Biochemical studies of the germinating conidia of aspergillus nidulans

Biochemical investigations of the germinating conidia of Aspergillus nidulans were carried out to elucidate the mechanisms controlling macromolecular synthesis during germ-tube emergence. Conidial germination of the wild type strain of A. nidulans, BWB 272, is accompanied by a hundredfold increase in a putrescine-stimulated S-adenosylmethionine decarboxylase activity and a rapid accumulation of spermidine and spermine. Putrescine levels remain low at all stages of growth. The highest specific rates of protein and nucleic acid synthesis occur coincident with germ-tube emergence. Use of metabolic inhibitors demonstrates the necessity of RNA and protein synthesis, but not DNA synthesis, for conidial germination. Comdia of the putrescine auxotroph, A. nidulans puA1, require putrescine for optimal rates of germination and growth. Putrescine starvation is a slow process resulting in a graoual run-down of a wide variety of metabolic processes. However a rapid change in the intracellular levels of spermidine and spermine occurs following the addition of putrescine to cultures starved for 12 hours. This results in immediate increases in the rates of protein and nucleic acid biosynthesis, oxygen consumption and polypeptide chain elongation. Also the average size of the isolated polysomes is three-fold larger and the proportion of ribosomal RNA synthesized increases two-fold. It is concluded that putrescine, spermidine and spermine are likely to have essential roles in macromolecular synthesis

Economic burden of adverse drug reactions and potential for pharmacogenomic testing in Singaporean adults.

Adverse drug reactions (ADRs) contribute to hospitalization but data on its economic burden is scant. Pre-emptive pharmacogenetic (PGx) testing can potentially reduce ADRs and its associated costs. The objectives of this study were to quantify the economic burden of ADRs and to estimate the breakeven cost of pre-emptive PGx testing in Singapore. We collected itemized costs for 1000 random non-elective hospitalizations of adults admitted to a tertiary-care general hospital in Singapore. The presence of ADRs at admission and their clinical characteristics were reported previously. The economic burden of ADRs was assessed from two perspectives: (1) Total cost and (2) incremental costs. The breakeven cost of PGx testing was estimated by dividing avoidable hospitalization costs for ADRs due to selected drugs by the number of patients taking those drugs. The total cost of 81 admissions caused by ADRs was US$570,404. Costs were significantly higher for bleeding/elevated international normalized ratio (US$9906 vs. US$2251, p = 6.58 × 10-3) compared to other ADRs, and for drugs acting on the blood coagulation system (US$9884 vs. US$2229, p = 4.41 × 10-3) compared to other drug classes. There were higher incremental laboratory costs due to ADRs causing or being present at admission. The estimated breakeven cost of a pre-emptive PGx test for patients taking warfarin, clopidogrel, chemotherapeutic and neuropsychiatric drugs was US$114 per patient. These results suggest that future studies designed to directly measure the clinical and cost impact of a pre-emptive genotyping program will help inform clinical practice and health policy decisions

The mind, the lab, and the field: Three kinds of populations in scientific practice

Scientists use models to understand the natural world, and it is important not to conflate model and nature. As an illustration, we distinguish three different kinds of populations in studies of ecology and evolution: theoretical, laboratory, and natural populations, exemplified by the work of R.A. Fisher, Thomas Park, and David Lack, respectively. Biologists are rightly concerned with all three types of populations. We examine the interplay between these different kinds of populations, and their pertinent models, in three examples: the notion of “effective” population size, the work of Thomas Park on /Tribolium/ populations, and model-based clustering algorithms such as /Structure/. Finally, we discuss ways to move safely between three distinct population types while avoiding confusing models and reality