University of Graz

Spintronics, or spin electronics, involves the study of active control and manipulation of spin degrees of freedom in solid-state systems. This article reviews the current status of this subject, including both recent advances and well-established results. The primary focus is on the basic physical principles underlying the generation of carrier spin polarization, spin dynamics, and spin-polarized transport in semiconductors and metals. Spin transport differs from charge transport in that spin is a nonconserved quantity in solids due to spin-orbit and hyperfine coupling. The authors discuss in detail spin decoherence mechanisms in metals and semiconductors. Various theories of spin injection and spin-polarized transport are applied to hybrid structures relevant to spin-based devices and fundamental studies of materials properties. Experimental work is reviewed with the emphasis on projected applications, in which external electric and magnetic fields and illumination by light will be used to control spin and charge dynamics to create new functionalities not feasible or ineffective with conventional electronics.

The International Panel on MS Diagnosis presents revised diagnostic criteria for multiple sclerosis (MS). The focus remains on the objective demonstration of dissemination of lesions in both time and space. Magnetic resonance imaging is integrated with dinical and other paraclinical diagnostic methods. The revised criteria facilitate the diagnosis of MS in patients with a variety of presentations, including "monosymptomatic" disease suggestive of MS, disease with a typical relapsing-remitting course, and disease with insidious progression, without clear attacks and remissions. Previously used terms such as "clinically definite" and "probable MS" are no longer recommended. The outcome of a diagnostic evaluation is either MS, "possible MS" (for those at risk for MS, but for whom diagnostic evaluation is equivocal), or "not MS."

DeepMind presented notably accurate predictions at the recent 14th Critical Assessment of Structure Prediction (CASP14) conference. We explored network architectures that incorporate related ideas and obtained the best performance with a three-track network in which information at the one-dimensional (1D) sequence level, the 2D distance map level, and the 3D coordinate level is successively transformed and integrated. The three-track network produces structure predictions with accuracies approaching those of DeepMind in CASP14, enables the rapid solution of challenging x-ray crystallography and cryo-electron microscopy structure modeling problems, and provides insights into the functions of proteins of currently unknown structure. The network also enables rapid generation of accurate protein-protein complex models from sequence information alone, short-circuiting traditional approaches that require modeling of individual subunits followed by docking. We make the method available to the scientific community to speed biological research.

Six DNA regions were evaluated as potential DNA barcodes for Fungi, the second largest kingdom of eukaryotic life, by a multinational, multilaboratory consortium. The region of the mitochondrial cytochrome c oxidase subunit 1 used as the animal barcode was excluded as a potential marker, because it is difficult to amplify in fungi, often includes large introns, and can be insufficiently variable. Three subunits from the nuclear ribosomal RNA cistron were compared together with regions of three representative protein-coding genes (largest subunit of RNA polymerase II, second largest subunit of RNA polymerase II, and minichromosome maintenance protein). Although the protein-coding gene regions often had a higher percent of correct identification compared with ribosomal markers, low PCR amplification and sequencing success eliminated them as candidates for a universal fungal barcode. Among the regions of the ribosomal cistron, the internal transcribed spacer (ITS) region has the highest probability of successful identification for the broadest range of fungi, with the most clearly defined barcode gap between inter- and intraspecific variation. The nuclear ribosomal large subunit, a popular phylogenetic marker in certain groups, had superior species resolution in some taxonomic groups, such as the early diverging lineages and the ascomycete yeasts, but was otherwise slightly inferior to the ITS. The nuclear ribosomal small subunit has poor species-level resolution in fungi. ITS will be formally proposed for adoption as the primary fungal barcode marker to the Consortium for the Barcode of Life, with the possibility that supplementary barcodes may be developed for particular narrowly circumscribed taxonomic groups.

Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases. Nevertheless, natural products also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization, which contributed to a decline in their pursuit by the pharmaceutical industry from the 1990s onwards. In recent years, several technological and scientific developments - including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances - are addressing such challenges and opening up new opportunities. Consequently, interest in natural products as drug leads is being revitalized, particularly for tackling antimicrobial resistance. Here, we summarize recent technological developments that are enabling natural product-based drug discovery, highlight selected applications and discuss key opportunities.

Although fire is now rarely used in synthetic chemistry, it was not until Robert Bunsen invented the burner in 1855 that the energy from this heat source could be applied to a reaction vessel in a focused manner. The Bunsen burner was later superseded by the isomantle, oil bath, or hot plate as a source for applying heat to a chemical reaction. In the past few years, heating and driving chemical reactions by microwave energy has been an increasingly popular theme in the scientific community. This nonclassical heating technique is slowly moving from a laboratory curiosity to an established technique that is heavily used in both academia and industry. The efficiency of "microwave flash heating" in dramatically reducing reaction times (from days and hours to minutes and seconds) is just one of the many advantages. This Review highlights recent applications of controlled microwave heating in modern organic synthesis, and discusses some of the underlying phenomena and issues involved.

The number of online experiments conducted with subjects recruited via online platforms has grown considerably in the recent past. While one commercial crowdworking platform – Amazon’s Mechanical Turk – basically has established and since dominated this field, new alternatives offer services explicitly targeted at researchers. In this article, we present www.prolific.ac and lay out its suitability for recruiting subjects for social and economic science experiments. After briefly discussing key advantages and challenges of online experiments relative to lab experiments, we trace the platform’s historical development, present its features, and contrast them with requirements for different types of social and economic experiments.

Abstract High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species 1–4 . To address this issue, the international Genome 10K (G10K) consortium 5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling highly accurate and nearly complete reference genomes. Here we present lessons learned from generating assemblies for 16 species that represent six major vertebrate lineages. We confirm that long-read sequencing technologies are essential for maximizing genome quality, and that unresolved complex repeats and haplotype heterozygosity are major sources of assembly error when not handled correctly. Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries. These include the identification of many false gene duplications, increases in gene sizes, chromosome rearrangements that are specific to lineages, a repeated independent chromosome breakpoint in bat genomes, and a canonical GC-rich pattern in protein-coding genes and their regulatory regions. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an international effort to generate high-quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences.

Medicinal plants have historically proven their value as a source of molecules with therapeutic potential, and nowadays still represent an important pool for the identification of novel drug leads. In the past decades, pharmaceutical industry focused mainly on libraries of synthetic compounds as drug discovery source. They are comparably easy to produce and resupply, and demonstrate good compatibility with established high throughput screening (HTS) platforms. However, at the same time there has been a declining trend in the number of new drugs reaching the market, raising renewed scientific interest in drug discovery from natural sources, despite of its known challenges. In this survey, a brief outline of historical development is provided together with a comprehensive overview of used approaches and recent developments relevant to plant-derived natural product drug discovery. Associated challenges and major strengths of natural product-based drug discovery are critically discussed. A snapshot of the advanced plant-derived natural products that are currently in actively recruiting clinical trials is also presented. Importantly, the transition of a natural compound from a "screening hit" through a "drug lead" to a "marketed drug" is associated with increasingly challenging demands for compound amount, which often cannot be met by re-isolation from the respective plant sources. In this regard, existing alternatives for resupply are also discussed, including different biotechnology approaches and total organic synthesis. While the intrinsic complexity of natural product-based drug discovery necessitates highly integrated interdisciplinary approaches, the reviewed scientific developments, recent technological advances, and research trends clearly indicate that natural products will be among the most important sources of new drugs also in the future.

A new high-resolution regional climate change ensemble has been established for Europe within the World Climate Research Program Coordinated Regional Downscaling Experiment (EURO-CORDEX) initiative. The first set of simulations with a horizontal resolution of 12.5 km was completed for the new emission scenarios RCP4.5 and RCP8.5 with more simulations expected to follow. The aim of this paper is to present this data set to the different communities active in regional climate modelling, impact assessment and adaptation. The EURO-CORDEX ensemble results have been compared to the SRES A1B simulation results achieved within the ENSEMBLES project. The large-scale patterns of changes in mean temperature and precipitation are similar in all three scenarios, but they differ in regional details, which can partly be related to the higher resolution in EURO-CORDEX. The results strengthen those obtained in ENSEMBLES, but need further investigations. The analysis of impact indices shows that for RCP8.5, there is a substantially larger change projected for temperature-based indices than for RCP4.5. The difference is less pronounced for precipitation-based indices. Two effects of the increased resolution can be regarded as an added value of regional climate simulations. Regional climate model simulations provide higher daily precipitation intensities, which are completely missing in the global climate model simulations, and they provide a significantly different climate change of daily precipitation intensities resulting in a smoother shift from weak to moderate and high intensities.

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Mobilization of fatty acids from triglyceride stores in adipose tissue requires lipolytic enzymes. Dysfunctional lipolysis affects energy homeostasis and may contribute to the pathogenesis of obesity and insulin resistance. Until now, hormone-sensitive lipase (HSL) was the only enzyme known to hydrolyze triglycerides in mammalian adipose tissue. Here, we report that a second enzyme, adipose triglyceride lipase (ATGL), catalyzes the initial step in triglyceride hydrolysis. It is interesting that ATGL contains a "patatin domain" common to plant acyl-hydrolases. ATGL is highly expressed in adipose tissue of mice and humans. It exhibits high substrate specificity for triacylglycerol and is associated with lipid droplets. Inhibition of ATGL markedly decreases total adipose acyl-hydrolase activity. Thus, ATGL and HSL coordinately catabolize stored triglycerides in adipose tissue of mammals.

In the X‐ray scattering curve of chain‐molecules in solution, essentially four regions may be distinguished as is shown by a more detailed mathematical discussion: The scattering at the smallest angles, showing an approximately Gaussean course, whose ordinate, when extrapolated to zero angle, is proportional to the square of the mol. weight. It is due to the diffraction effect of the whole coiled chain‐molecule. This is followed by a region of v ‐values where the scattering falls off as 1/ v 2 . It is due to parts of the chain molecule which themselves already occur in all possible orientations. After a transition region (which is also accounted for by the theory) there follows a scattering which is proportional to 1/ v . It is to be considered as the scattering of mostly straight parts of the molecule. The scattering at large angles, caused by smaller parts of the molecule (monomer group and single atoms), which at the same time indicates the periodicity (= length of structural unit in the direction of the chain axis) by a step, at an angle corresponding to Bragg's law. Its sharpness, too, is a measure for the coiling of the molecule. It can be shown that the abscissa of the intersecting point of the 1/ v 2 and 1/ v branches, when extrapolated to the transition region, is connected in a characteristic way with the statistical chain element or the “length of persistance”, which represent two different measures for the stiffness of the chain molecule. Measurements with polyvinyl bromide lead to a length of persistance of 11 ± 1 Å, which agrees satisfactorily with the value of 13 Å for polyvinyl chloride as derived from the birefringence of flow. At large angles two weak steps were found, one of which corresponds to the monomer length of 2.56 Å. Measurements on solutions of cellulose nitrate gave a curve ∼ 1/ v without any steeper ascent up to the smallest angles, corresponding to 300 Å. We have, therefore, to conclude that the chain‐element of cellulose nitrate is in any case larger than 150 Å, which again is in agreement with the results of other physical measurements. Though only a small number of experimental results is available so far, it seems to be established that the procedure yields a direct evaluation of the shape of chain molecules in solution and, in this respect, appears superior to other methods. However, the experimental difficulties are considerable.

The essential oil of black cumin seeds, Nigella sativa L., was tested for a possible antioxidant activity. A rapid evaluation for antioxidants, using two TLC screening methods, showed that thymoquinone and the components carvacrol, t-anethole and 4-terpineol demonstrated respectable radical scavenging property. These four constituents and the essential oil possessed variable antioxidant activity when tested in the diphenylpicrylhydracyl assay for non-specific hydrogen atom or electron donating activity. They were also effective.OH radical scavenging agents in the assay for non-enzymatic lipid peroxidation in liposomes and the deoxyribose degradation assay. GC-MS analysis of the essential oil obtained from six different samples of Nigella sativa seeds and from a commercial fixed oil showed that the qualitative composition of the volatile compounds was almost identical. Differences were mainly restricted to the quantitative composition.

Precipitation downscaling improves the coarse resolution and poor representation of precipitation in global climate models and helps end users to assess the likely hydrological impacts of climate change. This paper integrates perspectives from meteorologists, climatologists, statisticians, and hydrologists to identify generic end user (in particular, impact modeler) needs and to discuss downscaling capabilities and gaps. End users need a reliable representation of precipitation intensities and temporal and spatial variability, as well as physical consistency, independent of region and season. In addition to presenting dynamical downscaling, we review perfect prognosis statistical downscaling, model output statistics, and weather generators, focusing on recent developments to improve the representation of space-time variability. Furthermore, evaluation techniques to assess downscaling skill are presented. Downscaling adds considerable value to projections from global climate models. Remaining gaps are uncertainties arising from sparse data; representation of extreme summer precipitation, subdaily precipitation, and full precipitation fields on fine scales; capturing changes in small-scale processes and their feedback on large scales; and errors inherited from the driving global climate model.

Lipids are produced, transported, and recognized by the concerted actions of numerous enzymes, binding proteins, and receptors. A comprehensive analysis of lipid molecules, “lipidomics,” in the context of genomics and proteomics is crucial to understanding cellular physiology and pathology; consequently, lipid biology has become a major research target of the postgenomic revolution and systems biology. To facilitate international communication about lipids, a comprehensive classification of lipids with a common platform that is compatible with informatics requirements has been developed to deal with the massive amounts of data that will be generated by our lipid community. As an initial step in this development, we divide lipids into eight categories (fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, prenol lipids, saccharolipids, and polyketides) containing distinct classes and subclasses of molecules, devise a common manner of representing the chemical structures of individual lipids and their derivatives, and provide a 12 digit identifier for each unique lipid molecule. The lipid classification scheme is chemically based and driven by the distinct hydrophobic and hydrophilic elements that compose the lipid.This structured vocabulary will facilitate the systematization of lipid biology and enable the cataloging of lipids and their properties in a way that is compatible with other macromolecular databases. Lipids are produced, transported, and recognized by the concerted actions of numerous enzymes, binding proteins, and receptors. A comprehensive analysis of lipid molecules, “lipidomics,” in the context of genomics and proteomics is crucial to understanding cellular physiology and pathology; consequently, lipid biology has become a major research target of the postgenomic revolution and systems biology. To facilitate international communication about lipids, a comprehensive classification of lipids with a common platform that is compatible with informatics requirements has been developed to deal with the massive amounts of data that will be generated by our lipid community. As an initial step in this development, we divide lipids into eight categories (fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, prenol lipids, saccharolipids, and polyketides) containing distinct classes and subclasses of molecules, devise a common manner of representing the chemical structures of individual lipids and their derivatives, and provide a 12 digit identifier for each unique lipid molecule. The lipid classification scheme is chemically based and driven by the distinct hydrophobic and hydrophilic elements that compose the lipid. This structured vocabulary will facilitate the systematization of lipid biology and enable the cataloging of lipids and their properties in a way that is compatible with other macromolecular databases. The goal of collecting data on lipids using a “systems biology” approach to lipidomics requires the development of a comprehensive classification, nomenclature, and chemical representation system to accommodate the myriad lipids that exist in nature. Lipids have been loosely defined as biological substances that are generally hydrophobic in nature and in many cases soluble in organic solvents (1Smith A. Oxford Dictionary of Biochemistry and Molecular Biology. 2nd edition. Oxford University Press, Oxford, UK2000Google Scholar). These chemical properties cover a broad range of molecules, such as fatty acids, phospholipids, sterols, sphingolipids, terpenes, and others (2Christie W.W. Lipid Analysis. 3rd edition. Oily Press, Bridgewater, UK2003Google Scholar). The LIPID MAPS (LIPID Metabolites And Pathways Strategy; http://www.lipidmaps.org), Lipid Library (http://lipidlibrary.co.uk), Lipid Bank (http://lipidbank.jp), LIPIDAT (http://www.lipidat.chemistry.ohio-state.edu), and Cyberlipids (http://www.cyberlipid.org) websites provide useful online resources for an overview of these molecules and their structures. More accurate definitions are possible when lipids are considered from a structural and biosynthetic perspective, and many different classification schemes have been used over the years. However, for the purpose of comprehensive classification, we define lipids as hydrophobic or amphipathic small molecules that may originate entirely or in part by carbanion-based condensations of thioesters (fatty acids, polyketides, etc.) and/or by carbocation-based condensations of isoprene units (prenols, sterols, etc.). Additionally, lipids have been broadly subdivided into “simple” and “complex” groups, with simple lipids being those yielding at most two types of products on hydrolysis (e.g., fatty acids, sterols, and acylglycerols) and complex lipids (e.g., glycerophospholipids and glycosphingolipids) yielding three or more products on hydrolysis. The classification scheme presented here organizes lipids into well-defined categories that cover eukaryotic and prokaryotic sources and that is equally applicable to archaea and synthetic (manmade) lipids. Lipids may be categorized based on their chemically functional backbone as polyketides, acylglycerols, sphingolipids, prenols, or saccharolipids. However, for historical and bioinformatics advantages, we chose to separate fatty acyls from other polyketides, the glycerophospholipids from the other glycerolipids, and sterol lipids from other prenols, resulting in a total of eight primary categories. An important aspect of this scheme is that it allows for subdivision of the main categories into classes and subclasses to handle the existing and emerging arrays of lipid structures. Although any classification scheme is in part subjective as a result of the structural and biosynthetic complexity of lipids, it is an essential prerequisite for the organization of lipid research and the development of systematic methods of data management. The classification scheme presented here is chemically based and driven by the distinct hydrophobic and hydrophilic elements that constitute the lipid. Biosynthetically related compounds that are not technically lipids because of their water solubility are included for completeness in this classification scheme. The proposed lipid categories listed in Table 1 have names that are, for the most part, well accepted in the literature. The fatty acyls (FA) are a diverse group of molecules synthesized by chain elongation of an acetyl-CoA primer with malonyl-CoA (or methylmalonyl-CoA) groups that may contain a cyclic functionality and/or are substituted with heteroatoms. Structures with a glycerol group are represented by two distinct categories: the glycerolipids (GL), which include acylglycerols but also encompass alkyl and 1Z-alkenyl variants, and the glycerophospholipids (GP), which are defined by the presence of a phosphate (or phosphonate) group esterified to one of the glycerol hydroxyl groups. The sterol lipids (ST) and prenol lipids (PR) share a common biosynthetic pathway via the polymerization of dimethylallyl pyrophosphate/isopentenyl pyrophosphate but have obvious differences in terms of their eventual structure and function. Another well-defined category is the sphingolipids (SP), which contain a long-chain base as their core structure. This classification does not have a glycolipids category per se but rather places glycosylated lipids in appropriate categories based on the identity of their core lipids. It also was necessary to define a category with the term “saccharolipids” (SL) to account for lipids in which fatty acyl groups are linked directly to a sugar backbone. This SL group is distinct from the term “glycolipid” that was defined by the International Union of Pure and Applied Chemists (IUPAC) as a lipid in which the fatty acyl portion of the molecule is present in a glycosidic linkage. The final category is the polyketides (PK), which are a diverse group of metabolites from plant and microbial sources. Protein modification by lipids (e.g., fatty acyl, prenyl, cholesterol) occurs in nature; however, these proteins are not included in this database but are listed in protein databases such as GenBank (http://www.ncbi.nlm.nih.gov) and SwissProt (http://www.ebi.ac.uk/swissprot/).TABLE 1Lipid categories and examplesCategoryAbbreviationExampleFatty acyls FAdodecanoic acidGlycerolipids GL1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycerolGlycerophospholipids GP1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholineSphingolipids SPN-(tetradecanoyl)-sphing-4-enineSterol lipids STcholest-5-en-3β-olPrenol lipids PR2E,6E-farnesolSaccharolipids SLUDP-3-O-(3R-hydroxy-tetradecanoyl)-αd-N-acetylglucosaminePolyketides PKaflatoxin B1 Open table in a new tab A naming scheme must unambiguously define a lipid structure in a manner that is amenable to chemists, biologists, and biomedical researchers. The issue of lipid nomenclature was last addressed in detail by the International Union of Pure and Applied Chemists and the International Union of Biochemistry and Molecular Biology (IUPAC-IUBMB) Commission on Biochemical Nomenclature in 1976, which subsequently published its recommendations (3IUPAC-IUB Commission on Biochemical Nomenclature (CBN). The nomenclature of lipids (recommendations 1976). 1977. Eur. 1977. 1977. 1977. Lipid Scholar). a of to the naming of glycolipids Commission on Biochemical Nomenclature Nomenclature of glycolipids (recommendations Eur. Pure Commission on Biochemical Nomenclature Nomenclature of (recommendations Eur. and Commission on Biochemical Nomenclature Nomenclature of (recommendations Eur. have been by this and on the A of lipid classes have been the last three that have not been The present classification these new lipids and a with our proposed classification we provide of systematic (or names for the classes and subclasses of lipids. 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Another important of molecules is by the and which contain an to a core of and A. of a of and a on as well as the in are of this lipids classes and and Open table in a new tab and their important in the of phosphate and in in polymerization in to and its and in eukaryotic protein The and of phosphate and in the of Scholar). The and of phosphate from those of the we have in separate in which the to in the is are to 12 units in of to isoprene the of the three units are of prenol lipid structures are in structures for prenol have the term “glycolipid” in the classification scheme to a on lipid structures. eight lipid categories in the present scheme include important derivatives, the term with the goal of lipid in the term “saccharolipids” to compounds in which fatty are linked directly to a sugar structures that are compatible with the a sugar for the glycerol backbone that is present in glycerolipids and as or as The most are the of the lipid A of the in Scholar). lipid A molecules are of which are with as many as fatty acyl structure of Lipid in structural analysis of in and Scholar). that in naming these the total of fatty acyl groups are of the nature of the or The for in is a lipid A that is glycosylated with two the backbone of lipid A is by and of the of by from in the of lipid A molecules with acyl the has been also in this are the of and by such as The are of that are with a fatty acyl include fatty of which are by the units of lipids The of Scholar). of and also have been in fatty and in Scholar). structures are in classes and Open table in a new tab are synthesized by as well as and with that share with the fatty the of acyl proteins and and and of however, a of many of which have the of lipids. The in from to and complex systems are by and/or other polyketides are linked with synthesized to of the three classes are in used and are polyketides or of these include and polyketides are The of and the that polyketides has the for in the The of and of classes and polyketides polyketides Open table in a new tab this classification of polyketides as the step in a more scheme. It will be important to include as many structures as possible in a lipid database that be for and chemical The of the LIPID MAPS are to lipids and new to and in lipids that with cellular and to bioinformatics that lipid the of Lipid Bank are to and lipid structures and the with and the of the are to and and with lipid To the from three and to facilitate a comprehensive classification of lipids with a common platform that is compatible with informatics requirements must be developed to deal with the massive amounts of data that will be generated by the lipid community. The proposed classification, nomenclature, and chemical representation system was to accommodate the massive data that will result from the LIPID MAPS but it has been to accommodate as many lipids as also have to the system compatible with existing lipid databases and the lipids in It is to be new or subclasses be in the and will be on the LIPID MAPS The development of this system has been by with the in the that this system will be accepted and The the of the International Lipids and Nomenclature to on the of these This A. and representing LIPID representing the International on the of representing the and and representing the of the on the Biochemistry of The are most of and of this with is the of the Nomenclature of and the Commission on Biochemical The the for by at the of for with their nomenclature for glycosylated structures. are to at the of for to this This was by the LIPID MAPS from the of

The kinetics of the oxidation of human low density lipoprotein (LDL) can be measured continuously by monitoring the change of the 234 nm diene absorption. The time-course shows three consecutive phases, a lag-phase during which the diene absorption increases only weakly, a propagation phase with a rapid increase of the diene absorption and finally a decomposition phase. The increase of the dienes is highly correlated with the increase of MDA or lipid hydroperoxides. The duration of the lag-phase is determined by the endogenous antioxidants contained in LDL (vitamin E, carotenoids, retinylstearate). Water-soluble antioxidants (ascorbic acid, urate) added in micromolar concentrations prolong the lag-phase in a concentration-dependent manner. The determination of the lag-phase is a convenient and objective procedure for determining the susceptibility of LDL from different donors towards oxidation as well as effects of pro- and antioxidants.

In 2005, the International Lipid Classification and Nomenclature Committee under the sponsorship of the LIPID MAPS Consortium developed and established a “Comprehensive Classification System for Lipids” based on well-defined chemical and biochemical principles and using an ontology that is extensible, flexible, and scalable. This classification system, which is compatible with contemporary databasing and informatics needs, has now been accepted internationally and widely adopted. In response to considerable attention and requests from lipid researchers from around the globe and in a variety of fields, the comprehensive classification system has undergone significant revisions over the last few years to more fully represent lipid structures from a wider variety of sources and to provide additional levels of detail as necessary. The details of this classification system are reviewed and updated and are presented here, along with revisions to its suggested nomenclature and structure-drawing recommendations for lipids. In 2005, the International Lipid Classification and Nomenclature Committee under the sponsorship of the LIPID MAPS Consortium developed and established a “Comprehensive Classification System for Lipids” based on well-defined chemical and biochemical principles and using an ontology that is extensible, flexible, and scalable. This classification system, which is compatible with contemporary databasing and informatics needs, has now been accepted internationally and widely adopted. In response to considerable attention and requests from lipid researchers from around the globe and in a variety of fields, the comprehensive classification system has undergone significant revisions over the last few years to more fully represent lipid structures from a wider variety of sources and to provide additional levels of detail as necessary. The details of this classification system are reviewed and updated and are presented here, along with revisions to its suggested nomenclature and structure-drawing recommendations for lipids. In an effort to support the growing field of lipidomics and establish the importance of lipids as a major class of biomolecules, the International Lipid Classification and Nomenclature Committee (ILCNC) developed a “Comprehensive Classification System for Lipids” that was published in 2005 (1Fahy E. Subramaniam S. Brown H.A. Glass C.K. Merrill Jr., A.H. Murphy R.C. Raetz C.R. Russell D.W. Seyama Y. Shaw W. al et A comprehensive classification system for lipids.J. Lipid Res. 2005; 46: 839-862Abstract Full Text Full Text PDF PubMed Scopus (1141) Google Scholar). For the purpose of classification, we define lipids as hydrophobic or amphipathic small molecules that may originate entirely or in part by carbanion-based condensations of thioesters (fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, and polyketides) and/or by carbocation-based condensations of isoprene units (prenol lipids and sterol lipids). The comprehensive classification system organizes lipids into these eight well-defined categories (Table 1) that cover eukaryotic and prokaryotic sources. It has been adopted internationally and widely accepted by the lipidomics community. The system is also available online on the LIPID MAPS (2Schmelzer K. Fahy E. Subramaniam S. Dennis E.A. The lipid maps initiative in lipidomics.Methods Enzymol. 2007; 432: 171-183Crossref PubMed Scopus (115) Google Scholar) website (http://www.lipidmaps.org). The comprehensive classification system has been under the guidance of the ILCNC, 3The ILCNC currently consists of Dr. Edward A. Dennis, Chair, (US), Dr. Robert C. Murphy (US), Dr. Masahiro Nishijima (Japan), Dr. Christian R. H. Raetz (US), Dr. Takao Shimizu (Japan), Dr. Friedrich Spener (Austria), Dr. Gerrit van Meer (The Netherlands), and Dr. Michael Wakelam (UK). Dr. Shankar Subramaniam serves as Informatics Advisor, and Dr. Eoin Fahy serves as Director. Meetings were held May 7, 2006 and May 4, 2008 in La Jolla, CA. which meets periodically to propose changes and updates to classification, nomenclature, and structural representation.TABLE 1Lipid categories of the comprehensive classification system and the number of structures in the LIPID MAPS databaseCategoryAbbreviationStructures in DatabaseFatty acylsFA2678GlycerolipidsGL3009GlycerophospholipidsGP1970SphingolipidsSP620Sterol LipidsST1744Prenol LipidsPR610SaccharolipidsSL11PolyketidesPK132 Open table in a new tab The initial version of the comprehensive classification system was more heavily focused on mammalian lipids, reflecting a bias toward the experimental interests of the LIPID MAPS Consortium (2Schmelzer K. Fahy E. Subramaniam S. Dennis E.A. The lipid maps initiative in lipidomics.Methods Enzymol. 2007; 432: 171-183Crossref PubMed Scopus (115) Google Scholar). However, due to considerable attention and requests from lipid researchers in a variety of fields, the classification system has now been extended to more fully represent lipid structures from nonmammalian sources, such as plants, bacteria, and fungi. For example, two new main classes (Glycosyldiradylglycerols and Glycosylmonoradylglycerols) have been added to the Glycerolipids category to accommodate key plant structural lipids, such as the sulfoquinovosyldiacylglycerols (3Norman H.A. Mischke C.F. Allen B. Vincent J.S. Semi-preparative isolation of plant sulfoquinovosyldiacylglycerols by solid phase extraction and HPLC procedures.J. Lipid Res. 1996; 37: 1372-1376Abstract Full Text PDF PubMed Google Scholar) found in chloroplasts. Also, the list of subclasses under the Sterols main class has been expanded to include a set of 15 different core structures (Ergosterols, Gorgosterols, Furostanols, etc.), which provide a structure-based classification of these molecules that span multiple phyla. Another key development has been the adoption of existing hierarchies (4Buckingham J. Dictionary of Natural Products on CD-ROM, Version 6.1. Chapman & Hall, London1998Crossref Google Scholar) for the Polyketide category and Prenol Lipids/Isoprenoids subclasses where the majority of these molecules are derived from natural product sources and have been studied intensively from a pharmaceutical and ecological standpoint. This in turn has necessitated the expansion of the number of existing classification levels (category, main class, and subclass) to accommodate an additional level of stratification in the case of the C10 to C30 isoprenoid subclasses that now contain entries at a fourth level of detail. The “LM_ID” identifier, whose format provides a systematic means of assigning a unique identification to each lipid molecule, has accordingly been expanded in length in these particular cases, with an additional two characters being used to describe the fourth level. A detailed overview of the changes and updates to the comprehensive classification system is presented below. As a consequence of adding an extra level of classification detail, the length of the LM_ID identifier was lengthened from 12 characters to 14 in cases where a lipid defined with four levels of classification is being described (Table 2). In this case, characters 9 and 10 specify the level-4 class. It should be emphasized that all lipids that do not require a fourth level of detail (i.e., the vast majority of them) still use a 12-digit LM_ID identifier.TABLE 2Format of LIPID MAPS identifier (LM_ID) in the comprehensive classification systemCharactersDescriptionExampleComments1–2Fixed “LM” designationLMAlways LM3–4Two-letter category codePROne of eight categories5–6Two-digit class code01—7–8Two-digit subclass code03“00” when no subclass9–10Two-digit fourth level code06Only used for lipids with four levelsLast four digitsUnique four-character identifier within subclass or within fourth level0002First two of the last four digits are letters in the case of the Glycosphingolipid subclasses Open table in a new tab In keeping with the theme of having a classification system dictated by molecular structure and function, the sterol lipid subclasses Phytosterols, Marine sterols, and Fungal sterols were retired because these refer to the lipid source (marine) or biological kingdom (plants and fungi). It is possible to identify a particular sterol in more than one of these three sources. These subclasses have been replaced by a new set of subclasses based on the carbon skeleton of the sterol core structure (Ergosterols, Gorgosterols, Furostanols, etc.). The details are outlined under the Sterol Lipids section below, and the complete description of this category can be found on the LIPID MAPS website 4Supplementary tables that provide the complete list of the classes, subclasses, and fourth class level (where applicable) of each of the eight categories of lipids are available on the LIPID MAPS website at http://www.lipidmaps.org. (http://www.lipidmaps.org). The natural products chemistry and medicinal chemistry literature describes tens of thousands of molecules that fall under the scope of lipids, based on their biosynthetic origin. In particular, isoprenoids and polyketides from diverse sources, such as plant, fungi, algae, bacteria, and marine invertebrates, are well documented and have been reviewed and classified in detail. The Dictionary of Natural Products (4Buckingham J. Dictionary of Natural Products on CD-ROM, Version 6.1. Chapman & Hall, London1998Crossref Google Scholar), a database available from Chapman and Hall/CRC (http://dnp.chemnetbase.com), has a classification hierarchy that covers polyketides and isoprenoids in depth. The LIPID MAPS comprehensive classification system has now incorporated some of these hierarchies relevant to natural products, with a view to covering both mammalian and nonmammalian lipids comprehensively. 3The ILCNC currently consists of Dr. Edward A. Dennis, Chair, (US), Dr. Robert C. Murphy (US), Dr. Masahiro Nishijima (Japan), Dr. Christian R. H. Raetz (US), Dr. Takao Shimizu (Japan), Dr. Friedrich Spener (Austria), Dr. Gerrit van Meer (The Netherlands), and Dr. Michael Wakelam (UK). Dr. Shankar Subramaniam serves as Informatics Advisor, and Dr. Eoin Fahy serves as Director. Meetings were held May 7, 2006 and May 4, 2008 in La Jolla, CA. It was recognized that additional levels of stratification were required to classify certain types of lipids and that the current three-level system of category/main class/subclass needed to be expanded. For example, in the Prenol Lipids category, 3The ILCNC currently consists of Dr. Edward A. Dennis, Chair, (US), Dr. Robert C. Murphy (US), Dr. Masahiro Nishijima (Japan), Dr. Christian R. H. Raetz (US), Dr. Takao Shimizu (Japan), Dr. Friedrich Spener (Austria), Dr. Gerrit van Meer (The Netherlands), and Dr. Michael Wakelam (UK). Dr. Shankar Subramaniam serves as Informatics Advisor, and Dr. Eoin Fahy serves as Director. Meetings were held May 7, 2006 and May 4, 2008 in La Jolla, CA. the Sesquiterpene C15 subclass contains ∼90 known variants based on their carbon skeletons (Bisabolanes, Germacranes, etc.). A fourth level of detail has been added to the LIPID MAPS comprehensive classification system to handle cases such as these. In response to worldwide interest in the comprehensive classification system for lipids, the scope has been expanded to cover lipids from nonmammalian sources, such as plants, bacteria, fungi, algae, and marine organisms. To accomplish this, several new lipid classes have been added, such as fatty acyl glycosides, glycosyldiradylglycerols, and various sterol skeletons. The Polyketide category has also been revised comprehensively. 3The ILCNC currently consists of Dr. Edward A. Dennis, Chair, (US), Dr. Robert C. Murphy (US), Dr. Masahiro Nishijima (Japan), Dr. Christian R. H. Raetz (US), Dr. Takao Shimizu (Japan), Dr. Friedrich Spener (Austria), Dr. Gerrit van Meer (The Netherlands), and Dr. Michael Wakelam (UK). Dr. Shankar Subramaniam serves as Informatics Advisor, and Dr. Eoin Fahy serves as Director. Meetings were held May 7, 2006 and May 4, 2008 in La Jolla, CA. The nomenclature of lipids falls into two main categories: systematic names and common or trivial names. The latter includes abbreviations that are a convenient way to define acyl/alkyl chains in acylglycerols, sphingolipids, and glycerophospholipids and synonyms such as “phosphatidyl” for “glycerophospho.” The generally accepted guidelines for lipid systematic names have been defined by the International Union of Pure and Applied Chemists and the International Union of Biochemistry and Molecular Biology (IUPAC-IUBMB) Commission on Biochemical Nomenclature (http://www.chem.qmul.ac.uk/iupac/) (5IUPAC-IUB Commission on Biochemical Nomenclature (CBN). The nomenclature of lipids (Recommendations 1976). 1977. Eur. J. Biochem. 79: 11–21; 1977. Hoppe-Seylers Z. Physiol. Chem. 358: 617–631; 1977. Lipids 12: 455–468; 1977. Mol. Cell. Biochem. 17: 157–171; 1978. Chem. Phys. Lipids 21: 159–173; 1978. J. Lipid Res. 19: 114–128; 1978. Biochem. J. 171: 21–35. (http://www.chem.qmul.ac.uk/iupac/lipid/).Google Scholar, 6I. U. P. A. C-I. U. B. Joint Commission on Biochemical Nomenclature (JCBN). Nomenclature of glycolipids. (Recommendations 1997) 2000. Adv. Carbohydr. Chem. Biochem. 55: 311–326; 1988. Carbohydr. Res. 312: 167–175; 1998. Eur. J. Biochem. 257: 293–298; 1999. Glycoconjugate J. 16:1–6; 1999. J. Mol. Biol. 286: 963–970; 1997. Pure Appl. Chem. 69: 2475–2487. (http://www.chem.qmul.ac.uk/iupac/misc/glylp.html)Google Scholar, 7I. U. P. A. C-I. U. B. Joint Commission on Biochemical Nomenclature (JCBN). Nomenclature of prenols. (Recommendations 1987) 1987. Eur. J. Biochem. 167: 181–184. (http://www.chem.qmul.ac.uk/iupac/misc/prenol.html)Google Scholar, 8I. U. P. A. C-I. U. B. Joint Commission on Biochemical Nomenclature (JCBN). Nomenclature of steroids (Recommendations 1989) 1989. Eur. J. Biochem. 186: 429–458. (http://www.chem.qmul.ac.uk/iupac/steroid/).Google Scholar). In response to several requests from knowledgeable lipid experts, abbreviations for Glycerophospholipid classes (see http://www.lipidmaps.org for GP category 3The ILCNC currently consists of Dr. Edward A. Dennis, Chair, (US), Dr. Robert C. Murphy (US), Dr. Masahiro Nishijima (Japan), Dr. Christian R. H. Raetz (US), Dr. Takao Shimizu (Japan), Dr. Friedrich Spener (Austria), Dr. Gerrit van Meer (The Netherlands), and Dr. Michael Wakelam (UK). Dr. Shankar Subramaniam serves as Informatics Advisor, and Dr. Eoin Fahy serves as Director. Meetings were held May 7, 2006 and May 4, 2008 in La Jolla, CA.) have been changed now in the comprehensive classification system to the more universally used two-letter “PC/PE/PS/PA/PI” format. Consequently, glycerophospholipids in the LIPID MAPS structure database and LIPID MAPS standards database as well as all the Glycerophospholipids drawing tools and mass spectrometry prediction tools have been updated to conform to this new abbreviation format (Table 3).TABLE 3Changes in abbreviations for Glycerophospholipids in the comprehensive classification systemClassSynonymOldNewGlycerophosphocholinesPhosphatidylcholinesGPChoPCaFor abbreviations of monoradyglycerophospholipids (lysophospholipids), LPX may be used, for example, LPC, LPE, LPA, etc.GlycerophosphoethanolaminesPhosphatidylethanolaminesGPEtnPEGlycerophosphoserinesPhosphatidylserinesGPSerPSGlycerophosphoglycerolsPhosphatidylglycerolsGPGroPGGlycerophosphoglycerophosphatesPhosphatidylglycerol phosphatesGPGroPPGPGlycerophosphoinositolsPhosphatidylinositolsGPInsPIGlycerophosphoinositol monophosphatesPhosphatidylinositol phosphatesGPInsPPIPGlycerophosphoinositol bis-phosphatesPhosphatidylinositol bis-phosphatesGPInsP2PIP2Glycerophosphoinositol For abbreviations of monoradyglycerophospholipids (lysophospholipids), LPX may be used, for example, LPC, LPE, LPA, Open table in a new tab The LIPID MAPS Consortium has considerable effort to establish guidelines for drawing lipid structures in a and and lipids are to which to the use of unique that more than the lipid community. the structure-drawing is the in molecular of lipids. However, classes of lipids well as for structure-drawing due to their A of structure-drawing tools has been developed and that of systematic and abbreviations E. Subramaniam S. LIPID MAPS online tools for lipid Res. 2007; PubMed Scopus Google Scholar). The structures may be and in a variety of of the structure-drawing tools for fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, and sterols are available in the section of the LIPID MAPS website (http://www.lipidmaps.org). of the structures are in the importance of these molecules in and is to have a database of lipids with a defined ontology that is extensible, flexible, and scalable. The ontology of lipids classification, nomenclature, structure and structural of all in the have developed a available comprehensive database of lipid structures of lipid molecules from existing and from the LIPID MAPS This database Fahy E. Brown A. Dennis E.A. Glass C.K. Merrill Jr., A.H. Murphy R.C. Raetz C.R. Russell D.W. al et LIPID MAPS structure Res. 2007; PubMed Scopus Google Scholar, E. R. A. J. Y. Subramaniam S. for lipidomics.Methods Enzymol. 2007; 432: PubMed Scopus Google Scholar), in to as the to and of lipid also contains systematic classification, nomenclature, and structure of lipids along with mass where than lipid molecules are now available on the LIPID MAPS and these have been adopted by the for as well as the of and database structures have been classified and to LIPID MAPS A number of different molecular such as and the and are and nomenclature of these molecules are also The database is and the include and structure-based the category, the subclasses and have been changed to and to accommodate The names of the fatty subclasses and have been to and A new acyl main class has been added to cover the number of found in bacteria, and marine of natural of fatty and PubMed Scopus Google Scholar, and of the natural PubMed Scopus Google Scholar). subclasses include acyl of and and The Glycerolipids category was to include two new main classes (Glycosyldiradylglycerols and Glycosylmonoradylglycerols) that contain key plant structural lipids, such as the found in chloroplasts. The existing subclasses were to the that is to the of on the for and of structures in the LIPID MAPS structure database have been For with two different two different structural are for with three different different of drawing all possible structural an is used as a A along with the number of possible is to the abbreviation and and a unique LM_ID is of this format is the The structure to the LM_ID on the LIPID MAPS website to the in the and the is to all in the are also cases within the and classes where are due to by certain of both the or to and where the of the at is by the acyl from the of to the at or can an In such cases when a is can be with a for example, or the is with a for example, It should be that the two-letter abbreviation or all possible types of lipid for example, having and The is by the for example, and the by the for example, The to the classes within the Glycerophospholipids In cases where is and is abbreviations such as and may be used, where the within refer to the number of and of all the For the Glycerophospholipids category, the subclass has been replaced by the more due to the that in are the in H.A. J.S. S. in and PubMed Scopus Google Scholar). updates have been for the Glycerophospholipid The lipids class has been replaced by the class to of with than As we have changed to two-letter abbreviations to describe glycerophospholipids in are abbreviations for all molecular of their These names to and are used widely in lipid as to systematic names. This format one or two chains where the structures of the chains are within is at the carbon of and the is at the In cases of molecules with at of the and of the at the the of is to the abbreviation and the abbreviation format is for molecules with at the carbon of the the of is to the and the structure is with In cases where is and is such as may be used to of and for all and are by an or identifier, as in and In the latter case, the an at of and a at the or may be with a in the for example, The “phosphatidyl” is used to refer to classes all types of chains and not acyl as was by guidelines (5IUPAC-IUB Commission on Biochemical Nomenclature (CBN). The nomenclature of lipids (Recommendations 1976). 1977. Eur. J. Biochem. 79: 11–21; 1977. Hoppe-Seylers Z. Physiol. Chem. 358: 617–631; 1977. Lipids 12: 455–468; 1977. Mol. Cell. Biochem. 17: 157–171; 1978. Chem. Phys. Lipids 21: 159–173; 1978. J. Lipid Res. 19: 114–128; 1978. Biochem. J. 171: 21–35. (http://www.chem.qmul.ac.uk/iupac/lipid/).Google Scholar). The classification is from that in the in this (2Schmelzer K. Fahy E. Subramaniam S. Dennis E.A. The lipid maps initiative in lipidomics.Methods Enzymol. 2007; 432: 171-183Crossref PubMed Scopus (115) Google Scholar). of is that for of the Glycosphingolipid subclasses, the structure of the is known the structure of the is In these cases, the last two digits of the LIPID MAPS LM_ID identifier are as to an and the and fourth last digits are a different two-letter identifier for unique within that For example, in the subclass the structure is an LM_ID of where the digits specify the unique and the digits a the has a and is a LM_ID of The Sterol lipids subclasses Phytosterols, Marine sterols, and Fungal sterols have been and replaced with a set of subclasses (Ergosterols, sterols, Gorgosterols, Furostanols, and that in the of their sterol core structures and cover multiple A. Sterols in marine Scopus Google Scholar, Phytosterols, and their in structural and Lipid Res. PubMed Scopus Google Scholar). The class has been with the and the class now includes and The class has been to the Prenol Lipids category the of the core structure is at with the of the of the Sterol Lipids The subclass of the Prenol lipids category has been added to the class. are a of that are to A. have in of and As the C10 to C30 isoprenoid subclasses now contain entries at a fourth level of detail. The LM_ID contain an extra two digits that specify the fourth level class, for example, the is an LM_ID of The class has been to the Prenol Lipids category the Sterol Lipids For the the main class acyl has been added to cover a variety of from plants, bacteria, and fungi. is the from the plant and from the of Scopus Google Scholar). It should be that this category covers structures in which fatty acyl/alkyl are to a lipids to a are found in their The category was revised and on the classification hierarchy used by the Dictionary of Natural Products (4Buckingham J. Dictionary of Natural Products on CD-ROM, Version 6.1. Chapman & Hall, London1998Crossref Google Scholar). are from bacteria, fungi, plants, and and have been heavily studied by natural products and for The new classification format provides a of the structural within this The toward classification of lipids is the of an ontology that is extensible, flexible, and scalable. be to and represent these molecules in a that is to databasing and The ILCNC the comprehensive classification system in 2005 and has been in and on a to considerable attention and requests from lipid researchers in a variety of fields, the classification system has been extended to more fully represent lipid structures from nonmammalian sources, such as plants, bacteria, and fungi. This system has been internationally accepted and is now widely used in and for The LIPID MAPS classification system has also been adopted by where hierarchies lipids, and have been and by the in format of the In an effort to LIPID MAPS lipid structures are now available on website where have been The classification system is available online where has been with an database of lipids. This in to as the and of lipid also contains systematic classification, nomenclature, and structure of lipids along with mass where structures have been classified and to LIPID MAPS The format of the LM_ID identifier (Table provides a systematic means of the classification hierarchy and assigning a unique identification to each lipid It also for the of new classification in the The database is and the include and structure-based This database is described in detail Fahy E. Brown A. Dennis E.A. Glass C.K. Merrill Jr., A.H. Murphy R.C. Raetz C.R. Russell D.W. al et LIPID MAPS structure Res. 2007; PubMed Scopus Google Scholar, E. R. A. J. Y. Subramaniam S. for lipidomics.Methods Enzymol. 2007; 432: PubMed Scopus Google Scholar). A of lipid structure-drawing tools in the section of the LIPID MAPS has been developed to structure with LIPID MAPS These tools are also of systematic names and detailed and databasing of lipid and has been to and database and to classify and LIPID MAPS These tools be expanded and as the scope of the classification system and over the The the of lipid researchers around the have and to attention in the Classification System for which to be to new and in the lipid The are also to the LIPID MAPS Consortium for their and to Dr. at the of for to this

Electrodermal activity is characterized by the superposition of what appear to be single distinct skin conductance responses (SCRs). Classic trough-to-peak analysis of these responses is impeded by their apparent superposition. A deconvolution approach is proposed, which separates SC data into continuous signals of tonic and phasic activity. The resulting phasic activity shows a zero baseline, and overlapping SCRs are represented by predominantly distinct, compact impulses showing an average duration of less than 2 s. A time integration of the continuous measure of phasic activity is proposed as a straightforward indicator of event-related sympathetic activity. The quality and benefit of the proposed measure is demonstrated in an experiment with short interstimulus intervals as well as by means of a simulation study. The advances compared to previous decomposition methods are discussed.

Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy-related processes cause severe human pathologies. Here, we review and discuss preclinical data linking autophagy dysfunction to the pathogenesis of major human disorders including cancer as well as cardiovascular, neurodegenerative, metabolic, pulmonary, renal, infectious, musculoskeletal, and ocular disorders.