scholarly journals Interaction of saposin D with membranes: effect of anionic phospholipids and sphingolipids

2003 ◽  
Vol 373 (3) ◽  
pp. 785-792 ◽  
Author(s):  
Fiorella CIAFFONI ◽  
Massimo TATTI ◽  
Rosa SALVIOLI ◽  
Anna Maria VACCARO
Keyword(s):  
Critical Value ◽  
Structure And Function ◽  
Slow Process ◽  
Small Particles ◽  
Anionic Phospholipids ◽  
Lysobisphosphatidic Acid ◽  
Dynamic Association ◽  
Lipid Surface ◽  
Definition Of ◽  
And Function

Saposin (Sap) D is an endolysosomal protein that, together with three other similar proteins, Sap A, Sap B and Sap C, is involved in the degradation of sphingolipids and, possibly, in the solubilization and transport of gangliosides. We found that Sap D is able to destabilize and disrupt membranes containing each of the three anionic phospholipids most abundant in the acidic endolysosomal compartment, namely lysobisphosphatidic acid (LBPA), phosphatidylinositol (PI) and phosphatidylserine (PS). The breakdown of the membranes, which occurs when the Sap D concentration on the lipid surface reaches a critical value, is a slow process that gives rise to small particles. The Sap D–particle complexes formed in an acidic milieu can be dissociated by an increase in pH, suggesting a dynamic association of Sap D with membranes. The presence of anionic phospholipids is required also for the Sap D-induced perturbation and solubilization of membranes containing a neutral sphingolipid such as ceramide or a ganglioside such as GM1. At appropriate Sap D concentrations Cer and GM1 are solubilized as constituents of small phospholipid particles. Our findings imply that most functions of Sap D are dependent on its interaction with anionic phospholipids, which mediate the Sap D effect on other components of the membrane such as sphingolipids. On consideration of the properties of Sap D we propose that Sap D might have a role in the definition of the structure and function of membranes, such as the intra-endolysosomal membranes, that are rich in anionic phospholipids.

scholarly journals The Conceptual Structure of Commercial Law

2020 ◽  
pp. 899
Author(s):  
Tamara M. Buckwold
Keyword(s):  
Conceptual Structure ◽  
Structure And Function ◽  
Commercial Law ◽  
Structural Framework ◽  
Legal Regimes ◽  
Rights And Interests ◽  
Definition Of ◽  
And Function

This article argues that commercial law is not merely a collection of rules, but a doctrinally coherent and conceptually sophisticated body of law structured through conceptions of property. The analysis focuses specifically on the aspects of commercial law that govern recovery of debt. The argument advances two related themes; that commercial law is built around conceptions of property and reciprocally defines the conceptions of property around which it is built. The article first addresses the role of property as the structural framework of commercial law. Property creates the basis for assertion of rights and provides the conceptual interface between the legal regimes of secured financing, judgment enforcement, and bankruptcy. Further, property is the basis on which commercial law rights and interests are reconciled with rights and interests that fall outside its boundaries. The article then explores the means by which commercial law resolves practical problems through the creative definition of property. The article concludes with thoughts on the importance of understanding the central role of property in the structure and function of commercial law.

R&D Support Programs (the Need)

2017 ◽  
pp. 1-25
Keyword(s):  
Business Plan ◽  
Structure And Function ◽  
Support Program ◽  
Support Programs ◽  
Legal Environment ◽  
Support Tools ◽  
Different Types ◽  
Strategic Role ◽  
Definition Of ◽  
And Function

Any good business plan starts with the definition of the need for which it intends to base the entire business. Following that example, the discussion here should also start with the need for such programs, their strategic role as defined by research, and the rationale that makes them prevalent. When discussing R&D support programs, one needs to bear in mind that there are different types of such programs. The specific needs such programs were designed to answer, whether well or less so, the target audience or clients they address, and the specific legal environment they operate in, influence the different types and give rise to the need for different types of programs to begin with. In this chapter, we shall define the R&D support program and analyze examples of the influence the parameters mentioned above, have on the structure and function of the programs. The different types as well as support tools will be discussed at a later chapter (Chapter 05 – R&D support program types).

scholarly journals The N370S (Asn370→Ser) mutation affects the capacity of glucosylceramidase to interact with anionic phospholipid-containing membranes and saposin C

2005 ◽  
Vol 390 (1) ◽  
pp. 95-103 ◽  
Author(s):  
Rosa Salvioli ◽  
Massimo Tatti ◽  
Susanna Scarpa ◽  
Sabrina Maria Moavero ◽  
Fiorella Ciaffoni ◽  
...  
Keyword(s):  
Amino Acid Position ◽  
Anionic Phospholipid ◽  
Anionic Phospholipids ◽  
Saposin C ◽  
Normal Enzyme ◽  
Lysobisphosphatidic Acid ◽  
Lipid Surface ◽  
Prevalent Mutation ◽  
N370s Mutation

The properties of the endolysosomal enzyme GCase (glucosylceramidase), carrying the most prevalent mutation observed in Gaucher patients, namely substitution of an asparagine residue with a serine at amino acid position 370 [N370S (Asn370→Ser) GCase], were investigated in the present study. We previously demonstrated that Sap (saposin) C, the physiological GCase activator, promotes the association of GCase with anionic phospholipid-containing membranes, reconstituting in this way the enzyme activity. In the present study, we show that, in the presence of Sap C and membranes containing high levels of anionic phospholipids, both normal and N370S GCases are able to associate with the lipid surface and to express their activity. Conversely, when the amount of anionic phospholipids in the membrane is reduced (∼20% of total lipids), Sap C is still able to promote binding and activation of the normal enzyme, but not of N370S GCase. The altered interaction of the mutated enzyme with anionic phospholipid-containing membranes and Sap C was further demonstrated in Gaucher fibroblasts by confocal microscopy, which revealed poor co-localization of N370S GCase with Sap C and lysobisphosphatidic acid, the most abundant anionic phospholipid in endolysosomes. Moreover, we found that N370S Gaucher fibroblasts accumulate endolysosomal free cholesterol, a lipid that might further interfere with the interaction of the enzyme with Sap C and lysobisphosphatidic acid-containing membranes. In summary, our results show that the N370S mutation primarily affects the interaction of GCase with its physiological activators, namely Sap C and anionic phospholipid-containing membranes. We thus propose that the poor contact between N370S GCase and its activators may be responsible for the low activity of the mutant enzyme in vivo.

14 Analysis on the System Configuration of Digital Substations

2013 ◽  
Vol 765-767 ◽  
pp. 2559-2562
Author(s):  
Fei Ma ◽  
Ze Ju Ma ◽  
Ying Ying Su
Keyword(s):  
Structure And Function ◽  
System Configuration ◽  
Iec 61850 ◽  
Network Solution ◽  
Electronic Transformer ◽  
Spacer Layer ◽  
Digital Substation ◽  
Definition Of ◽  
And Function

In accordance with the definition of the IEC 61850 standard, a digital substation is hierarchically distributed and divided into the process layer, the spacer layer and the station layer. On the basis of the analysis of its structure and function, this work is focused on the configuration of different layers and that of the dual bus wiring electronic transformer and merged unit, as well as the GOOSE network solution under the relay double configuration.

scholarly journals Attitudes

Psychology ◽  
2012 ◽  
Author(s):  
Jay K. Wood ◽  
Leandre R. Fabrigar
Keyword(s):  
Cognitive Structure ◽  
Historical Review ◽  
Structure And Function ◽  
Past Century ◽  
The Social ◽  
Potential Impact ◽  
Definition Of ◽  
And Function ◽  
Tremendous Impact ◽  
Shed Light

The attitude construct is one of the oldest and most-studied constructs in social psychology, and as such, it has had a tremendous impact on the social sciences over the past century. This long history notwithstanding, a historical review of the attitudes literature reveals a construct whose popularity has waxed and waned over the decades and that has generated a number of passionate debates. One area of contention over the years is probably the most fundamental: what exactly are attitudes? Although the definition of the term attitude has gone through many incarnations since its early definition as a “mental and neural state of readiness” (Allport 1935, cited under General Overviews, p. 810; see also the special issue of the journal Social Cognition 25.5 for a variety of perspectives on the definition of attitudes), most current researchers use the term to refer to a valenced evaluation of something, be it a person, object, concept, event, action, etc. (i.e., the attitude object). Most theorists consider attitudes to be relatively enduring (i.e., they are typically not transitory like phenomena such as mood states); however, the extent to which they are stable and enduring would be expected to fall on a continuum, and is determined by factors such as variations in cognitive structure. Furthermore, many contemporary researchers suggest that a distinction can be made between attitudes that are deliberative and within an individual’s control, and those that are nondeliberative and automatic (i.e., explicit versus implicit attitudes). Much of the research on attitudes has focused on issues such as the structure and function of attitudes, how they influence behavior and judgment, how they can be changed, and even whether we need them and if they exist at all. The citations that were chosen for inclusion in this article were selected for a number of reasons: Some are particularly comprehensive or well-written overviews of a topic, others are seminal works or significantly advance our understanding of the construct, and still others shed light on a particular point of contention in the literature. The article begins with General Overviews, Textbooks, and selective Journals that publish high-quality attitudes research and review articles. Next, attention is turned to measurement issues in attitudes research. The largest section of the article is devoted to Attitude Formation and Change (i.e., persuasion), as this is the subtopic that has historically received the most attention from attitudes researchers, as is indicated by the corresponding volume of literature. The article then looks at attitude structure and function before concluding with coverage of the potential impact of attitudes on behavior.

Structure and function of aquaporin water channels

2000 ◽  
Vol 278 (1) ◽  
pp. F13-F28 ◽  
Author(s):  
A. S. Verkman ◽  
Alok K. Mitra
Keyword(s):  
High Throughput Screening ◽  
Plasma Membranes ◽  
Fluid Transport ◽  
Freeze Fracture ◽  
Structure And Function ◽  
Membrane Spanning ◽  
Definition Of ◽  
Protein Density ◽  
Basic Features ◽  
And Function

The aquaporins (AQPs) are a family of small membrane-spanning proteins (monomer size ∼30 kDa) that are expressed at plasma membranes in many cells types involved in fluid transport. This review is focused on the molecular structure and function of mammalian aquaporins. Basic features of aquaporin structure have been defined using mutagenesis, epitope tagging, and spectroscopic and freeze-fracture electron microscopy methods. Aquaporins appear to assemble in membranes as homotetramers in which each monomer, consisting of six membrane-spanning α-helical domains with cytoplasmically oriented amino and carboxy termini, contains a distinct water pore. Medium-resolution structural analysis by electron cryocrystallography indicated that the six tilted helical segments form a barrel surrounding a central pore-like region that contains additional protein density. Several of the mammalian aquaporins (e.g., AQP1, AQP2, AQP4, and AQP5) appear to be highly selective for the passage of water, whereas others (recently termed aquaglyceroporins) also transport glycerol (e.g., AQP3 and AQP8) and even larger solutes (AQP9). Evidence for possible movement of ions and carbon dioxide through the aquaporins is reviewed here, as well as evidence for direct regulation of aquaporin function by posttranslational modification such as phosphorylation. Important unresolved issues include definition of the molecular pathway through which water and solutes move, the nature of monomer-monomer interactions, and the physiological significance of aquaporin-mediated solute movement. Recent results from knockout mice implicating multiple physiological roles of aquaporins suggest that the aquaporins may be suitable targets for drug discovery by structure-based and/or high-throughput screening strategies.

Structure and function of neural networks in the retina

1988 ◽  
Vol 46 ◽  
pp. 26-27
Author(s):  
Peter Sterling
Keyword(s):  
Ganglion Cells ◽  
Three Dimensional ◽  
Structure And Function ◽  
Synaptic Connections ◽  
Visual Axis ◽  
One Dimensional ◽  
Cat Retina ◽  
Ultrathin Sections ◽  
And Function ◽  
Insight Into

The synaptic connections in cat retina that link photoreceptors to ganglion cells have been analyzed quantitatively. Our approach has been to prepare serial, ultrathin sections and photograph en montage at low magnification (˜2000X) in the electron microscope. Six series, 100-300 sections long, have been prepared over the last decade. They derive from different cats but always from the same region of retina, about one degree from the center of the visual axis. The material has been analyzed by reconstructing adjacent neurons in each array and then identifying systematically the synaptic connections between arrays. Most reconstructions were done manually by tracing the outlines of processes in successive sections onto acetate sheets aligned on a cartoonist's jig. The tracings were then digitized, stacked by computer, and printed with the hidden lines removed. The results have provided rather than the usual one-dimensional account of pathways, a three-dimensional account of circuits. From this has emerged insight into the functional architecture.

Osseointegration interface of calcified bone and endosseous implants

1992 ◽  
Vol 50 (2) ◽  
pp. 1096-1097
Author(s):  
K.E. Krizan ◽  
J.E. Laffoon ◽  
M.J. Buckley
Keyword(s):  
Structure And Function ◽  
Titanium Implants ◽  
En Bloc ◽  
Endosseous Implants ◽  
Ultrastructural Studies ◽  
The Past ◽  
Cacodylate Buffer ◽  
One Year ◽  
And Function

With increase use of tissue-integrated prostheses in recent years it is a goal to understand what is happening at the interface between haversion bone and bulk metal. This study uses electron microscopy (EM) techniques to establish parameters for osseointegration (structure and function between bone and nonload-carrying implants) in an animal model. In the past the interface has been evaluated extensively with light microscopy methods. Today researchers are using the EM for ultrastructural studies of the bone tissue and implant responses to an in vivo environment. Under general anesthesia nine adult mongrel dogs received three Brånemark (Nobelpharma) 3.75 × 7 mm titanium implants surgical placed in their left zygomatic arch. After a one year healing period the animals were injected with a routine bone marker (oxytetracycline), euthanized and perfused via aortic cannulation with 3% glutaraldehyde in 0.1M cacodylate buffer pH 7.2. Implants were retrieved en bloc, harvest radiographs made (Fig. 1), and routinely embedded in plastic. Tissue and implants were cut into 300 micron thick wafers, longitudinally to the implant with an Isomet saw and diamond wafering blade [Beuhler] until the center of the implant was reached.

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