We have isolated suppressor mutants that suppress temperature-sensitive colony formation and anucleate cell production of a mukB mutation. A linkage group (smbB) of the suppressor mutations is located in the rne/ams/hmp gene encoding the processing endoribonuclease RNase E. All of the rne (smbB) mutants code for truncated RNase E polypeptides lacking a carboxyl-terminal half. The amount of MukB protein was higher in these rne mutants than that in the rne ؉ strain. These rne mutants grew nearly normally in the mukB ؉ genetic background. The copy number of plasmid pBR322 in these rne mutants was lower than that in the rne ؉ isogenic strain. The results suggest that these rne mutations increase the half-lives of mukB mRNA and RNAI of pBR322, the antisense RNA regulating ColE1-type plasmid replication. We have demonstrated that the wild-type RNase E protein bound to polynucleotide phosphorylase (PNPase) but a truncated RNase E polypeptide lacking the C-terminal half did not. We conclude that the C-terminal half of RNase E is not essential for viability but plays an important role for binding with PNPase. RNase E and PNPase of the multiprotein complex presumably cooperate for effective processing and turnover of specific substrates, such as mRNAs and other RNAs in vivo.RNase E was first defined as a processing endoribonuclease that catalyzes the maturation of 5S rRNA (2,3,17). Mutations in the rne/ams gene have a stabilizing effect on the bulk of mRNAs (4,37,44). This enzyme also cleaves RNAI (27, 33, 52), the antisense RNA regulating ColE1-type plasmid replication (53), and is involved in the processing and turnover of many bacterial and bacteriophage mRNAs (14, 16, 23, 28-30, 35, 42, 46) (for a review, see reference 11). The Escherichia coli rne/ams/hmp gene codes for the RNase E protein of 1,061 amino acids (8). The RNase E protein migrates as a 170-to 180-kDa polypeptide in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (7,12,35). Taraseviciene et al. (50) concluded that the RNA binding domain and catalytic functions overlap in the N-terminal half of the protein. The more precise mapping reported that, while the catalytic function of RNase E is in the N-terminal half, the RNA binding domain is located in the C-terminal half and does not overlap with the catalytic domain (31). It would be more accurate to state that the N-terminal half of Rne (residues 1 to 498) has the catalytic function of RNase E (31, 50) while a nonoverlapping RNA binding activity has been mapped near the start of the C-terminal half (50). RNase E, polynucleotide phosphorylase (PNPase), and 3Ј-to-5Ј exonucleases were found in the same multiprotein complex in E. coli cell extracts (6, 45).The MukB protein of E. coli has an important role in proper partitioning of the replicated sister chromosomes into two daughter cells (40,41,57,59,60). The MukB protein consists of 1,484 amino acid residues (57). MukB has been suggested to be a motor protein essential for chromosome partitioning (41) (for reviews, see references 18 and...

The sphingolipid activator proteins (saposins A, B, C and D) are small homologous glycoproteins that are encoded by a single gene in tandem within a large precursor protein (prosaposin) and are required for in vivo degradation of some sphingolipids with relatively short carbohydrate chains. Human patients with prosaposin or specific saposin B or C deficiency are known, and prosaposin- and saposin A-deficient mouse lines have been generated. Experimental evidence suggests that saposin D may be a lysosomal acid ceramidase activator. However, no specific saposin D deficiency state is known in any mammalian species. We have generated a specific saposin D(-/-) mouse by introducing a mutation (C509S) into the saposin D domain of the mouse prosaposin gene. Saposin D(-/-) mice developed progressive polyuria at around 2 months and ataxia at around 4 months. Pathologically, the kidney of saposin D(-/-) mice showed renal tubular degeneration and eventual hydronephrosis. In the nervous system, progressive and selective loss of the cerebellar Purkinje cells in a striped pattern was conspicuous, and almost all Purkinje cells disappeared by 12 months. Biochemically, ceramides, particularly those containing hydroxy fatty acids accumulated in the kidney and the brain, most prominently in the cerebellum. These results not only indicate the role of saposin D in in vivo ceramide metabolism, but also suggest possible cytotoxicity of ceramide underlying the cerebellar Purkinje cell and renal tubular cell degeneration.

Abstract-Hypertensive cardiovascular damage is accelerated by salt loading but counteracted by dietary potassium supplementation. We suggested recently that antioxidant actions of potassium contribute to protection against salt-induced cardiac dysfunction. Therefore, we examined whether potassium supplementation ameliorated cuff-induced vascular injury in salt-sensitive hypertension via suppression of oxidative stress. Four-week-old Dahl salt-sensitive rats were fed a normal-salt (0.3% NaCl), high-salt (8% NaCl), or high-salt plus high-potassium (8% KCl) diet for 5 weeks, and some of the rats fed a high-salt diet were also given antioxidants. One week after the start of the treatments, a silicone cuff was implanted around the femoral artery. Examination revealed increased cuff-induced neointimal proliferation with adventitial macrophage infiltration in arteries from salt-loaded Dahl salt-sensitive rats compared with that in arteries from non-salt-loaded animals (intima/media ratio: 0.471Ϯ0.070 versus 0.302Ϯ0.037; PϽ0.05), associated with regional superoxide overproduction and reduced nicotinamide-adenine dinucleotide phosphate oxidase activation and mRNA overexpression. On the other hand, simultaneous potassium supplementation attenuated salt-induced neointimal hyperplasia (intima/media ratio: 0.205Ϯ0.012; PϽ0.001), adventitial macrophage infiltration, superoxide overproduction, and reduced nicotinamide-adenine dinucleotide phosphate oxidase activation and overexpression. Antioxidants, which decrease vascular oxidative stress, also reduced neointima formation induced by salt excess. In conclusion, high-potassium diets seems to have a protective effect against the development of vascular damage induced by salt loading mediated, at least in part, through suppression of the production of reactive oxygen species probably generated by reduced nicotinamide-adenine dinucleotide phosphate oxidase. Key Words: hypertension Ⅲ sodium Ⅲ potassium Ⅲ antioxidants Ⅲ arteries N umerous studies have demonstrated that excessive salt intake causes cardiovascular damage and that this was counteracted by potassium supplementation. 1 According to the earlier report, 2 salt loading reduced the survival rate of Dahl salt-sensitive (DS) rats, a model of salt-sensitive hypertension, whereas potassium supplementation alleviated this salt-induced premature mortality, independent of its hypotensive action. It has been speculated that this may be a result of the vasoprotective effect of potassium, because potassium supplementation has been shown to ameliorate vascular endothelial dysfunction in salt-loaded DS rats. 3 Also, Ma et al 4 clearly demonstrated that high-potassium intake inhibited neointimal formation in several vascular injury models, such as a balloon injury of rat carotid and swine coronary 5 arteries from animals without hypertension. Thus, dietary potassium may have vasoprotective mechanisms beyond the blood pressure (BP)-lowering effect. Although it has been shown in in vitro experiments that potassium inhibited migration 6 an...

We study the effect of correlation on the Bragg reflection in the 3D electron gas, the 1D Luttinger liquid, and the 1D Hubbard model in an alternating periodic potential at half-filling. In the last system, we suggest a Luttinger-liquid-type quasi-metallic state in the crossover region from the band insulator to the Mott insulator. We explain the appearance of this state in terms of the incompatibility of the Bragg reflection with the concept of Luttinger liquids.Comment: 4 pages, 3 figure

BackgroundBortezomib offers a novel approach to the treatment of multiple myeloma producing rapid control. The aim of this study was to investigate the outcomes of bortezomib and dexamethasone-treated patients with multiple myeloma.MethodsWe conducted a retrospective study of 44 consecutively-treated multiple myeloma patients with bortezomib (1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day cycle or 1.3 mg/m2 intravenously 1, 8, 15, and 22 of every 35-day cycle) and dexamethasone.ResultsThe median time to progression, progression free survival time, and overall survival time in the treatment groups was 14.9, 14.9, and 38.3 months, respectively. The present study also suggests the possibility that the prognosis of patients with high levels of AST and LDH might be worse.ConclusionsOur results indicate that the treatment of multiple myeloma with bortezomib and dexamethasone is feasible.