Glucose ester enabled acylation in plant specialized metabolism

Acylation of core compound skeletons, together with other modifications, plays a significant role in producing the incredible diversity of plant specialized metabolites. Two major classes of acyltransferases, the BAHD and serine carboxypeptidase-like (SCPL) acyltransferases, can bring together through acylation compounds from the same or divergent metabolic pathways. BAHD acyltransferases (BAHD-ATs) employ CoA thioesters as the activated substrate, SCPL acyltransferases (SCPL-ATs), on the other hand, utilize β-acetal esters, typically glucose esters formed by UDP glycosyltransferases (UGTs). While the general trend of high energy glucose ester enabled acyltransfers is seen throughout the spermatophytes (seed plants), the specific metabolites that are conjugated appear to be lineage specific. In this review, we examine the reaction mechanism, biochemical property and evolutionary relationship of SCPL-ATs that utilize various glucose ester donors and acceptors from the same or different plant specialized metabolic pathways. The occurrence and taxonomic distribution of galloylated flavan-3-ols, hydrolyzable tannins and galloylated flavonols are also evaluated. Furthermore, glucose ester (acyl donor)-forming UGT activities and the subcellular localization of the UGT and SCPL-AT catalyzed reactions are discussed.     

Mechanism of Zinc absorption in plants: uptake,transport, translocation and accumulation

Zinc (Zn) is an essential micronutrient for plants and animals. Unfortunately, deficiency of Zn in humans has increased on a global scale. The main reason of this micronutrient deficiency is dietary intakes of food with low Zn levels. Adoption of biofortification approaches would result in Zn enrichment of target tissue to a considerable extent. However, there is a basic need to understand Zn absorption mechanisms in plants prior to exploitation of such practical approaches. Zn absorption is a complex physiological trait which is mainly governed by Zn transporters and metal chelators of plant system. Plant growth stage, edaphic factors, season etc. also influence Zn efficiency of particular species. Molecular studies in Zn hyperaccumulators have already demonstrated the participation of specific Zn transporters, vacuolar sequestration and detoxification mechanisms in maintenance of Zn homeostasis. These have been described in detail in present review and provide opportunities for utilization in biofortification programmes. However, issues such as lesser bioavailability of Zn in target organ, uptake of toxic divalent cations (Cd, Ni, Pb, As etc.) along with Zn, sink activity and dilution in Zn concentration in response to sink number etc. in biofortified crops need further investigation. In order to design novel strategy in biofortification programmes, future researches should focus on physiological performance and yield penalties in concerned crop, metabolic load in term of organic acid production and crosstalk of Zn with other mineral nutrients under low and high Zn conditions.     

High-value products from macroalgae: the potential uses of the invasive brown seaweed<Emphasis Type="Italic">, Sargassum muticum</Emphasis>

Marine seaweeds represent an abundant source of natural products and may harbour valuable chemicals. The brown seaweed Sargassum muticum is an invasive species to the coasts of the British Isles, mainland Europe and North America. Attempts at its eradication and control have generally not been successful, although time-consuming and costly. Commercial exploration of this biomass for food, fuel and pharmaceutical products could encourage its harvesting and control. Though S. muticum might be unsuitable as a source of biofuel due to high ash and water content, this rapidly growing macroalga has a naturally high content of antioxidants, carotenoids and phenols, including the well-known anti-cancer compound fucoxanthin, making this species a potential source of a range of pharmaceutically relevant materials.     

Genetic Evidence That Captured Retroviral Envelope syncytins Contribute to Myoblast Fusion and Muscle Sexual Dimorphism in Mice

Syncytins are envelope genes from endogenous retroviruses, “captured” for a role in placentation. They mediate cell-cell fusion, resulting in the formation of a syncytium (the syncytiotrophoblast) at the fetomaternal interface. These genes have been found in all placental mammals in which they have been searched for. Cell-cell fusion is also pivotal for muscle fiber formation and repair, where the myotubes are formed from the fusion of mononucleated myoblasts into large multinucleated structures. Here we show, taking advantage of mice knocked out for syncytins, that these captured genes contribute to myoblast fusion, with a >20% reduction in muscle mass, mean muscle fiber area and number of nuclei per fiber in knocked out mice for one of the two murine syncytin genes. Remarkably, this reduction is only observed in males, which subsequently show muscle quantitative traits more similar to those of females. In addition, we show that syncytins also contribute to muscle repair after cardiotoxin-induced injury, with again a male-specific effect on the rate and extent of regeneration. Finally, ex vivo experiments carried out on murine myoblasts demonstrate the direct involvement of syncytins in fusion, with a >40% reduction in fusion index upon addition of siRNA against both syncytins. Importantly, similar effects are observed with primary myoblasts from sheep, dog and human, with a 20–40% reduction upon addition of siRNA against the corresponding syncytins. Altogether, these results show a direct contribution of the fusogenic syncytins to myogenesis, with a demonstrated male-dependence of the effect in mice, suggesting that these captured genes could be responsible for the muscle sexual dimorphism observed in placental mammals.     

Patients with heart failure with preserved ejection fraction and low levels of natriuretic peptides

Aims

Heart failure with preserved ejection fraction (HFpEF) is common and its management remains difficult. B-type natriuretic peptide (BNP) levels are used to diagnose heart failure, and as an entry criterion for inclusion into trials. We investigated a population of HFpEF patients who had been randomised into a study based on clinical parameters, and compared those with low BNP levels to those with elevated BNP levels.

Methods

We examined patients who had been enrolled in the Coordinating study evaluating Outcomes of Advising and Counselling in Heart Failure (COACH), with preserved left ventricular ejection fraction (LVEF ≥ 40 %), and compared those with low BNP (< 100 pg/ml; n = 30) to those with elevated BNP (≥ 100 pg/ml; n = 127). Baseline characteristics, comorbidities, biomarkers, quality of life, and outcome parameters (hospitalisations and death) were compared between the groups. To validate our findings, we repeated all analyses for NT-proBNP (< 300 pg/ml and ≥ 300 pg/ml).

Results

Patients were similar with regard to most clinical characteristics (including age, sex, and LVEF), biomarkers, and comorbidities. In contrast, patients with a low BNP had higher body mass index levels (31 kg/m² vs. 27 kg/m²; p < 0.01) and lower cardiac troponin I (9 pg/ml vs. 15 pg/ml; p = 0.02). In addition, these patients were less frequently prescribed diuretics and beta-blockers. No differences in quality of life, heart failure related symptoms and the primary and secondary outcomes were observed between these groups. These observations were confirmed for NT-proBNP.

Conclusion

Among the patients with clinically diagnosed HFpEF, those with low BNP are strikingly similar to those with elevated BNP levels, except for BMI, which was significantly higher in these patients.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-016-0816-8) contains supplementary material, which is available to authorized users.     

Treatment of pulmonary arterial hypertension in congenital heart disease in Singapore versus the Netherlands: age exceeds ethnicity in influencing clinical outcome

Background

Advanced treatment of pulmonary arterial hypertension (PAH) in congenital heart disease (CHD) is increasingly applied worldwide following the—mainly Western world based—international PAH-CHD guidelines. However, studies comparing clinical presentation and outcome after the initiation of PAH-specific treatment are lacking. We aimed to analyse this in a Singaporean and Dutch cohort of PAH-CHD patients.

Methods

Adult CHD patients starting PAH-specific therapy, enrolled in two nationwide registries, were analysed. Patients received phosphodiesterase-type-5 inhibitors, endothelin receptor antagonists, or a combination. Change in six-minute walk test (6MWT) during follow-up was analysed using linear mixed model analysis. Determinants for mortality were assessed using Cox proportional hazard analyses.

Results

A total of 74 patients, 45 Dutch (mean age 47?±?14 years) and 29 Singaporean (mean age 41?±?14 years) were analysed. Despite a lower 6MWT (312 versus 395 metres, p?=?0.01) and peak VO₂ (35 versus 49?% of predicted, p?=?0.01) at baseline in Singaporean patients, the treatment effect was similar in the two populations. Age at initiation of therapy (per 5 year lower age, β?=?+?4.5, p?=?0.017) was the strongest predictor of improvement in exercise capacity, corrected for ethnicity, baseline 6MWT, sex and CHD defect.

Conclusions

Patients from Singapore had a worse clinical performance at baseline compared with the PAH-CHD patients from the Netherlands. No relation between ethnicity and improvement in 6MWT after PAH-specific therapy was found. Age at initiation of PAH-specific therapy was the strongest predictor of treatment efficacy and mortality, emphasising the need for early initiation of treatment in these patients.

     

Out-of-hospital cardiac arrest: the prospect of E-CPR in the Maastricht region

Aim

The current outcome of out-of-hospital cardiac arrest (OHCA) patients in the Maastricht region was analysed with the prospect of implementing extracorporeal cardiopulmonary resuscitation (E-CPR).

Methods

A retrospective analysis of adult patients who were resuscitated for OHCA during a 24-month period was performed.

Results

195 patients (age 66 [57–75] years, 82 % male) were resuscitated for OHCA by the emergency medical services and survived to admission at the emergency department. Survival to hospital discharge was 46.2 %. Notable differences between non-survivors and survivors were observed and included: age (70 [58–79] years) vs. (63 [55–72] years, p = 0.01), chronic heart failure (18 vs. 7 %, p = 0.02), shockable rhythm (67 vs. 99 %, p < 0.01), and return of spontaneous circulation (ROSC) at departure from the site of the arrest (46 vs. 99 %, p < 0.01) and on arrival to the emergency department (43 vs. 98 %, p < 0.01), respectively. Acute coronary syndrome was diagnosed in 32 % of non-survivors vs. 59 % among survivors, p < 0.01. Therapeutic hypothermia was provided in non-survivors (20 %) vs. survivors (43 %), p < 0.01. Percutaneous coronary intervention (PCI) was performed in 14 % of non-survivors while 52 % of survivors received PCI (p < 0.01). No statistical significance was observed in terms of gender, witnessed arrest, bystander CPR, or automated external defibrillator deployed among the cohort. At hospital discharge, moderately severe neurological disability was present in six survivors.

Conclusion

These observations are compatible with the notion that a shockable rhythm, ROSC, and post-arrest care improve survival outcome. Potentially, initiating E-CPR in the resuscitation phase in patients with a shockable rhythm and no ROSC might serve as a bridge to definite treatment and improve survival outcome.     

Generic reclassification and species boundaries in the rediscovered freshwater mussel ‘<Emphasis Type="Italic">Quadrula’ mitchelli</Emphasis> (Simpson in Dall, 1896)

The Central Texas endemic freshwater mussel, Quadrula mitchelli (Simpson in Dall, 1896), had been presumed extinct until relict populations were recently rediscovered. To help guide ongoing and future conservation efforts focused on Q. mitchelli we set out to resolve several uncertainties regarding its evolutionary history, specifically its unknown generic position and untested species boundaries. We designed a molecular matrix consisting of two loci (cytochrome c oxidase subunit I and internal transcribed spacer I) and 57 terminal taxa to test the generic position of Q. mitchelli using Bayesian inference and maximum likelihood phylogenetic reconstruction. We also employed two Bayesian species validation methods to test five a priori species models (i.e. hypotheses of species delimitation). Our study is the first to test the generic position of Q. mitchelli and we found robust support for its inclusion in the genus Fusconaia. Accordingly, we introduce the binomial, Fusconaia mitchelli comb. nov., to accurately represent the systematic position of the species. We resolved F. mitchelli individuals in two well supported and divergent clades that were generally distinguished as distinct species using Bayesian species validation methods, although alternative hypotheses of species delineation were also supported. Despite strong evidence of genetic isolation within F. mitchelli, we do not advocate for species-level status of the two clades as they are allopatrically distributed and no morphological, behavioral, or ecological characters are known to distinguish them. These results are discussed in the context of the systematics, distribution, and conservation of F. mitchelli.     

Landscape genetics of a tropical rescue pollinator

Pollination services are increasingly threatened by the loss and modification of natural habitats, posing a risk to the maintenance of both native plant biodiversity and agricultural production. In order to safeguard pollination services, it is essential to examine the impacts of habitat degradation on the population dynamics of key pollinators and identify potential “rescue pollinators” capable of persisting in these human-altered landscapes. Using a landscape genetic approach, we assessed the impact of landscape structure on genetic differentiation in the widely-distributed tropical stingless bee Trigona spinipes (Apidae: Meliponini) across agricultural landscape mosaics composed of coffee plantations and Atlantic forest fragments in southeastern Brazil. We genotyped 115 bees at 16 specific and highly polymorphic microsatellite loci, developed using next-generation sequencing. Our results reveal that T. spinipes is capable of dispersing across remarkably long distances, as we did not find genetic differentiation across a 200 km range, nor fine-scale spatial genetic structure. Furthermore, gene flow was not affected by forest cover, land cover, or elevation, indicating that reproductive individuals are able to disperse well through agricultural landscapes and across altitudinal gradients. We also found evidence of a recent population expansion, suggesting that this opportunistic stingless bee is capable of colonizing degraded habitats. Our results thus suggest that T. spinipes can persist in heavily-altered landscapes and can be regarded as a rescue pollinator, potentially compensating for the decline of other native pollinators in degraded tropical landscapes.