Mapping energy transport networks in proteins

The response of proteins to chemical reactions or impulsive excitation that occurs within the molecule has fascinated chemists for decades. In recent years ultrafast X-ray studies have provided ever more detailed information about the evolution of protein structural change following ligand photolysis, and time-resolved IR and Raman techniques, e.g., have provided detailed pictures of the nature and rate of energy transport in peptides and proteins, including recent advances in identifying transport through individual amino acids of several heme proteins. Computational tools to locate energy transport pathways in proteins have also been advancing. Energy transport pathways in proteins have since some time been identified by molecular dynamics (MD) simulations, and more recent efforts have focused on the development of coarse graining approaches, some of which have exploited analogies to thermal transport in other molecular materials. With the identification of pathways in proteins and protein complexes, network analysis has been applied to locate residues that control protein dynamics and possibly allostery, where chemical reactions at one binding site mediate reactions at distance sites of the protein. In this chapter we review approaches for locating computationally energy transport networks in proteins. We present background into energy and thermal transport in condensed phase and macromolecules that underlies the approaches we discuss before turning to a description of the approaches themselves. We also illustrate the application of the computational methods for locating energy transport networks and simulating energy dynamics in proteins with several examples

Classical Phase Space Revealed by Coherent Light

We study the far field characteristics of oval-resonator laser diodes made of an AlGaAs/GaAs quantum well. The resonator shapes are various oval geometries, thereby probing chaotic and mixed classical dynamics. The far field pattern shows a pronounced fine structure that strongly depends on the cavity shape. Comparing the experimental data with ray-model simulations for a Fresnel billiard yields convincing agreement for all geometries and reveals the importance of the underlying classical phase space for the lasing characteristics.Comment: 4 pages, 5 figures (reduced quality), accepted for publication in Physical Review Letter

Light emission patterns from stadium-shaped semiconductor microcavity lasers

We study light emission patterns from stadium-shaped semiconductor (GaAs) microcavity lasers theoretically and experimentally. Performing systematic wave calculations for passive cavity modes, we demonstrate that the averaging by low-loss modes, such as those realized in multi-mode lasing, generates an emission pattern in good agreement with the ray model's prediction. In addition, we show that the dependence of experimental far-field emission patterns on the aspect ratio of the stadium cavity is well reproduced by the ray model.Comment: 5 pages, 4 figure

Direct optical observations of surface thermal motions at sub-shot noise levels

We measure spectral properties of surface thermal fluctuations of liquids, solids, complex fluids and biological matter using light scattering methods. The random thermal fluctuations are delineated from random noise at sub-shot noise levels. The principle behind this extraction, which is quite general and is not limited to surface measurements, is explained. An optical lever is used to measure the spectrum of fluctuations in the inclinations of surfaces down to $\sim 10^{-17}\rm rad^2/Hz$ at $1\sim10 \mu$W optical intensity, corresponding to $\sim 10^{-29} \rm m^2/\rm Hz$ in the vertical displacement, in the frequency range $1{\rm}\rm kHz\sim10 MHz$. The dynamical evolution of the surface properties is also investigated. The measurement requires only a short amount of time and is essentially passive, so that it can be applied to a wide variety of surfaces.Comment: 5pp, 5 figure

Wave Chaos in Rotating Optical Cavities

It is shown that, even when the eigenmodes of an optical cavity are wave-chaotic, the frequency splitting due to the rotation of the cavity occurs and the frequency difference is proportional to the angular velocity although the splitting eigenmodes are still wave-chaotic and do not correspond to any unidirectionally-rotating waves.Comment: 4 pages, 6 figure

Dynamics of Toroidal Spiral Strings around Five-dimensional Black Holes

We examine the separability of the Nambu-Goto equation for test strings in a shape of toroidal spiral in a five-dimensional Kerr-AdS black hole. In particular, for a `{\it Hopf loop}\rq string which is a special class of the toroidal spiral strings, we show the complete separation of variables occurs in two cases, Kerr background and Kerr-AdS background with equal angular momenta. We also obtain the dynamical solution for the Hopf loop around a black hole and for the general toroidal spiral in Minkowski background.Comment: 16 pages, 1 figure, minor changes, references adde

Crx, a Novel otx-like Homeobox Gene, Shows Photoreceptor-Specific Expression and Regulates Photoreceptor Differentiation

AbstractWe have isolated a novel otx-like homeobox gene, Crx, from the mouse retina. Crx expression is restricted to developing and mature photoreceptor cells. CRX bound and transactivated the sequence TAATCC/A, which is found upstream of several photoreceptor-specific genes, including the opsin genes from many species. Overexpression of Crx using a retroviral vector increased the frequency of clones containing exclusively rod photoreceptors and reduced the frequency of clones containing amacrine interneurons and Müller glial cells. In addition, presumptive photoreceptor cells expressing a dominant-negative form of CRX failed to form proper photoreceptor outer segments and terminals. Crx is a novel photoreceptor-specific transcription factor and plays a crucial role in the differentiation of photoreceptor cells

Astrocytic LRP1 mediates brain Aβ clearance and impacts amyloid deposition

Accumulation and deposition of amyloid-β (Aβ) in the brain represent an early and perhaps necessary step in the pathogenesis of Alzheimer's disease (AD). Aβ accumulation leads to the formation of Aβ aggregates, which may directly and indirectly lead to eventual neurodegeneration. While Aβ production is accelerated in many familial forms of early-onset AD, increasing evidence indicates that impaired clearance of Aβ is more evident in late-onset AD. To uncover the mechanisms underlying impaired Aβ clearance in AD, we examined the role of low-density lipoprotein receptor-related protein 1 (LRP1) in astrocytes. Although LRP1 has been shown to play critical roles in brain Aβ metabolism in neurons and vascular mural cells, its role in astrocytes, the most abundant cell type in the brain responsible for maintaining neuronal homeostasis, remains unclear. Here, we show that astrocytic LRP1 plays a critical role in brain Aβ clearance. LRP1 knockdown in primary astrocytes resulted in decreased cellular Aβ uptake and degradation. In addition, silencing of LRP1 in astrocytes led to downregulation of several major Aβ-degrading enzymes, including matrix metalloproteases MMP2, MMP9, and insulin-degrading enzyme. More important, conditional knock-out of theLrp1gene in astrocytes in the background of APP/PS1 mice impaired brain Aβ clearance, exacerbated Aβ accumulation, and accelerated amyloid plaque deposition without affecting its production. Together, our results demonstrate that astrocytic LRP1 plays an important role in Aβ metabolism and that restoring LRP1 expression and function in the brain could be an effective strategy to facilitate Aβ clearance and counter amyloid pathology in AD.SIGNIFICANCE STATEMENTAstrocytes represent a major cell type regulating brain homeostasis; however, their roles in brain clearance of amyloid-β (Aβ) and underlying mechanism are not clear. In this study, we used both cellular models and conditional knock-out mouse models to address the role of a critical Aβ receptor, the low-density lipoprotein receptor-related protein 1 (LRP1) in astrocytes. We found that LRP1 in astrocytes plays a critical role in brain Aβ clearance by modulating several Aβ-degrading enzymes and cellular degradation pathways. Our results establish a critical role of astrocytic LRP1 in brain Aβ clearance and shed light on specific Aβ clearance pathways that may help to establish new targets for AD prevention and therapy.</jats:p