ABSTRACT
Plant defense and adaptation to adverse environmental conditions rely on gene expression control, such as mRNA transcription, processing, stability, and translation. Sudden temperature changes are common in the era of global warming; thus, understanding plant acclimation responses at the molecular level becomes imperative. mRNA translation initiation regulation has a pivotal role in achieving the synthesis of the appropriate battery of proteins needed to cope with temperature stress. In this study, we analyzed the role of translation initiation factors belonging to the eIF4E family in Arabidopsis acclimation to cold temperatures and freezing tolerance. Using knockout (KO) and overexpressing mutants of AteIF4E1 or AteIF(iso)4E, we found that AteIF4E1 but not AteIF(iso)4E overexpressing lines displayed enhanced tolerance to freezing without previous acclimation at 4°C. However, KO mutant lines, eif(iso)4e-1 and eif4e1-KO, were more sensitive to the stress. Cold acclimation in wild-type plants was accompanied by increased levels of eIF4E1 and eIF(iso)4E transcript levels, polysomes (P) enrichment, and shifts of these factors from translationally non-active to active fractions. Transcripts, previously found as candidates for eIF(iso)4E or eIF4E1 selective translation, changed their distribution in both P and total RNA in the presence of cold. Some of these transcripts changed their polysomal distribution in the mutant and one eIF4E1 overexpressing line. According to this, we propose a role of eIF4E1 and eIF(iso)4E in cold acclimation and freezing tolerance by regulating the expression of stress-related genes.
ABSTRACT
BACKGROUND: Between April 2001 and March 2004, the Directly Observed Therapy-Short course (DOTS) program was successfully implemented by the National Tuberculosis control program, with assistance from the Canadian Lung Association, in three provinces of Ecuador, where 52% of the population of the country reside. METHODS: Markov modelling was used to project TB-related morbidity, mortality and costs if the former TB control program (status quo) had continued or if the newly expanded DOTS program is maintained over 20 years. Extensive sensitivity analyses were used to determine the effect on projected outcomes of varying key assumptions. RESULTS: If DOTS is maintained over the next 20 years, we predict that 18,760 cases and 15,812 TB-related deaths will be prevented, resulting in societal savings of dollars 203 million and government savings of dollars 7.1 million (all costs in dollars US). These findings were robust in extensive sensitivity analyses. Given the initial investment of dollars 3 million for DOTS implementation, this would mean a cost of dollars 190 per life saved. CONCLUSIONS: Implementation of DOTS could yield very substantial public health and economic benefits for Ecuador. These results demonstrate the benefits from Canadian government support for DOTS implementation in low- and middle-income countries.