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A study was conducted to gain insight into the potential of [beta]-sheet proteins to form amphiphilic helices and the underlying mechanism of [alpha]-helical intermediates which rapidly disassembles during folding. The findings suggested that the formation of an [alpha]-helix could be a rate-limiting step during folding of a predominantly [beta]-sheet protein and further supported the role of highly [alpha]-helical intermediates in the folding of all globular proteins.

A study was conducted to evaluate changes associated with the host-bacterium relationship in mice monoassociated with Escherichia coli K-12 over a period of 1,031 days. The obtained results demonstrated the possible use of monoassociated mice as a tool for characterizing niches occupied by the intestinal flora and potentially as a method of targeting the evolution of bacteria for applications in biotechnology.

Antibodies produced by an individual without a known history of sensitization to the relevant antigen are called ”natural" antibodies. Some natural antibodies, called xenoreactive antibodies, react with the cells of foreign species. Most xenoreactive antibodies in humans and higher primates bind to a nonreducing terminal galactose expressed by pigs and other lower mammals. Although human natural antibodies which bind to one or more of a variety of terminal α‐galactosylstructures have been identified previously, the antigen recognized by anti‐α‐galactosyl antibodies on the cells of foreign species is thought to be exclusively Galα1-3Gal. Thus, anti‐α‐galactosyl antibodies which do not react with Galα1-3Gal are thought to be nonxenoreactive. Here, we identify natural antibodies in human serum which bind to Galα1-6Hexosepyrranosides but not Galα1-3Gal, indicating that these antibodies are not xenoreactive. Various lowermammals were found to have natural anti‐Galα1-2Galantibodies in their sera, suggesting that at least some anti‐Galα1-2Gal antibodies might not be xenoreactive andindicating, surprisingly, that anti‐α‐galactosyl antibodies are much more phylogenetically disperse than previously known. Also surprising was the finding that some natural antibodies which bind to Galα1-3Gal in vitro do not bind to porcine xenografts. These studies show that naturally occurring anti‐α‐galactosyl antibodies in mammalian serum include antibodies with a greater variety of reactivities than previously thought, only some of which would bind to a porcine xenograft. Further, these studies show that the methods used todetect anti‐α‐galactosyl antibodies of relevance in xenotransplantation must be carefully evaluated to avoid detection of anti‐α‐galactosyl antibodies which would not bind to a porcine organ and which therefore are not involved in xenograft rejection. [ABSTRACT FROM PUBLISHER]

The binding of proteins to cell surface carbohydrates contributes to cell–cell interactions in development, immunity, and various physiologic processes. Such interactions are presumably dictated not only by the chemical structure of the carbohydrate but also reflect the properties of the protein and the microenvironment in which the protein–carbohydrate interaction occurs. To explore the factors influencing the recognition of cell surface carbohydrates by proteins, the extent to which three classes of proteins—anti‐Galα1–3Gal IgM found in higher primates, Griffonia simplicifolia type I lectin, isolectin B4 (GS‐IB4), and α‐galactosidase—interact with Galα1–3Gal on porcine cell surfaces was tested. Although the Galα1–3Gal residues expressed on porcine endothelial cells and recognized by anti‐Galα1–3Gal IgM and GS‐IB4 were both sensitive to cleavage by α‐galactosidase, the sites recognized by GS‐IB4 were more sensitive to cleavage than sites recognized by anti‐Galα1–3Gal IgM. Cross‐blocking studies on porcine cell surfaces revealed that a significant proportion of anti‐Galα1–3Gal IgM bound to sites not recognized by GS‐IB4; however, anti‐Galα1–3Gal IgM and GS‐IB4 recognized the same sites on solubilized membrane proteins and model compounds. These results suggest that features of the cell surface such as the three‐dimensional arrangement of Galα1–3Gal and characteristics of the protein such as size and valency play critical roles in specific interactions on cell surfaces. [ABSTRACT FROM PUBLISHER]

Objectives: Chronic aspiration of gastric fluid contents can decrease long-term survival of pulmonary transplants due to development of obliterative bronchiolitis. However, little is known about the early immune response and the cascade of events involved in the development of obliterative bronchiolitis., Materials and Methods: We utilized a rat orthotopic pulmonary transplant model and a single aspiration of either gastric fluid or normal saline to investigate the histologic, cellular, and cytokine changes associated with an acute gastric fluid aspiration event compared with normal saline at 2 and 10 days after aspiration., Results: Our observations included a decrease in pulmonary compliance and increased airway inflammation and acute rejection of the transplanted lung, as well as increases in macrophages, granulocytes, and proinflammatory cytokines such as interleukin 1β, transforming growth factor β1 and β2, and tumor necrosis factor α in bronchoalveolar lavage fluid from the transplanted lung of gastric fluid-aspirated rats compared with normal saline-aspirated rats., Conclusions: The acute inflammatory response observed in the present study is consistent with changes found in chronic models of aspiration-associated injury and suggests a potentially important role for mast cells in the development of obliterative bronchiolitis.

This review assesses the current state of knowledge regarding the cecal appendix, its apparent function, and its evolution. The association of the cecal appendix with substantial amounts of immune tissue has long been taken as an indicator that the appendix may have some immune function. Recently, an improved understanding of the interactions between the normal gut flora and the immune system has led to the identification of the appendix as an apparent safe-house for normal gut bacteria. Further, a variety of observations related to the evolution and morphology of the appendix, including the identification of the structure as a "recurrent trait" in some clades, the presence of appendix-like structures in monotremes and some non-mammalian species, and consistent features of the cecal appendix such as its narrow diameter, provide direct support for an important function of the appendix. This bacterial safe-house, which is likely important in the event of diarrheal illness, is presumably of minimal importance to humans living with abundant nutritional resources, modern medicine and modern hygiene practices that include clean drinking water. Consistent with this idea, epidemiologic studies demonstrate that diarrheal illness is indeed a major source of selection pressure in developing countries but not in developed countries, whereas appendicitis shows the opposite trend, being associated with modern hygiene and medicine. The cecal appendix may thus be viewed as a part of the immune system that, like those immune compartments that cause allergy, is vital to life in a "natural" environment, but which is poorly suited to post-industrialized societies., (Copyright © 2011 Wiley-Liss, Inc.)

The disaccharide Gal(alpha)1-3Gal is found on more than 45 different molecules on the endothelium of porcine cells and has recently attracted considerable interest, being the major target recognized by xenoreactive antibodies. In this study, the distribution and topology of Gal(alpha)1-3Gal on porcine endothelial cells was examined to access whether some Gal(alpha)1-3Gal-containing molecules might be preferentially recognized by antibodies binding to Gal(alpha)1-3Gal. Thirteen percent of the Gal(alpha)1-3Gal was found on glycolipid and 87% on glycoproteins. Of all the glycoproteins and glycolipids containing Gal(alpha)1-3Gal, two molecules, fibronectin and the integrin beta1 subunit, were most intensely labeled by galactose oxidase, suggesting that these molecules may be preferentially exposed on the apical surface of the endothelium. Binding of anti-Gal(alpha)1-3Gal antibodies to endothelial cell surfaces significantly diminished labeling of fibronectin and the integrin beta1 subunit by galactose oxidase, indicating that these glycoproteins are targets for the antibodies when binding to intact porcine cells.