No abstract

Composition of central nervous system lipoproteins affects the metabolism of lipoprotein constituents within the brain. The ⑀4 allele of apolipoprotein E (apoE) is a risk factor for Alzheimer's disease via an unknown mechanism(s). As glia are the primary central nervous system cell type that synthesize apoE, we characterized lipoproteins secreted by astrocytes from wild type (WT), apoE (؊/؊), and apoE transgenic mice expressing human apoE3 or apoE4 in a mouse apoE (؊/؊) background. Nondenaturing size exclusion chromatography demonstrates that WT, apoE3, and apoE4 astrocytes secrete particles the size of plasma high density lipoprotein (HDL) composed of phospholipid, free cholesterol, and protein, primarily apoE and apoJ. However, the lipid:apoE ratio of particles containing human apoE is significantly lower than WT. ApoE localizes across HDL-like particle sizes. ApoJ localizes to the smallest HDL-like particles. ApoE (؊/؊) astrocytes secrete little phospholipid or free cholesterol despite comparable apoJ expression, suggesting that apoE is required for normal secretion of astrocyte lipoproteins. Further, particles were not detected in apoE (؊/؊) samples by electron microscopy. Nondenaturing immunoprecipitation experiments indicate that apoE and apoJ reside predominantly on distinct particles. These studies suggest that apoE expression influences the unique structure of astrocyte lipoproteins, a process further modified by apoE species.The composition and type of lipoproteins present in the brain have implications not only for lipid delivery but also for the transport of apolipoprotein (apo) 1 and other lipoprotein constituents within the central nervous system (CNS). Glia, in particular astrocytes, are the primary cell type in the CNS that synthesize apoE (1, 2), whereas apoJ is expressed by astrocytes and neurons (3-5). We have previously observed that primary rat astrocytes secrete discoidal particles the size of large plasma high density lipoproteins (HDLs) that contain apoE and apoJ (6). As a ligand for lipoprotein receptors, apoE helps to regulate plasma lipid and cholesterol metabolism. This process may also be operating in the parenchyma of the brain, as neural cells express a variety of receptors in the low density lipoprotein receptor family (7-10). The role of apoJ in lipid transport in both the periphery and within the CNS is less clear, and gp330 (megalin), the only known receptor for mammalian apoJ (11), appears to be expressed only by ependymal and endothelial cells in the brain (12, 13). Thus, lipoprotein secretion by isolated glial cells may provide a system in which to further dissect the role of apoE and apoJ in lipoprotein synthesis, secretion and function in the brain. In terms of function, several lines of evidence suggest that apoE and apoJ may be involved in neural homeostasis beyond their capacity to transport lipid. Both apoE and apoJ increase in response to different brain insults (3, 14 -16). In addition, apoE and apoJ may play a role in the pathogenesis of Alzheimer's disease (AD), as...

Our data indicate that intracytoplasmic sperm injection (ICSI) outcomes are not influenced by ASA levels on sperm.

Background: Over the last several decades, as a result of an evolution in manufacturing processes, a marked development has been made in the field of gonadotropins for ovarian stimulation. Initially, therapeutic gonadotropins were produced from a simple process of urine extraction and purification; now they are produced via a complex system involving recombinant technology, which yields gonadotropins with high levels of purity, quality, and consistency.

Animation enhances transparency and name agreement, especially for verbs, which reduces the instructional burden that comes with nontransparent symbols. Animation does not enhance identification accuracy. Verbs are easier to identify than prepositions. A developmental effect was observed for each measure. Limitations and implications for future research are discussed.