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The resistance genes drrABC from Streptomyces peucetius ATCC 27952 were cloned into the pIBR25 expression vector under a strong ermE* promoter to enhance doxorubicin (DXR) production. The recombinant expression plasmids, pDrrAB25, pDrrC25 and pDrrABC25, were constructed to overexpress drrAB, drrC and drrABC, respectively, in S. peucetius ATCC 27952. The recombinant strains produced more DXR than the parental strain: a 2.2-fold increase with pDrrAB25, a 5.1-fold increase with pDrrC25, and a 2.4-fold increase with pDrrABC25. We also studied the relative ratios of doxorubicin, daunorubicin and ε-rhodomycinone produced in these recombinant strains.
<P><B>Abstract</B></P><P>To enhance doxorubicin (DXR) production, the structural sugar biosynthesis genes <I>desIII</I> and <I>desIV</I> from <I>Streptomyces venezuelae</I> ATCC 15439 and the glycosyltransferase pair <I>dnrS/dnrQ</I> from <I>Streptomyces peucetius</I> ATCC 27952 were cloned into the expression vector pIBR25, which contains a strong <I>ermE⁎</I> promoter. The recombinant plasmids pDnrS25 and pDnrQS25 were constructed for overexpression of <I>dnrS</I> and the <I>dnrS/dnrQ</I> pair, whereas pDesSD25 and pDesQS25 were constructed to express <I>desIII/desIV</I> and <I>dnrS/dnrQ–desIII/desIV</I>, respectively. All of these recombinant plasmids were introduced into <I>S. peucetius</I> ATCC 27952. The recombinant strains produced more DXR than the <I>S. peucetius</I> parental strain: a 1.2-fold increase with pDnrS25, a 2.8-fold increase with pDnrQS25, a 2.6-fold increase with pDesSD25, and a 5.6-fold increase with pDesQS25. This study showed that DXR production was significantly enhanced by overexpression of potential biosynthetic sugar genes and glycosyltransferase.</P>
Doxorubicin (DXR), produced by Streptomyces peucetius ATCC 27952, exhibits potent antitumor activity against various cancer cell lines. Considerable time has lapsed since the biosynthesis of DXR and its overproduction was first summarized. Based on biosynthetic studies and product analysis, various factors affecting its production by the parental strain, S. peucetius ATCC 27952, are reviewed to better circumvent any bottlenecks in DXR production, thereby providing ideas to genetically engineered industrial strains of S. peucetius.
Truss type structures are attractive to a variety of engineering applications on earth as well as in space due to their high stiffness to mass ratios and ease of construction and fabrication. During the service life, an individual member of a truss structure may lose load carrying capacity due to many reasons, which may lead to collapse of the structure. An analytical and computational procedure has been developed to study the response of truss structures subject to member failure under static and dynamic loadings. Emphasis is given to the dynamic effects of member failure and the propagation of local damage to other parts of the structure. The methodology developed is based on nonlinear finite element analysis technique and considers elasto-plastic material nonlinearity, postbuckling of members, and large deformation geometric nonlinearity. The pseudo force approach is used to represent the member failure. Results obtained for a planar nine-bay indeterminate truss undergoing sequential member failure show that failure of one member can initiate failure of several members in the structure.
Parkinson's disease (PD) patients frequently have several spinal deformities leading to postural instabilities including camptocormia, myopathy-induced postural deformity, Pisa syndrome, and progressive degeneration, all of which adversely affect daily life activities. To improve these postural deformities and relieve the related neurologic symptoms, patients often undergo spinal instrumentation surgery. Due to progressive degenerative changes related to PD itself and other complicating factors, patients and surgeons are faced with instrument failure-related complications, which can ultimately result in multiple revision surgeries yielding various postoperative complications and morbidities. Here, we report a representative case of a 70-year-old PD patient with flat back syndrome who had undergone several revision surgeries, including anterior and posterior decompression and fusion for a lumbosacral spinal deformity. The patient ultimately benefitted from a relatively short segment fixation and corrective fusion surgery.
Intrathoracic meningoceles are relatively rare entities found in patients with neurofibromatosis type I (NF1). Given that both the BRCA1 and NF-1 genes are located on the same long arm of chromosome 17, one would expect concurrence of neurofibromatosis and breast cancer. However, incidence of such co-disorders is very rare in the literature. Here, the authors report a case of a 50-year-old female patient with NF-1 and concurrent cancer of the left breast, who had a huge bilobulated intrathoracic meningocele with thoracic dystrophic scoliosis, treated surgically via a posterior-only approach for the meningocele and spinal deformity in the same setting.