Cystinosis is an autosomal recessive metabolic disease that belongs to the family of lysosomal storage disorders. The defective gene is CTNS encoding the lysosomal cystine transporter, cystinosin. Cystine accumulates in every organ in the body and leads to organ damage and dysfunction, including renal defects. Using the murine model for cystinosis, Ctns ؊/؊ mice, we performed syngeneic bone marrow cell (BMC), hematopoietic stem cell (HSC), and mesenchymal stem cell transplantation. Organ-specific cystine content was reduced by 57% to 94% in all organs tested in the BMC-treated mice. Confocal microscopy and quantitative polymerase chain reaction revealed a large quantity of transplanted BMC in all organs tested, from 5% to 19% of the total cells. Most of these cells were not from the lymphoid lineage but part of the intrinsic structure of the organ. The natural progression of renal dysfunction was prevented, and deposition of corneal cystine crystals was significantly improved in the BMC-treated mice. HSC had the same therapeutic effect as whole BMC. In contrast, mesenchymal stem cell did not integrate efficiently in any organ. This work is a proof of concept for using HSC transplantation as a therapy for cystinosis and highlights the efficiency of this strategy for a chronic, progressive degenerative disease. (Blood. 2009;

Field strains of Foot-and-mouth disease virus (FMDV) use a number of av-integrins as receptors to initiate infection on cultured cells, and integrins are believed to be the receptors used to target epithelial cells in animals. In this study, immunofluorescence confocal microscopy and real-time RT-PCR were used to investigate expression of two of the integrin receptors of FMDV, avb6 and avb3, within various epithelia targeted by this virus in cattle. These studies show that avb6 is expressed constitutively on the surfaces of epithelial cells at sites where infectious lesions occur during a natural infection, but not at sites where lesions are not normally formed. Expression of avb6 protein at these sites showed a good correlation with the relative abundance of b6 mRNA. In contrast, avb3 protein was only detected at low levels on the vasculature and not on the epithelial cells of any of the tissues investigated. Together, these data suggest that in cattle, avb6, rather than avb3, serves as the major receptor that determines the tropism of FMDV for the epithelia normally targeted by this virus. INTRODUCTIONFoot-and-mouth disease virus (FMDV) is the aetiological agent responsible for foot-and-mouth disease, a severe vesicular disease of cloven-hoofed animals. FMDV shows a strong tropism for epithelial cells and, following a natural infection, initial virus uptake and/or replication is thought to take place in the pharynx and soft palate (Alexandersen et al., , 2002a(Alexandersen et al., , c, 2003 Brown et al., 1996; Burrows et al., 1981;McVicar & Sutmoller, 1971, 1976Oleksiewicz et al., 2001; Prato Murphy et al., 1994, 1999Zhang & Kitching, 2000). During disease, virus is widely disseminated throughout the body and adult animals develop highly infectious lesions on the feet and mouth (Alexandersen et al., , 2002bBrown et al., 1995 Brown et al., , 1996 Burrows et al., 1981). In cattle, goats and sheep (but not pigs) infection is commonly persistent (Alexandersen et al., 2002b Burrows, 1966;McVicar & Sutmoller, 1969;Salt, 1993Salt, , 1998. The mechanisms of persistence are currently unknown, although it has been demonstrated that the dorsal soft-palate provide sites of virus persistence in infected animals (Alexandersen et al., 2002bPrato Murphy et al., 1999;Woodbury et al., 1995;Zhang & Kitching, 2001).Several receptors for FMDV have been identified, these are the integrins (Jackson et al., 2003) and heparan sulfate proteoglycans (HSPGs) (Jackson et al., 1996). Currently there is no convincing evidence of a role for HSPG in cell entry by field viruses (Baranowski et al., 1998(Baranowski et al., , 2000Escarmis et al., 1998;Martinez et al., 1997;Neff et al., 1998; Sa-Carvalho et al., 1997). Instead, field viruses depend on integrins for infection in vitro, and integrins are believed to be the receptors used in animals (McKenna et al., 1995;Neff et al., 1998).Integrins are a family of integral membrane receptors that function as cell adhesion molecules (Hynes, 2002). Each integrin is a heterodimer formed by the ...

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The call for dialogue became a core part of our sociality in the later part of the twentieth century, and it clearly continues as a social hope as we confront the problems of a new era. International conflicts that bear on local interests, increasing interdependence and renewed isolationism, calls for diversity and pluralism coupled with new forms of destruction and annihilation, are all situations in a complex world context for dialogue. Although many still tout the promise of the information age, with the mass reproduction of meaning that new information technologies make possible, the need for discussion and negotiation persists. The struggle of our time is to build the practices of working together. This is the hope of a dialogic theory of communication. Using the word "dialogue," rather than simply "communication," foregrounds specific normative hopes. "Dialogue " has been useful in drawing together alternative and often more hopeful understandings and practices of communication. The hopes of different conceptions and practices of dialogue are not all the same, however. In the twentieth century, three dominant positions on dialogue evolved. The first, a liberal humanist perspective, is rooted in notions of internally located meaning and grounded in the works of Maslow (1970, 1973) and Rogers (1965, 1969, 1980). These scholars advocate an interactional orientation founded on principles of understanding, empathy, and active listening. The thrust of communication from this perspective is to find common ground so that a community can comfortably co-exist. The second position, a critical hermeneutic orientation, is reflected in the writing of Gadamer (1975,