Positive regulation of meiotic DNA double-strand break formation by activation of the DNA damage checkpoint kinase Mec1(ATR)

During meiosis, formation and repair of programmed DNA double-strand breaks (DSBs) create genetic exchange between homologous chromosomes-a process that is critical for reductional meiotic chromosome segregation and the production of genetically diverse sexually reproducing populations. Meiotic DSB formation is a complex process, requiring numerous proteins, of which Spo11 is the evolutionarily conserved catalytic subunit. Precisely how Spo11 and its accessory proteins function or are regulated is unclear. Here, we use Saccharomyces cerevisiae to reveal that meiotic DSB formation is modulated by the Mec1(ATR) branch of the DNA damage signalling cascade, promoting DSB formation when Spo11-mediated catalysis is compromised. Activation of the positive feedback pathway correlates with the formation of single-stranded DNA (ssDNA) recombination intermediates and activation of the downstream kinase, Mek1. We show that the requirement for checkpoint activation can be rescued by prolonging meiotic prophase by deleting the NDT80 transcription factor, and that even transient prophase arrest caused by Ndt80 depletion is sufficient to restore meiotic spore viability in checkpoint mutants. Our observations are unexpected given recent reports that the complementary kinase pathway Tel1(ATM) acts to inhibit DSB formation. We propose that such antagonistic regulation of DSB formation by Mec1 and Tel1 creates a regulatory mechanism, where the absolute frequency of DSBs is maintained at a level optimal for genetic exchange and efficient chromosome segregation

Long-range electron transfer in structurally engineered pentaammineruthenium (histidine-62) cytochrome c

In many biological processes, long-range electron transfer (ET) plays a key role. When the three-dimensional structures of proteins are accurately known, use of modified proteins and protein-protein complexes provides an experimental approach to study ET rates between two metal centers. For Ru(His)- modified proteins, the introduction of histidine residues at any desired surface location by site-directed mutagenesis opens the way for systematic investigations of ET pathways

Optimal time for sensing in open quantum systems

We study the time-dependent quantum Fisher information (QFI) in an open quantum system satisfying the Gorini-Kossakowski-Sudarshan-Lindblad master equation. We also study the dynamics of the system from an effective non-Hermitian dynamics standpoint and use it to understand the scaling of the QFI when multiple probes are used. A focus of our work is how the QFI is maximized at certain times suggesting that the best precision in parameter estimation can be achieved by focusing on these times. The propagation of errors analysis allows us to confirm and better understand this idea. We also propose a parameter estimation procedure involving relatively low resource consuming measurements followed by higher resource consuming measurements and demonstrate it in simulation.Comment: 11 pages,8 Figure

Achieving the Heisenberg limit with Dicke states in noisy quantum metrology

Going beyond the standard quantum limit in noisy quantum metrology is an important and challenging task. Here we show how Dicke states can be used to surpass the standard quantum limit and achieve the Heisenberg limit in open quantum systems. The system we study has qubits symmetrically coupled to a resonator and our objective is to estimate the coupling between the qubits and the resonator. The time-dependent quantum Fisher information with respect to the coupling is studied for this open quantum system where the same decay rates are assumed on all qubits. We show that when the system is initialized to a Dicke state with an optimal excitation number one can go beyond the standard quantum limit and achieve the Heisenberg limit even for finite values of the decays on the qubit and the resonator, particularly when the qubits and resonator are strongly coupled. We compare our results against the highly entangled GHZ state and a completely separable state and show that the GHZ state performs quite poorly whereas under certain noise conditions the separable state is able to go beyond the standard quantum limit due to subsequent interactions with a resonator.Comment: 11 pages, 7 Figures, typos corrected and references adde

Family Correlates of Daughter’s and Son’s Locus of Control Expectancies during Childhood

Children who expect they can bring about good outcomes and avoid bad outcomes tend to experience more personal successes. Little is known about factors that contribute to these ‘control expectancies’. The purpose of the present study was to determine whether children’s internal control expectancies occur in the context of parents’ internal control expectancies, low family strain, and high family cohesiveness and whether these factors are more strongly related to daughters’ than sons’ control expectancies. A community sample of 85 children aged 9 to 11 years old and their parents (85 mothers; 63 fathers) completed rating scales. Fathers’ more internal control expectancies and mothers’ reports of fewer family strains were associated with daughters’ but not sons’ greater internal control expectancies, and greater family cohesiveness was related to both daughters’ and sons’ internal control orientations. These findings suggest that family factors may contribute to children’s, particularly daughters’, development of internal control expectancies

Enhanced quantum sensing mediated by a cavity in open systems

We simulate the dynamics of systems with $N$ = 1-20 qubits coupled to a cavity in order to assess their potential for quantum metrology of a parameter in the open systems limit. The qubits and the cavity are both allowed to have losses and the system is studied under various coupling strength regimes. The focus is primarily on the coupling between the qubits using the quantum Fisher information as the measured parameter. Some results on estimating the qubit-cavity detuning parameter are also presented. We investigate the scaling of the uncertainty in the estimate of the qubit-cavity coupling with the number of qubits and for different initial states of the qubits that act as the quantum probe. As initial probe states, we consider Dicke states with varying excitation numbers, the GHZ state, and separable X-polarized states. It is shown that in the strong coupling regime, i.e., when the coupling between the qubits and the cavity is greater than the decay parameters of both the qubits and the cavity, Dicke states with a large excitation number can achieve the Heisenberg limit, with the precision scaling improving as the excitation number increases. A particularly intriguing finding of our study is that in the weak coupling regime, as well as in situations where either the qubit or cavity decay parameters exceed the coupling, the separable $X$-polarized state is the best in terms of scaling and is even able to achieve the Heisenberg limit in these lossy regimes for the range of $N$ considered

Plasticity and learning in a network of coupled phase oscillators

A generalized Kuramoto model of coupled phase oscillators with slowly varying coupling matrix is studied. The dynamics of the coupling coefficients is driven by the phase difference of pairs of oscillators in such a way that the coupling strengthens for synchronized oscillators and weakens for non-synchronized pairs. The system possesses a family of stable solutions corresponding to synchronized clusters of different sizes. A particular cluster can be formed by applying external driving at a given frequency to a group of oscillators. Once established, the synchronized state is robust against noise and small variations in natural frequencies. The phase differences between oscillators within the synchronized cluster can be used for information storage and retrieval.Comment: 10 page

Biochemical Reconstitution of Hemorrhagic-Fever Arenavirus Envelope Glycoprotein-Mediated Membrane Fusion

The membrane-anchored proteins of enveloped viruses form labile spikes on the virion surface, primed to undergo large-scale conformational changes culminating in virus-cell membrane fusion and viral entry. The prefusion form of these envelope glycoproteins thus represents an important molecular target for antiviral intervention. A critical roadblock to this endeavor has been our inability to produce the prefusion envelope glycoprotein trimer for biochemical and structural analysis. Through our studies of the GPC envelope glycoprotein of the hemorrhagic fever arenaviruses, we have shown that GPC is unique among class I viral fusion proteins in that the mature complex retains a stable signal peptide (SSP) in addition to the conventional receptor-binding and transmembrane fusion subunits. In this report we show that the recombinant GPC precursor can be produced as a discrete native-like trimer and that its proteolytic cleavage generates the mature glycoprotein. Proteoliposomes containing the cleaved GPC mediate pH-dependent membrane fusion, a characteristic feature of arenavirus entry. This reaction is inhibited by arenavirus-specific monoclonal antibodies and small-molecule fusion inhibitors. The in vitro reconstitution of GPC-mediated membrane-fusion activity offers unprecedented opportunities for biochemical and structural studies of arenavirus entry and its inhibition. To our knowledge, this report is the first to demonstrate functional reconstitution of membrane fusion by a viral envelope glycoprotein