Metabolic flux analysis for calcium dependent antibiotic (CDA) production in Streptomyces coelicolor

The calcium dependent antibiotic (CDA) is a nonribosomal lipopeptide produced by Streptomyces coelicolor. We constructed a metabolic network of more than 400 reactions for the primary and secondary metabolism of S. coelicolor and used computational metabolic flux balancing to investigate some of the factors affecting growth and production of CDA. Computational results indicated that the CDA production was concomitant with growth. Computational specific growth rates were twice as high as the experimental specific growth rates. Metabolic flux distributions and sensitivity analyses computed for various phases of the batch culture indicated that the specific CDA production rate was affected by nitrogen assimilation, pentose phosphate pathway, shikimate biosynthesis, and oxoglutarate fluxes. Consequently, these metabolic targets were tested using genetic deletions in the model which increased the in silico specific CDA production rate.     

Valproic acid and lamotrigine treatment during pregnancy. The risk of chromosomal abnormality

A baby born to an epileptic mother had dysmorphological features associated with 47,XXX karyotype. The mother had been treated with valproic acid (1800mg per day) and lamotrigine (100mg per day) throughout pregnancy. Dysmorphological features detected in baby were intrauterine growth retardation, hypertelorism, flattened nasal bridge, low set malformed auriculas, micrognathia, very small an bow-shaped mouth with thin upper lip, cleft palate, arachnodactyly, camptodactyly, secundum atrial septal defect, bilateral hammer toes and decreased creases on the soles. At 6 months old she showed motor retardation. The molecular analysis of parents revealed that extra X chromosome was inherited from the mother. In this case whether the dysmorphological features and 47,XXX karyotype were caused by lamotrigine and valproic acid treatment during pregnancy or coincidence is in question.     

Effect of bioreactor configuration on the growth and maturation of Picea sitchensis somatic embryo cultures

Somatic embryo suspension cultures of Picea sitchensis (Sitka spruce) derived from two cell lines, SS03 and SS10, were grown in shake flasks, air-lift, bubble, stirred tank and hanging stirrer bar bioreactors. Cell line SS03 yielded freely suspended and individual stage 1 embryos, while the embryos of SS10 were present in large aggregates. Compared to shake flasks, proliferation in bioreactors resulted in increased biomass; however, cell line morphology influenced the effect of different bioreactor configurations on growth and maturation of embryo cultures. Somatic embryos grown in shake flasks and bioreactors were matured on gelled solid medium and in submerged culture where gelled solid medium was covered with a layer of liquid medium. The number of stage 3 (mature) embryos produced from SS03 in the bubble bioreactor was significantly higher than those from stirred tank and hanging stirrer bar bioreactors with both solid medium and submerged culture. Submerged culture was unsuitable for SS10 embryo maturation. This revised version was published online in June 2006 with corrections to the Cover Date.     

The preventive effect of vitamin D3 on radiation-induced hair toxicity in a rat model

Our aim is to investigate the protective effect of vitamin D3 especially from radiation-induced hair toxicity. A model of skin radiation injury was developed and a single fraction of 20 Gy Gamma irradiation was applied to the right dorsal skin of fourteen rats. All animals were randomly divided into 2 groups: Group I: irradiation alone (n = 7) and Group II: irradiation and 0.2 microg vitamin D3 given IM (n = 7). Fifty days after post-irradiation rats were sacrificed. The outcomes were evaluated on the basis of histopathological findings and immunohistochemical staining for Vitamin D receptor (VDR) in skin and hair follicles. The number of hair follicles in the radiation field for the group of animals irradiated without pretreatment was significantly lower than outside of the irradiated area (p = 0.016) as it is expected. Contrarily the number of hair follicles did not show significant difference in the pretreated group between the irradiated field and outside of the fields (p = 0,14). Skin of the vitamin D3 pretreated group demonstrated stronger immunoreactivity for VDR compared to irradiation alone group. These results indicate that administration of vitamin D3 may protect hair follicles from radiation toxicity. Further clinical trials should be conducted to prove the preventive effect of vitamin D3 as well as dosing and timing of the agent on radiation-induced alopecia.     

SMOC1 is essential for ocular and limb development in humans and mice

Microphthalmia with limb anomalies (MLA) is a rare autosomal-recessive disorder, presenting with anophthalmia or microphthalmia and hand and/or foot malformation. We mapped the MLA locus to 14q24 and successfully identified three homozygous (one nonsense and two splice site) mutations in the SPARC (secreted protein acidic and rich in cysteine)-related modular calcium binding 1 (SMOC1) in three families. Smoc1 is expressed in the developing optic stalk, ventral optic cup, and limbs of mouse embryos. Smoc1 null mice recapitulated MLA phenotypes, including aplasia or hypoplasia of optic nerves, hypoplastic fibula and bowed tibia, and syndactyly in limbs. A thinned and irregular ganglion cell layer and atrophy of the anteroventral part of the retina were also observed. Soft tissue syndactyly, resulting from inhibited apoptosis, was related to disturbed expression of genes involved in BMP signaling in the interdigital mesenchyme. Our findings indicate that SMOC1/Smoc1 is essential for ocular and limb development in both humans and mice.     

<Emphasis Type="Italic">Streptomyces coelicolor</Emphasis> increases the production of undecylprodigiosin when interacted with <Emphasis Type="Italic">Bacillus subtilis</Emphasis>

Purpose of work  

Undecylprodigiosin has antimicrobial, immunosuppressive and anticancer properties. Pure cultures of Streptomyces coelicolor produce only low concentrations of undecylprodigiosin. We have therefore sought to increase this by interacting the cells with a bacterium.     

EFFECT OF RHUS CORIARIA L. (ANACARDIACEAE) ON SUPEROXIDE RADICAL SCAVENGING AND XANTHINE OXIDASE ACTIVITY

Rhus coriaria L. (Anacardiaceae) is a well-known spice in the Middle-East and grown in the Central and East Anatolia region of Turkey. A methanolic extract (water-soluble part constituents) of R. coriaria, was found to be an uncompetitive inhibitor of xanthine oxidase and scavenger of superoxide radical in vitro with IC 50 values of 172.5 μg/mL and 232 μg/mL respectively. Superoxide radicals were generated either by an enzymatic or a non-enzymatic system, and scavenging ability was evaluated by the inhibition of nitroblue tetrazolium reduction. This study provides evidence that a crude extract of R. coriaria exhibits interesting antioxidant properties, expressed either by the capacity to scavenge superoxide radical or to uncompetitively inhibit xanthine oxidase.