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Biomedical subjects

N Axelrod

Publications and source records attributed to N Axelrod.

9 recordsLinked to original sources

Artificial linear mini-chromosomes for Trypanosoma brucei.

We have constructed artificial linear mini- chromosomes for the parasitic protozoan Trypanosoma brucei. These chromosomes exist at approx. 2 copies per cell, are indefinitely stable under selection but are lost from 50% of the transformed population in approx. 7 generations when grown in the absence of selective pressure. Consistent with results obtained earlier with natural chromosomes in T.brucei, the telomeres on these artificial chromosomes grow, adding approx. 1- 1.5 telomeric repeats per generation. The activity of a procyclic acidic repetitive protein (parp) gene promoter on these elements is unaffected by its proximity to a telomere, implying the lack of a telomere-proximal position effect (TPE) in procyclic trypanosomes. Among other things, these autonomously replicating dispensable genetic elements will provide a defined system for the study of nuclear DNA replication, karyotypic plasticity and other aspects of chromosomal behavior in this ancient eukaryotic lineage.

Animals↗

Of telomeres and tumors.

The enzyme, telomerase, may be switched on in tumor cells. Inhibitors of this enzyme might constitute a new class of anti-cancer drugs.

Animals↗

Construction of trypanosome artificial mini-chromosomes.

We report the preparation of two linear constructs which, when transformed into the procyclic form of Trypanosoma brucei, become stably inherited artificial mini-chromosomes. Both of the two constructs, one of 10 kb and the other of 13 kb, contain a T.brucei PARP promoter driving a chloramphenicol acetyltransferase (CAT) gene. In the 10 kb construct the CAT gene is followed by one hygromycin phosphotransferase (Hph) gene, and in the 13 kb construct the CAT gene is followed by three tandemly linked Hph genes. At each end of these linear molecules are telomere repeats and subtelomeric sequences. Electroporation of these linear DNA constructs into the procyclic form of T.brucei generated hygromycin-B resistant cell lines. In these cell lines, the input DNA remained linear and bounded by the telomere ends, but it increased in size. In the cell lines generated by the 10 kb construct, the input DNA increased in size to 20-50 kb. In the cell lines generated by the 13 kb constructs, two sizes of linear DNAs containing the input plasmid were detected: one of 40-50 kb and the other of 150 kb. The increase in size was not the result of in vivo tandem repetitions of the input plasmid, but represented the addition of new sequences. These Hph containing linear DNA molecules were maintained stably in cell lines for at least 20 generations in the absence of drug selection and were subsequently referred to as trypanosome artificial mini-chromosomes, or TACs.

Animals↗

The Governance Symposium--Part II. A new context for trustees.

Today you are a hospital trustee. If health care reform doesn't scare you away, tomorrow you could be governing a system, a network, a physician/hospital organization, or a community hospital that belongs to one of these other entities. managed care will change your priorities, your responsibilities, and the expectations others have of you as well as the health care delivery system. To learn more about the trustee's role in a reformed health care system, the American Hospital Association and Trustee recently convened a governance symposium (see the list of participants on the opposite page). The first part of the discussion from that symposium was presented in the August issue (see "Quantum leap," page 6). The second part focuses on the issues of board accountability and compensation and realigning incentives for the future.

Governing Board↗