Correction: Popular interest in vertebrates does not reflect extinction risk and is associated with bias in conservation investment.

[This corrects the article DOI: 10.1371/journal.pone.0203694.].

Robust entropy requires strong and balanced excitatory and inhibitory synapses.

It is widely appreciated that balanced excitation and inhibition are necessary for proper function in neural networks. However, in principle, balance could be achieved by many possible configurations of excitatory and inhibitory synaptic strengths and relative numbers of excitatory and inhibitory neurons. For instance, a given level of excitation could be balanced by either numerous inhibitory neurons with weak synapses or a few inhibitory neurons with strong synapses. Among the continuum of different but balanced configurations, why should any particular configuration be favored? Here, we address this question in the context of the entropy of network dynamics by studying an analytically tractable network of binary neurons. We find that entropy is highest at the boundary between excitation-dominant and inhibition-dominant regimes. Entropy also varies along this boundary with a trade-off between high and robust entropy: weak synapse strengths yield high network entropy which is fragile to parameter variations, while strong synapse strengths yield a lower, but more robust, network entropy. In the case where inhibitory and excitatory synapses are constrained to have similar strength, we find that a small, but non-zero fraction of inhibitory neurons, like that seen in mammalian cortex, results in robust and relatively high entropy.

Popular interest in vertebrates does not reflect extinction risk and is associated with bias in conservation investment.

The interrelationship between public interest in endangered species and the attention they receive from the conservation community is the 'flywheel' driving much effort to abate global extinction rates. Yet big international conservation non-governmental organisations have typically focused on the plight of a handful of appealing endangered species, while the public remains largely unaware of the majority. We quantified the existence of bias in popular interest towards species, by analysing global internet search interest in 36,873 vertebrate taxa. Web search interest was higher for mammals and birds at greater risk of extinction, but this was not so for fish, reptiles and amphibians. Our analysis reveals a global bias in popular interest towards vertebrates that is undermining incentives to invest financial capital in thousands of species threatened with extinction. Raising the popular profile of these lesser known endangered and critically endangered species will generate clearer political and financial incentives for their protection.

Programmatic access to bioinformatics tools from EMBL-EBI update: 2017.

Since 2009 the EMBL-EBI provides free and unrestricted access to several bioinformatics tools via the user's browser as well as programmatically via Web Services APIs. Programmatic access to these tools, which is fundamental to bioinformatics, is increasingly important as more high-throughput data is generated, e.g. from proteomics and metagenomic experiments. Access is available using both the SOAP and RESTful approaches and their usage is reviewed regularly in order to ensure that the best, supported tools are available to all users. We present here an update describing the latest enhancement to the Job Dispatcher APIs as well as the governance under it.

Uncatalysed diaryldiazo cyclopropanations on bicyclic lactams: access to annulated prolines.

The uncatalysed cycloaddition of substituted diaryldiazo compounds onto bicyclic unsaturated lactams derived from pyroglutamic acid efficiently leads to highly functionalised azatricyclononanes. The products are readily elaborated to deprotected pyroglutamate derivatives, providing rapid access to conformationally constrained amino acids and their analogues. Preliminary assessment of antibacterial activity against one Gram positive and one Gram negative organism indicated high levels of efficacy in some cases.

The EBI Search engine: providing search and retrieval functionality for biological data from EMBL-EBI.

The European Bioinformatics Institute (EMBL-EBI-https://www.ebi.ac.uk) provides free and unrestricted access to data across all major areas of biology and biomedicine. Searching and extracting knowledge across these domains requires a fast and scalable solution that addresses the requirements of domain experts as well as casual users. We present the EBI Search engine, referred to here as 'EBI Search', an easy-to-use fast text search and indexing system with powerful data navigation and retrieval capabilities. API integration provides access to analytical tools, allowing users to further investigate the results of their search. The interconnectivity that exists between data resources at EMBL-EBI provides easy, quick and precise navigation and a better understanding of the relationship between different data types including sequences, genes, gene products, proteins, protein domains, protein families, enzymes and macromolecular structures, together with relevant life science literature.

The EMBL-EBI bioinformatics web and programmatic tools framework.

Since 2009 the EMBL-EBI Job Dispatcher framework has provided free access to a range of mainstream sequence analysis applications. These include sequence similarity search services (https://www.ebi.ac.uk/Tools/sss/) such as BLAST, FASTA and PSI-Search, multiple sequence alignment tools (https://www.ebi.ac.uk/Tools/msa/) such as Clustal Omega, MAFFT and T-Coffee, and other sequence analysis tools (https://www.ebi.ac.uk/Tools/pfa/) such as InterProScan. Through these services users can search mainstream sequence databases such as ENA, UniProt and Ensembl Genomes, utilising a uniform web interface or systematically through Web Services interfaces (https://www.ebi.ac.uk/Tools/webservices/) using common programming languages, and obtain enriched results with novel visualisations. Integration with EBI Search (https://www.ebi.ac.uk/ebisearch/) and the dbfetch retrieval service (https://www.ebi.ac.uk/Tools/dbfetch/) further expands the usefulness of the framework. New tools and updates such as NCBI BLAST+, InterProScan 5 and PfamScan, new categories such as RNA analysis tools (https://www.ebi.ac.uk/Tools/rna/), new databases such as ENA non-coding, WormBase ParaSite, Pfam and Rfam, and new workflow methods, together with the retirement of depreciated services, ensure that the framework remains relevant to today's biological community.

Using EMBL-EBI Services via Web Interface and Programmatically via Web Services.

The European Bioinformatics Institute (EMBL-EBI) provides access to a wide range of databases and analysis tools that are of key importance in bioinformatics. As well as providing Web interfaces to these resources, Web Services are available using SOAP and REST protocols that enable programmatic access to our resources and allow their integration into other applications and analytical workflows. This unit describes the various options available to a typical researcher or bioinformatician who wishes to use our resources via Web interface or programmatically via a range of programming languages.

Bis{(Z)-[(E)-2-(pyridin-2-yl-methyl-idene)hydrazin-1-yl-idene][(pyridin-2-yl)methyl-sulfan-yl]methane-thiol-ato}nickel(II).

The title compound, [Ni(C13H11N4S2)2], was obtained by the reaction of S-2-picolyldi-thio-carbazate and pyridine-2-carbaldehyde with nickel(II) acetate. The Ni(II) atom is located on a twofold rotation axis and is bonded to four N atoms at distances of 2.037 (8) and 2.109 (9) Å, and to two S atoms at a distance of 2.406 (3) Å, leading to a distorted octa-hedral coordination. The angle between the mean planes of the coordinating moieties of the two symmetry-related tridentate ligands is 83.3 (2)°. In the crystal, complex mol-ecules are linked by weak C-H⋯S hydrogen bonds, π-π inter-actions between the pyridine rings [centroid-centroid distance = 3.775 (9) Å] and C-H⋯π inter-actions. The hydrogen-bonding inter-actions lead to the formation of layers parallel to (010); π-π inter-actions link these layers into a three-dimensional network.

Analysis Tool Web Services from the EMBL-EBI.

Since 2004 the European Bioinformatics Institute (EMBL-EBI) has provided access to a wide range of databases and analysis tools via Web Services interfaces. This comprises services to search across the databases available from the EMBL-EBI and to explore the network of cross-references present in the data (e.g. EB-eye), services to retrieve entry data in various data formats and to access the data in specific fields (e.g. dbfetch), and analysis tool services, for example, sequence similarity search (e.g. FASTA and NCBI BLAST), multiple sequence alignment (e.g. Clustal Omega and MUSCLE), pairwise sequence alignment and protein functional analysis (e.g. InterProScan and Phobius). The REST/SOAP Web Services (http://www.ebi.ac.uk/Tools/webservices/) interfaces to these databases and tools allow their integration into other tools, applications, web sites, pipeline processes and analytical workflows. To get users started using the Web Services, sample clients are provided covering a range of programming languages and popular Web Service tool kits, and a brief guide to Web Services technologies, including a set of tutorials, is available for those wishing to learn more and develop their own clients. Users of the Web Services are informed of improvements and updates via a range of methods.

Synthesis of new bulky bis(pyrazolyl)methane carboxylate (heteroscorpionate) ligands and their complexes with iron, manganese and nickel.

Three new sterically demanding ligands based on the bispyrazolylacetic acid motif have been prepared and complexes with Fe(II), Fe(III), Ni(II) and Mn(II) have been synthesised and characterised. Single crystal X-ray structures are included for two of the ligands in the protonated form and ten other complexes. Additionally, a new general route to amide derivatives has been established, a range of amide derivatives synthesised and their coordination chemistry investigated. Only one metal complex was synthesised from the amide ligands, and was bound via the hydroxylamine groups in preference to the pyrazole and carboxylate donor set.

PSI-Search: iterative HOE-reduced profile SSEARCH searching.

UNLABELLED: Iterative similarity searches with PSI-BLAST position-specific score matrices (PSSMs) find many more homologs than single searches, but PSSMs can be contaminated when homologous alignments are extended into unrelated protein domains-homologous over-extension (HOE). PSI-Search combines an optimal Smith-Waterman local alignment sequence search, using SSEARCH, with the PSI-BLAST profile construction strategy. An optional sequence boundary-masking procedure, which prevents alignments from being extended after they are initially included, can reduce HOE errors in the PSSM profile. Preventing HOE improves selectivity for both PSI-BLAST and PSI-Search, but PSI-Search has ~4-fold better selectivity than PSI-BLAST and similar sensitivity at 50% and 60% family coverage. PSI-Search is also produces 2- for 4-fold fewer false-positives than JackHMMER, but is ~5% less sensitive. AVAILABILITY AND IMPLEMENTATION: PSI-Search is available from the authors as a standalone implementation written in Perl for Linux-compatible platforms. It is also available through a web interface (www.ebi.ac.uk/Tools/sss/psisearch) and SOAP and REST Web Services (www.ebi.ac.uk/Tools/webservices).

Spirocyclic systems derived from pyroglutamic acid.

The synthesis and likely conformational structure of rigid spirocyclic bislactams and lactam-lactones derived from pyroglutamic acid, and their suitability as lead structures for applications in drug development programmes using cheminformatic analysis, has been investgated.

(3R,4R,5R)-5-(Acetamido-meth-yl)-N-benzyl-3,4-dihy-droxy-tetra-hydro-furan-3-carboxamide.

X-ray crystallographic analysis with Cu Kα radiation established the relative configurations of the stereogenic centers in the title compound, C(15)H(20)N(2)O(5), and clarified mechanistic ambiguities in the synthesis. The conformation of the five-membered ring approximates twisted, about a C-O bond. The absolute configuration of this carbon-branched dipeptide isostere was known based on the use of d-ribose as the starting material. Refinement of the Flack parameter gave an ambiguous result but the refined Hooft parameter is in agreement with the assumed (d-ribose) absolute structure. The crystal structure consists of N-H⋯O and O-H⋯O hydrogen-bonded bi-layers, with the terminal methyl and phenyl groups forming a hydro-phobic inter-layer inter-face. Some weak C-H⋯O inter-actions are also present.

Cryophotolysis of a caged oxygen compound for use in low temperature biological studies.

Mechanistic investigations of biological enzymatic processes require controlled initiation and monitoring of catalytic reactions. A well-known technique to trap and observe reaction intermediates building up along a reaction pathway is the use of low temperature conditions. Here, we report a kinetically competent system for the release of molecular oxygen at cryogenic temperature, using a cobalt-based caged oxygen molecule, (micro-peroxo)(micro-hydroxo)bis[bis(bipyridyl)cobalt(III)] nitrate. Cryophotolysis of this compound was induced using 266 nm laser light and monitored by absorption microspectrophotometry. Furthermore, to verify that photo-fragmentation was accompanied by release of the active caged molecule, the production of dioxygen during cryophotolysis was directly visualized. This work lays the foundations for the use of low temperature reaction triggering as a tool to prolong the lifetime of normally unstable intermediate states in oxygen-dependent enzymes.

Multimetallic arrays: symmetrical bi-, tri- and tetrametallic complexes based on the group 10 metals and the functionalisation of gold nanoparticles with nickel-phosphine surface units.

Homobimetallic complexes of nickel, palladium and platinum, [(L2M)2(S2CNC4H8NCS2)]2+, are formed on reaction of the piperazine bis(dithiocarbamate) linker, KS2CNC4H8NCS2K, with [MCl2L2] (M=Ni, L2=dppe, dppf; M=Pd, L2=dppf; M=Pt, L=PEt3, PMePh2, PPh3, L2=dppf). [{Pd(C,N-C6H4CH2NMe2)}2(S2CNC4H8NCS2)] can be obtained in the same way. On reaction of [MCl2L2] (M=Pd, Pt) with the zwitterion S2CNC4H8NH2, a symmetrisation process occurs to yield a mixture of the complexes [M(S2CNC4H8NH2)L2]2+ and [(L2M)2(S2CNC4H8NCS2)]2+. However, the monometallic complexes [L2Ni(S2CNC4H8NH2)]2+ (L2=dppe, dppf) and [(L2Ni)2(S2CNC4H8NCS2)]2+ can be prepared without ready symmetrisation. Starting from the previously reported [(dppm)Ru(S2CNC4H8NH2)]2+, the heterotrimetallic products [(dppm)Ru(S2CNC4H8NCS2)M(dppf)]2+ (M=Pd, Pt) can be prepared without symmetrisation occurring. The crystal structures of five complexes are reported. The metalla-dithiocarbamate complexes [L2Ni(S2CNC4H8NCS2)] (L2=dppe, dppf) were used to functionalise the surface of gold nanoparticles by the displacement of a citrate shell to yield NiAu and FeNiAu materials.

Bifunctional dithiocarbamates: a bridge between coordination chemistry and nanoscale materials.

A dithiocarbamate-based methodology is employed to prepare linked heteromultimetallic complexes and then further exploited in the surface functionalisation of gold nanoparticles.

Stable crystalline annulated diaminocarbenes: coordination with rhodium(I), iridium(I) and catalytic hydroformylation studies.

Stable annulated diaminocarbene ligands 7,9-bis(2,4,6-trimethylphenyl)-6b,9a-dihydroace naphtha[1,2-d]imidazolin-2-ylidene and 7,9-bis(2,6-diisopropylphenyl)-6b,9a-dihydroacenaphtho[1,2-d]imidazolin-2-ylidene; designated as (BIAN-SIMes, 5a,) and (BIAN-SIPr, 5b), respectively, have been prepared. The base dependent decomposition of imidazolinium salts via ring opening at the backbone was also observed. The corresponding rhodium(I) and iridum(I) complexes (4-1,5-COD)M(BIAN-SIMes)Cl and (4-1,5-COD)M(BIAN-SIPr)Cl; M= Rh (6a, 6b) and Ir (7a, 7b) have been synthesised by the reaction of free carbene with [M(4-1,5-COD)(-Cl)]2; where M= Rh, Ir. The cationic Ir(I) complexes [(4-1,5-COD)Ir(BIAN-SIMes)Py]BF4 8a and [(4-1,5-COD)Ir(BIAN -SIPr)Py]PF6 8b have also been synthesised. Compounds 4b, 5a, 6a, 6b, 7b and 8b have been structurally characterised. The catalytic activities for the rhodium(I) complexes 6a and 6b were evaluated for the hydroformylation of 1-octene.

Catalytic enantioselective intermolecular hydroacylation: rhodium-catalyzed combination of beta-S-aldehydes and 1,3-disubstituted allenes.

A rhodium(I) catalyst incorporating the Me-DuPhos ligand promotes enantioselective intermolecular hydroacylation between beta-S-aldehydes and 1,3-disubstituted allenes. The nonconjugated enone products are obtained in good yields and with high enantioselectivities.

Enantiomerically pure bicyclo[3.3.1]nona-2,6-diene as the sole source of enantioselectivity in BIPHEP-Rh asymmetric hydrogenation.

In situ resolution of the rapidly racemising diphosphine BIPHEP and its relatives with the cationic Rh complex of (S,S)-bicyclonona-2,6-diene permits the asymmetric hydrogenation of dehydroamino esters.