in S1P levels. Moreover, human plasma contains enzymatically active Sphk1 (46 pmol·min−1·g−1). These results suggest that export of Sphk-1a occurs under physiological conditions and may contribute to the establishment of the vascular S1P gradient.

/pdf/extracellular-export-of-sphingosine-kinase-1a-contributes-to-1kfarikg44.pdf

Extracellular export of sphingosine kinase-1a contributes to the vascular S1P gradient.

Internet of things (IoT) is realized by the idea of free flow of information amongst various low-power embedded devices that use the Internet to communicate with one another It is predicted that the IoT will be widely deployed and will find applicability in various domains of life Demands of IoT have lately attracted huge attention, and organizations are excited about the business value of the data that will be generated by deploying such networks On the contrary, IoT has various security and privacy concerns for the end users that limit its proliferation In this paper, we have identified, categorized, and discussed various security challenges and state-of-the-art efforts to resolve these challenges

/pdf/understanding-security-requirements-and-challenges-in-24vf64t7da.pdf

Understanding Security Requirements and Challenges in Internet of Things (IoT): A Review

Internet of Things (IoT) is realized by the idea of free flow of information amongst various low power embedded devices that use Internet to communicate with one another. It is predicted that the IoT will be widely deployed and it will find applicability in various domains of life. Demands of IoT have lately attracted huge attention and organizations are excited about the business value of the data that will be generated by the IoT paradigm. On the other hand, IoT have various security and privacy concerns for the end users that limit its proliferation. In this paper we have identified, categorized and discussed various security challenges and state of the art efforts to resolve these challenges.

Understanding Security Requirements and Challenges in Internet of Things (IoTs): A Review

In recent years, wireless sensor networks have many potential applications for both civil and military tasks. However, sensor networks are susceptible to many types of attacks because they are deployed in open and unprotected environment. So it is necessary to use effective mechanisms to protect sensor networks against many types of attacks on routing protocols. Intrusion detection is one of the major and efficient defense methods against attacks in a computer network and system. Because of different characteristics of sensor networks, security solutions have to be designed with limited usage of computation and resources. In this paper, we proposed a hybrid, lightweight intrusion detection system integrated for sensor networks. Our intrusion detection scheme take advantage of cluster-based protocol to build a hierarchical network and provide an intrusion framework based both on anomaly and misuse techniques. Our scheme can prevent most of routing attacks on sensor networks.

Hybrid intrusion detection system for wireless sensor networks

Smart metering application has received a lot of attention from the research community lately. Usually, LLN based network runs on RPL protocol which constructs a DAG structure for its normal operation. In this paper, we devise a wormhole attack scenario in such a network. Furthermore, we propose a Merkle tree based authentication protocol which runs on the notion of constructing a tree of hashed security information. We evaluated the approach by formulating the wormhole problem as graph theoretic problem and have shown the effectiveness of the proposed Merkle tree based approach for authenticating communications. Furthermore, we perform simulations in NS 2 to observe the network performance by adopting Merkle tree based to prevent from disrupting the links and observed boost in throughput, reduction in jitter and end to end delay. In the end, we have taken the step towards optimizing the performance of the algorithm by proposing an effective tree traversal algorithm which works on the notion of electing nodes as root in a large scale network from where a Merkle tree will be originated this will assist in managing the authentication in a huge sized network broken down into many trees avoiding wormhole attacks in the network.

Faraz Idris Khan

Papers

Extracellular export of sphingosine kinase-1a contributes to the vascular S1P gradient.

Understanding Security Requirements and Challenges in Internet of Things (IoT): A Review

Understanding Security Requirements and Challenges in Internet of Things (IoTs): A Review

Hybrid intrusion detection system for wireless sensor networks

Wormhole attack prevention mechanism for RPL based LLN network