The innate immunity of a marine red alga involves oxylipins from both the eicosanoid and octadecanoid pathways

The oxygenated derivatives of fatty acids, known as oxylipins, are pivotal signaling molecules in animals and terrestrial plants. In animal systems, eicosanoids regulate cell differentiation, immune responses, and homeostasis. In contrast, terrestrial plants use derivatives of C18 and C16 fatty acids as developmental or defense hormones. Marine algae have emerged early in the evolution of eukaryotes as several distinct phyla, independent from the animal and green-plant lineages. The occurrence of oxylipins of the eicosanoid family is well documented in marine red algae, but their biological roles remain an enigma. Here we address the hypothesis that they are involved with the defense mechanisms of the red alga Chondrus crispus. By investigating its association with a green algal endophyte Acrochaete operculata, which becomes invasive in the diploid generation of this red alga, we showed that (1) when challenged by pathogen extracts, the resistant haploid phase of C. crispus produced both C20 and C18 oxylipins, (2) elicitation with pathogen extracts or methyl jasmonate activated the metabolism of C20 and C18 polyunsaturated fatty acids to generate hydroperoxides and cyclopentenones such as prostaglandins and jasmonates, and (3) C20 and C18 hydroperoxides as well as methyl jasmonate did induce shikimate dehydrogenase and Phe ammonialyase activities in C. crispus and conferred an induced resistance to the diploid phase, while inhibitors of fatty acid oxidation reduced the natural resistance of the haploid generation. The dual nature of oxylipin metabolism in this alga suggests that early eukaryotes featured both animal- (eicosanoids) and plant-like (octadecanoids) oxylipins as essential components of innate immunity mechanisms.     

Stochastic multi-attribute analysis (SMAA) as an interpretation method for comparative life-cycle assessment (LCA)

Purpose

Comparative life-cycle assessments (LCAs) today lack robust methods of interpretation that help decision makers understand and identify tradeoffs in the selection process. Truncating the analysis at characterization is misleading and existing practices for normalization and weighting may unwittingly oversimplify important aspects of a comparison. This paper introduces a novel approach based on a multi-criteria decision analytic method known as stochastic multi-attribute analysis for life-cycle impact assessment (SMAA-LCIA) that uses internal normalization by means of outranking and exploration of feasible weight spaces.

Methods

To contrast different valuation methods, this study performs a comparative LCA of liquid and powder laundry detergents using three approaches to normalization and weighting: (1) characterization with internal normalization and equal weighting, (2) typical valuation consisting of external normalization and weights, and (3) SMAA-LCIA using outranking normalization and stochastic weighting. Characterized results are often represented by LCA software with respect to their relative impacts normalized to 100 %. Typical valuation approaches rely on normalization references, single value weights, and utilizes discrete numbers throughout the calculation process to generate single scores. Alternatively, SMAA-LCIA is capable of exploring high uncertainty in the input parameters, normalizes internally by pair-wise comparisons (outranking) and allows for the stochastic exploration of weights. SMAA-LCIA yields probabilistic, rather than discrete comparisons that reflect uncertainty in the relative performance of alternatives.

Results and discussion

All methods favored liquid over powder detergent. However, each method results in different conclusions regarding the environmental tradeoffs. Graphical outputs at characterization of comparative assessments portray results in a way that is insensitive to magnitude and thus can be easily misinterpreted. Typical valuation generates results that are oversimplified and unintentionally biased towards a few impact categories due to the use of normalization references. Alternatively, SMAA-LCIA avoids the bias introduced by external normalization references, includes uncertainty in the performance of alternatives and weights, and focuses the analysis on identifying the mutual differences most important to the eventual rank ordering.

Conclusions

SMAA-LCIA is particularly appropriate for comparative LCAs because it evaluates mutual differences and weights stochastically. This allows for tradeoff identification and the ability to sample multiple perspectives simultaneously. SMAA-LCIA is a robust tool that can improve understanding of comparative LCA by decision or policy makers.     

Coexistence of Low Coral Cover and High Fish Biomass at Farquhar Atoll,Seychelles

We report a reef ecosystem where corals may have lost their role as major reef engineering species but fish biomass and assemblage structure is comparable to unfished reefs elsewhere around the world. This scenario is based on an extensive assessment of the coral reefs of Farquhar Atoll, the most southern of the Seychelles Islands. Coral cover and overall benthic community condition at Farquhar was poor, likely due to a combination of limited habitat, localized upwelling, past coral bleaching, and cyclones. Farquhar Atoll harbors a relatively intact reef fish assemblage with very large biomass (3.2 t ha⁻¹) reflecting natural ecological processes that are not influenced by fishing or other local anthropogenic factors. The most striking feature of the reef fish assemblage is the dominance by large groupers, snappers, and jacks with large (>1 m) potato cod (Epinephelus tukula) and marbled grouper (E. polyphekadion), commonly observed at many locations. Napoleon wrasse (Cheilinus undulatus) and bumphead parrotfish (Bolbometopon muricatum) are listed as endangered and vulnerable, respectively, but were frequently encountered at Farquhar. The high abundance and large sizes of parrotfishes at Farquhar also appears to regulate macroalgal abundance and enhance the dominance of crustose corallines, which are a necessary condition for maintenance of healthy reef communities. Overall fish biomass and biomass of large predators at Farquhar are substantially higher than other areas within the Seychelles, and are some of the highest recorded in the Indian Ocean. Remote islands like Farquhar Atoll with low human populations and limited fishing pressure offer ideal opportunities for understanding whether reefs can be resilient from global threats if local threats are minimized.     

Alteration in mitochondrial Ca<Superscript>2+</Superscript> uptake disrupts insulin signaling in hypertrophic cardiomyocytes

Background

Cardiac hypertrophy is characterized by alterations in both cardiac bioenergetics and insulin sensitivity. Insulin promotes glucose uptake by cardiomyocytes and its use as a substrate for glycolysis and mitochondrial oxidation in order to maintain the high cardiac energy demands. Insulin stimulates Ca²⁺ release from the endoplasmic reticulum, however, how this translates to changes in mitochondrial metabolism in either healthy or hypertrophic cardiomyocytes is not fully understood.

Results

In the present study we investigated insulin-dependent mitochondrial Ca²⁺ signaling in normal and norepinephrine or insulin like growth factor-1-induced hypertrophic cardiomyocytes. Using mitochondrion-selective Ca²⁺-fluorescent probes we showed that insulin increases mitochondrial Ca²⁺ levels. This signal was inhibited by the pharmacological blockade of either the inositol 1,4,5-triphosphate receptor or the mitochondrial Ca²⁺ uniporter, as well as by siRNA-dependent mitochondrial Ca²⁺ uniporter knockdown. Norepinephrine-stimulated cardiomyocytes showed a significant decrease in endoplasmic reticulum-mitochondrial contacts compared to either control or insulin like growth factor-1-stimulated cells. This resulted in a reduction in mitochondrial Ca²⁺ uptake, Akt activation, glucose uptake and oxygen consumption in response to insulin. Blocking mitochondrial Ca²⁺ uptake was sufficient to mimic the effect of norepinephrine-induced cardiomyocyte hypertrophy on insulin signaling.

Conclusions

Mitochondrial Ca²⁺ uptake is a key event in insulin signaling and metabolism in cardiomyocytes.

     

Inhibition of bromodomain and extra‐terminal proteins increases sensitivity to venetoclax in chronic lymphocytic leukaemia

The development of drugs able to target BTK, PI3k‐delta and BCL2 has dramatically improved chronic lymphocytic leukaemia (CLL) therapies. However, drug resistance to these therapies has already been reported due to non‐recurrent changes in oncogenic pathways and genes expression signatures. In this study, we investigated the cooperative role of the BCL2 inhibitor venetoclax and the BRD4 inhibitor JQ1. In particular, we found that JQ1 shows additional activity with venetoclax, in CLL cell lines and in ex vivo isolated primary CD19⁺ lymphocytes, arguing in favour of combination strategies. Lastly, JQ1 is also effective in venetoclax‐resistant CLL cell lines. Together, our findings indicated that the BET inhibitor JQ1 could be a promising therapy in CLL, both as first‐line therapy in combination with venetoclax and as second‐line therapy, after the emergence of venetoclax‐resistant clones.     

Environmental impacts of household goods in Europe: a process-based life cycle assessment model to assess consumption footprint

The International Journal of Life Cycle Assessment - Current patterns of household goods consumption generate relevant environmental pressures and impacts. Environmental impacts are not only...     

EspI regulates the ESX‐1 secretion system in response to ATP levels in Mycobacterium tuberculosis

The function of EspI, a 70 kDa protein in Mycobacterium tuberculosis, has remained unclear. Although EspI is encoded by a gene within the esx‐1 locus, in this study we clarify previous conflicting results and show that EspI is not essential for ESX‐1‐mediated secretion or virulence in M. tuberculosis. We also provide evidence that reduction of cellular ATP levels in wild‐type M. tuberculosis using the drug bedaquiline completely blocks ESX‐1‐mediated secretion. Remarkably, M. tuberculosis lacking EspI fails to exhibit this phenotype. Furthermore, mutagenesis of a highly conserved ATP‐binding motif in EspI renders M. tuberculosis incapable of shutting down ESX‐1‐mediated secretion during ATP depletion. Collectively these results show that M. tuberculosis EspI negatively regulates the ESX‐1 secretion system in response to low cellular ATP levels and this function requires the ATP‐binding motif. In light of our results the potential significance of EspI in ESX‐1 function during latent tuberculosis infection and reactivation is also discussed.     

Life in a fragment: Evolution of foraging strategies of translocated collared brown lemurs,Eulemur collaris,over an 18-year period

While the drivers of primate persistence in forest fragments have been often considered at the population level, the strategies to persist in these habitats have been little investigated at the individual or group level. Considering the rapid variation of fragment characteristics over time, longitudinal data on primates living in fragmented habitats are necessary to understand the key elements for their persistence. Since translocated animals have to cope with unfamiliar areas and face unknown fluctuations in food abundance, they offer the opportunity to study the factors contributing to successful migration between fragments. Here, we illustrated the evolution of the foraging strategies of translocated collared brown lemurs (Eulemur collaris) over an 18-year period in the Mandena Conservation Zone, south-east Madagascar. Our aim was to explore the ability of these frugivorous lemurs to adjust to recently colonized fragmented forests. Although the lemurs remained mainly frugivorous throughout the study period, over the years we identified a reduction in the consumption of leaves and exotic/pioneer plant species. These adjustments were expected in frugivorous primates living in a degraded area, but we hypothesize that they may also reflect the initial need to cope with an unfamiliar environment after the translocation. Since fragmentation is often associated with the loss of large trees and native vegetation, we suggest that the availability of exotic and/or pioneer plant species can provide an easy-to-access, nonseasonal food resource and be a key factor for persistence during the initial stage of the recolonization.