Synthetic Physiology

Optogenetic tools are DNA-encoded molecules that, when genetically targeted to cells, enable the control of specific physiological processes within those cells through exposure to light. These tools can pinpoint how these specific processes affect the emergent properties of a complex biological system, such as a mammalian organ or even an entire animal. They can also allow control of a biological system for therapeutic or bioengineering purposes. Many of the optical control tools explored to date are single-component reagents containing a photoactive signaling domain. An interesting question is raised by comparing optogenetics to synthetic biology. In the latter, interchangeable and modular DNA-encoded parts are assembled into complex biological circuits, thus enabling sophisticated logic and computation as well as the production of biologics and reagents (1, 2). Is it possible to devise strategies for the temporally precise cell-targeted optical control of complex engineered biological computational or chemical-synthetic pathways? Such a marriage of optogenetics and synthetic biology—which one might call synthetic physiology—would open up the ability to use optogenetics to trigger and regulate engineered synthetic biology systems, which in turn could execute computational and biological programs of great complexity (3). On page 1565 of this issue, Ye et al. (4) explore such a hybrid approach to controlling a biological system, as well as the bioengineering and preclinical capabilities opened up by such an approach

Creativity and Autonomy in Swarm Intelligence Systems

This work introduces two swarm intelligence algorithms -- one mimicking the behaviour of one species of ants (\emph{Leptothorax acervorum}) foraging (a `Stochastic Diffusion Search', SDS) and the other algorithm mimicking the behaviour of birds flocking (a `Particle Swarm Optimiser', PSO) -- and outlines a novel integration strategy exploiting the local search properties of the PSO with global SDS behaviour. The resulting hybrid algorithm is used to sketch novel drawings of an input image, exploliting an artistic tension between the local behaviour of the `birds flocking' - as they seek to follow the input sketch - and the global behaviour of the `ants foraging' - as they seek to encourage the flock to explore novel regions of the canvas. The paper concludes by exploring the putative `creativity' of this hybrid swarm system in the philosophical light of the `rhizome' and Deleuze's well known `Orchid and Wasp' metaphor

The Role of PAS Kinase in PASsing the Glucose Signal

PAS kinase is an evolutionarily conserved nutrient responsive protein kinase that regulates glucose homeostasis. Mammalian PAS kinase is activated by glucose in pancreatic beta cells, and knockout mice are protected from obesity, liver triglyceride accumulation, and insulin resistance when fed a high-fat diet. Yeast PAS kinase is regulated by both carbon source and cell integrity stress and stimulates the partitioning of glucose toward structural carbohydrate biosynthesis. In our current model for PAS kinase regulation, a small molecule metabolite binds the sensory PAS domain and activates the enzyme. Although bona fide PAS kinase substrates are scarce, in vitro substrate searches provide putative targets for exploration

Swarmic sketches and attention mechanism

This paper introduces a novel approach deploying the mechanism of ‘attention’ by adapting a swarm intelligence algorithm – Stochastic Diffusion Search – to selectively attend to detailed areas of a digital canvas. Once the attention of the swarm is drawn to a certain line within the canvas, the capability of another swarm intelligence algorithm – Particle Swarm Intelligence – is used to produce a ‘swarmic sketch’ of the attended line. The swarms move throughout the digital canvas in an attempt to satisfy their dynamic roles – attention to areas with more details – associated to them via their fitness function. Having associated the rendering process with the concepts of attention, the performance of the participating swarms creates a unique, non-identical sketch each time the ‘artist’ swarms embark on interpreting the input line drawings. The detailed investigation of the ‘creativity’ of such systems have been explored in our previous work; nonetheless, this papers provides a brief account of the ‘computational creativity’ of the work through two prerequisites of creativity within the swarm intelligence’s two infamous phases of exploration and exploitation; these phases are described herein through the attention and tracing mechanisms respectively

Swarmic paintings and colour attention

Swarm-based multi-agent systems have been deployed in non-photorealistic rendering for many years. This paper introduces a novel approach in adapting a swarm intelligence algorithm – Stochastic Diffusion Search – for producing non-photorealistic images. The swarm-based system is presented with a digital image and the agents move throughout the digital canvas in an attempt to satisfy the dynamic roles – attention to different colours - associated to them via their fitness function. Having associated the rendering process with the concepts of ‘attention’ in general and colour attention in particular, this papers briefly discusses the ‘computational creativity’ of the work through two prerequisites of creativity (i.e. freedom and constraints) within the swarm intelligence’s two infamous phases of exploration and exploitation

Characterization of the Blue-Light-Activated Adenylyl Cyclase mPAC by Flash Photolysis and FTIR Spectroscopy

The recently discovered photo-activated adenylyl cyclase (mPAC from Microcoleus chthonoplastes) is the first PAC that owes a light-, oxygen- and voltage-sensitive (LOV) domain for blue-light sensing. The photoreaction of the mPAC receptor was studied by time-resolved UV/vis and light-induced Fourier transform infrared (FTIR) absorption difference spectroscopy. The photocycle comprises of the typical triplet state LOV715 and the thio-adduct state LOV390. While the adduct state decays with a time constant of 8 s, the lifetime of the triplet state is with 656 ns significantly shorter than in all other reported LOV domains. The light-induced FTIR difference spectrum shows the typical bands of the LOV390 and LOV450 intermediates. The negative S-H stretching vibration at 2573 cm−1 is asymmetric suggesting two rotamer configurations of the protonated side chain of C194. A positive band at 3632 cm−1 is observed, which is assigned to an internal water molecule. In contrast to other LOV domains, mPAC exhibits a second positive feature at 3674 cm−1 which is due to the O-H stretch of a second intrinsic water molecule and the side chain of Y476. We conclude that the latter might be involved in the dimerization of the cyclase domain which is crucial for ATP binding

BLUF Domain Function Does Not Require a Metastable Radical Intermediate State

BLUF (blue light using flavin) domain proteins are an important family of blue light-sensing proteins which control a wide variety of functions in cells. The primary light-activated step in the BLUF domain is not yet established. A number of experimental and theoretical studies points to a role for photoinduced electron transfer (PET) between a highly conserved tyrosine and the flavin chromophore to form a radical intermediate state. Here we investigate the role of PET in three different BLUF proteins, using ultrafast broadband transient infrared spectroscopy. We characterize and identify infrared active marker modes for excited and ground state species and use them to record photochemical dynamics in the proteins. We also generate mutants which unambiguously show PET and, through isotope labeling of the protein and the chromophore, are able to assign modes characteristic of both flavin and protein radical states. We find that these radical intermediates are not observed in two of the three BLUF domains studied, casting doubt on the importance of the formation of a population of radical intermediates in the BLUF photocycle. Further, unnatural amino acid mutagenesis is used to replace the conserved tyrosine with fluorotyrosines, thus modifying the driving force for the proposed electron transfer reaction; the rate changes observed are also not consistent with a PET mechanism. Thus, while intermediates of PET reactions can be observed in BLUF proteins they are not correlated with photoactivity, suggesting that radical intermediates are not central to their operation. Alternative nonradical pathways including a keto–enol tautomerization induced by electronic excitation of the flavin ring are considered

Femtosecond Stimulated Raman Study of the Photoactive Flavoprotein AppABLUF

Femtosecond stimulated Raman Spectroscopy (FSRS) is applied to study the photocycle of a blue light using flavin (BLUF) domain photoreceptor, AppABLUF. It is shown that FSRS spectra are sensitive to the light adapted state of the protein and probe its excited state dynamics. The dominant contribution to the most sensitive excited state Raman active modes is from flavin ring modes. However, TD-DFT calculations for excited state structures indicate that reproduction and assignment of the experimentally observed spectral shift will require high level calculations on the flavin in its specific protein environment

On the Dynamic Stability of Cool Supergiant Atmospheres

We have developed a new formalism to compute the thermodynamic coefficient Gamma1 in the theory of stellar and atmospheric stability. We generalize the classical derivation of the first adiabatic index, which is based on the assumption of thermal ionization and equilibrium between gas and radiation temperature, towards an expression which incorporates photo-ionization due to radiation with a temperature T_rad different from the local kinetic gas temperature.Our formalism considers the important non-LTE conditions in the extended atmospheres of supergiant stars. An application to the Kurucz grid of cool supergiant atmospheres demonstrates that models with T_rad =~ T_eff between 6500 K and 7500 K become most unstable against dynamic perturbations, according to Ledoux' stability integral . This results from Gamma1 and acquiring very low values, below 4/3, throughout the entire stellar atmosphere, which causes very high gas compression ratios around these effective temperatures. Based on detailed NLTE-calculations, we discuss atmospheric instability of pulsating massive yellow supergiants, like the hypergiant rho Cas (Ia+), which exist in the extension of the Cepheid instability strip, near the Eddington luminosity limit.Comment: 54 pages including figures and the Appendix, 7 figures, Accepted for The Astrophysical Journal, Main Journal, 558, Sept. 200

Information sharing impact of stochastic diffusion search on differential evolution algorithm

This work details the research aimed at applying the powerful resource allocation mechanism deployed in stochastic diffusion search (SDS) to the differential evolution (DE), effectively merging a nature inspired swarm intelligence algorithm with a biologically inspired evolutionary algorithm. The results reported herein suggest that the hybrid algorithm, exploiting information sharing between the population elements, has the potential to improve the optimisation capability of classical DE algorithms. This claim is verified by running several experiments using state-of-the-art benchmarks. Additionally, the significance of the frequency within which SDS introduces communication and information exchange is also investigated