Dynamic and redundant regulation of LRRK2 and LRRK1 expression

Background  

Mutations within the leucine-rich repeat kinase 2 (LRRK2) gene account for a significant proportion of autosomal-dominant and some late-onset sporadic Parkinson's disease. Elucidation of LRRK2 protein function in health and disease provides an opportunity for deciphering molecular pathways important in neurodegeneration. In mammals, LRRK1 and LRRK2 protein comprise a unique family encoding a GTPase domain that controls intrinsic kinase activity. The expression profiles of the murine LRRK proteins have not been fully described and insufficiently characterized antibodies have produced conflicting results in the literature.     

Charge rearrangement and screening in a quantum point contact

Compressibility measurements are performed on a quantum point contact (QPC). Screening due to mobile charges in the QPC is measured quantitatively, using a second point contact. These measurements are performed from pinch-off through the opening of the first few modes in the QPC. While the measured signal closely matches a Thomas-Fermi-Poisson prediction, deviations from the classical behavior are apparent near the openings of the different modes. Density functional calculations attribute the deviations to a combination of a diverging density of states at the opening of each one-dimensional mode and exchange interaction, which is strongest for the first mode.     

Self-assembly of nanoparticles on the surface of ionic crystals: Structural properties

With a suitable combination of ligand-stabilised nanoparticle suspension and ionic salt solutions, it is possible to produce microcrystals that are coated with nanoparticles. The self-assembly process of coating microcrystals by gold nanoparticles (NP) is mediated by the crystal lattice. This is the so-called CLAMS process - a generic process for self-organisation of nanoparticles on the surface of crystals [M. Murugeshan, D. Cunningham, J.-L. Martnez-Albertos, R. Vrcelj, B.D. Moore, Chem. Commun. (2005) 2677]. We are exploring here the structural properties of these self-assembled structures by using different imaging techniques.     

Cavity nonlinear optics at low photon numbers from collective atomic motion

We report on Kerr nonlinearity and dispersive optical bistability of a Fabry-Perot optical resonator due to the displacement of ultracold atoms trapped within. In the driven resonator, such collective motion is induced by optical forces acting upon up to 10(5) 87Rb atoms prepared in the lowest band of a one-dimensional intracavity optical lattice. The longevity of atomic motional coherence allows for strongly nonlinear optics at extremely low cavity photon numbers, as demonstrated by the observation of both branches of optical bistability at photon numbers below unity.     

How many black holes fit on the head of a pin?

The Bekenstein–Hawking entropy of certain black holes can be computed microscopically in string theory by mapping the elusive problem of counting microstates of a strongly gravitating black hole to the tractable problem of counting microstates of a weakly coupled D-brane system, which has no event horizon, and indeed comfortably fits on the head of a pin. We show here that, contrary to widely held beliefs, the entropy of spherically symmetric black holes can easily be dwarfed by that of stationary multi-black-hole “molecules” of the same total charge and energy. Thus, the corresponding pin-sized D-brane systems do not even approximately count the microstates of a single black hole, but rather those of a zoo of entropically dominant multicentered configurations. Fourth Award in the 2007 Essay Competition of the Gravity Research Foundation.     

Modeling binaural loudness

A survey of data on the perception of binaurally presented sounds indicates that loudness summation across ears is less than perfect; a diotic sound is less than twice as loud as the same sound presented monaurally. The loudness model proposed by Moore et al. [J. Audio Eng. Soc. 45, 224-240 (1997)] determines the loudness of binaural stimuli by a simple summation of loudness across ears. It is described here how the model can be modified so as to give more accurate predictions of the loudness of binaurally presented sounds, including cases where the sounds at the two ears differ in level, frequency or both. The modification is based on the idea that there are inhibitory interactions between the internal representations of the signals at the two ears, such that a signal at the left ear inhibits (reduces) the loudness evoked by a signal at the right ear, and vice versa. The inhibition is assumed to spread across frequency channels. The modified model gives reasonably accurate predictions of a variety of data on the loudness of binaural stimuli, including data obtained using loudness scaling and loudness matching procedures.     

Internal friction due to negative stiffness in the indium–thallium martensitic phase transformation

Internal friction and dynamic shear modulus in an indium–21?at.% thallium alloy were measured as functions of frequency and cooling rate using broadband viscoelastic spectroscopy during the martensitic transformation which occurs in this material occurs around 50°C. Microstructural evolution of martensitic bands was captured using time-lapse optical microscopy. The amplitude of damping peaks due to the temperature-induced transformation in the polycrystalline alloy was found to exceed those reported by others for single crystals of similar alloy compositions, in contrast to the usual reduction in damping in polycrystals. The high temperature portion of the damping peak occurs before martensitic bands are observed; therefore this portion cannot be due to interfacial motion. Constrained negative stiffness of the grains can account for this damping, as well as for amplification of internal friction peaks in these polycrystals and for sigmoid-shaped anomalies in the shear modulus at high cooling rates. Surface features associated with a previously unreported pre-martensitic phenomenon are seen at temperatures above martensite-start.     

Nmr and Mass Spectroscopic Studies of the Competitive-Angiotensin II Antagonist “Sarmesin”

Fast atom bombardment mass spectrometry (FAB-MS) and high resolution (400 Mz) proton nuclear magnetic resonance (NMR spectroscopy) on the competitive angiotensin II antagonist, |Sar¹, Tyr(Me)⁴ (ANGII (Sarmesin) and its he-ptapeptide homolog, [Tyr(Me)³ |ANGIII, yield spectra which provide confirmation of structure and molecular weight. The characteristics of the spectra are discussed and compared with the spectra of natural ANG II, ANG III and |Sar¹|ANG II. The NMR data are suggestive of interactions in angiotensin between: 1) the phenolic hydroxyl group and the imidazole ring, and 2) the N-terminal amino group and the Tyrring. These interactions may be important for the formation of the proposed charge transfer system in angiotensin II involving the phenoxyl and α-carboxylate groups.     

Mechanisms of modulation gap detection

It has been postulated that the central auditory system contains an array of modulation filters, each responsive to a different range of modulation frequencies present at the outputs of the (peripheral) auditory filters. In the present experiments, we tested what we call the "dip hypothesis," that a gap in modulation is detected using the "dip" in the output of the modulation filter tuned to the modulator frequency. In experiment 1, the task was to detect a gap in the sinusoidal amplitude modulation imposed on a 4-kHz carrier. The modulator preceding the gap ended with a positive-going zero-crossing. There were three conditions, differing in the phase at which the modulator started at the end of the gap; zero-phase, at a positive-going zero-crossing; pi-phase, at a negative-going zero-crossing; and "preserved" phase, at the phase the modulator would have had if it had continued without interruption. Modulation frequencies were 5, 10, 20, and 40 Hz. Psychometric functions for detection of the gap were measured using a two-alternative forced-choice task. For the zero-phase and preserved-phase conditions, the detectability index, d', increased monotonically with increasing gap duration. For the pi-phase condition, performance was good (d' > 1) for small gap durations, and initially worsened with increasing gap duration, before improving again for longer gap durations. This is the pattern of results expected from the dip hypothesis, provided that the modulation filters have Q values of 2 or more. However, it is also possible that a rhythm cue was used to improve performance in the pi-phase condition for short gap durations; the introduction of the gap markedly disrupted the regular rhythm produced by the modulator peaks. In experiment 2, the rhythm cue was disrupted by varying the modulator period randomly around its nominal value, except for the modulator periods immediately before and after the gap. This markedly impaired performance, and resulted in psychometric functions that were very similar for the zero-phase and pi-phase conditions. This pattern of results is inconsistent with the dip hypothesis. For both experiments, modulation gap "thresholds" (d' approximately 1) were roughly constant when expressed as a proportion of the modulator period. Possible mechanisms of modulation gap detection are discussed and evaluated.