Model complexes suggest certain S-state changes of the photosynthetic water-oxidation enzyme may involve an Mn(II)-Mn(III) transition

The ultraviolet-visible absorbance differences spectra of Mn(II,III) and Mn(III,III) oxo-bridged carboxylate complexes are reported. The difference spectra are remarkably similar to those of the photosynthetic water-oxidation enzyme complex reported by Dekker et al. [(1984) Biochim. Biophys. Acta 764, 301-309] which were interpreted as being due exclusively to Mn(II----IV) transitions. This result indicates that certain S-state changes of the enzyme complex may instead involve Mn(II----III) transitions, and that difference spectra alone cannot be used with confidence to assign the Mn oxidation state changes during water oxidation.     

Quantitative relationships between boron and mannitol concentrations in phloem exudates of Olea europaea leaves under contrasting boron supply conditions

Root exudates are implicated in the chemical defense of plants, but testing such hypotheses has been hindered by the difficulties of quantifying allelochemical concentrations in soil. Here we describe a new, simple method to quantify the dynamics of non-polar root exudates in soil. Novel soil probes were constructed using stainless steel wire inserted into polydimethylsiloxane (PDMS) tubing. Probes were inserted into soil for 24 h, removed and extracted, and analyzed by HPLC. Lipophilic thiophenes produced by roots of Tagetes and Rudbeckia species were chosen as candidate compounds to test the method. Probes recovered microgram quantities of the highly phytotoxic thiophenes 5-(3-buten-1-ynyl)-2,2′-bithienyl (BBT) and α-terthienyl per probe per day from the root zone of Tagetes patula, and distribution of thiophenes beneath plants was spatially and temporally heterogeneous. Flux-proportional sampling of soil provides a means to test hypotheses about the role of root exudates in plant–plant and other interactions.     

Decrypting distributed ledger design—taxonomy,classification and blockchain community evaluation

More than 1000 distributed ledger technology (DLT) systems raising $600 billion in investment in 2016 feature the unprecedented and disruptive potential of blockchain technology. A systematic and data-driven analysis, comparison and rigorous evaluation of the different design choices of distributed ledgers and their implications is a challenge. The rapidly evolving nature of the blockchain landscape hinders reaching a common understanding of the techno-socio-economic design space of distributed ledgers and the cryptoeconomies they support. To fill this gap, this paper makes the following contributions: (i) A conceptual architecture of DLT systems with which (ii) a taxonomy is designed and (iii) a rigorous classification of DLT systems is made using real-world data and wisdom of the crowd. (iv) A DLT design guideline is the end result of applying machine learning methodologies on the classification data. Compared to related work and as defined in earlier taxonomy theory, the proposed taxonomy is highly comprehensive, robust, explanatory and extensible. The findings of this paper can provide new insights and better understanding of the key design choices evolving the modeling complexity of DLT systems, while identifying opportunities for new research contributions and business innovation.

     

Conformational requirements for molecular recognition of acetylcholine receptor main immunogenic region (MIR) analogues by monoclonal anti-MIR antibody: A two-dimensional nuclear magnetic resonance and molecular dynamics approach

The conformational properties of two [D -A⁷⁰, A⁷⁶] and [Aib⁷⁰, A⁷⁶] analogues of the α67–76 Torpedo acetylcholine receptor fragment, with low binding capacity for the anti main immunogenic region (MIR) antibodies, were studied in DMSO by two-dimensional nmr techniques and molecular dynamics simulations. The results were compared to the free and bound conformations of the [A⁷⁶] analogue, which has twice more affinity for the anti-MIR monoclonal antibody 6 (mAb6), than the natural Torpedo sequence. It appeared that a single substitution of the A⁷⁰, at a crucial position, by the D -A⁷⁰ or Aib⁷⁰, could modify completely the conformational behavior of the peptide and reduced its recognition by the anti-MIR antibody. The WNPADY rigid structure at the N-terminal part was essential for antibody recognition. The adjacent more flexible C-terminal sequence (GGIK) gives additional stability to the monoclonal antibody–peptide complex probably due to an adequate orientation of the peptide side chains in the complex, by setting them in close contact with the antibody. © 1993 John Wiley & Sons, Inc.     

Application of the fourth universal definition of myocardial infarction in clinical practice

Abstract

Purpose: The Fourth Universal Definition of Myocardial Infarction (MI) has highlighted the different pathophysiological mechanisms that may lead to ischaemic and non-ischaemic myocardial injury and has emphasised that the diagnosis of myocardial infarction requires the presence of acute myocardial ischaemia in the setting of acute myocardial injury. This case based review intends to illustrate basic principles on how to apply this new, revised definition in clinical practice.

Methods and Results: The distinction between different types of MIs (type 1 or type 2) and the delineation of MI from acute non-ischaemic myocardial injury may be challenging in individual patients, which is illustrated by presenting and discussing real-life routine cases.

Conclusions: Type 1?MI is a consequence of coronary plaque rupture or erosion with intracoronary thrombus formation that is usually apparent on coronary angiography. Plausible triggering mechanisms causing myocardial oxygen supply/demand mismatch must be identified for the diagnosis of type 2?MI and its treatment should focus initially on management of the underlying disease attributable to acute myocardial ischaemia.     

A simplified techno-economic model for the molecular pharming of antibodies

By the end of 2017, the Food and Drug Administration had approved a total of 77 therapeutic monoclonal antibodies (mAbs), most of which are still manufactured today. Furthermore, global sales of mAbs topped $90 billion in 2017 and are projected to reach $125 billion by 2020. The mAbs approved for human therapy are mostly produced using Chinese hamster ovary (CHO) cells, which require expensive infrastructure for production and purification. Molecular pharming in plants is an alternative approach with the benefits of lower costs, greater scalability, and intrinsic safety. For some platforms, the production cycle is also much quicker. But do these advantages really stack up in economic terms? Earlier techno-economic evaluations have focused on specific platforms or processes and have used different methods, making direct comparisons challenging and the overall benefits of molecular pharming difficult to gauge. Here, we present a simplified techno-economic model for the manufacturing of mAbs, which can be applied to any production platform by focusing on the most important factors that determine the efficiency and cost of bulk drug manufacturing. This model develops economic concepts to identify variables that can be used to achieve cost savings by simultaneously modeling the dynamic costs of upstream production at different scales and the corresponding downstream processing costs for different manufacturing modes (sequential, serial, and continuous). The use of simplified models will help to achieve meaningful comparisons between diverse manufacturing technologies.     

Species co-occurrence: the case of congeneric species and a causal approach to patterns of species association

Aim To test whether congeneric species are significantly associated with one another in space, either positively or negatively. Also, to provide a framework for a causal investigation of co‐occurrence patterns by a parallel comparison of interactions in geographical and ecological data matrices. Location For the analysis of congeneric species’ co‐occurrences we used 30 matrices covering a wide range of taxa and geographical areas, while for the causal investigation we used the distribution of 50 terrestrial isopod species on 20 islands and 264 sampling stations in the central Aegean archipelago, as well as a number of ecological variables for each sampling station. Methods We developed a software program (cooc ) that incorporates the species‐by‐species approach to co‐occurrence analysis using EcoSim's output of prior null model analysis of co‐occurrence. We describe this program in detail, and use it to investigate one of the most common assembly rules, namely, the decreased levels of co‐occurrence among congeneric species pairs. For the causal analysis, we proceed likewise, cross‐checking the results from the geographical and the ecological matrices. There is only one possible combination of results that can support claims for direct competition among species. Results We do not get any strong evidence for widespread competition among congeneric species, while most communities investigated do not show significant patterns of species associations. The causal analysis suggests that the principal factors behind terrestrial isopod species associations are of historical nature. Some exceptional cases are also discussed. Main conclusions Presence/absence data for a variety of taxa do not support the assembly rule that congeneric species are under more intense competition compared to less related species. Also, these same data do not suggest strong interactions among species pairs, regardless of taxonomic status. When significant species associations can be seen in such matrices, they mainly reflect the effects of history or of habitat requirements.