Diurnal fluctuations in chloroplast GSH redox state regulate susceptibility to oxidative stress and cell fate in a bloom‐forming diatom

Diatoms are one of the key phytoplankton groups in the ocean, forming vast oceanic blooms and playing a significant part in global primary production. To shed light on the role of redox metabolism in diatom's acclimation to light–dark transition and its interplay with cell fate regulation, we generated transgenic lines of the diatom Thalassiosira pseudonana that express the redox‐sensitive green fluorescent protein targeted to various subcellular organelles. We detected organelle‐specific redox patterns in response to oxidative stress, indicating compartmentalized antioxidant capacities. Monitoring the GSH redox potential (E_GSH) in the chloroplast over diurnal cycles revealed distinct rhythmic patterns. Intriguingly, in the dark, cells exhibited reduced basal chloroplast E_GSH but higher sensitivity to oxidative stress than cells in the light. This dark‐dependent sensitivity to oxidative stress was a result of a depleted pool of reduced glutathione which accumulated during the light period. Interestingly, reduction in the chloroplast E_GSH was observed in the light phase prior to the transition to darkness, suggesting an anticipatory phase. Rapid chloroplast E_GSH re‐oxidation was observed upon re‐illumination, signifying an induction of an oxidative signaling during transition to light that may regulate downstream metabolic processes. Since light–dark transitions can dictate metabolic capabilities and susceptibility to a range of environmental stress conditions, deepening our understanding of the molecular components mediating the light‐dependent redox signals may provide novel insights into cell fate regulation and its impact on oceanic bloom successions.     

Improved antimicrobial peptides based on acyl-lysine oligomers

We describe peptidomimetic oligomers that show rapid, nonhemolytic, broad-spectrum bactericidal properties in mice and do not induce the emergence of resistance. The oligomers contain acyl chains, which prevent the formation of stable secondary structure. This design appears advantageous over conventional antimicrobial peptides with respect to in vivo efficacy and safety, and may provide a convenient platform for the development of peptide antibiotics.     

Metabolic-network-driven analysis of bacterial ecological strategies

Background  

The growth-rate of an organism is an important phenotypic trait, directly affecting its ability to survive in a given environment. Here we present the first large scale computational study of the association between ecological strategies and growth rate across 113 bacterial species, occupying a variety of metabolic habitats. Genomic data are used to reconstruct the species' metabolic networks and habitable metabolic environments. These reconstructions are then used to investigate the typical ecological strategies taken by organisms in terms of two basic species-specific measures: metabolic variability - the ability of a species to survive in a variety of different environments; and co-habitation score vector - the distribution of other species that co-inhabit each environment.     

Metabolic innovations towards the human lineage

Background  

We describe a function-driven approach to the analysis of metabolism which takes into account the phylogenetic origin of biochemical reactions to reveal subtle lineage-specific metabolic innovations, undetectable by more traditional methods based on sequence comparison. The origins of reactions and thus entire pathways are inferred using a simple taxonomic classification scheme that describes the evolutionary course of events towards the lineage of interest. We investigate the evolutionary history of the human metabolic network extracted from a metabolic database, construct a network of interconnected pathways and classify this network according to the taxonomic categories representing eukaryotes, metazoa and vertebrates.     

IKAP/hELP1 downregulation in neuroblastoma cells causes enhanced cell adhesion mediated by contactin overexpression

A splicing mutation in the IKBKAP gene encoding the IKAP/hELP1 (IKAP) protein was found to be the major cause of Familial Dysautonomia (FD). This mutation affects both the normal development and survival of sensory and sympathetic neurons of the peripheral nervous system (PNS). To understand the FD phenotype it is important to study the specific role played by IKAP in developing and mature PNS neurons. We used the neuroblastoma SHSY5Y cell line, originated from neural crest adrenal tumor and simulated the FD phenotype by reducing IKAP expression with retroviral constructs. We observed that IKAP-downregulated cells formed cell clusters compared to control cells under regular culture conditions. We examined the ability of these cells to differentiate into mature neurons in the presence of laminin, an essential extracellular matrix for developing PNS neurons. We found that the cells showed reduced attachment to laminin, morphological changes and increased cell-to-cell adhesion resulting in cell aggregates. We identified Contactin as the adhesion molecule responsible for this phenotype. We show that Contactin expression is related to IKAP expression, suggesting that IKAP regulates Contactin levels for appropriate cell-cell adhesion that could modulate neuronal growth of PNS neurons during development.Key words: Familial Dysautonomia, IKAP/hELP1, neuronal differentiation, laminin, contactin, peripheral nervous system     

Stratification of co-evolving genomic groups using ranked phylogenetic profiles

Background  

Previous methods of detecting the taxonomic origins of arbitrary sequence collections, with a significant impact to genome analysis and in particular metagenomics, have primarily focused on compositional features of genomes. The evolutionary patterns of phylogenetic distribution of genes or proteins, represented by phylogenetic profiles, provide an alternative approach for the detection of taxonomic origins, but typically suffer from low accuracy. Herein, we present rank-BLAST, a novel approach for the assignment of protein sequences into genomic groups of the same taxonomic origin, based on the ranking order of phylogenetic profiles of target genes or proteins across the reference database.     

Emergence, development and diversification of the TGF- β signalling pathway within the animal kingdom

Background  

The question of how genomic processes, such as gene duplication, give rise to co-ordinated organismal properties, such as emergence of new body plans, organs and lifestyles, is of importance in developmental and evolutionary biology. Herein, we focus on the diversification of the transforming growth factor- β (TGF- β) pathway – one of the fundamental and versatile metazoan signal transduction engines.     

In vivo administration of BL-3050: highly stable engineered PON1-HDL complexes

Background  

Serum paraoxonase (PON1) is a high density lipoprotein (HDL)-associated enzyme involved in organophosphate (OP) degradation and prevention of atherosclerosis. PON1 comprises a potential candidate for in vivo therapeutics, as an anti-atherogenic agent, and for detoxification of pesticides and nerve agents. Because human PON1 exhibits limited stability, engineered, recombinant PON1 (rePON1) variants that were designed for higher reactivity, solubility, stability, and bacterial expression, are candidates for treatment. This work addresses the feasibility of in vivo administration of rePON1, and its HDL complex, as a potentially therapeutic agent dubbed BL-3050.