Immunohistochemical detection of macrophage migration inhibitory factor in fetal and adult bovine epididymis: Release by the apocrine secretion mode?

Originally defined as a lymphokine inhibiting the random migration of macrophages, the macrophage migration inhibitory factor (MIF) is an important mediator of the host response to infection. Beyond its function as a classical cytokine, MIF is currently portrayed as a multifunctional protein with growth-regulating properties present in organ systems beyond immune cells. In previous studies, we detected substantial amounts of MIF in the rat epididymis and epididymal spermatozoa, where it appears to play a role during post-testicular sperm maturation and the acquisition of fertilization ability. To explore its presence in other species not yet examined in this respect, we extended the range of studies to the bull. Using a polyclonal antibody raised against MIF purified from bovine eye lenses, we detected MIF in the epithelium of the adult bovine epididymis with the basal cells representing a prominently stained cell type. A distinct accumulation of MIF at the apical cell pole of the epithelial cells and in membranous vesicles localized in the lumen of the epididynnal duct was obvious. In the fetal bovine epididymis, we also detected MIF in the epithelium, whereas MIF accumulation was evident at the apical cell surface and in apical protrusions. By immuno-electron microscopy of the adult bovine epididymis, we localized MIF in apical protrusions of the epithelial cells and in luminal membrane-bound vesicles that were found in close proximity to sperm cells. Although the precise origin of the MIF-containing vesicles remains to be delineated, our morphological observations support the hypothesis that they become detached from the apical surface of the epididymal epithelial cells. Additionally, an association of MIF with the outer dense fibers of luminal spermatozoa was demonstrated. Data obtained in this study suggest MIF release by an apocrine secretion mode in the bovine epididymis. Furthermore, MIF localized in the basal cells of the epithelium and in the connective tissue could be responsible for regulating the migration of macrophages in order to avoid contact of immune cells with spermatozoa that carry a wide range of potent antigens. Copyright (c) 2006 S. Karger AG, Basel

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Phase equilibria in the metal-sulfur-oxygen system and selective reduction of metal oxides and sulfides : Part I. The carbothermic reduction and calcination of complex mineral sulfides

Copyright 2006 Elsevier B.V., All rights reserved.The difference in the standard Gibbs free energy for the formation of any two oxides or sulfides is the chemical potential for selective reduction of metals from complex minerals. The magnitude of the Gibbs free energy difference is shown by plotting the univariant relationships for relevant sulfides and oxides. In this investigation, three examples of mineral sulfides are considered, and the experimental results are compared with the predicted thermodynamic calculations. These examples include the reduction conditions for nickel and iron sulfides and pentlandite (Fe,Ni)S and chalcopyrite (CuFeS) minerals. The reduction behavior of mineral sulfides, such as those of nickel, cobalt, iron, and copper, is illustrated by referring to both the sulfide and alloy phase equilibria. In particular, the solution thermodynamic properties of the metallic phase equilibria are featured for determining the physical chemistry of preferential or selective reduction of the metal oxides and sulfides. The mechanism for the reduction of the aforementioned sulfide minerals is explained with the aid of the governing phase equilibria for the calcination process. The results from the carbothermic reduction of sulfide minerals are also compared. The important roles of lime and calcium sulfate in controlling the emission of sulfurous gases during the reduction reaction are explained. A qualitative analysis of reduction reactions of nickel and iron sulfides is reviewed to provide a comparison of the mechanism for complex nickel-bearing minerals. The importance of these results in producing alloy and pure metallic phases is also examined.Peer reviewe