Paradoxical signaling regulates structural plasticity in dendritic spines

Transient spine enlargement (3-5 min timescale) is an important event associated with the structural plasticity of dendritic spines. Many of the molecular mechanisms associated with transient spine enlargement have been identified experimentally. Here, we use a systems biology approach to construct a mathematical model of biochemical signaling and actin-mediated transient spine expansion in response to calcium-influx due to NMDA receptor activation. We have identified that a key feature of this signaling network is the paradoxical signaling loop. Paradoxical components act bifunctionally in signaling networks and their role is to control both the activation and inhibition of a desired response function (protein activity or spine volume). Using ordinary differential equation (ODE)-based modeling, we show that the dynamics of different regulators of transient spine expansion including CaMKII, RhoA, and Cdc42 and the spine volume can be described using paradoxical signaling loops. Our model is able to capture the experimentally observed dynamics of transient spine volume. Furthermore, we show that actin remodeling events provide a robustness to spine volume dynamics. We also generate experimentally testable predictions about the role of different components and parameters of the network on spine dynamics

Loose mechanochemical coupling of molecular motors

In living cells, molecular motors convert chemical energy into mechanical work. Its thermodynamic energy efficiency, i.e. the ratio of output mechanical work to input chemical energy, is usually high. However, using two-state models, we found the motion of molecular motors is loosely coupled to the chemical cycle. Only part of the input energy can be converted into mechanical work. Others is dissipated into environment during substeps without contributions to the macro scale unidirectional movement

Acetylation of BMAL1 by TIP60 controls BRD4-P-TEFb recruitment to circadian promoters.

Many physiological processes exhibit circadian rhythms driven by cellular clocks composed of interlinked activating and repressing elements. To investigate temporal regulation in this molecular oscillator, we combined mouse genetic approaches and analyses of interactions of key circadian proteins with each other and with clock gene promoters. We show that transcriptional activators control BRD4-PTEFb recruitment to E-box-containing circadian promoters. During the activating phase of the circadian cycle, the lysine acetyltransferase TIP60 acetylates the transcriptional activator BMAL1 leading to recruitment of BRD4 and the pause release factor P-TEFb, followed by productive elongation of circadian transcripts. We propose that the control of BRD4-P-TEFb recruitment is a novel temporal checkpoint in the circadian clock cycle

Study of photosensitized decomposition of hydroperoxides Final report

Photosensitized decomposition of hydroperoxide

Queen control of a key life-history event in a eusocial insect

In eusocial insects, inclusive fitness theory predicts potential queen–worker conflict over the timing of events in colony life history. Whether queens or workers control the timing of these events is poorly understood. In the bumble-bee Bombus terrestris, queens exhibit a ‘switch point’ in which they switch from laying diploid eggs yielding females (workers and new queens) to laying haploid eggs yielding males. By rearing foundress queens whose worker offspring were removed as pupae and sexing their eggs using microsatellite genotyping, we found that queens kept in the complete absence of adult workers still exhibit a switch point. Moreover, the timing of their switch points relative to the start of egg-laying did not differ significantly from that of queens allowed to produce normal colonies. The finding that bumble-bee queens can express the switch point in the absence of workers experimentally demonstrates queen control of a key life-history event in eusocial insects. In addition, we found no evidence that workers affect the timing of the switch point either directly or indirectly via providing cues to queens, suggesting that workers do not fully express their interests in queen–worker conflicts over colony life history

The mean velocity of two-state models of molecular motor

The motion of molecular motor is essential to the biophysical functioning of living cells. In principle, this motion can be regraded as a multiple chemical states process. In which, the molecular motor can jump between different chemical states, and in each chemical state, the motor moves forward or backward in a corresponding potential. So, mathematically, the motion of molecular motor can be described by several coupled one-dimensional hopping models or by several coupled Fokker-Planck equations. To know the basic properties of molecular motor, in this paper, we will give detailed analysis about the simplest cases: in which there are only two chemical states. Actually, many of the existing models, such as the flashing ratchet model, can be regarded as a two-state model. From the explicit expression of the mean velocity, we find that the mean velocity of molecular motor might be nonzero even if the potential in each state is periodic, which means that there is no energy input to the molecular motor in each of the two states. At the same time, the mean velocity might be zero even if there is energy input to the molecular motor. Generally, the velocity of molecular motor depends not only on the potentials (or corresponding forward and backward transition rates) in the two states, but also on the transition rates between the two chemical states

USING SHIN LENGTH TO DETERMINE KICK PLATE POSITION OPTIMIZES SELECT SWIM START MECHANICS IN ELITE SWIMMERS

The track start kick plate position is often decided by the level of comfort of the swimmer. The purpose of this study was to use shin length as a measure to determine kick plate position and effects on performance. 20 elite swimmers performed 3 starts at 3 kick plate distances (\u3c shin length, shin length, and \u3e shin length). Differences in reaction time, block phase time (BT), flight phase time, flight distance, underwater phase time, time to the 15 m mark, knee flexion and ankle dorsiflexion angles were examined between the positions. BT was significantly different, (F(2,38)=4.264, p=.026). BT was lower when the kick plate distance was one shin’s length versus \u3c shin length (0.691+0.055 vs 0.715+0.056 sec) and \u3e shin length (0.691+0.055 vs 0.698+0.056 sec), p\u3c.05. Shin length is a quick and individualized measure that can be used by coaches to set the kick plate position without compromising performance

EFFECTS OF STANDARDIZING KICK PLATE POSITION ON TRACK START BIOMECHANICS IN ELITE SWIMMERS

Kick plate position in the track start is arbitrary but may influence performance. The purpose of this study was to investigate the influence of standardizing kick plate position based on shin length. 15 elite swimmers performed 3 starts at 3 kick plate positions (\u3c shin length, shin length, and \u3e shin length). Differences in reaction time (RT), block phase time, flight phase time, flight distance, underwater phase time, and time to the 15 m mark were examined between kick plate positions. Only RT was significantly different, (F(2,28)=4.713, p=.017). RT was lower when the kick plate distance was one shin’s length versus \u3c shin length (0.173+0.034vs 0.194+0.061 sec) and \u3e shin length (0.173+0.034 vs 0.195+0.047 sec),