A collection of open source applications for mass spectrometry data mining

We present several bioinformatics applications for the identification and quantification of phosphoproteome components by MS. These applications include a front‐end graphical user interface that combines several Thermo RAW formats to MASCOT? Generic Format extractors (EasierMgf), two graphical user interfaces for search engines OMSSA and SEQUEST (OmssaGui and SequestGui), and three applications, one for the management of databases in FASTA format (FastaTools), another for the integration of search results from up to three search engines (Integrator), and another one for the visualization of mass spectra and their corresponding database search results (JsonVisor). These applications were developed to solve some of the common problems found in proteomic and phosphoproteomic data analysis and were integrated in the workflow for data processing and feeding on our LymPHOS database. Applications were designed modularly and can be used standalone. These tools are written in Perl and Python programming languages and are supported on Windows platforms. They are all released under an Open Source Software license and can be freely downloaded from our software repository hosted at GoogleCode.     

The role of the interactome in the maintenance of deleterious variability in human populations

Recent genomic projects have revealed the existence of an unexpectedly large amount of deleterious variability in the human genome. Several hypotheses have been proposed to explain such an apparently high mutational load. However, the mechanisms by which deleterious mutations in some genes cause a pathological effect but are apparently innocuous in other genes remain largely unknown. This study searched for deleterious variants in the 1,000 genomes populations, as well as in a newly sequenced population of 252 healthy Spanish individuals. In addition, variants causative of monogenic diseases and somatic variants from 41 chronic lymphocytic leukaemia patients were analysed. The deleterious variants found were analysed in the context of the interactome to understand the role of network topology in the maintenance of the observed mutational load. Our results suggest that one of the mechanisms whereby the effect of these deleterious variants on the phenotype is suppressed could be related to the configuration of the protein interaction network. Most of the deleterious variants observed in healthy individuals are concentrated in peripheral regions of the interactome, in combinations that preserve their connectivity, and have a marginal effect on interactome integrity. On the contrary, likely pathogenic cancer somatic deleterious variants tend to occur in internal regions of the interactome, often with associated structural consequences. Finally, variants causative of monogenic diseases seem to occupy an intermediate position. Our observations suggest that the real pathological potential of a variant might be more a systems property rather than an intrinsic property of individual proteins.     

Six new non-native ants (Formicidae) in the Canary Islands and their possible impacts

Biological invasions are one of the main causes of biodiversity loss, especially on oceanic islands. Ants are among the most damaging pests in the world. After systematic sampling of more than 1,000 localities in the Canary Islands, six new exotic ant species are reported for the first time: Pheidole bilimeki (Myrmicinae), Pheidole navigans (Myrmicinae), Strumigenys membranifera (Myrmicinae), Brachymyrmex cordemoyi (Formicinae), Tapinoma darioi (Dolichoderinae) and Technomyrmex pallipes (Dolichoderinae). Moreover, another two recently reported species have been genetically confirmed. Morphological and genetic data were analysed to confirm the identity of the new records. For each species, information regarding identification, distribution, global invasive records and possible impacts is given. The arrival of these species may endanger local biodiversity.     

Structural determinants stabilizing the axial channel of ClpP for substrate translocation

Acyldepsipeptides (ADEPs) antibiotics bind to Escherichia coli ClpP mimicking the interactions that the IGL/F loops in ClpA or ClpX ATPases establish with the hydrophobic pockets surrounding the axial pore of the tetradecamer that the protease forms. ADEP binding induces opening of the gates blocking the axial channel of ClpP and allowing protein substrates to be translocated and hydrolysed in the degradation chamber. To identify the structural determinants stabilizing the open conformation of the axial channel for efficient substrate translocation, we constructed ClpP variants with amino acid substitutions in the N‐terminal region that forms the axial gates. We found that adoption of a β‐hairpin loop by this region and the integrity of the hydrophobic cluster at the base of this loop are necessary elements for the axial gate to efficiently translocate protein substrates. Analysis of ClpP variants from Bacillus subtilis suggested that the identified structural requirements of the axial channel for efficient translocation are conserved between Gram‐positive and Gram‐negative bacteria. These findings provide mechanistic insights into the activation of ClpP by ADEPs as well as the gating mechanism of the protease in the context of the ClpAP and ClpXP complexes.     

Cell therapy with autologous mesenchymal stromal cells in post-traumatic syringomyelia

Background aims

Recently, clinical studies show that cell therapy with mesenchymal stromal cells (MSCs) improves the sequelae chronically established in paraplegic patients, being necessary to know which of them can obtain better benefit.

Effects of salinity on the CO<Subscript>2</Subscript> permeation across lipid bilayer for microalgae biofixation: a molecular dynamics study

The continuous threat of increasing CO₂ concentration in the atmosphere has altered the carbon balance of our planet causing global climate change. Biological fixation of atmospheric CO₂ by unicellular microorganisms such as microalgae is a promising technology pursued extensively by researchers as a means for carbon capture. The study aimed to provide an atomic level of study that will demonstrate the effect of the salinity on the mechanism of CO₂ absorption across microalgae lipid bilayer. Molecular dynamics simulations were utilized to calculate the free energies of CO₂ molecule as it permeates inside the microalgae cell. In thermodynamics, the transport process of a molecule can be demonstrated through its free energy gradient. Thus, calculating the free energies of CO₂ molecule across microalgae lipid bilayer can elucidate the mechanisms of permeation processes. Four microalgae lipid bilayer structures were constructed that contains 128-DPPC (dipalmitoylphosphatidylcholine) lipid bilayer with 3640 water molecules with different NaCl concentrations: 0, 3, 13, and 19 NaCl molecules which correspond to a salinity level of 0, 50, 200, and 300 mM, respectively. The cavity insertion Widom method was used to calculate the free energy of CO₂ molecule along the lipid bilayer. The results demonstrated that the salinity does not affect the free energies significantly, thus, it does not hamper CO₂ transport across microalgae lipid membrane.     

The primary structure of a chondrichthyan protamine: A new apparent contradiction in protamine evolution

We have determined the primary structure of protamine R3 from ratfish (Hydrolagus colliei), a species belonging to the order Chimaeriformes (an old phylogenetic line among the chondrichthyes). Protamine R3 contains 48 residues organized as follows: ARRRH SMKKK RKSVR RRKTR KNQRK RKNSL GRSFK (Q/A)HGFL KQPPR FRP. Comparison of this sequence with both protamine Z3 fromScyliorhinus canicula (a chondrichthyan) and typical protamines from bony fish generates an apparent contradiction: Two relatively close species (H. colhei andS. canicula, both chondichthyes) display different protamines, whereas species more distant in evolution (S. canicula and bony fish) contain very similar protamine molecules. We note that this is not an isolated case in the evolution of sperm nuclear basic proteins (SNBPs) and discuss the possible significance of this fact. Correspondence to: M. Chiva