SUMMARY When the process of cell-fate determination is examined at single-cell resolution, it is often observed that individual cells undergo different fates even when subject to identical conditions. This “noisy” phenotype is usually attributed to the inherent stochasticity of chemical reactions in the cell. Here we demonstrate how the observed single-cell heterogeneity can be explained by a cascade of decisions occurring at the sub-cellular level. We follow the post-infection decision in bacteriophage lambda at single-virus resolution, and show that a choice between lysis and lysogeny is first made at the level of the individual virus. The decisions by all viruses infecting a single cell are then integrated in a precise (noise-free) way, such that only a unanimous vote by all viruses leads to the establishment of lysogeny. By detecting and integrating over the sub-cellular “hidden variables”, we are able to predict the level of noise measured at the single-cell level.

To understand and better model the hydrodynamic force acting on a finite-sized particle moving in a wall-bounded linear shear flow, here we consider the two limiting cases of (a) a rigid stationary spherical particle in a linear wall-bounded shear flow and (b) a rigid spherical particle in rectilinear motion parallel to a wall in a quiescent ambient flow. In the present computations, the particle Reynolds number ranges from 2 to 250 at separation distances to the wall from nearly sitting on the wall to far away from the wall. First we characterize the structure of the wake for a stationary particle in a linear shear flow and compare with those for a particle moving parallel to a wall in a quiescent ambient [see L. Zeng, S. Balachandar, and P. Fischer, J. Fluid Mech. 536, 1 (2005)]. For both these cases we present drag and lift results and obtain composite drag and lift correlations that are valid for a wide range of Re and distance from the wall. These correlations have been developed to be consistent with all available low Reynolds number theories and approach the appropriate uniform flow results at large distance from the wall. Particular attention is paid to the case of particle in contact with the wall and the computational results are compared with those from experiments.

We perform direct numerical simulations of a rigid sphere translating parallel to a flat wall in an otherwise quiescent ambient fluid. A spectral element method is employed to perform the simulations with high accuracy. For $Re\,{<}\,100$, we observe the lift coefficient to decrease with both Reynolds number and distance from the wall. In this regime the present results are in good agreement with the low-Reynolds-number theory of Vasseur & Cox (1977), with the recent experiments of Takemura & Magnaudet (2003) and with the simulations of Kim et al. (1993). The most surprising result from the present simulations is that the wall-induced lift coefficient increases dramatically with increasing $Re$ above about 100. Detailed analysis of the flow field around the sphere suggests that this increase is due to an imperfect bifurcation resulting in the formation of a double-threaded wake vortical structure. In addition to a non-rotating sphere, we also simulate a freely rotating sphere in order to assess the importance of free rotation on the translational motion of the sphere. We observe the effect of sphere rotation on lift and drag forces to be small. We also explore the effect of the wall on the onset of unsteadiness.

Many bacterial species deploy Type IV Secretion Systems (T4SSs) to deliver DNA, protein, or other macromolecules to bacterial or eukaryotic cell targets (Li et al., 2019;Waksman, 2019). The T4SSs are composed mainly of two subfamilies, the conjugation systems and effector translocators (Cascales and Christie, 2003). Conjugation systems are of considerable medical concern for their roles in dissemination of mobile genetic elements (MGEs), often encoding resistance to heavy metals or antibiotics (Cabezon et al., 2015;Huddleston, 2014;Koraimann, 2018). The effector translocators mainly deliver proteins to eukaryotic target cells, although recent studies have also documented the interkingdom transfer of DNA,

Prokaryotes evolved numerous systems that defend against predation by bacteriophages. In addition to well-known restriction-modification and CRISPR-Cas immunity systems, many poorly characterized systems exist. One class of such systems, named BREX, consists of a putative phosphatase, a methyltransferase and four other proteins. A Bacillus cereus BREX system provides resistance to several unrelated phages and leads to modification of specific motif in host DNA. Here, we study the action of BREX system from a natural Escherichia coli isolate. We show that while it makes cells resistant to phage λ infection, induction of λ prophage from cells carrying BREX leads to production of viruses that overcome the defense. The induced phage DNA contains a methylated adenine residue in a specific motif. The same modification is found in the genome of BREX-carrying cells. The results establish, for the first time, that immunity to BREX system defense is provided by an epigenetic modification.