Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing.

Mammalian circadian rhythms are generated by a transcription-based feedback loop in which CLOCK:BMAL1 drives transcription of its repressors (PER1/2, CRY1/2), which ultimately interact with CLOCK:BMAL1 to close the feedback loop with ~24 hr periodicity. Here we pinpoint a key difference between CRY1 and CRY2 that underlies their differential strengths as transcriptional repressors. Both cryptochromes bind the BMAL1 transactivation domain similarly to sequester it from coactivators and repress CLOCK:BMAL1 activity. However, we find that CRY1 is recruited with much higher affinity to the PAS domain core of CLOCK:BMAL1, allowing it to serve as a stronger repressor that lengthens circadian period. We discovered a dynamic serine-rich loop adjacent to the secondary pocket in the photolyase homology region (PHR) domain that regulates differential binding of cryptochromes to the PAS domain core of CLOCK:BMAL1. Notably, binding of the co-repressor PER2 remodels the serine loop of CRY2, making it more CRY1-like and enhancing its affinity for CLOCK:BMAL1

Domain Dynamics in Piezoresponse Force Microscopy: Quantitative Deconvolution and Hysteresis Loop Fine Structure

Domain dynamics in the Piezoresponse Force Spectroscopy (PFS) experiment is studied using the combination of local hysteresis loop acquisition with simultaneous domain imaging. The analytical theory for PFS signal from domain of arbitrary cross-section is developed and used for the analysis of experimental data on Pb(Zr,Ti)O3 polycrystalline films. The results suggest formation of oblate domain at early stage of the domain nucleation and growth, consistent with efficient screening of depolarization field within the material. The fine structure of the hysteresis loop is shown to be related to the observed jumps in the domain geometry during domain wall propagation (nanoscale Barkhausen jumps), indicative of strong domain-defect interactions.Comment: 17 pages, 3 figures, 2 Appendices, to be submmited to Appl. Phys. Let

Comparison of polarization switching in ferroelectric TGS and relaxor SBN crystals

The comparative experimental analysis of polarization reversal kinetics in conventional homogeneous triglycine sulfate ((NH_{2}CH_{2}COOH)_{3} \cdot H_{2}SO_{4}; TGS) and relaxor strontium barium niobate (Sr_{0.61}Ba_{0.39}Nb_{2}O_{6}; SBN) crystals have been performed in a broad range of measurement conditions. The experimental data have been collected from microscopic observation of the domain structure, switching current and D-E hysteresis loop registration. The hysteresis loop and dielectric spectra have a strong link to the configuration of ferroelectric microdomains. The domain structure dynamics was examined by the nematic liquid crystal (NLC) method.Comment: 6 pages, 6 figure

Characterization of the catalytic flexible loop in the dihydroorotase domain of the human multi-enzymatic protein CAD

The dihydroorotase (DHOase) domain of the multifunctional protein carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase (CAD) catalyzes the third step in the de novo biosynthesis of pyrimidine nucleotides in animals. The crystal structure of the DHOase domain of human CAD (huDHOase) revealed that, despite evolutionary divergence, its active site components are highly conserved with those in bacterial DHOases, encoded as monofunctional enzymes. An important element for catalysis, conserved from Escherichia coli to humans, is a flexible loop that closes as a lid over the active site. Here, we combined mutagenic, structural, biochemical, and molecular dynamics analyses to characterize the function of the flexible loop in the activity of CAD's DHOase domain. A huDHOase chimera bearing the E. coli DHOase flexible loop was inactive, suggesting the presence of distinctive elements in the flexible loop of huDHOase that cannot be replaced by the bacterial sequence. We pinpointed Phe-1563, a residue absolutely conserved at the tip of the flexible loop in CAD's DHOase domain, as a critical element for the conformational equilibrium between the two catalytic states of the protein. Substitutions of Phe-1563 with Ala, Leu, or Thr prevented the closure of the flexible loop and inactivated the protein, whereas substitution with Tyr enhanced the interactions of the loop in the closed position and reduced fluctuations and the reaction rate. Our results confirm the importance of the flexible loop in CAD's DHOase domain and explain the key role of Phe-1563 in configuring the active site and in promoting substrate strain and catalysi

One-loop surface tensions of (supersymmetric) kink domain walls from dimensional regularization

We consider domain walls obtained by embedding the 1+1-dimensional $\phi^4$-kink in higher dimensions. We show that a suitably adapted dimensional regularization method avoids the intricacies found in other regularization schemes in both supersymmetric and non-supersymmetric theories. This method allows us to calculate the one-loop quantum mass of kinks and surface tensions of kink domain walls in a very simple manner, yielding a compact d-dimensional formula which reproduces many of the previous results in the literature. Among the new results is the nontrivial one-loop correction to the surface tension of a 2+1 dimensional N=1 supersymmetric kink domain wall with chiral domain-wall fermions.Comment: 23 pages, LATeX; v2: 25 pages, 2 references added, extended discussion of renormalization schemes which dispels apparent contradiction with previous result

Loop models on random maps via nested loops: case of domain symmetry breaking and application to the Potts model

We use the nested loop approach to investigate loop models on random planar maps where the domains delimited by the loops are given two alternating colors, which can be assigned different local weights, hence allowing for an explicit Z_2 domain symmetry breaking. Each loop receives a non local weight n, as well as a local bending energy which controls loop turns. By a standard cluster construction that we review, the Q = n^2 Potts model on general random maps is mapped to a particular instance of this problem with domain-non-symmetric weights. We derive in full generality a set of coupled functional relations for a pair of generating series which encode the enumeration of loop configurations on maps with a boundary of a given color, and solve it by extending well-known complex analytic techniques. In the case where loops are fully-packed, we analyze in details the phase diagram of the model and derive exact equations for the position of its non-generic critical points. In particular, we underline that the critical Potts model on general random maps is not self-dual whenever Q \neq 1. In a model with domain-symmetric weights, we also show the possibility of a spontaneous domain symmetry breaking driven by the bending energy.Comment: 44 pages, 13 figure

Ultraviolet Behavior of the Gluon Propagator in the Maximal Abelian Gauge

The ultraviolet asymptotic behavior of the gluon propagator is evaluated in the maximal Abelian gauge in the SU(2) gauge theory on the basis of the renormalization-group improved perturbation theory at the one-loop level. Square-root singularities obtained in the Euclidean domain are attributed to artifacts of the one-loop approximation in the maximal Abelian gauge and the standard normalization condition for the propagator used in our study. It is argued that this gauge is essentially nonperturbative.Comment: 15 pages, 2 figure

Modification of Loop 1 Affects the Nucleotide Binding Properties of Myo1c, the Adaptation Motor in the Inner Ear

Myo1c is one of eight members of the mammalian myosin I family of actin-associated molecular motors. In stereocilia of the hair cells in the inner ear, Myo1c presumably serves as the adaptation motor, which regulates the opening and closing of transduction channels. Although there is conservation of sequence and structure among all myosins in the N-terminal motor domain, which contains the nucleotide- and actin-binding sites, some differences include the length and composition of surface loops, including loop 1, which lies near the nucleotide-binding domain. To investigate the role of loop 1, we expressed in insect cells mutants of a truncated form of Myo1c, Myo1c1IQ, as well as chimeras of Myo1c1IQ with the analogous loop from other myosins. We found that replacement of the charged residues in loop 1 with alanines or the whole loop with a series of alanines did not alter the ATPase activity, transient kinetics properties, or Ca2+ sensitivity of Myo1c1IQ. Substitution of loop 1 with that of the corresponding region from tonic smooth muscle myosin II (Myo1c1IQ-tonic) or replacement with a single glycine (Myo1c1IQ-G) accelerated the release of ADP from A.M 2?3-fold in Ca2+, whereas substitution with loop 1 from phasic muscle myosin II (Myo1c1IQ-phasic) accelerated the release of ADP 35-fold. Motility assays with chimeras containing a single ?-helix, or SAH, domain showed that Myo1cSAH-tonic translocated actin in vitro twice as fast as Myo1cSAH-WT and 3-fold faster than Myo1cSAH-G. The studies show that changes induced in Myo1c via modification of loop 1 showed no resemblance to the behavior of the loop donor myosins or to the changes previously observed with similar Myo1b chimeras

QCD strings ending on domain walls --- a complete wetting phenomenon in SUSY QCD

In the context of M-theory, Witten has argued that an intriguing phenomenon occurs, namely that QCD strings can end on domain walls. We present a simpler explanation of this effect using effective field theory to describe the behavior of the Polyakov loop and the gluino condensate in N = 1 supersymmetric QCD. We describe how domain walls separating distinct confined phases appear in this effective theory and how these interfaces are completely wet by a film of deconfined phase at the high-temperature phase transition. This gives the Polyakov loop a non-zero expectation value on the domain wall. Consequently, a static test quark which is close to the interface has a finite free energy and the string emanating from it can end on the wall.Comment: LATTICE98(hightemp), 3 pages, 2 figure