Insights into Activation Mechanisms of Store-Operated TRPC1 Channels in Vascular Smooth Muscle.

In vascular smooth muscle cells (VMSCs), the stimulation of store-operated channels (SOCs) mediate Ca2+ influx pathways which regulate important cellular functions including contraction, proliferation, migration, and growth that are associated with the development of vascular diseases. It is therefore important that we understand the biophysical, molecular composition, activation pathways, and physiological significance of SOCs in VSMCs as these maybe future therapeutic targets for conditions such as hypertension and atherosclerosis. Archetypal SOCs called calcium release-activated channels (CRACs) are composed of Orai1 proteins and are stimulated by the endo/sarcoplasmic reticulum Ca2+ sensor stromal interaction molecule 1 (STIM1) following store depletion. In contrast, this review focuses on proposals that canonical transient receptor potential (TRPC) channels composed of a heteromeric TRPC1/C5 molecular template, with TRPC1 conferring activation by store depletion, mediate SOCs in native contractile VSMCs. In particular, it summarizes our recent findings which describe a novel activation pathway of these TRPC1-based SOCs, in which protein kinase C (PKC)-dependent TRPC1 phosphorylation and phosphatidylinositol 4,5-bisphosphate (PIP2) are obligatory for channel opening. This PKC- and PIP2-mediated gating mechanism is regulated by the PIP2-binding protein myristoylated alanine-rich C kinase (MARCKS) and is coupled to store depletion by TRPC1-STIM1 interactions which induce Gq/PLCβ1 activity. Interestingly, the biophysical properties and activation mechanisms of TRPC1-based SOCs in native contractile VSMCs are unlikely to involve Orai1

Visual processing of words in a patient with visual form agnosia: A behavioural and fMRI study

Patient D.F. has a profound and enduring visual form agnosia due to a carbon monoxide poisoning episode suffered in 1988. Her inability to distinguish simple geometric shapes or single alphanumeric characters can be attributed to a bilateral loss of cortical area LO, a loss that has been well established through structural and functional fMRI. Yet despite this severe perceptual deficit, D.F. is able to “guess” remarkably well the identity of whole words. This paradoxical finding, which we were able to replicate more than 20 years following her initial testing, raises the question as to whether D.F. has retained specialized brain circuitry for word recognition that is able to function to some degree without the benefit of inputs from area LO. We used fMRI to investigate this, and found regions in the left fusiform gyrus, left inferior frontal gyrus, and left middle temporal cortex that responded selectively to words. A group of healthy control subjects showed similar activations. The left fusiform activations appear to coincide with the area commonly named the visual word form area (VWFA) in studies of healthy individuals, and appear to be quite separate from the fusiform face area. We hypothesize that there is a route to this area that lies outside area LO, and which remains relatively unscathed in D.F

Funicular direct inguinal hernia

No Abstrac

An experimental proposal to study collapse of the wave function in travelling-wave parametric amplifiers

The read-out of a microwave qubit state occurs using an amplification chain that enlarges the quantum state to a signal detectable with a classical measurement apparatus. However, at what point in this process did we really `measure' the quantum state? In order to investigate whether the `measurement' takes place in the amplification chain, we propose to construct a microwave interferometer that has a parametric amplifier added to each of its arms. Feeding the interferometer with single photons, the visibility depends on the gain of the amplifiers and whether a measurement collapse has taken place during the amplification process. We calculate the interference visibility as given by standard quantum mechanics as a function of gain, insertion loss and temperature and find a magnitude of $1/3$ in the limit of large gain without taking into account losses. This number reduces to $0.26$ in case the insertion loss of the amplifiers is $2.2$ dB at a temperature of $50$ mK. We show that if the wave function collapses within the interferometer, we will measure a reduced visibility compared to the prediction from standard quantum mechanics once this collapse process sets in.Comment: 21 pages and 23 figures (including appendices and subfigures). v4: Abstract and introduction rewritten and note on stochasticity of quantum state collapse added to section 6. v5: no content changes w.r.t. v

A Terraced Scanning Superconducting Quantum Interference Device Susceptometer with Sub-Micron Pickup Loops

Superconducting Quantum Interference Devices (SQUIDs) can have excellent spin sensitivity depending on their magnetic flux noise, pick-up loop diameter, and distance from the sample. We report a family of scanning SQUID susceptometers with terraced tips that position the pick-up loops 300 nm from the sample. The 600 nm - 2 um pickup loops, defined by focused ion beam, are integrated into a 12-layer optical lithography process allowing flux-locked feedback, in situ background subtraction and optimized flux noise. These features enable a sensitivity of ~70 electron spins per root Hertz at 4K.Comment: See http://stanford.edu/group/moler/publications.html for an auxiliary document containing additional fabrication details and discussio

Archaea at St Andrews

A report of the Biochemical Society meeting 'The Molecular Biology of Archaea', St Andrews, UK, 19-21 August 2008