For example, two LPL missense mutations, C418Y and E421K, were identified in patients with severe chylomicronemia ( 7, 8) but are located in the carboxyl terminus of LPL, distant from the aminoterminal catalytic domain and downstream from carboxyl-terminal sequences implicated in binding lipid substrates ( 9). In a few instances, the importance and functional relevance of some mutations identified in patients with severe chylomicronemia has remained mysterious. Some mutations abolished catalytic activity, whereas others blocked LPL secretion or interfered with the formation of stable homodimers. After the cDNA for LPL was cloned, many LPL mutations causing chylomicronemia were identified ( 1, 5, 6), the majority of which were missense mutations in the aminoterminal catalytic domain. More than 50 years ago, Havel and Gordon ( 4) showed that a deficiency of LPL causes severe hypertriglyceridemia (i.e., chylomicronemia). Lipoprotein lipase (LPL) is a homodimeric enzyme required for the lipolytic processing of triglycerid-rich lipoproteins (chylomicrons and very low density lipoproteins) ( 1 – 3). Together, these data define a mechanism by which LPL mutations could elicit disease and provide insights into LPL sequences required for binding to GPIHBP1. Also, changing cLPL residues 421 to 425, 426 to 430, and 431 to 435 to alanine blocks cLPL binding to GPIHBP1 without inhibiting catalytic activity. In support of this idea, a chicken LPL (cLPL)–specific monoclonal antibody, xCAL 1–11 (epitope, cLPL amino acids 416–435), blocks cLPL binding to GPIHBP1 but not to heparin. These findings suggest that sequences downstream from LPL's principal heparin-binding domain (amino acids 403–407) are important for GPIHBP1 binding. Both mutations abolish LPL transport across endothelial cells by GPIHBP1. Here, we report that two LPL missense mutations initially identified in patients with chylomicronemia, C418Y and E421K, abolish LPL's ability to bind to GPIHBP1 without interfering with LPL catalytic activity or binding to heparin. Any such mutation would provide insights into LPL sequences required for GPIHBP1 binding. We hypothesized that some cases of chylomicronemia might be caused by LPL mutations that interfere with LPL's ability to bind to GPIHBP1. Earlier studies have established that chylomicronemia can be caused by LPL mutations that interfere with catalytic activity. An absence of GPIHBP1 prevents the entry of LPL into capillaries, blocking LPL-mediated triglyceride hydrolysis and leading to markedly elevated triglyceride levels in the plasma (i.e., chylomicronemia). GPIHBP1, a glycosylphosphatidylinositol-anchored protein of capillary endothelial cells, shuttles lipoprotein lipase (LPL) from subendothelial spaces to the capillary lumen. This was a guest post by Vend certified partner, Kara Haas CPA. How are you using tags? Do you have a method for creation? When applying multiple tags, we can use “ “ to separate each. Items can be exported, updated and imported. Or, as your product line expands, you may find the need to narrow the search field further. As you continue to use the system, your reporting needs may become more sophisticated. In this case, my product may hold the tag “Lamp” and “Accessory” and included in both reports. I may also need to see Sales by Supplier and a broader classification, such as “Accessory” to encompass additional accent pieces. What elements do they need to view? In my furniture store, I may want to see product sales by Supplier and then add the tag “Lamp” to narrow my focus. Who will be conducting product searches? What word(s) are they most likely to use in a search?Ĭonsider those designing the reports and making decisions. When a user searches the tag “Lamp”, several products may be inadvertently excluded if the creator used “Lamps” instead.Ĭonsider daily users. Will you use singular or plural? Possible tags: Lamp, Lamps, Light, Lights and Lighting. Let’s explore some considerations in creating tags for it.Ĭonsider a uniform naming convention in order to maximize searches and reporting. Using the example of a furniture store I have the item, Blue Table Lamp. Tags serve to: group data, provide organization, provide an additional dimension to reporting, identify items quickly and prioritize. Listening to customer needs, here is what I have observed to date: What exactly are tags? I am still learning that myself. The power of these features, I find, is that each store is able to apply them to suit their own, internal needs. One of my favorite elements of Vend is its ability to remain clean and maintain a simple user interface, all the while some powerful features are working in the background.
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