Bacterial toxin-antitoxin (TA) modules are abundant genetic elements that encode a toxin protein capable of inhibiting cell growth and an antitoxin that counteracts the toxin. The majority of toxins are enzymes that interfere with translation or DNA replication, but a wide variety of molecular activities and cellular targets have been described. Antitoxins are proteins or RNAs that often control their cognate toxins through direct interactions and, in conjunction with other signaling elements, through transcriptional and translational regulation of TA module expression. Three major biological functions of TA modules have been discovered, post-segregational killing ("plasmid addiction"), abortive infection (bacteriophage immunity through altruistic suicide), and persister formation (antibiotic tolerance through dormancy). In this review, we summarize the current state of the field and highlight how multiple levels of regulation shape the conditions of toxin activation to achieve the different biological functions of TA modules.

Most studies on granular physics have focused on dry granular media, with no liquids between the grains. However, in geology and many real world applications (e.g., food processing, pharmaceuticals, ceramics, civil engineering, constructions, and many industrial applications), liquid is present between the grains. This produces inter-grain cohesion and drastically modifies the mechanical properties of the granular media (e.g., the surface angle can be larger than 90 degrees). Here we present a review of the mechanical properties of wet granular media, with particular emphasis on the effect of cohesion. We also list several open problems that might motivate future studies in this exciting but mostly unexplored field.

Individual mRNAs are translated by multiple ribosomes that initiate translation with an interval of a few seconds. The ribosome speed is codon dependent, and ribosome queuing has been suggested to explain specific data for translation of some mRNAs in vivo. By modeling the stochastic translation process as a traffic problem, we here analyze conditions and consequences of collisions and queuing. The model allowed us to determine the on-rate (0.8 to 1.1 initiations/s) and the time (1 s) the preceding ribosome occludes initiation for Escherichia coli lacZ mRNA in vivo. We find that ribosome collisions and queues are inevitable consequences of a stochastic translation mechanism that reduce the translation efficiency substantially on natural mRNAs. The cells minimize collisions by having its mRNAs being unstable and by a highly selected codon usage in the start of the mRNA. The cost of mRNA breakdown is offset by the concomitant increase in translation efficiency.

The competitive exclusion principle states that phage diversity M should not exceed bacterial diversity N. By analyzing the steady-state solutions of multistrain equations, we find a new constraint: the diversity N of bacteria living on the same resources is constrained to be M or M þ 1 in terms of the diversity of their phage predators. We quantify how the parameter space of coexistence exponentially decreases with diversity. For diversity to grow, an open or evolving ecosystem needs to climb a narrowing 'diversity staircase' by alternatingly adding new bacteria and phages. The unfolding coevolutionary arms race will typically favor high growth rate, but a phage that infects two bacterial strains differently can occasionally eliminate the fastest growing bacteria. This contextdependent fitness allows abrupt resetting of the 'Red-Queen's race' and constrains the local diversity.

We study the effect of pre-collisional velocity correlations on granular shear flow by molecular dynamics simulations of the inelastic hard sphere system. Comparison of the simulations with the kinetic theory reveals that the theory overestimates both the energy dissipation rate and the normal stress in the dense flow region. We find that the relative normal velocity of colliding particles is smaller than that expected from random collisions, and the discrepancies in the dissipation and the normal stress can be adjusted by introducing the idea of the collisional temperature, from which we conclude that the velocity correlation neglected in the kinetic theory is responsible for the discrepancies. Our analysis of the distributions of the pre-collisional velocity suggests that the correlation grows through multiple inelastic collisions during the time scale of the inverse of the shear rate. As for the shear stress, the discrepancy is also found in the dense region, but it depends strongly on the particle inelasticity.

Cells can often choose among several stably heritable phenotypes. Examples are the expression of genes in eukaryotic cells where long chromosomal regions can adopt persistent and heritable silenced or active states, that may be associated with positive feedback in dynamic modification of nucleosomes. We generalize this mechanism in terms of bistability associated with valleys in an epigenetic landscape. A transfer matrix method was used to rigorously follow the system through the disruptive process of cell division. This combined treatment of noisy dynamics both between and during cell division provides an efficient way to calculate the stability of alternative states in a broad range of epigenetic systems.

Many toxin–antitoxin (TA) loci are known to strongly repress their own transcription. This auto-inhibition is often called ‘conditional cooperativity’ as it relies on cooperative binding of TA complexes to operator DNA that occurs only when toxins are in a proper stoichiometric relationship with antitoxins. There has recently been an explosion of interest in TA systems due to their role in bacterial persistence, however the role of conditional cooperativity is still unclear. We reveal the biological function of conditional cooperativity by constructing a mathematical model of the well studied TA system, relBE of Escherichia coli . We show that the model with the in vivo and in vitro established parameters reproduces experimentally observed response to nutritional stress. We further demonstrate that conditional cooperativity stabilizes the level of antitoxin in rapidly growing cells such that random induction of relBE is minimized. At the same time it enables quick removal of free toxin when the starvation is terminated.

Ecological systems comprise an astonishing diversity of species that cooperate or compete with each other forming complex mutual dependencies. The minimum requirements to maintain a large species diversity on long time scales are in general unknown. Using lichen communities as an example, we propose a model for the evolution of mutually excluding organisms that compete for space. We suggest that chain-like or cyclic invasions involving three or more species open for creation of spatially separated sub-populations that subsequently can lead to increased diversity. In contrast to its non-spatial counterpart, our model predicts robust co-existence of a large number of species, in accordance with observations on lichen growth. It is demonstrated that large species diversity can be obtained on evolutionary timescales, provided that interactions between species have spatial constraints. In particular, a phase transition to a sustainable state of high diversity is identified.Introduction.-Interactions between biological species may well be as old as life itself [1-3] with competition and predation as major determinants for species diversity [4,5]. Competitive exclusion [6,7] has been suggested to reduce ecosystem diversity when several species compete for the same resources. Real ecosystems, on the other hand, consist of multiple species and have a robustness that may even increase with diversity [8,9]. To obtain robustness of ecosystem diversity in theoretical models one needs first of all to limit the exponential growth by assuming a maximum carrying capacity for the population of each species [10]. Extreme version of such models [11,12] indeed predicts a sustainable but fragile coexistence of multiple species.A more robust way to maintain high diversity is to include space [13][14][15][16][17][18] e.g. in combination with hypercycles [19] or predator-prey cycles [20][21][22][23]. Studying ecosystems in marine hard-substrate environments Jackson & Buss [24] suggested that non-transitive allelopathic relationships between species could maintain species diversity on a longer timescale than pure hierarchical predation relationships. This was confirmed in a model on two-dimensional lattice where sessile species compete for space [25,26]. As in the "Buss" model [25,26] we consider a 2-dimensional lattice where the competition for resources is a zero sum game about available space. In our model, however, the focus is on the dynamic balance between an introduction of new species and exclusion of older species. With this complementary model we, for the first time show that: a) There is a sharp transition from multiple to single species as the number of interactions is increased. b) Both cycles and chain-like (hierarchical) relationships lead to spatial fragmentation of species population thus creating isolated niches for new species and increased diversity.The model is inspired by the spatial dynamics of lichen communities. Lichens have existed for as long as ∼600 million years [27] and are organisms consisting of fungi and ...