Structural balance theory affirms that signed social networks (i.e., graphs whose signed edges represent friendly/hostile interactions among individuals) tend to be organized so as to avoid conflictual situations, corresponding to cycles of negative parity. Using an algorithm for ground-state calculation in large-scale Ising spin glasses, in this paper we compute the global level of balance of very large online social networks and verify that currently available networks are indeed extremely balanced. This property is explainable in terms of the high degree of skewness of the sign distributions on the nodes of the graph. In particular, individuals linked by a large majority of negative edges create mostly "apparent disorder," rather than true "frustration."combinatorial optimization | social network theory O nline social networks are examples of large-scale communities of interacting individuals in which local ties between users (friend, fan, colleague, but also friend/foe, trust/distrust, etc.) give rise to a complex, multidimensional web of aggregated social behavior (1-4). For such complex networks, the emergence of global properties from local interactions is an intriguing subject, so far investigated mostly at structural and topological level (2,(5)(6)(7)(8). In social network theory (9-11), however, the content of the relationships is often even more important than their topology, and this calls for the development of appropriate analytical and computational tools, able to extrapolate content-related features out of the set of interactions of a social community. Obtaining efficient tools is particularly challenging when, as in social networks retrieved from online media, the size of the community is very big, of the order of 10 5 individuals or higher.A global property that has recently attracted some attention (1,(12)(13)(14) is determining the structural balance of a signed social network. Structural (or social) balance theory was first formulated by Heider (15) in order to understand the structure and origin of tensions and conflicts in a network of individuals whose mutual relationships are characterizable in terms of friendship and hostility. It was modeled in terms of signed graphs by Cartwright and Harary (16); see refs. 10 and 11 for an overview of the theory. The nodes of the graph represent users and the positive/ negative edges their friendly/hostile relationships. It has been known for some time how to interpret structural balance on such networks (16): The potential source of tensions are the cycles of the graph (i.e., the closed paths beginning and ending on the same node), notably those of negative sign (i.e., having an odd number of negative edges). It follows that the concept of balance is not related to the actual number of negative edges on the cycles but only to their parity; see Fig. 1 for an illustration on basic graphs. In particular, a signed graph is exactly balanced (i.e., tensions are completely absent) if and only if all its cycles are positive (16). As such, structural balance ...

SUMMARY Drug-resistant bacterial pathogens pose an urgent public-health crisis. Here, we report the discovery, from microbial-extract screening, of a nucleoside-analog inhibitor that inhibits bacterial RNA polymerase (RNAP) and exhibits antibacterial activity against drug-resistant bacterial pathogens: pseudouridimycin (PUM). PUM is a natural product comprising a formamidinylated, N-hydroxylated Gly-Gln dipeptide conjugated to 6′-amino-pseudouridine. PUM potently and selectively inhibits bacterial RNAP in vitro, inhibits bacterial growth in culture, and clears infection in a mouse model of Streptococcus pyogenes peritonitis. PUM inhibits RNAP through a binding site on RNAP (the NTP addition site) and mechanism (competition with UTP for occupancy of the NTP addition site) that differ from those of the RNAP inhibitor and current antibacterial drug rifampin (Rif). PUM exhibits additive antibacterial activity when co-administered with Rif, exhibits no cross-resistance with Rif, and exhibits a spontaneous resistance rate an order-of-magnitude lower than that of Rif. PUM is a highly promising lead for antibacterial therapy.

SummaryHow cell size is determined and maintained remains unclear, even in simple model organisms. In proliferating cells, cell size is regulated by coordinating growth and division through sizer, adder, or timer mechanisms or through some combination [1, 2]. Currently, the best-characterized example of sizer behavior is in fission yeast, Schizosaccharomyces pombe, which enters mitosis at a minimal cell size threshold. The peripheral membrane kinase Cdr2 localizes in clusters (nodes) on the medial plasma membrane and promotes mitotic entry [3]. Here, we show that the Cdr2 nodal density, which scales with cell size, is used by the cell to sense and control its size. By analyzing cells of different widths, we first show that cdr2+ cells divide at a fixed cell surface area. However, division in the cdr2Δ mutant is more closely specified by cell volume, suggesting that Cdr2 is essential for area sensing and supporting the existence of a Cdr2-independent secondary sizer mechanism more closely based on volume. To investigate how Cdr2 nodes may sense area, we derive a minimal mathematical model that incorporates the cytoplasmic kinase Ssp1 as a Cdr2 activator. The model predicts that a cdr2 mutant in an Ssp1 phosphorylation site (cdr2-T166A) [4] should form nodes whose density registers cell length. We confirm this prediction experimentally and find that thin cells now follow this new scaling by dividing at constant length instead of area. This work supports the role of Cdr2 as a sizer factor and highlights the importance of studying geometrical aspects of size control.

Cell size is partly determined through coordination between cell growth and division. How this coordination is achieved mechanistically remains mostly unknown. However, quantitative experiments together with computational modelling have reinvigorated the field and are elucidating underlying molecular processes. Size homeostasis may be achieved through different modes of regulation, including “sizers”, “adders” and “timers.” For sizer regulation, the cell division cycle does not proceed until a minimal size has been reached, requiring that the cell monitors its own size. Here, we highlight progress in defining sizer mechanisms in fission and budding yeasts showing how accumulation or dilution of key molecules can be used to monitor cell size during growth. We also discuss a potential role for sizers in bacterial size control.

Sensory systems adapt, i.e., they adjust their sensitivity to external stimuli according to the ambient level. In this paper we show that single cell electrophysiological responses of vertebrate olfactory receptors and of photoreceptors to different input protocols exhibit several common features related to adaptation, and that these features can be used to investigate the dynamical structure of the feedback regulation responsible for the adaptation. In particular, we point out that two different forms of adaptation can be observed, in response to steps and to pairs of pulses. These two forms of adaptation appear to be in a dynamical trade-off: the more adaptation to a step is close to perfect, the slower is the recovery in adaptation to pulse pairs and viceversa. Neither of the two forms is explained by the dynamical models currently used to describe adaptation, such as the integral feedback model.