Highlighting type A RRs as potential regulators of the dkHK1 multi-step phosphorelay pathway in Populus

In previous studies, we highlighted a multistep phosphorelay (MSP) system in poplars composed of two hybrid-type Histidine aspartate Kinases, dkHK1a and dkHK1b, which interact with three Histidine Phosphotransfer proteins, dkHPt2, 7, and 9, which in turn interact with six type B Response Regulators. These interactions correspond to the dkHK1a-b/dkHPts/dkRRBs MSP. This MSP is putatively involved in an osmosensing pathway, as dkHK1a-b are orthologous to the Arabidopsis osmosensor AHK1, and able to complement a mutant yeast deleted for its osmosensors. Since type A RRs have been characterized as negative regulators in cytokinin MSP signaling due to their interaction with HPt proteins, we decided in this study to characterize poplar type A RRs and their implication in the MSP. For a global view of this MSP, we isolated 10 poplar type A RR cDNAs, and determined their subcellular localization to check the in silico prediction experimentally. For most of them, the in planta subcellular localization was as predicted, except for three RRAs, for which this experimental approach gave a more precise localization. Interaction studies using yeast two-hybrid and in planta BiFC assays, together with transcript expression analysis in poplar organs led to eight dkRRAs being singled out as partners which could interfere the dkHK1a-b/dkHPts/dkRRBs MSP identified in previous studies. Consequently, the results obtained in this study now provide an exhaustive view of dkHK1a-b partners belonging to a poplar MSP

Results of a meta-analysis comparing the tolerability of lercanidipine and other dihydropyridine calcium channel blockers

Background. Results from clinical studies suggest that the dihydropyridine calcium channel blocker (d-CCB) lercanidipine may be associated with a lower incidence of peripheral edema than are older d-CCBs. Aim. To conduct a meta-analysis of published data from randomized controlled trials (RCTs) to assess the relative risk (RR) of d-CCB-specific adverse events (AE) with lercanidipine versus the older d-CCBs (first generation: amlodipine, felodipine, and nifedipine), and versus the other lipophilic d-CCBs (second generation: lacidipine and manidipine). Material and methods. A systematic literature search (all years, through August 11 2008) of MEDLINE, EMBASE, and the Cochrane Library was conducted for English-language reports of single- or double-blind RCTs of ≥4 weeks’ duration that compared the tolerability of lercanidipine with other d-CCBs in participants with mild (140- 159/90-99 mm Hg) and moderate (160-179/100-109 mm Hg) hypertension. Results. Eight RCTs (6 used first-generation drugs, and 4 used second-generation drugs) met the criteria for inclusion. Efficacy outcomes for lowering blood pressure did not differ statistically between lercanidipine and either generation of d-CCBs. Compared with the first generation, lercanidipine was associated with a reduced risk of peripheral edema (52/742 with lercanidipine vs. 88/627 with first generation; RR=0,44 [95% CI 0,31-0,63]), but not flushing or headache. The frequency of peripheral edema, flushing, and headache did not differ statistically between lercanidipine and the second generation drugs. Study participants were less likely to withdraw from the RCTs because of peripheral edema (RR=0,24 [95% CI 0,12-0,47]) or any AE (RR=0,51 [95% CI 0,33-0,77]) when treated with lercanidipine rather than a drug from the first generation, but not when treated with lercanidipine rather than second-generation drugs. Conclusion. Lercanidipine was associated with a lower risk of peripheral edema and a lower risk of treatment withdrawal because of peripheral edema than were the first-generation, but not the second-generation, d-CCBs

De novo acute type B aortic dissection in two patients with previous infrarenal endovascular aortic aneurysm repair with EndoAnchors

Acute aortic dissection in the immediate postoperative period after endovascular abdominal aortic aneurysm repair (EVAR) has been linked to technical factors such as excessive endograft oversizing or aortic wall injuries during the procedure. In contrast, dissections that occur later are more likely to be de novo. Regardless of their etiology, aortic dissection can extend into the abdominal aorta, causing collapse and occlusion of the endograft with devastating complications. To the best of our knowledge, no studies have reported on aortic dissection in EVAR patients in whom EndoAnchors (Medtronic, Minneapolis, MN) had been used. We present two cases of de novo type B aortic dissection after EVAR with entry tears in the descending thoracic aorta. In both of our patients, the dissection flap appeared to stop abruptly at the site of endograft fixation with the EndoAnchors, suggesting that EndoAnchors might prevent the propagation of aortic dissection beyond the EndoAnchor fixation level and thus protect the EVAR from collapse

Evaluation of type-B RR dimerization in poplar: A mechanism to preserve signaling specificity?

International audienc

Deleterious effect of suboptimal diet on rest-activity cycle in Anastrepha ludens manifests itself with age

Activity patterns and sleep-wake cycles are among the physiological processes that change most prominently as animals age, and are often good indicators of healthspan. In this study, we used the video-based high-resolution Behavioral Monitoring System (BMS) to monitor the daily activity cycle of tephritid fruit flies Anastrepha ludens over their lifetime. Surprisingly, there was no dramatic change in activity profile with respect to age if flies were consistently fed with a nutritionally balanced diet. However, if flies were fed with sugar-only diet, their activity profile decreased in amplitude at old age, suggesting that suboptimal diet affected activity patterns, and its detrimental effect may not manifest itself until the animal ages. Moreover, by simulating different modes of behavior monitoring with a range of resolution and comparing the resulting conclusions, we confirmed the superior performance of video-based monitoring using high-resolution BMS in accurately representing activity patterns in an insect model

Biosynthesis of natural and halogenated plant monoterpene indole alkaloids in yeast

Monoterpenoid indole alkaloids (MIAs) represent a large class of plant natural products with marketed pharmaceutical activities against a wide range of indications, including cancer, malaria and hypertension. Halogenated MIAs have shown improved pharmaceutical properties; however, synthesis of new-to-nature halogenated MIAs remains a challenge. Here we demonstrate a platform for de novo biosynthesis of two MIAs, serpentine and alstonine, in baker’s yeast Saccharomyces cerevisiae and deploy it to systematically explore the biocatalytic potential of refactored MIA pathways for the production of halogenated MIAs. From this, we demonstrate conversion of individual haloindole derivatives to a total of 19 different new-to-nature haloserpentine and haloalstonine analogs. Furthermore, by process optimization and heterologous expression of a modified halogenase in the microbial MIA platform, we document de novo halogenation and biosynthesis of chloroalstonine. Together, this study highlights a microbial platform for enzymatic exploration and production of complex natural and new-to-nature MIAs with therapeutic potential.</p

Reliability and variability of sleep and activity as biomarkers of ageing in Drosophila

There are currently no reliable biomarkers of ageing. A biomarker should indicate biological age, that is, the amount of an animal's total lifespan it has lived and, therefore, the amount of time it has remaining. Some potential biomarkers cannot be validated as their measurement involves harm or death of the animal, such that its ultimate lifespan cannot be determined. A non-destructive biomarker would allow us to test molecular markers potentially involved directly in the ageing process, to monitor the effectiveness of therapeutic interventions to delay ageing, and provide a useful measure of general health of the organism. In the model organism Drosophila, various behavioural phenotypes change directionally with age, but we do not know whether they predict lifespan. Here we measure activity and sleep parameters in 64 wild type male flies from two recently wild-caught populations over the course of their natural lives, and determine whether such measures may predict biological age and ultimate lifespan. Indices of sleep fragmentation and circadian rhythm were the best predictors of lifespan, though population differences were evident. However, when used to predict a biological age of 50 % lifespan elapsed our best behavioural measure was slightly less accurate and less precise compared with using chronological age as predictor