Journal of Biological Physics and Chemistry

Published by Collegium Basilea
Online ISSN: 1512-0856
Sizes of microbial fingerprints on an array of L = 1000 randomly chosen 12-mers with GC content m = 6. Every point represents a genome, the horizontal axis being the genome length. Fingerprint sizes for 105 real genomes (blue) are compared to the ones for random-sequence genomes with the same length and GC content (red) and for random genomes with the same length and uniform nucleotide distribution p A = p C = p G = p T = 1/4 (green). 
The same as Fig. 3 except that the GC content m = 8.
Intersections of fingerprints for 105 microbial genomes on an array of L = 1000 randomly chosen 12-mers with GC content m = 6. Intersection sizes for real genomes are shown against the intersection sizes for random genomes with the same length and GC content. For most of the genome pairs intersection sizes are close to the ones for random "genomes" (i.e. the points on the scatter plot are close to the solid line (x = y). Deviations are observed for closely related species; some of them are marked and listed in Table 1. 
The same as Fig. 5 but for GC content m = 8. 
Ratios, (size of intersection of positive probes)/(size of union of positive probes), for pairs of fingerprints of 105 microbial genomes on the given chip of L = 1000 and m = 6. Results for real genomes are shown against the ones for random "genomes" with the same length and GC content. Close relatives appear far from the rest of the points. Even the most similar pairs (strains of the same species; designated by their genome-list indices) can be distinguished. 
It is shown that the presence/absence pattern of 1000 random oligomers of length 12-13 in a bacterial genome is sufficiently characteristic to readily and unambiguously distinguish any known bacterial genome from any other. Even genomes of extremely closely-related organisms, such as strains of the same species, can be thus distinguished. One evident way to implement this approach in a practical assay is with hybridization arrays. It is envisioned that a single universal array can be readily designed that would allow identification of any bacterium that appears in a database of known patterns. We performed in silico experiments to test this idea. Calculations utilizing 105 publicly-available completely-sequenced microbial genomes allowed us to determine appropriate values of the test oligonucleotide length, n, and the number of probe sequences. Randomly chosen n-mers with a constant G + C content were used to form an in silico array and verify (a) how many n-mers from each genome would hybridize on this chip, and (b) how different the fingerprints of different genomes would be. With the appropriate choice of random oligomer length, the same approach can also be used to identify viral or eukaryotic genomes.
The leakage of tricresyl phosphate-containing engine lubricants into aircraft cabin air, either from worn or defective engine seals or under normal operating conditions, is a serious concern for both the health and safety of the cabin occupants, since the oil contains one to five percent tricresyl phosphate (TCP) esters, known neurotoxins. The exposure of pilots is a particular concern since their impairment can affect their safe operation of the aircraft. Mass spectrometric (MS)-based protocols for documenting exposures of individuals are described that entail a rapid purification of the TCP-modified plasma enzyme butyrylcholinesterase (BChE). Following protease digestion of BChE, the modified active site peptide is characterized by MS analysis. Approaches for identifying safer engine oil additives are also described. Some general comments regarding the necessity of improving the quality and safety of the cabin air supply are presented.
Many see modern science as having serious defects, intellectual, social, moral. Few see this as having anything to do with the philosophy of science. I argue that many diverse ills of modern science are a consequence of the fact that the scientific community has long accepted, and sought to implement, a bad philosophy of science, which I call standard empiricism. This holds that the basic intellectual aim is truth, the basic method being impartial assessment of claims to knowledge with respect to evidence. Standard empiricism is, however, untenable. Furthermore, the attempt to put it into scientific practice has many damaging consequences for science. The scientific community urgently needs to bring about a revolution in both the conception of science, and science itself. It needs to be acknowledged that the actual aims of science make metaphysical, value and political assumptions and are, as a result, deeply problematic. Science needs to try to improve its aims and methods as it proceeds. Standard empiricism needs to be rejected, and the more rigorous philosophy of science of aim-oriented empiricism needs to be adopted and explicitly implemented in scientific practice instead. The outcome would be the emergence of a new kind of science, of greater value in both intellectual and humanitarian terms.
We show that network motifs found in natural regulatory networks may also be found in an artificial regulatory network model created through a duplication / divergence process. It is shown that these network motifs exist more frequently in a genome created through the aforementioned process than in randomly generated genomes. These results are then compared with a network motif analysis of the gene expression networks of Escherichia Coli and Saccharomyces cerevisiae. In addition, it is shown that certain individual network motifs may arise directly from the duplication / divergence mechanism.
Mammalian embryo (Mus musculus) developmental stages. Top left: embryo at 2-cell stage. Top right: 4-cell stage. Bottom left: late 8-cell stage, compaction has occured, the rounding effect is clearly visible. Bottom right: 16-cell stage.
Surface energy term in the cellular Potts model.  
Simulation of the mammalian embryo at various stages. Top left: embryo at 2-cell stage (3D view, only frontiers are represented using the "Marching Cubes" algorithm, and the zona pellucida (ZP) surrounding the simulated embryo is not shown). Top right: same embryo at 4-cell stage. Bottom left: late 8-cell stage, compaction is occuring, the cell flattening is clearly visible. Bottom right: A slice of the 16-cell stage, in order to better see the cell arrangement inside the embryo. The zona pellucida is drawn in red. This simulation has been done on a 128 3 lattice, and took 16000 MCS from stage 1-cell to stage 16-cell. Simulation parameters: 128 3 lattice, kT = 1.0, E0 = 600.0, r 0 zygote = 56.0, η = 0.4, ν = 2.0, rzp = 60.0, J [1-8] c,c = 10.0, J [8-16] c,c = 20.0.
Calibration using confocal images (only one z-slice is shown). At this 2-cell stage, angle measurements at the contact point between cell A, cell B and the extracellular medium provide numerical constraints on the model parameters. γA,m, γB,m and γA,B are the surface tensions at the interfaces between, respectively, cell A and the medium, cell B and the medium, and between cells A and B.
Calibration using confocal images. At this 8-cell stage only 5 cells are visible on this z-slice. γAB, γAC and γBC are the surface tensions at the interfaces between, respectively, cells A and B, A and C, and B and C.
The early development of the mammalian embryo leads to the formation of a structure composed by an outer layer of polarized cells surrounding an inner mass of nonpolarized cells. Experimental biology has shown that this organization results from changes in cell polarity, cell shape and intercellular contacts at the 8 and 16-cell stages. In order to examine how the physical properties of embryo cells (adhesion, cortical tension) influence the organization of the cells within the embryo, our team has developed a 3D mechanical model of the dividing early embryo, based on cellular Potts models. In this paper we will present the principles of our simulations, the methodology used and we will show that a very simple mechanical model can reproduce the main structural features (geometry, cell arrangement) of the mammalian embryo during its early developmental stages, up to the 16-cell stage.
An ascending aortic aneurysm is an asymptomatic disease that, if left untreated, could lead to death through its eventual rupture. Current clinical management practices are based primarily on the monitoring of an aneurysm's growth, followed by surgical resection of the affected aortic segment when its diameter reaches 5 to 5.5 centimetres. Unfortunately, this method is based solely on clinical observations and is frequently inaccurate in predicting the risk of an imminent rupture. More sophisticated tools have been developed and do not depend on aneurysm size alone, but these have focused mostly on the distribution of stresses within an aneurismal aortic wall and do not give clinicians an estimate of the time to failure. This present work incorporates the temporal aspect by examining the effects of fatigue on aortic wall properties, and adopts an energetics approach to evaluating the aorta's resistance to rupture. Tissue samples from porcine aortas were fatigued and were subjected to both biaxial and guillotine tests to assess stiffness and fracture toughness. The experiments indicate that both properties decreased according to a power function. After 1 000 000 loading cycles, the final/initial stiffness ratio dropped to 0.85, while its toughness counterpart fell to 0.80. This work constitutes the first tentative steps towards the development of a clinical tool that can evaluate the fracture toughness of aneurismal aortic tissues and predict the temporal likelihood of aneurismal rupture. L'anévrisme de l'aorte ascendante est une maladie asymptomatique. Sans traitement, un anévrisme peut se rompre, ce qui est fatal. Les pratiques cliniques actuelles reposent d'abord sur l'observation de la croissance de la taille de l'anévrisme qui est suivie de la résection chirurgicale de l'aorte lorsque son diamètre atteint 5 à 5,5 cm. Malheureusement, cette méthode est peu précise comme indicateur de risque de rupture et ne s'appuie que sur les observations cliniques pour justifier son application. Plusieurs outils de prédiction plus sophistiqués sont en voie de développement, mais les efforts récents se concentrent surtout sur la distribution des tensions au sein des parois anévrysmales, mais les résultats ne donnent aucune prédiction sur le délai avant que la résection soit nécessaire. Ce travail incorpore l'aspect temporel en examinant l'effet de la fatigue sur les propriétés mécaniques des parois aortiques, tout en adoptant l'approche énergétique pour évaluer la résistance à la rupture du vaisseau. À cette fin, des échantillons de tissus d'aortes porcines sont étirés cycliquement. Leur rigidité et leur résistance à la rupture sont ensuite mesurées grâce aux tests biaxiaux et aux tests à la guillotine. Les résultats expérimentaux montrent une décroissance selon une loi de puissance. Après un million de cycles de tension, le rapport rigidité finale/rigidité initiale a baissé à 0,85, et celui de la résistance à la rupture a chuté jusqu'à 0,80. Ce travail est une première étape dans le développement d'un outil clinique pour mesurer la résistance à la rupture des tissus aortiques anévrysmaux afin de prédire la probabilité d'une rupture sur une échelle de temps.
Table of the 40 variations of products observed under stationary growth phase condition. 
Representation of genetical interactions. (A) Negative regulation (repression) of gene f iu by the transcription factor F ur represented as f ur → f iu −. (B) Biological interaction of genes ihf A and ihf B forming the protein-complex IHF represented as ihf A → IHF + and ihf B → IHF +, positive regulation of gene aceA by the protein complex IHF represented by IHF → aceA + 
Table of 42 products inferred under stationary phase condition. 
Global E.coli regulatory network with transcriptional and sigma-factors interactions (3883 interactions and 1529 products). Blue and red interactions represent activation or, respectively, repression. Green and blue nodes correspond to positive and negative observations (40). Red nodes (381) are the total inferred variations of products under stationary growth phase condition. 
(Left) Percentage of validation of the 381 predicted variations of genes with microarray data sets from GEO (Gene Expression Omnibus) for stationary phase after 20 and 60 minutes. For both experiments we validate the 381 predictions with different sets of microarray observations considering only those genes which absolute value of expression is above certain value (threshold). (Right) Number of genes considered for the validation for the different used thresholds of both microarray data sets. 
We proposed in previous articles a qualitative approach to check the compatibility between a model of interactions and gene expression data. The purpose of the present work is to validate this methodology on a real-size setting. We study the response of E.coli regulatory network to nutritional stress, and compare it to publicly available DNA microarray experiments. We show how the incompatibilities we found reveal missing interactions in the network, as well as observations in contradiction with available literature.
interpolation in mini-elements.
Nowadays, modelling surgery of soft tissues appears to be a promising and helpful way of predicting and teaching surgical operations. This work aimed at predicting the mechanical response of complex organs (composed of a thin membrane and underlying tissues) undergoing multiaxial loadings using a finite element code (VSurgeon3). This software was developed in our laboratory and is based on tetrahedron P1+/P1 elements and on a mixed pressure-velocity formulation. The constitutive equations used to represent the behaviour of the membrane and adjacent tissues represent hyperelastic models. Three different models (neo-Hookean, Mooney-Rivlin, and a third one (Fung) with a higher degree of nonlinearity) and a kill element method have been implemented in VSurgeon3.
Elevated levels of plasma cholesterol pose significant health risks and are causal to diseases including angina, cardiovascular disorders and diabetes. Although the long-term effect of elevated plasma cholesterol is known for its accretion in arterial walls, little is understood of its immediate effects. Since cholesterol levels in red blood cell (RBC) membranes are inversely associated with O 2 transport, and the RBC water channel AQP1 is also capable of transporting CO 2 , the detrimental effect of cholesterol on active water transport, and likely on the CO 2 and O 2 transport in RBC, was hypothesized and tested in the present study. The rapid gating of water into isolated rat RBC and the corresponding increase in their volume and surface area was determined using dynamic light scattering. Similarly, the entry of CO 2 into the RBC was determined using zeta potential measurements, as increase in intracellular acidity reduces the negative charge at the RBC membrane. Results from our study demonstrate for the first time that the immediate effect of elevated plasma cholesterol is dysfunction of active water and CO 2 transport, possibly via the AQP1 channel at the RBC membrane. Since there is growing evidence that PLA2 may play a key role in atherogenesis, and statins significantly reduce blood PLA2 levels, the effect of the PLA2 inhibitor on ameliorating the detrimental effects of cholesterol was investigated. Interestingly, the PLA2 inhibitor ONO-RS-082 was found to reverse the cholesterol effect on RBC function.
Clues to the evolution of multicellularity are emerging from comparative genomics and functional genetics studies of monophyletic unicellular/multicellular species pairs with recent divergence [1, 2]. Such studies have not revealed significant innovation at the genomic or protein domain level, but have identified a causative plexus in the coöption of unicellular functionalities into genes and pathways responsive to developmental cues [3–6]. We argue that without proteomic innovation, this coöption could only materialize with a degree of functional coöperativity well above unicellular levels. What raw properties of a unicellular proteome are harnessed by such functional exaptations? This work addresses the question by examining the structural dependence of proteins (Q) across species. This parameter differentiates unicellular and multicellular species by globally characterizing their proteome interdependence, and identifies the unicellular volvocine alga Chlamydomonas reinhardtii [3] as the sole outlier, with a level of structural dependence closer to that of a multicellular species. This result is significant since volvocine algae provide a model for the evolution of multicellularity [1–7] and is revealing since structural dependence implies a lack of functional autonomy that enables coöption without the need to innovate at the proteomic level.
The cellular Potts model (CPM) is a cellular automaton (CA) for modelling morphogenesis. It characterizes a cell by a volume, a surface and a type. We have extended this model to add the notion of energetic exchange between cells via the secretion and consumption of molecules. These molecules are transformed into energy, allowing the cells to maintain themselves and to divide. To test our adaptation of the CPM we improve the realism of known simulations dealing with embryogenesis. Thanks to the CPM the shape of the cell is more complex than a simple pixel. Our simulation shows multilayer proliferation, similar to the bilayer proliferation described in the literature. In addition it reveals dynamic tissue regeneration, morphogenesis of disjunctive tissues and the dynamic stability of global shape.
Controlling complex systems means dealing with their time-varying aspects as well as their nonlinearity. Bioprocesses are an interesting example, due to their complexity and the impossibility of fully describing the microörganisms involved in such reactions, nor their behaviour. In order to overcome these difficulties, we propose an adaptive and generic approach for the control of bioprocesses. This approach relies on the use of an adaptive multi-agent system (AMAS) acting as the controller of a bioprocess. The resulting adaptability enables its application to a wide range of problems and the ability to react to dynamic modifications of the system controlled. The global control problem is thereby turned into a sum of local problems. Interactions between local agents, which solve their own inverse problem and act in a coöperative way, enable the emergence of an adequate global function for solving the global problem while fulfilling the user’s requests. Bioprocesses are often modelled as equation systems, including both differential and classical equations. An instantiation of this approach is applied to an equation-solving problem, and a differential equation-solving problem. The results are detailed and discussed.
Myelin basic protein (MBP) is one of the candidate autoantigens of the human inflammatory demyelinating disease multiple sclerosis, which is characterized by the active degradation of the myelin sheath. MBP has extensive posttranslational modifications, including deimination of arginine residues. The deiminated (citrullinated) MBP C8 isomer is divided into two fractions: stathmin-containing C8a; and C8b. Here, we report our investigation of the adhesion of these component fractions to myelin lipids and our finding that the adsorption–desorption characteristics of C8a and C8b are different. The area on the lipid bilayer that is occupied by C8a is slightly smaller than for C8b and the rate coefficient for the association preceding adhesion is also smaller for C8a than for C8b. Taking into account that stathmin is the main component of C8a it is inferred that the stathmin–MBP complex changes the conformation of citrullinated C8 and depresses its capacity to adsorb. Furthermore, we have determined the production of nitric oxide (NO) by astrocytes and by mixed primary glial cells under the actions of C8a and C8b. We have found that NO synthesis is not changed in astrocytes in the presence of the C8a and C8b fractions, whereas in the primary glia the production of NO is significantly increased. We suggest that this increase is due to the presence of microglia in mixed primary glial cells, which are the primary targets of the various forms of MBP.
There is presently concern regarding toxins, especially neurotoxins, which have been detected in aircraft cabin air. Among them, the tricresyl phosphates (TCP) are especially problematical, because of their ability to engender organophosphate-induced delayed neuropathy (OPIDN), leading to lasting damage of the central nervous system. The low volatility of TCP in principle offers some protection, since any contaminants emerging from the jet engines that supply hot compressed air to the cabin will tend to condense on the inner walls of the ducts leading to the cabin, where they have indeed been found. Were it not for that, cabin air concentrations would presumably be considerably higher. Alongside various organic compounds, high levels of fine and ultrafine particles (of unknown composition) have also been detected in aircraft cabin air. This paper firstly examines whether volatilized jet oil could account for the measured particle numbers. Since the two are not well correlated, an alternative hypothesis, that the particles are mineral debris, is examined. If coated with monolayer of TCP, such particles could transport a significant quantity of TCP into the lungs. A definitive evaluation requires more parameters to be measured, such as the chemical nature and distribution of diameters of the particles measured in aircraft cabin air.
Top-cited authors
Jeremy Ramsden
  • Collegium Basilea (Institute of Advanced Study), Basel, Switzerland
François Fages
  • Inria National Institute for Research in Computer Science and Control
A. G. Mamalis
  • National Center for Scientific Research Demokritos
Stephanie Seneff
  • Massachusetts Institute of Technology
Sergiy N. Lavrynenko
  • National Technical University "Kh.P.I."