Drug resistance of leukemic blasts is correlated to event-free survival and might be predicted by mRNA expression of drug resistance-related proteins. Methotrexate (MTX) is an important component in the treatment of childhood leukemia. Mechanisms of MTX resistance include (1) decreased transport via the reduced folate carrier (RFC), (2) altered levels of target enzymes, eg dihydrofolate reductase (DHFR) and thymidylate synthase (TS), (3) decreased ratio of folylpolyglutamate synthetase (FPGS)/folylpolyglutamate hydrolase (FPGH). We designed competitive templates for each of these genes to measure mRNA expression by quantitative RT-PCR and normalized the expression to that of -actin. T-lineage acute lymphoblastic leukemia (T-ALL), relatively MTX resistant compared to common/preB-ALL, displayed higher mRNA levels of DHFR and TS (three-and four-fold higher, respectively; P Ͻ 0.001), while FPGS expression was lower (three-fold, P ؍ 0.006) compared to common/preB-ALL. The ratio of (DHFR ؋ FPGH)/(RFC ؋ FPGS) was more discriminating between T-ALL and c/preB-ALL (eight-fold higher; P Ͻ 0.001) than either target independently. Acute myeloid leukemia (AML) cells, considered MTX resistant, expressed two-fold lower levels of FPGS mRNA compared to c/preB-ALL (P ؍ 0.04). The ratio of FPGH/FPGS was more discriminating between AML and c/preB-ALL (fourfold higher; P ؍ 0.001) than either target independently. For the total group of 79 leukemic samples, mRNA expression of DHFR varied 549-fold and paralleled TS mRNA expression (r ؍ 0.80; P Ͻ 0.001). Although variations in mRNA expression resembled variations in functional activity, no direct correlations were found for RFC (58-fold variation in mRNA expression), FPGS (95-fold) and FPGH (178-fold). In conclusion, differences in mRNA expression of MTX resistance parameters between leukemic subtypes as detected by competitive RT-PCR are in line with known differences in MTX resistance. Leukemia (2000) 14, 2166-2175.
Striga and Orobanche seeds germinate in response to a host-derived germination stimulant. Dose-response curves of the synthetic strigolactone analogues GR 24 and Nijmegen 1 were determined, and their activities were compared to that of the naturally occurring stimulant sorgolactone. Typical sigmoidal curves were obtained. ED(50) values for GR 24 were in the order of 10(-)(9)-10(-)(8) mol/L; for Nijmegen 1 these values were 3 orders of magnitude higher. Both synthetic stimulants are appreciably active at low concentrations and merit investigation as agents for the suicidal germination approach (i.e., treatment of the soil with stimulant in the absence of a host).
Copper tolerance in Silene vulgaris seems to be controlled by two major genes. One segregates only in crosses to non-tolerants but never in crosses between tolerants originating from different isolated populations. The second segregates only in crosses to plants from the most tolerant population. The level of tolerance in tolerant plants seems to be controlled by two additional genes, which are hypostatic to the first major gene. They segregate in crosses to non-tolerants but not in crosses between equally homozygous tolerant plants from different populations. It is argued that all the genes are involved in the control of an exclusion mechanism operating at the plasmalemma.
A key question in microbial ecology is what the driving forces behind the persistence of large biodiversity in natural environments are. We studied a microbial community with more than 100 different types of species which evolved in a 15-years old bioreactor with benzene as the main carbon and energy source and nitrate as the electron acceptor. Using genome-centric metagenomics plus metatranscriptomics, we demonstrate that most of the community members likely feed on metabolic left-overs or on necromass while only a few of them, from families Rhodocyclaceae and Peptococcaceae, are candidates to degrade benzene. We verify with an additional succession experiment using metabolomics and metabarcoding that these few community members are the actual drivers of benzene degradation. As such, we hypothesize that high species richness is maintained and the complexity of a natural community is stabilized in a controlled environment by the interdependencies between the few benzene degraders and the rest of the community members, ultimately resulting in a food web with different trophic levels.
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