Dynamic calcium-mediated stress response and recovery signatures in the fungal pathogen, Candida albicans.

IMPORTANCE: Intracellular calcium signaling plays an important role in the resistance and adaptation to stresses encountered by fungal pathogens within the host. This study reports the optimization of the GCaMP fluorescent calcium reporter for live-cell imaging of dynamic calcium responses in single cells of the pathogen, Candida albicans, for the first time. Exposure to membrane, osmotic or oxidative stress generated both specific changes in single cell intracellular calcium spiking and longer calcium transients across the population. Repeated treatments showed that calcium dynamics become unaffected by some stresses but not others, consistent with known cell adaptation mechanisms. By expressing GCaMP in mutant strains and tracking the viability of individual cells over time, the relative contributions of key signaling pathways to calcium flux, stress adaptation, and cell death were demonstrated. This reporter, therefore, permits the study of calcium dynamics, homeostasis, and signaling in C. albicans at a previously unattainable level of detail.

Subregional statistical shape modelling identifies lesser trochanter size as a possible risk factor for radiographic hip osteoarthritis, a cross-sectional analysis from the Osteoporotic Fractures in Men Study.

OBJECTIVE: Statistical shape modelling (SSM) of hip dual-energy X-ray absorptiometry (DXA) scans has identified relationships between hip shape and radiographic hip OA (rHOA). We aimed to further elucidate shape characteristics related to rHOA by focusing on subregions identified from whole-hip shape models. METHOD: SSM was applied to hip DXAs obtained in the Osteoporotic Fractures in Men Study. Whole-hip shape modes (HSMs) associated with rHOA were combined to form a composite at-risk-shape. Subsequently, subregional HSMs (cam-type and lesser trochanter modes) were built, and associations with rHOA were examined by logistic regression. Subregional HSMs were further characterised, by examining associations with 3D-HSMs derived from concurrent hip CT scans. RESULTS: 4,098 participants were identified with hip DXAs and radiographs. Composite shapes from whole-hip HSMs revealed that lesser trochanter size and cam-type femoral head are related to rHOA. From sub-regional models, lesser trochanter mode (LTM)1 [OR 0.74; 95%CI 0.63.0.87] and cam-type mode (CTM)3 [OR 1.27; 1.13.1.42] were associated with rHOA, associations being similar to those for whole hip HSMs. 515 MrOS participants had hip DXAs and 3D-HSMs derived from hip CT scans. LTM1 was associated with 3D-HSMs that also represented a larger lesser trochanter [3D-HSM7 (beta (ß)-0.23;-0.33,-0.14) and 3D-HSM9 (ß0.36; 0.27.0.45)], and CTM3 with 3D-HSMs describing cam morphology [3D-HSM3 (ß-0.16;-0.25,-0.07) and 3D-HSM6 (ß 0.19; 0.10.0.28)]. CONCLUSION: Subregional SSM of hip DXA scans suggested larger lesser trochanter and cam morphology underlie associations between overall hip shape and rHOA. 3D hip modelling suggests our subregional SSMs represent true anatomical variations in hip shape, warranting further investigation.

Mean-field versus stochastic models for transcriptional regulation.

We introduce a minimal model description for the dynamics of transcriptional regulatory networks. It is studied within a mean-field approximation, i.e., by deterministic ODE's representing the reaction kinetics, and by stochastic simulations employing the Gillespie algorithm. We elucidate the different results that both approaches can deliver, depending on the network under study, and in particular depending on the level of detail retained in the respective description. Two examples are addressed in detail: The repressilator, a transcriptional clock based on a three-gene network realized experimentally in E. coli, and a bistable two-gene circuit under external driving, a transcriptional network motif recently proposed to play a role in cellular development.

Criticality on networks with topology-dependent interactions.

Weighted scale-free networks with topology-dependent interactions are studied. It is shown that the possible universality classes of critical behavior, which are known to depend on topology, can also be explored by tuning the form of the interactions at fixed topology. For a model of opinion formation, simple mean field and scaling arguments show that a mapping gamma'=(gamma-mu)(1-mu) describes how a shift of the standard exponent gamma of the degree distribution can absorb the effect of degree-dependent pair interactions J(ij) proportional to (k(i)k(j))(-mu), where k(i) stands for the degree of vertex i. This prediction is verified by extensive numerical investigations using the cavity method and Monte Carlo simulations. The critical temperature of the model is obtained through the Bethe-Peierls approximation and with the replica technique. The mapping can be extended to nonequilibrium models such as those describing the spreading of a disease on a network.

Trading interactions for topology in scale-free networks.

Scale-free networks with topology-dependent interactions are studied. It is shown that the universality classes of critical behavior, which conventionally depend only on topology, can also be explored by tuning the interactions. A mapping, gamma'=(gamma-mu)/(1-mu), describes how a shift of the standard exponent gamma of the degree distribution P(q) can absorb the effect of degree-dependent pair interactions J(ij)proportional to(q(i)q(j))(-mu). The replica technique, cavity method, and Monte Carlo simulation support the physical picture suggested by Landau theory for the critical exponents and by the Bethe-Peierls approximation for the critical temperature. The equivalence of topology and interaction holds for equilibrium and nonequilibrium systems, and is illustrated with interdisciplinary applications.