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The M variant of encephalomyocarditis (EMC) 1 virus produces a diabetes-like syndrome in mice by infecting and destroying pancreatic beta cells (1-3). The severity of the diabetes correlates with the degree of virus-induced beta cell damage (4, 5). Only certain inbred strains of mice develop diabetes, and susceptibility to EMC virusinduced diabetes is inherited as an autosomal recessive trait (2, 6-8). The genetic factors controlling susceptibility operate at the level of the beta cell, and whether a particular strain of mouse develops diabetes appears to be related to differences in the permissiveness of beta cells to infection with EMC virus (9, 10).Previous experiments (5) showed that when mice were inoculated with a high concentration of mouse-passaged EMC virus (10 8 plaque-forming units [PFU]), fewer animals developed diabetes than when inoculated with a low concentration of the same virus (10 ~ PFU). Moreover, the diabetogenic capacity of the virus was markedly diminished after passage in mouse fibroblast cultures, but was restored when passaged in mice. This raised the possibility that the stock pool of EMC virus was made up of two populations of virus: one that had a tropism for beta cells and produced diabetes and the other that did not have a tropism for beta cells and was nondiabetogenic (5).The present investigation was initiated to see, first, whether our stock pool of the M variant of EMC virus was made up of a mixture of diabetogenic and nondiabetogenic virus and, second, whether the nondiabetogenic virus inhibited the development of diabetes. Materials and MethodsMice. Unless otherwise indicated, SJL/J male mice, 5-6 wk old, obtained from The Jackson Laboratory, Bar Harbor, Maine, were used in all experiments. Animals were inoculated with virus by the intraperitoneal route.Pancreatic Beta Cell Cultures. Pancreata were aseptically removed from suckling SJL/J mice, and beta cell cultures were prepared as described previously (9). The cultures were refed at 2-d intervals, and at 6 d the monolayers were used to passage virus. Staining of the monolayers with fluorescein isothiocyanate-labeled antibody to insulin indicated that 40-70% of the cells were beta cells (9).Virus. The M variant of EMC virus (1), prepared as described elsewhere, was passaged five J Abbrev.iations used in this paper: EMC, encephalomyocarditis; FITC, fluorescein isothiocyanate; IRI, immunoreactive insulin; PFU, plaque-forming units; SME, secondary mouse embryo; VSV, vesicular stomatitis virus.

Bone is continuously remodeled to adopt a volume appropriate for the local environment; the amount of bone deposited depends on the balance between bone formation and resorption by bone cells, osteoblasts, osteoclasts, and osteocytes (1). Osteoblasts are bone-forming cells that differentiate from mesenchymal stem cells and secrete extracellular matrix (ECM) 4 proteins, which are subsequently mineralized. Osteoclasts are bone-resorbing cells that differentiate from hematopoietic stem cells and degrade bone ECM proteins after demineralization in the extracellular space (Howship's lacunae) adjacent to the ruffled borders. In contrast to osteoblasts and osteoclasts, which act at bone surfaces, osteocytes, cells of osteoblastic lineage, are embedded in bone and are terminally differentiated. Osteocytes extend their dendritic processes into the bone matrix to constitute a well developed canalicular network with other cells. Although osteocytes are the most abundant cell type in bone tissue, their role in bone metabolism is not firmly established.ECM production and degradation by bone cells are critical steps in bone metabolism (1), and disturbed ECM turnover leads to bone disease. Type I collagen is a major ECM component. Secreted type I collagen molecules are processed by propeptidases and cross-linked by lysyl oxidases into mature collagen. Mutations of genes encoding type I collagen cause the bone disease osteogenesis imperfecta (2). Type I collagens are mainly degraded by matrix metalloproteinases (MMPs), which exert their enzymatic activity at a neutral pH in a zinc ion-dependent manner (3, 4). Several MMPs are expressed in bone tissue (5-9). MMPs may play a role in osteoclastic bone resorption (4, 5). Osteoblasts and osteocytes also produce MMPs such as MMP-2 and MMP-13 (7-9). Recent linkage analysis suggests that a loss of function mutation of MMP2 causes a human autosomal recessive disorder with multicentric nodulosis, arthropathy with joint erosion, and osteolysis, termed NAO syndrome (10, 11). This syndrome also includes facial abnormalities and generalized * This work was supported in part by a grant from the Ministry for Welfare and Health of Japan (to S. I.), by a Sasagawa Scientific Research Grant from the Japan Science Society (to K. I.), by a grant from the Japan Space Forum, National Space Development Agency of Japan (NASDA) (to N. M.), and by a research grant from the National Institutes of Health (to S. M. K.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 4 The abbreviations used are: ECM, extracellular matrix; DMP-1, dentin matrix protein 1; DMEM, Dulbecco's modified Eagle's medium; MMP, matrix metalloproteinase; NAO, nodulosis, arthropathy, and osteolysis; BMD, bone mineral density; pQCT, peripheral quantitative computed tomography; MAR, mineral apposition rate; BFR/BS, ratio of bone formation rate to bone surface.

Recent studies have shown that plasma can efficiently inactivate microbial pathogens such as bacteria, fungi, and viruses in addition to degrading toxins. Moreover, this technology is effective at inactivating pathogens on the surface of medical and dental devices, as well as agricultural products. The current practical applications of plasma technology range from sterilizing therapeutic medical devices to improving crop yields, as well as the area of food preservation. This review introduces recent advances and future perspectives in plasma technology, especially in applications related to disinfection and sterilization. We also introduce the latest studies, mainly focusing on the potential applications of plasma technology for the inactivation of microorganisms and the degradation of toxins.

The biocathode of a microbial fuel cell (MFC) offers a promising potential for the reductive treatment of oxidized pollutants. In this study, we demonstrated biological Cr(VI) reduction in the cathode of a MFC and identified putative Cr(VI) reducing microorganisms. The MFC was continuously monitored for Cr(VI) reduction and power generation. Acetate was provided to the anode compartment as substrate and bicarbonate was added to the cathode compartment as the sole external carbon source. The contribution of biomass decay and abiotic processes on Cr(VI) reduction was minimal, confirming that most of the Cr(VI) reduction was assisted by microbial activity in the cathode, which utilizes electrons and protons generated from the oxidation of acetate in the anode compartment. Relatively fast Cr(VI) reduction was observed at initial Cr(VI) concentrations below 80 mg/L. However, at 80 mg Cr(VI)/L, Cr(VI) reduction was extremely slow. A maximum Cr(VI) reduction rate of 0.46 mg Cr(VI)/g VSS.h was achieved, which resulted in a current and power density of 123.4 mA/m(2) and 55.5 mW/m(2), respectively. The reduced chromium was nondetectable in the supernatant of the catholyte which indicated complete removal of chromium as Cr(OH)(3) precipitate. Analysis of the 16S rRNA gene based clone library revealed that the cathode biomass was largely dominated by phylotypes closely related to Trichococcus pasteurii and Pseudomonas aeruginosa, the putative Cr(VI) reducers.

It is commonly assumed that the physiological isoform of prion protein, PrP C , is cleaved during its normal processing between residues 111/112, whereas the pathogenic isoform, PrP Sc , is cleaved at an alternate site in the octapeptide repeat region around position 90. Here we demonstrated both in cultured cells and in vivo, that PrP C is subject to a complex set of post-translational processing with the molecule being cleaved upstream of position 111/112, in the octapeptide repeat region or at position 96. PrP has therefore two main cleavage sites that we decided to name a and b. Cleavage of PrP C at these sites leads us to re-evaluate the function of both N-and C-terminus fragments thus generated.

A healthy 10-year-old boy was admitted to the hospital in diabetic ketoacidosis within three days of onset of symptoms of a flu-like illness. He died seven days later and post-mortem examination showed lymphocytic infiltration of the islets of Langerhans and necrosis of beta cells. Inoculation of mouse, monkey and human cell cultures with homogenates from the patient's pancreas led to isolation of a virus. Serologic studies revealed a rise in the titer of neutralizing antibody to this virus from less than 4 on the second hospital day to 32 on the day of death. Neutralization data showed that the virus was related to a diabetogenic variant derived from Coxsackievirus B4. Inoculation of mice with the human isolate produced hyperglycemia, inflammatory cells in the islets of Langerhans and beta-cell necrosis. Staining of mouse pancreatic sections with fluorescein-labeled antiviral antibody revealed viral antigens in beta cells. Both the clinical picture and animal studies suggested that the patient's diabetes was virus induced.

There are 425 million people with diabetes mellitus in the world. By 2045, this figure will grow to over 600 million. Diabetes mellitus is classified among noncommunicable diseases. Evidence points to a key role of microbes in diabetes mellitus, both as infectious agents associated with the diabetic status and as possible causative factors of diabetes mellitus. This review takes into account the different forms of diabetes mellitus, the genetic determinants that predispose to type 1 and type 2 diabetes mellitus (especially those with possible immunologic impact), the immune dysfunctions that have been documented in diabetes mellitus. Common infections occurring more frequently in diabetic vs. nondiabetic individuals are reviewed. Infectious agents that are suspected of playing an etiologic/triggering role in diabetes mellitus are presented, with emphasis on enteroviruses, the hygiene hypothesis, and the environment. Among biological agents possibly linked to diabetes mellitus, the gut microbiome, hepatitis C virus, and prion-like protein aggregates are discussed. Finally, preventive vaccines recommended in the management of diabetic patients are considered, including the bacillus calmette-Guerin vaccine that is being tested for type 1 diabetes mellitus. Evidence supports the notion that attenuation of immune defenses (both congenital and secondary to metabolic disturbances as well as to microangiopathy and neuropathy) makes diabetic people more prone to certain infections. Attentive microbiologic monitoring of diabetic patients is thus recommendable. As genetic predisposition cannot be changed, research needs to identify the biological agents that may have an etiologic role in diabetes mellitus, and to envisage curative and preventive ways to limit the diabetes pandemic.