The following paper discusses exploratory factor analysis and gives an overview of the statistical technique and how it is used in various research designs and applications. A basic outline of how the technique works and its criteria, including its main assumptions are discussed as well as when it should be used. Mathematical theories are explored to enlighten students on how exploratory factor analysis works, an example of how to run an exploratory factor analysis on SPSS is given, and finally a section on how to write up the results is provided. This will allow readers to develop a better understanding of when to employ factor analysis and how to interpret the tables and graphs in the output. The broad purpose of factor analysis is to summarize data so that relationships and patterns can be easily interpreted and understood. It is normally used to regroup variables into a limited set of clusters based on shared variance. Hence, it helps to isolate constructs and concepts. Note that both Sean Pearce and An Gie Yong should be considered as first authors as they contributed equally and substantially in the preparation of this manuscript. The authors would like to thank Dr. Louise Lemyre and her team, Groupe d'Analyse Psychosociale Santé (GAP-Santé), for their generous feedback; in particular, Dr. Lemyre who took the time to provide helpful suggestions and real world data for the tutorial. The authors would also like to thank Levente Orbán and Dr. Sylvain Chartier for their guidance.

SummaryDendritic cells, but not macrophages, efficiently phagocytose apoptotic cells and cross-present viral, tumor, and self-antigens to CD8 ϩ T cells. This in vitro pathway corresponds to the in vivo phenomena of cross-priming and cross-tolerance. Here, we demonstrate that phagocytosis of apoptotic cells is restricted to the immature stage of dendritic cell (DC) development, and that this process is accompanied by the expression of a unique profile of receptors, in particular the ␣ v ␤ 5 integrin and CD36. Upon maturation, these receptors and, in turn, the phagocytic capacity of DCs, are downmodulated. Macrophages engulf apoptotic cells more efficiently than DCs, and although they express many receptors that mediate this uptake, they lack the ␣ v ␤ 5 integrin. Furthermore, in contrast to DCs, macrophages fail to cross-present antigenic material contained within the engulfed apoptotic cells. Thus, DCs use unique pathways for the phagocytosis, processing, and presentation of antigen derived from apoptotic cells on class I major histocompatibility complex. We suggest that the ␣ v ␤ 5 integrin plays a critical role in the trafficking of exogenous antigen by immature DCs in this cross-priming pathway.

A null mutation in the scavenger receptor gene CD36 was created in mice by targeted homologous recombination. These mice produced no detectable CD36 protein, were viable, and bred normally. A significant decrease in binding and uptake of oxidized low density lipoprotein was observed in peritoneal macrophages of null mice as compared with those from control mice. CD36 null animals had a significant increase in fasting levels of cholesterol, nonesterified free fatty acids, and triacylglycerol. The increase in cholesterol was mainly within the high density lipoprotein fraction, while the increase in triacylglycerol was within the very low density lipoprotein fraction. Null animals had lower fasting serum glucose levels when compared with wild type controls. Uptake of 3 H-labeled oleate was significantly reduced in adipocytes from null mice. However, the decrease was limited to the low ratios of fatty acid:bovine serum albumin, suggesting that CD36 was necessary for the high affinity component of the uptake process. The data provide evidence for a functional role for CD36 in lipoprotein/fatty acid metabolism that was previously underappreciated.Scavenger receptors are integral membrane glycoproteins, distinct from the classic low density lipoprotein (LDL) 1 receptor, that mediate binding and uptake of native and modified lipoproteins by macrophages (1-8). There are at least two major classes of mammalian monocyte/macrophage scavenger receptors, SR-A and SR-B, based on molecular sequence and protein structural homology (1, 2, 9 -11). Scavenger receptors have broad ligand specificity and may have evolved from the primitive immune system as pattern recognition molecules, which are able to recognize common structural motifs on microbial surfaces (1,6,(12)(13)(14)(15)(16)(17). They also function in the recognition and clearance of damaged, senescent, or apoptotic cells before lysis, tissue damage, and inflammation can ensue (11, 18 -21) and in the modulation of cytokine release and host immune responses (14,15,22). Scavenger receptors may be important in the pathogenesis of atherosclerosis, since there is significant evidence in support of the hypothesis that uptake of oxidatively modified LDL by monocytes/macrophages is one of the key early events in lesion development (23-26).The class A receptors, which are expressed on liver sinusoidal endothelial and Kupffer cells (27)(28)(29), and monocytes/ macrophages (9, 10, 30) result from an alternative splice from a single gene (31, 32). SR-AI/II are trimeric, integral membrane glycoprotein receptors for oxidized LDL, acetylated LDL, and other anionic ligands including polyinosinic acid and maleylated albumin (5, 9, 10, 33-35). Monocytes/macrophages isolated from a null mouse carrying a mutation in the class A receptors showed partial loss in the ability to bind and internalize oxidized LDL (ϳ30%) (36), and a lack of murine SR-AI/II receptors in the context of an atherogenic environment was partially protective against the formation of atherogenic lesions, decreasing lesion...

Thrombospondin-1 (TSP-1) is a naturally occurring inhibitor of angiogenesis that is able to make normal endothelial cells unresponsive to a wide variety of inducers. Here we use both native TSP-1 and small antiangiogenic peptides derived from it to show that this inhibition is mediated by CD36, a transmembrane glycoprotein found on microvascular endothelial cells. Both IgG antibodies against CD36 and glutathione-S-transferase–CD36 fusion proteins that contain the TSP-1 binding site blocked the ability of intact TSP-1 and its active peptides to inhibit the migration of cultured microvascular endothelial cells. In addition, antiangiogenic TSP-1 peptides inhibited the binding of native TSP-1 to solid phase CD36 and its fusion proteins, as well as to CD36-expressing cells. Additional molecules known to bind CD36, including the IgM anti-CD36 antibody SM∅, oxidized (but not unoxidized) low density lipoprotein, and human collagen 1, mimicked TSP-1 by inhibiting the migration of human microvascular endothelial cells. Transfection of CD36-deficient human umbilical vein endothelial cells with a CD36 expression plasmid caused them to become sensitive to TSP-1 inhibition of their migration and tube formation. This work demonstrates that endothelial CD36, previously thought to be involved only in adhesion and scavenging activities, may be essential for the inhibition of angiogenesis by thrombospondin-1.

The protooncogene p21ras, a monomeric G protein family member, plays a critical role in converting extracellular signals into intracellular biochemical events. Here, we report that nitric oxide (NO) activates p21ras in human T cells as evidenced by an increase in GTP-bound p21ras. In vitro studies using pure recombinant p21ras demonstrate that the activation is direct and reversible. Circular dichroism analysis reveals that NO induces a profound conformational change in p21ras in association with GDP/GTP exchange. The mechanism of activation is due to S-nitrosylation of a critical cysteine residue which stimulates guanine nucleotide exchange. Furthermore, we demonstrate that p21ras is essential for NO-induced downstream signaling, such as NF-kappa B activation, and that endogenous NO can activate p21ras in the same cell. These studies identify p21ras as a target of the same cell. These studies identify p21ras as a target of NO in T cells and suggest that NO activates p21ras by an action which mimics that of guanine nucleotide exchange factors.

Erythrocytes infected with mature forms of Plasmodium falciparum do not circulate but are withdrawn from the peripheral circulation; they are bound to the endothelial lining and to uninfected erythrocytes in the microvasculature. Blockage of the blood flow, hampered oxygen delivery, and severe malaria may follow if binding is excessive. The NH2-terminal head structure (Duffy binding–like domain 1 [DBL1α]–cysteine-rich interdomain region [CIDR1α]) of a single species of P. falciparum erythrocyte membrane protein 1 (PfEMP1) is here shown to mediate adherence to multiple host receptors including platelet-endothelial cell adhesion molecule 1 (PECAM-1)/CD31, the blood group A antigen, normal nonimmune immunoglobulin M, three virulence-associated receptor proteins, a heparan sulfate–like glucosaminoglycan, and CD36. DBL2δ was found to mediate additional binding to PECAM-1/CD31. The exceptional binding activity of the PfEMP1 head structure and its relatively conserved nature argues that it holds an important role in erythrocyte sequestration and therefore in the virulence of the malaria parasite.

No abstract

Mal II, a 19-residue peptide derived from the second type 1 properdin-like repeat of the antiangiogenic protein thrombospondin-1 (TSP-1), was inactive in angiogenesis assays. Yet the substitution of any one of three L-amino acids by their D-enantiomers conferred on this peptide a potent antiangiogenic activity approaching that of the intact 450-kDa TSP-1. Substituted peptides inhibited the migration of capillary endothelial cells with an ED50 of 8.5 nM for the D-Ile-15 substitution, 10 nM for the D-Ser-4 substitution, and 0.75 nM for the D-Ser-5 substitution. A peptide with D-Ile at position 15 could be shortened to its last seven amino acids with little loss in activity. Like whole TSP-1, the Mal II D-Ile derivative inhibited a broad range of angiogenic inducers, was selective for endothelial cells, and required CD36 receptor binding for activity. A variety of end modifications further improved peptide potency. An ethylamide-capped heptapeptide was also active systemically in that when injected i.p. it rendered mice unable to mount a corneal angiogenic response, suggesting the potential usefulness of such peptides as antiangiogenic therapeutics.