Dynamics of a minimal model of interlocked positive and negative feedback loops of transcriptional regulation by cAMP-response element binding proteins.

cAMP-response element binding (CREB) proteins are involved in transcriptional regulation in a number of cellular processes (e.g., neural plasticity and circadian rhythms). The CREB family contains activators and repressors that may interact through positive and negative feedback loops. These loops can be generated by auto- and cross-regulation of expression of CREB proteins, via CRE elements in or near their genes. Experiments suggest that such feedback loops may operate in several systems (e.g., Aplysia and rat). To understand the functional implications of such feedback loops, which are interlocked via cross-regulation of transcription, a minimal model with a positive and negative loop was developed and investigated using bifurcation analysis. Bifurcation analysis revealed diverse nonlinear dynamics (e.g., bistability and oscillations). The stability of steady states or oscillations could be changed by time delays in the synthesis of the activator (CREB1) or the repressor (CREB2). Investigation of stochastic fluctuations due to small numbers of molecules of CREB1 and CREB2 revealed a bimodal distribution of CREB molecules in the bistability region. The robustness of the stable HIGH and LOW states of CREB expression to stochastic noise differs, and a critical number of molecules was required to sustain the HIGH state for days or longer. Increasing positive feedback or decreasing negative feedback also increased the lifetime of the HIGH state, and persistence of this state may correlate with long-term memory formation. A critical number of molecules was also required to sustain robust oscillations of CREB expression. If a steady state was near a deterministic Hopf bifurcation point, stochastic resonance could induce oscillations. This comparative analysis of deterministic and stochastic dynamics not only provides insights into the possible dynamics of CREB regulatory motifs, but also demonstrates a framework for understanding other regulatory processes with similar network architecture.

A model of late long-term potentiation simulates aspects of memory maintenance.

Late long-term potentiation (L-LTP) denotes long-lasting strengthening of synapses between neurons. L-LTP appears essential for the formation of long-term memory, with memories at least partly encoded by patterns of strengthened synapses. How memories are preserved for months or years, despite molecular turnover, is not well understood. Ongoing recurrent neuronal activity, during memory recall or during sleep, has been hypothesized to preferentially potentiate strong synapses, preserving memories. This hypothesis has not been evaluated in the context of a mathematical model representing ongoing activity and biochemical pathways important for L-LTP. In this study, ongoing activity was incorporated into two such models - a reduced model that represents some of the essential biochemical processes, and a more detailed published model. The reduced model represents synaptic tagging and gene induction simply and intuitively, and the detailed model adds activation of essential kinases by Ca(2+). Ongoing activity was modeled as continual brief elevations of Ca(2+). In each model, two stable states of synaptic strength/weight resulted. Positive feedback between synaptic weight and the amplitude of ongoing Ca(2+) transients underlies this bistability. A tetanic or theta-burst stimulus switches a model synapse from a low basal weight to a high weight that is stabilized by ongoing activity. Bistability was robust to parameter variations in both models. Simulations illustrated that prolonged periods of decreased activity reset synaptic strengths to low values, suggesting a plausible forgetting mechanism. However, episodic activity with shorter inactive intervals maintained strong synapses. Both models support experimental predictions. Tests of these predictions are expected to further understanding of how neuronal activity is coupled to maintenance of synaptic strength. Further investigations that examine the dynamics of activity and synaptic maintenance can be expected to help in understanding how memories are preserved for up to a lifetime in animals including humans.

Plant Adenosine 5′-phosphosulfate Reductase Is a Novel Iron-Sulfur Protein

Adenosine 5′-phosphosulfate reductase (APR) catalyzes the two-electron reduction of adenosine 5′-phosphosulfate to sulfite and AMP, which represents the key step of sulfate assimilation in higher plants. Recombinant APRs from both Lemna minorand Arabidopsis thaliana were overexpressed inEscherichia coli and isolated as yellow-brown proteins. UV-visible spectra of these recombinant proteins indicated the presence of iron-sulfur centers, whereas flavin was absent. This result was confirmed by quantitative analysis of iron and acid-labile sulfide, suggesting a 4Fe-4S cluster as the cofactor. EPR spectroscopy of freshly purified enzyme showed, however, only a minor signal at g = 2.01. Therefore, Mössbauer spectra of 57Fe-enriched APR were obtained at 4.2 K in magnetic fields of up to 7 tesla, which were assigned to a diamagnetic 4Fe-4S2+ cluster. This cluster was unusual because only three of the iron sites exhibited the same Mössbauer parameters. The fourth iron site gave, because of the bistability of the fit, a significantly smaller isomer shift or larger quadrupole splitting than the other three sites. Thus, plant assimilatory APR represents a novel type of adenosine 5′-phosphosulfate reductase with a 4Fe-4S center as the sole cofactor, which is clearly different from the dissimilatory adenosine 5′-phosphosulfate reductases found in sulfate reducing bacteria.

Two-wavelength switching with a distributed-feed back semiconductor optical amplifier (DFBSOA)

Switching of a signal beam by another control beam at different wavelength is demonstrated experimentally using the optical bistability occurring in a 1.55 mm-distributed feedback semiconductor optical amplifier (DFBSOA) working in reflection. Counterclockwise (S-shaped) and reverse (clockwise) bistability are observed in the output of the control and the signal beam respectively, as the power of the input control signal is increased. With this technique an optical signal can be set in either of the optical input wavelengths by appropriate choice of the powers of the input signals. The switching properties of the DFBSOA are studied experimentally as the applied bias current is increased from below to above threshold and for different levels of optical power in the signal beam and different wavelength detunings between both input signals. Higher on-off extinction ratios, wider bistable loops and lower input power requirements for switching are obtained when the DFBSOA is operated slightly above its threshold value.

All-optical logic gates with 1550nm Fabry-Perot and distributed feedback semiconductor laser amplifiers

The optical bistability occurring in laser diode amplifiers is used to design an all-optical logic gate capable to provide the whole set of logic functions. The structure of the reported logic gate is based on two connected 1550nm laser amplifiers (Fabry-Perot and distributed feedback laser amplifiers).

Optical Nonlinearities at the Interface between Glass and Liquid Crystal

In this paper, the optical behavior of a nonlinear interface is studied. The nonlinear medium has been a nematic liquid crystal, namely MBBA, and the nonlinear one, glasses of different types (F-10 and F-2) depending on the experimental needs. The anchoring forces at the boundary have been found to inhibit the action of the evanescent field in the case of total internal reflection. Most of observed nonlinearities are due to thermal effects. As a consequence, liquid crystals do not seem to be good candidates for total internal reflection optical bistability.

Optical Multistability and Oscillations in Hybrid Optical Bistable Systems with Short Delay Times

Optical instabilities in the output light from a bistable optical device (BOD) with a delayed feedback was predicted by Ikeda [1]. Gibbs et al. [2] gave the first experimental verification of this type of instabilities. From that time several groups have studied the instabilities of the BOD for different relations between the delay time tR and the time constant ح of the system. In a previous paper [3] an empirical and analytical study of instabilities in hybrid BOD was reported by us. The employed set up is shown in Fig. 1.

Optical memory with twisted nematic liquid crystal (TNLC) devices

A design for obtaining memory in optical bistability with liquid crystals is reported. This design uses optical feedback on a twisted nematie liquid crystal ( TNLC ) through an optoelectronic system. A constant input light is the read-out and its value depends on the desired initial working point, usually at the bottom of the T(V) vs. V curve. Light levels depend on the feedback. An input light pulse change the working point to the top of the transmission curve. When this pulse vanishes, the working point remains at the upper part of the curve. Hence a memory function is obtained. Minimum pulse width needed was 1msec. ON-OPF ratio was 100:3.

Optical bistable devices as sensing elements

The nonlinear optical properties of many materials and devices have been the main object of research as potential candidates for sensing in different places. Just one of these properties has been, in most of the cases, the basis for the sensing operation. As a consequence, just one parameter can be detected. In this paper, although just one property will be employed too, we will show the possibility to sense different parameters with just one type of sensor. The way adopted in this work is the use of the optical bistability obtained from different photonic structures. Because this optical bistability has a strong dependence on many different parameters the possibility to sense different inputs appears. In our case, we will report the use of some non-linear optical devices, mainly Semiconductor Optical Amplifiers, as sensing elements. Because their outputs depend on many parameters, as the incident light wavelength, polarization, intensity and direction, applied voltage and feedback characteristics, they can be employed to detect, at the same time, different type of signals. This is because the way these different signals affect to the sensor response is very different too and appears under a different set of characteristics.

Old concepts for new times in photonics sensing: from inconvenient to practical

After a brief review of some old concepts getting application when new technologies have been developed, this paper offers a short review to some optical bistability concepts. It is shown how different concepts can be employed today in many fields, after being considered as inconvenient when they were found. Some practical applications and some proposals will be reported.

Optical nonlinearities at the interface between liquid crystal and glass: behavior of the transmitted beam.

During the past years a great interest has been devoted to the study of possible applications of non-linear interfaces, mainly in the field of Optical Bistability. Several papers have been published in this field, and some of them dealing with liquid crystals as non-linear material.

Empirical and analytical study of instabilities in hybrid optical bistable systems

As it is well known from the work by Gibbs et al., optical turbulence and periodic oscillations are easily seen in hybrid optical bistable devices when a delay is added to the feedback. Such effects, as it was pointed out by Gibbs, may be used to convert cw laser power into a train of light pulses.

Self-beating instabilities in bistable devices

Since the observation of optical bistability by Gibbs et al., optical bistability has been the field where researchers from many fields have found a common place to work. More recently, when Ikeda and co-workers discussed the effect of a delayed feedback on instability of a ring cavity containing a non linear dielectric medium, and pointed out that the transmitted light from the ring cavity can be periodic or chaotic in time under a certain condition, optical bistable devices have shown new possibilities to be applied in many different fields. The novel phenomenon has been predicted to be observed in the hybrid optical device and has been confirmed by Gibbs et al. Moreover, as we have shown, a similar effect can be obtained when liquid crystal cells are employed as non linear element.

Wavelength monitoring with semiconductor laser amplifiers

The semiconductor laser diodes that are typically used in applications of optical communications, when working as amplifiers, present under certain conditions optical bistability, which is characterized by abruptly switching between two different output states and an associated hysteresis cycle. This bistable behavior is strongly dependent on the frequency detuning between the frequency of the external optical signal that is injected into the semiconductor laser amplifier and its own emission frequency. This means that small changes in the wavelength of an optical signal applied to a laser amplifier causes relevant changes in the characteristics of its transfer function in terms of the power requirements to achieve bistability and the width of the hysteresis. This strong dependence in the working characteristics of semiconductor laser amplifiers on frequency detuning suggest the use of this kind of devices in optical sensing applications for optical communications, such as the detection of shifts in the emission wavelength of a laser, or detect possible interference between adjacent channels in DWDM (Dense Wavelength Division Multiplexing) optical communication networks

Optical memory with TNLC devices (1982)

In this paper we describe a twisted nematic liquid crystal (TNLC) device structure with optical feedback capable of bistable operation and optical memory. Its structure is the conventional one as employed in hybrid optical bistability.