Silencing of toxic gene expression by Fis

Bacteria and bacteriophages have evolved DNA modification as a strategy to protect their genomes. Mom protein of bacteriophage Mumodifies the phage DNA, rendering it refractile to numerous restriction enzymes and in turn enabling the phage to successfully invade a variety of hosts. A strong fortification, a combined activity of the phage and host factors, prevents untimely expression of mom and associated toxic effects. Here, we identify the bacterial chromatin architectural protein Fis as an additional player in this crowded regulatory cascade. Both in vivo and in vitro studies described here indicate that Fisacts as a transcriptional repressor of mom promoter. Further, our data shows that Fis mediates its repressive effect by denying access to RNA polymerase at mom promoter. We propose that a combined repressive effect of Fis and previously characterized negative regulatory factors could be responsible to keep the gene silenced most of the time. We thus present a new facet of Fis function in Mu biology. In addition to bringing about overall downregulation of Mu genome, it also ensures silencing of the advantageous but potentially lethal mom gene.

ATM- and ATR-mediated phosphorylation of XRCC3 regulates DNA double-strand break-induced checkpoint activation and repair

The RAD51 paralogs XRCC3 and RAD51C have been implicated in homologous recombination (HR) and DNA damage responses. However, the molecular mechanism(s) by which these paralogs regulate HR and DNA damage signaling remains obscure. Here, we show that an SQ motif serine 225 in XRCC3 is phosphorylated by ATR kinase in an ATM signaling pathway. We find that RAD51C but not XRCC2 is essential for XRCC3 phosphorylation, and this modification follows end resection and is specific to S and G(2) phases. XRCC3 phosphorylation is required for chromatin loading of RAD51 and HR-mediated repair of double-strand breaks (DSBs). Notably, in response to DSBs, XRCC3 participates in the intra-S-phase checkpoint following its phosphorylation and in the G(2)/M checkpoint independently of its phosphorylation. Strikingly, we find that XRCC3 distinctly regulates recovery of stalled and collapsed replication forks such that phosphorylation is required for the HR-mediated recovery of collapsed replication forks but is dispensable for the restart of stalled replication forks. Together, these findings suggest that XRCC3 is a new player in the ATM/ATR-induced DNA damage responses to control checkpoint and HR-mediated repair.

Bounds on the sum-rate capacity of the Gaussian MIMO X channel

We consider the MIMO X channel (XC), a system consisting of two transmit-receive pairs, where each transmitter communicates with both the receivers. Both the transmitters and receivers are equipped with multiple antennas. First, we derive an upper bound on the sum-rate capacity of the MIMO XC under individual power constraint at each transmitter. The sum-rate capacity of the two-user multiple access channel (MAC) that results when receiver cooperation is assumed forms an upper bound on the sum-rate capacity of the MIMO XC. We tighten this bound by considering noise correlation between the receivers and deriving the worst noise covariance matrix. It is shown that the worst noise covariance matrix is a saddle-point of a zero-sum, two-player convex-concave game, which is solved through a primal-dual interior point method that solves the maximization and the minimization parts of the problem simultaneously. Next, we propose an achievable scheme which employs dirty paper coding at the transmitters and successive decoding at the receivers. We show that the derived upper bound is close to the achievable region of the proposed scheme at low to medium SNRs.

Fair Scheduling in Cellular Systems in the Presence of Noncooperative Mobiles

We consider the problem of ``fair'' scheduling the resources to one of the many mobile stations by a centrally controlled base station (BS). The BS is the only entity taking decisions in this framework based on truthful information from the mobiles on their radio channel. We study the well-known family of parametric alpha-fair scheduling problems from a game-theoretic perspective in which some of the mobiles may be noncooperative. We first show that if the BS is unaware of the noncooperative behavior from the mobiles, the noncooperative mobiles become successful in snatching the resources from the other cooperative mobiles, resulting in unfair allocations. If the BS is aware of the noncooperative mobiles, a new game arises with BS as an additional player. It can then do better by neglecting the signals from the noncooperative mobiles. The BS, however, becomes successful in eliciting the truthful signals from the mobiles only when it uses additional information (signal statistics). This new policy along with the truthful signals from mobiles forms a Nash equilibrium (NE) that we call a Truth Revealing Equilibrium. Finally, we propose new iterative algorithms to implement fair scheduling policies that robustify the otherwise nonrobust (in presence of noncooperation) alpha-fair scheduling algorithms.

The Structure of the Holo-Acyl Carrier Protein of Leishmania major Displays a Remarkably Different Phosphopantetheinyl Transferase Binding Interface

The genome of Leishmania major encodes a type II fatty acid biosynthesis pathway for which no structural or biochemical information exists. Here, for the first time, we have characterized the central player of the pathway, the acyl carrier protein (LmACP), using nuclear magnetic resonance (NMR). Structurally, the LmACP molecule is similar to other type II ACPs, comprising a four-helix bundle, enclosing a hydrophobic core. Dissimilarities in sequence, however, exist in helix II (recognition helix) of the protein. The enzymatic conversion of apo-LmACP into the holo form using type I (Escherichia coli AcpS) and type II (Sfp type) phosphopantetheinyl transferases (PPTs) is relatively slow. Mutagenesis studies underscore the importance of the residues present at the protein protein interaction interface of LmACP in modulating the activity of PPTs. Interestingly, the cognate PPT for this ACP, the L. major 4'-phosphopantetheinyl transferase (LmPPT), does not show any enzymatic activity toward it, though it readily converts other type I and type II ACPs into their holo forms. NMR chemical shift perturbation studies suggest a moderately tight complex between LmACP and its cognate PPT, suggesting inhibition. We surmise that the unique surface of LmACP might have evolved to complement its cognate enzyme (LmPPT), possibly for the purpose of regulation.

Necessary and sufficient conditions for optimality in constrained general sum stochastic games

In this paper we first derive a necessary and sufficient condition for a stationary strategy to be the Nash equilibrium of discounted constrained stochastic game under certain assumptions. In this process we also develop a nonlinear (non-convex) optimization problem for a discounted constrained stochastic game. We use the linear best response functions of every player and complementary slackness theorem for linear programs to derive both the optimization problem and the equivalent condition. We then extend this result to average reward constrained stochastic games. Finally, we present a heuristic algorithm motivated by our necessary and sufficient conditions for a discounted cost constrained stochastic game. We numerically observe the convergence of this algorithm to Nash equilibrium. (C) 2015 Elsevier B.V. All rights reserved.