Predicting how cells spread and migrate

Efficient cell migration is central to the normal development of tissues and organs and is involved in a wide range of human diseases, including cancer metastasis, immune responses, and cardiovascular disorders. Mesenchymal migration is modulated by focal-adhesion proteins, which organize into large integrin-rich protein complexes at the basal surface of adherent cells. Whether the extent of clustering of focal-adhesion proteins is actually required for effective migration is unclear. We recently demonstrated that the depletion of major focal-adhesion proteins, as well as modulation of matrix compliance, actin assembly, mitochondrial activity, and DNA recombination, all converged into highly predictable, inter-related, biphasic changes in focal adhesion size and cell migration. Herein, we further discuss the role of focal adhesions in controlling cell spreading and test their potential role in cell migration.     

Crop seed oil bodies: From challenges in protein identification to an emerging picture of the oil body proteome

Oleaginous seeds store lipids in specialized structures called oil bodies (OBs). These organelles consist of a core of neutral lipids bound by proteins embedded in a phospholipid monolayer. OB proteins are well conserved in plants and have long been grouped into only two categories: structural proteins or enzymes. Recent work, however, which identified other classes of proteins associated with OBs, clearly shows that this classification is obsolete. Proteomics‐mediated OB protein identification is facilitated in plants for which the genome is sequenced and annotated. However, it is not clear whether this knowledge can be dependably transposed to less well‐characterized plants, including the well‐established commercial sources of seed oil as well as the many others being proposed as novel sources for biodiesel, especially in Africa and Asia. Toward an update of the current data available on OB proteins this review discusses (i) the specific difficulties for proteomic studies of organelles; (ii) a 2012 census of the proteins found in seed OBs from various crops; (iii) the oleosin composition of OBs and their role in organelle stability; (iv) PTM of OB proteins as an emerging field of investigation; and finally we describe the emerging model of the OB proteome from oilseed crops.     

Failure modelling of trabecular bone using a non-linear combined damage and fracture voxel finite element approach

Trabecular bone tissue failure can be considered as consisting of two stages: damage and fracture; however, most failure analyses of 3D high-resolution trabecular bone samples are confined to damage mechanisms only, that is, without fracture. This study aims to develop a computational model of trabecular bone consisting of an explicit representation of complete failure, incorporating damage criteria, fracture criteria, cohesive forces, asymmetry and large deformation capabilities. Following parameter studies on a test specimen, and experimental testing of bone sample to complete failure, the asymmetric critical tissue damage and fracture strains of ovine vertebral trabecular bone were calibrated and validated to be compression damage ?1.16 %, tension damage 0.69 %, compression fracture ?2.91 % and tension fracture 1.98 %. Ultimate strength and post–ultimate strength softening were captured by the computational model, and the failure of individual struts in bending and shear was also predicted. This modelling approach incorporated a cohesive parameter that provided a facility to calibrate ductile–brittle behaviour of bone tissue in this non-linear geometric and non-linear constitutive property analyses tool. Finally, the full accumulation of tissue damage and tissue fracture has been monitored from range of small magnitude (normal daily loading) through to specimen yielding, ultimate strength and post–ultimate strength softening.     

Real-Time Imaging of the Intracellular Glutathione Redox Potential in the Malaria Parasite Plasmodium falciparum

In the malaria parasite Plasmodium falciparum, the cellular redox potential influences signaling events, antioxidant defense, and mechanisms of drug action and resistance. Until now, the real-time determination of the redox potential in malaria parasites has been limited because conventional approaches disrupt sub-cellular integrity. Using a glutathione biosensor comprising human glutaredoxin-1 linked to a redox-sensitive green fluorescent protein (hGrx1-roGFP2), we systematically characterized basal values and drug-induced changes in the cytosolic glutathione-dependent redox potential (E _GSH) of drug-sensitive (3D7) and resistant (Dd2) P. falciparum parasites. Via confocal microscopy, we demonstrated that hGrx1-roGFP2 rapidly detects E _GSH changes induced by oxidative and nitrosative stress. The cytosolic basal E _GSH of 3D7 and Dd2 were estimated to be −314.2±3.1 mV and −313.9±3.4 mV, respectively, which is indicative of a highly reducing compartment. We furthermore monitored short-, medium-, and long-term changes in E _GSH after incubation with various redox-active compounds and antimalarial drugs. Interestingly, the redox cyclers methylene blue and pyocyanin rapidly changed the fluorescence ratio of hGrx1-roGFP2 in the cytosol of P. falciparum, which can, however, partially be explained by a direct interaction with the probe. In contrast, quinoline and artemisinin-based antimalarial drugs showed strong effects on the parasites'' E _GSH after longer incubation times (24 h). As tested for various conditions, these effects were accompanied by a drop in total glutathione concentrations determined in parallel with alternative methods. Notably, the effects were generally more pronounced in the chloroquine-sensitive 3D7 strain than in the resistant Dd2 strain. Based on these results hGrx1-roGFP2 can be recommended as a reliable and specific biosensor for real-time spatiotemporal monitoring of the intracellular E _GSH in P. falciparum. Applying this technique in further studies will enhance our understanding of redox regulation and mechanisms of drug action and resistance in Plasmodium and might also stimulate redox research in other pathogens.     

The geometry and genetics of hybridization

When divergent populations form hybrids, hybrid fitness can vary with genome composition, current environmental conditions, and the divergence history of the populations. We develop analytical predictions for hybrid fitness, which incorporate all three factors. The predictions are based on Fisher's geometric model, and apply to a wide range of population genetic parameter regimes and divergence conditions, including allopatry and parapatry, local adaptation, and drift. Results show that hybrid fitness can be decomposed into intrinsic effects of admixture and heterozygosity, and extrinsic effects of the (local) adaptedness of the parental lines. Effect sizes are determined by a handful of geometric distances, which have a simple biological interpretation. These distances also reflect the mode and amount of divergence, such that there is convergence toward a characteristic pattern of intrinsic isolation. We next connect our results to the quantitative genetics of line crosses in variable or patchy environments. This means that the geometrical distances can be estimated from cross data, and provides a simple interpretation of the “composite effects.” Finally, we develop extensions to the model, involving selectively induced disequilibria, and variable phenotypic dominance. The geometry of fitness landscapes provides a unifying framework for understanding speciation, and wider patterns of hybrid fitness.     

Configurational Temperature for Brownian Dynamics

Abstract

Expressions for the configurational temperature are evaluated in Brownian dynamics simulations of a Lennard-Jones fluid and compared with the input temperature which is used to generate the random displacements. It is found that the two temperatures agree in the limit of large numbers of particles, and even for moderate system sizes the configurational temperature is a useful check on the correctness of the simulation algorithm. Investigation of the autocorrelation functions shows that for Lennard-Jones and power-law fluids, the correlation time of the configurational temperature is shorter than other typical thermodynamic quantities, and it generally increases with the range of the potential.