Biomedical subjects

M Milnamow

Publications and source records attributed to M Milnamow.

3 recordsLinked to original sources

PubMed2000

ZEITLUPE encodes a novel clock-associated PAS protein from Arabidopsis.

We have conducted genetic screens for period length mutants in Arabidopsis using a transgenic bioluminescence phenotype. This screen identified mutations at a locus, ZEITLUPE (ZTL), that lengthen the free-running period of clock-controlled gene transcription and cell expansion, and alter the timing of the daylength-dependent transition from vegetative to floral development. Map-based cloning of ZTL identified a novel 609 amino acid polypeptide consisting of an amino-terminal PAS domain, an F box and six carboxy-terminal kelch repeats. The PAS region is highly similar to the PAS domain of the Arabidopsis blue-light receptor NPH1, and the Neurospora circadian-associated protein WHITE COLLAR-1 (WC-1). The striking fluence rate-dependent effect of the ztl mutations suggests that ZTL plays a primary role in the photocontrol of circadian period in higher plants.

Amino Acid Sequence↗

PubMed2000

The biosynthetic gene cluster for the microtubule-stabilizing agents epothilones A and B from Sorangium cellulosum So ce90.

BACKGROUND: Epothilones are produced by the myxobacterium Sorangium cellulosum So ce90, and, like paclitaxel (Taxol((R))), they inhibit microtubule depolymerisation and arrest the cell cycle at the G2-M phase. They are effective against P-glycoprotein-expressing multiple-drug-resistant tumor cell lines and are more water soluble than paclitaxel. The total synthesis of epothilones has been achieved, but has not provided an economically viable alternative to fermentation. We set out to clone, sequence and analyze the gene cluster responsible for the biosynthesis of the epothilones in S. cellulosum So ce90. RESULTS: A cluster of 22 open reading frames spanning 68,750 base pairs of the S. cellulosum So ce90 genome has been sequenced and found to encode nine modules of a polyketide synthase (PKS), one module of a nonribosomal peptide synthetase (NRPS), a cytochrome P450, and two putative antibiotic transport proteins. Disruptions in the genes encoding the PKS abolished epothilone production. The first PKS module and the NRPS module are proposed to co-operate in forming the thiazole heterocycle of epothilone from an acetate and a cysteine by condensation, cyclodehydration and subsequent dehydrogenation. The remaining eight PKS modules are responsible for the elaboration of the rest of the epothilone carbon skeleton. CONCLUSIONS: The overall architecture of the gene cluster responsible for epothilone biosynthesis has been determined. The availability of the cluster should facilitate the generation of designer epothilones by combinatorial biosynthesis approaches, and the heterologous expression of epothilones in surrogate microbial hosts.

Anti-Bacterial Agents↗

PubMed1996

A revised teacher rating scale for reactive and proactive aggression.

A teacher rating scale of reactive aggression, proactive aggression, and covert antisocial behavior was evaluated in a normative sample of third- to fifth-grade predominantly white lower middle class boys (N = 186). Factor analysis revealed independent and internally consistent Reactive Aggression (six reactive items), and Proactive Aggression (five proactive items, five covert items) factors. Although the factors were intercorrelated (r = .67), and each factor was significantly correlated with negative peer social status (r = .26 for each, controlling for grade), the independence of the factors was supported by the unique relation of Reactive Aggression with in-school detentions (r = .31), controlling for Proactive Aggression and grade. These results supported the reliability and validity of Reactive and Proactive Aggression as rated by teachers, which should facilitate further research of these constructs.

Aggression↗