Relationships between polyamine metabolism and RNA synthesis in post-ischemic liver cell repair

In liver cells recovering from reversible ischemia the increase in RNA synthesis by isolated nuclei is preceded by activation of ornithine decarboxylase, leading in turn to an increase in putrescine concentration. Treatment of the animals with 1,3-diaminopropane and putrescine prevents ornithine decarboxylase activation but does not hinder the enhancement of RNA synthesis in post-ischemic liver nuclei; therefore, ornithine decarboxylase activation does not seem to be a necessary prerequisite for the increase in RNA synthesis. Hypophysectomy does not prevent the post-ischemic increases of ornithine decarboxylase and RNA synthesis; but pre-treatment of the animals with cycloheximide—which has a dual effect on the activity of ornithine decarboxylase—abolishes the post-ischemic enhancement of RNA synthesis. In contrast with regenerating liver, changes in ornithine decarboxylase activity and putrescine concentrations in reversible ischemia are not associated to changes in S-adenosylmethionine decarboxylase activity and in spermine and spermidine concentrations that seem to be characteristic of tissues where increases in RNA synthesis are followed by DNA synthesis and cell multiplication.     

Promoter diversity in multigene transformation

Multigene transformation (MGT) is becoming routine in plant biotechnology as researchers seek to generate more complex and ambitious phenotypes in transgenic plants. Every nuclear transgene requires its own promoter, so when coordinated expression is required, the introduction of multiple genes leads inevitably to two opposing strategies: different promoters may be used for each transgene, or the same promoter may be used over and over again. In the former case, there may be a shortage of different promoters with matching activities, but repetitious promoter use may in some cases have a negative impact on transgene stability and expression. Using illustrative case studies, we discuss promoter deployment strategies in transgenic plants that increase the likelihood of successful and stable multiple transgene expression.     

Clonality disguises the vulnerability of a threatened arid zone Acacia

Long‐lived, widespread plant species are expected to be genetically diverse, reflecting the interaction between large population sizes, overlapping generations, and gene flow. Such species are thought to be resilient to disturbance, but may carry an extinction debt due to reproductive failure. Genetic studies of Australian arid zone plant species suggest an unusually high frequency of asexuality, polyploidy, or both. A preliminary AFLP genetic study implied that the naturally fragmented arid zone tree, Acacia carneorum, is almost entirely dependent on asexual reproduction through suckering, and stands may have lacked genetic diversity and interconnection even prior to the onset of European pastoralism. Here we surveyed microsatellite genetic variation in 20 stands to test for variation in life histories and further assessed the conservation status of the species by comparing genetic diversity within protected stands in National Parks and disturbed range lands. Using herbarium records, we estimate that 219 stands are extant, all of which occur in the arid zone, west of the Darling River in southeastern Australia. With two exceptions, all surveyed stands comprised only one multilocus genet and at least eight were putatively polyploid. Although some stands comprise thousands of stems, our findings imply that the species as a whole may represent ~240 distinct genetic individuals, many of which are polyploid, and most are separated by >10 km of unsuitable habitat. With only 34% of stands (and therefore genets) occurring within conservation reserves, A. carneorum may be at much greater risk of extinction than inferred from on‐ground census data. Land managers should prioritize on‐ground preservation of the genotypes within existing reserves, protecting both vegetative suckers and seedlings from herbivory. Importantly, three stands are known to set viable seed and should be used to generate genetically diverse germ‐plasm for ex situ conservation, population augmentation, or translocation.     

Cost-Minimization Analysis Favours Intravenous Ferric Carboxymaltose over Ferric Sucrose for the Ambulatory Treatment of Severe Iron Deficiency

Objective

Intravenous iron is widely used to treat iron deficiency in day-care units. Ferric carboxymaltose (FCM) allows administration of larger iron doses than iron sucrose (IS) in each infusion (1000 mg vs. 200 mg). As FCM reduces the number of infusions required but is more expensive, we performed a cost-minimization analysis to compare the cost impact of the two drugs.

Materials and Methods

The number of infusions and the iron dose of 111 consecutive patients who received intravenous iron at a gastrointestinal diseases day-care unit from 8/2007 to 7/2008 were retrospectively obtained. Costs of intravenous iron drugs were obtained from the Spanish regulatory agencies. The accounting department of the Hospital determined hospital direct and indirect costs for outpatient iron infusion. Non-hospital direct costs were calculated on the basis of patient interviews. In the pharmacoeconomic model, base case mean costs per patient were calculated for administering 1000 mg of iron per infusion using FCM or 200 mg using IS. Sensitivity analysis and Monte Carlo simulation were performed.

Results

Under baseline assumptions, the estimated cost of iron infusion per patient and year was €304 for IS and €274 for FCM, a difference of €30 in favour of FCM. Adding non-hospital direct costs to the model increased the difference to €67 (€354 for IS vs. €287 for FCM). A Monte Carlo simulation taking into account non-hospital direct costs favoured the use of FCM in 97% of simulations.

Conclusion

In this pharmacoeconomic analysis, FCM infusion reduced the costs of iron infusion at a gastrointestinal day-care unit.     

Autophagy regulation depends on ER homeostasis controlled by lipid droplets

Macroautophagy (hereafter autophagy) is a highly conserved homeostasis and quality control process critically linked to neurodegeneration, metabolic diseases, cancer, and aging. A key feature of autophagy is the de novo formation of autophagosomes, double-membrane vesicular structures encapsulating cytoplasmic cargo for vacuolar turnover and recycling. The membrane rearrangements underlying nucleation, expansion, closure, and vacuolar fusion of autophagosomes are driven by multicomponent core autophagy machinery in cooperation with numerous factors involved in a variety of cellular processes. Our current understanding of the origin and contribution of diverse membrane sources to autophagosome biogenesis and of cellular functions enabling stress-appropriate autophagy responses critical for cell health and survival remains limited. Here, we summarize and discuss our recent findings analyzing the role of lipid droplets (LDs), conserved intracellular storage compartments for neutral lipids, for autophagy regulation. Our data indicate that LDs are dispensable as membrane sources, but fulfill critical functions for maintaining endoplasmic reticulum (ER) homeostasis, including buffering of newly synthesized fatty acids and maintenance of phospholipid composition, required for intact autophagy regulation and cell survival during nutrient stress.