The genetic landscape of the childhood cancer medulloblastoma

Medulloblastoma (MB) is the most common malignant brain tumor of children. To identify the genetic alterations in this tumor type, we searched for copy number alterations using high-density microarrays and sequenced all known protein-coding genes and microRNA genes using Sanger sequencing in a set of 22 MBs. We found that, on average, each tumor had 11 gene alterations, fewer by a factor of 5 to 10 than in the adult solid tumors that have been sequenced to date. In addition to alterations in the Hedgehog and Wnt pathways, our analysis led to the discovery of genes not previously known to be altered in MBs. Most notably, inactivating mutations of the histone-lysine N-methyltransferase genes MLL2 or MLL3 were identified in 16% of MB patients. These results demonstrate key differences between the genetic landscapes of adult and childhood cancers, highlight dysregulation of developmental pathways as an important mechanism underlying MBs, and identify a role for a specific type of histone methylation in human tumorigenesis.     

Wound healing,decay and chemical treatment of cut potato tuber tissue

Potato tuber tissue inoculated at cutting withFusarium spp. orErwinia carotovora and exposed to conditions favorable for infection did not heal rapidly enough to prevent decay. Seven days of wound healing at 20 C and high relative humidity prior to inoculation were necessary to provide protection againstFusarium and two days were required to protect againstErwinia. Histological examination of cut and chemically treated tuber tissue revealed that the wound healing process was only minimally affected by mancozeb, zineb-streptomycin, zineb-fir bark, captan, captan-mertect, captan-fir bark, and sodium hypochlorite. Ethylmercury p-toluene-sulfonanalide and pyrrolidine induced formation of discontinuous wound periderm after 21 days of healing. Streptomycin and captan-rhodamine had very detrimental effects on wound healing and suberin formation. In general, the seed-piece treatment chemicals tested had only minor effects on normal wound healing. It is concluded that wound healing alone may not be sufficient to controlFusarium caused seed piece decay and chemical treatment is recommended to provide protection until wound healing can occur. At least two days of wound healing are required for control of decay caused byErwinia carotovora.     

Effects of graded doses of propofol for anesthesia induction on cardiovascular parameters and intraocular pressures in normal dogs

ObjectiveTo determine the effects of graded doses of propofol on cardiovascular parameters and intraocular pressures (IOP) in normal dogs.Study designProspective, randomized, modified Latin square, cross-over experimental study.AnimalsEleven adult random-source dogs weighing 20.2 ± 5.7 kg.MethodsThere were three treatment groups: propofol 8 mg kg^?1 intravenous (IV) until loss of jaw tone (Group P), propofol until loss of jaw tone +20% (Group P20), and propofol until loss of jaw tone +50% (Group P50). Atracurium 0.1 mg kg^?1 IV was administered in all treatments immediately after the propofol. All dogs received the three treatments in a randomized order, with at least a one week interval between treatments. Direct arterial blood pressure and IOP by applanation tonometry were obtained at baseline, after 5 minutes of pre-oxygenation (before induction), before, and after intubation. Blood gas samples were obtained at baseline, after pre-oxygenation, and before intubation.ResultsThere was no significant difference in IOP readings at any time point among groups. The IOP was significantly higher before intubation versus before induction in all three groups. There was a significantly smaller change in systolic, mean (MAP), and diastolic (DAP) arterial pressures in the P50 group compared with the P group after intubation. There was a significantly smaller change in MAP and DAP in the P50 group compared with the P20 group after intubation. The increase in CO₂ from before induction to before intubation was significantly greater in the P50 group than in the P or P20 groups.Conclusions and clinical relevanceGraded doses of propofol did not affect the increase in IOP observed with propofol induction in normal dogs. Higher doses of propofol are of no apparent additional benefit in animals who cannot tolerate an abrupt increase in IOP but may be of benefit in dogs who cannot tolerate an abrupt increase in blood pressure accompanying orotracheal intubation.     

Molecular characteristics of an immobilization antigen gene of the fish-parasitic protozoan Ichthyophthirius multifiliis strain ARS-6

Ichthyophthirius multifiliis (Ich), a ciliated protozoan parasite of fish, expresses surface antigens (i-antigens), which react with host antibodies that render them immobile. The nucleotide sequence of an i-antigen gene of I. multifiliis strain ARS-6 was deduced. The predicted protein of 47 493 Da is comprised of 460 amino acids (aa's) arranged into five imperfect repeats with periodic cysteine residues with the structure: CX₍₁₉₎₂₀CX₂CX₁₆₋₂₇CX₂CX₂₀₍₂₁₎CX₃. The N-terminal aa's typify a signal peptide motif while a stretch of C-terminal aa's resemble a glycosyl–phosphatidyl–inositol (GPI)-anchor addition site. The degree of deduced i-antigen aa sequence identity of strain ARS-6 (GenBank accession # ACH87654 and # ACH95659) with other I. multifiliis i-antigen sequences present in GenBank ranges from 99% to 36% identity with 52 kDa i-antigens of I. multifiliis strain G5 (accession #s AAK94941 and AAK01661 respectively). Immunoblot analysis of i-antigens following exposure of I. multifiliis theronts to catfish anti- I. multifiliis immune serum did not show any appreciable alteration in i-antigen expression. The mechanism that regulates i-antigen expression in I. multifiliis remains a puzzling question.     

Homology modelling of Drosophila cytochrome P450 enzymes associated with insecticide resistance

BACKGROUND: Overexpression of the cytochrome P450 gene Cyp6g1 confers resistance against DDT and a broad range of other insecticides in Drosophila melanogaster Meig. In the absence of crystal structures of CYP6G1 or complexes with its substrates, structural studies rely on homology modelling and ligand docking to understand P450–substrate interactions. RESULTS: Homology models are presented for CYP6G1, a P450 associated with resistance to DDT and neonicotinoids, and two other enzymes associated with insecticide resistance in D. melanogaster, CYP12D1 and CYP6A2. The models are based on a template of the X‐ray structure of the phylogenetically related human CYP3A4, which is known for its broad substrate specificity. The model of CYP6G1 has a much smaller active site cavity than the template. The cavity is also ‘V’‐shaped and is lined with hydrophobic residues, showing high shape and chemical complementarity with the molecular characteristics of DDT. Comparison of the DDT–CYP6G1 complex and a non‐resistant CYP6A2 homology model implies that tight‐fit recognition of this insecticide is important in CYP6G1. The active site can accommodate differently shaped substrates ranging from imidacloprid to malathion but not the pyrethroids permethrin and cyfluthrin. CONCLUSION: The CYP6G1, CYP12D1 and CYP6A2 homology models can provide a structural insight into insecticide resistance in flies overexpressing P450 enzymes with broad substrate specificities. Copyright © 2010 Society of Chemical Industry