A thermophilic, acidophilic procaryote lacking a cell wall has been isolated from a coal refuse pile which had undergone self-heating. Electron micrographs, chemical assays for hexosamine, and the inability of vancomycin to inhibit growth confirm the lack of a cell wall. The apparent ability of the organism to reproduce by budding and the low guanine plus cytosine content of its DNA indicate a relation to the mycoplasmas. The temperature optimum of the organism is 59 degrees C, and growth occurs over a range of 45 degrees to 62 degrees C. No growth occurs at 37 degrees C or at 65 degrees C. The optimum pH for growth is between 1 and 2, and growth occurs between pH 0.96 and 3.5 but does not occur at pH 0.35 and only poorly at pH 4.0. We propose to call this organism Thermoplasma acidophila. The existence of this organism extends considerably the range of habitats in which mycoplasma may occur.

SUMMARYFourteen cultures of thermophilic acidophilic bacteria have been isolated from a variety of thermal acid environments by enrichment at elevated temperatures and low pH. Morphological and physiological properties suggest that the bacteria are members of a homogeneous group of aerobic spore-forming rods. The base composition of the DNA is about 62 % guanine plus cytosine, and this fact together with the physiological properties suggests that relationship to other species in the genus Bacillus is rather distant. The isolates are hence classified in a new species, Bacillus acidocaldarius.The species is characterized by the ability to grow at temperatures from 45" to 70" (optimum 60" to 65") and at pH values from 2.0 to 6.0 (optimum 3 to 4).

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Without inhibiting COX-2 enzyme, META060 reduces the inflammation by inhibiting multiple kinases involved in NF-kappaB pathway, and may have potential as a safe anti-inflammatory therapeutic.

Aims/HypothesisWe developed KDT501, a novel substituted 1,3-cyclopentadione chemically derived from hop extracts, and evaluated it in various in vitro and in vivo models of diabetes and insulin sensitivity.MethodsKDT501 was evaluated for anti-inflammatory effects in monocyte/macrophage cells; agonistic activity for peroxisome proliferator-activated receptors (PPAR); lipogenesis and gene expression profile in human subcutaneous adipocytes. Body composition, glucose, insulin sensitivity, and lipids were assessed in diet-induced obesity (DIO) mice and Zucker Diabetic Fatty (ZDF) rats after oral administration.ResultsKDT501 mediated lipogenesis in 3T3L1 and human subcutaneous adipocytes; however, the gene expression profile of KDT501 differed from that of the full PPARγ agonist rosiglitazone, suggesting that KDT501 has pleiotropic biological activities. In addition, KDT501 showed only modest, partial PPARγ agonist activity and exhibited anti-inflammatory effects in monocytes/macrophages that were not observed with rosiglitazone. In a DIO mouse model, oral administration of KDT501 significantly reduced fed blood glucose, glucose/insulin AUC following an oral glucose bolus, and body fat. In ZDF rats, oral administration of KDT501 significantly reduced fed glucose, fasting plasma glucose, and glucose AUC after an oral glucose bolus. Significant, dose-dependent reductions of plasma hemoglobin A1c, weight gain, total cholesterol, and triglycerides were also observed in animals receiving KDT501.ConclusionThese results indicate that KDT501 produces a unique anti-diabetic profile that is distinct in its spectrum of pharmacological effects and biological mechanism from both metformin and pioglitazone. KDT501 may thus constitute a novel therapeutic agent for the treatment of Type 2 diabetes and associated conditions.

Toluene-treated cell suspensions of Bacteroides fragilis were used to screen clinical isolates for the production of f3lactamase. Approximately one-third of the isolates possessed considerable cephalosporinase activity. A significant correlation was found between f3lactamase production and resistance to cephalosporin antibiotics. Several isolates were resistant to cefuroxime and cefamandole and produced enzymes capable of hydrolyzing these antibiotics. However, none of the 79 strains tested could hydrolyze the cephamycin derivative, cefoxitin. A large percentage (>90%) of the strains were susceptible to cefoxitin. Therefore, resistance to lactamase hydrolysis is a major factor for the effectiveness of cefoxitin against B. fragilis. Detailed studies of four isolates suggest that two different enzymes may be produced. Both are cephalosporinases but differ with regard to cellular distribution and substrate specificity. Cefoxitin is not a substrate for either enzyme, but it is an excellent competitive inhibitor (Ki -0.1 FM).Cephalosporins are broad-spectrum antibiotics with activity against most gram-positive and gram-negative bacteria. Among the exceptions to this general rule are members of the gram-negative species Bacteroides fragilis. Martin et al. (11) in a study of 195 clinical isolates, found that only 9% were susceptible to 25 ,g or less of cephalothin per ml. Although cephaloridine has generally proven to be more effective, Kislak (9) found only 50% of 40 isolates to be sensitive to 25 ug or less per ml. These observations have since been confirmed by others (21,22).Recently, cefoxitin (a semisynthetic cephamycin analogue) was demonstrated to be considerably more effective against B. fragilis than the cephalosporins now in use (21,22). Over 95% of the strains tested by the two groups were susceptible to 32 ,ug or less of cefoxitin per ml. Of the several hypotheses available to explain the effectiveness of cefoxitin against this group of bacteria, perhaps the most attrac-

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A microscopic survey made to detect the presence of bacteria in hot springs of varying temperature and pH characteristics revealed that in neutral and alkaline hot springs bacteria are found at temperatures up to the boiling point of water (92 degrees to 100 degrees C, depending on the altitude). In hot springs of increasing acidity the upper temperature limit at which bacteria are found decreases; at pH 2 to 3 the upper temperature limit is 75 degrees to 80 degrees C. Bacteria have thus been able to evolve with the ability to grow at either high temperature or high acidity, but not at both high temperature and high acidity. These results suggest that there are physicochemical limitations of the environment beyond which life is impossible.