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

SUMSS: A Wide-Field Radio Imaging Survey of the Southern Sky. I. Science goals, survey design and instrumentation

The Molonglo Observatory Synthesis Telescope, operating at 843 MHz with a 5 square degree field of view, is carrying out a radio imaging survey of the sky south of declination -30 deg. This survey (the Sydney University Molonglo Sky Survey, or SUMSS) produces images with a resolution of 43" x 43" cosec(Dec.) and an rms noise level of about 1 mJy/beam. SUMSS is therefore similar in sensitivity and resolution to the northern NRAO VLA Sky Survey (NVSS; Condon et al. 1998). The survey is progressing at a rate of about 1000 square degrees per year, yielding individual and statistical data for many thousands of weak radio sources. This paper describes the main characteristics of the survey, and presents sample images from the first year of observation.Comment: 27 pages, 12 figures (figures 2, 8, 10 in jpg format); AJ, in pres

Stochastic control in microscopic nonequilibrium systems

Quantifying energy flows at nanometer scales promises to guide future research in a variety of disciplines, from microscopic control and manipulation, to autonomously operating molecular machines. A general understanding of the thermodynamic costs of nonequilibrium processes would illuminate the design principles for efficient microscopic machines. Considerable effort has gone into finding and classifying the deterministic control protocols that drive a system rapidly between states at minimum energetic cost. But for autonomous microscopic systems, driving processes are themselves stochastic. Here we generalize a linear-response framework to incorporate such protocol variability, deriving a lower bound on the work that is realized at finite protocol duration, far from the quasistatic limit. Our findings are confirmed in model systems. This theory provides a thermodynamic rationale for rapid operation, independent of functional incentives.Comment: 11 pages, 4 figure

Identification of floodwater source areas in Nepal using SCIMAP‐Flood

Practical approaches for managing flooding from fluvial sources are moving away from mitigation solely at the point of impact and towards integrated catchment management. This considers the source areas, flow pathways of floodwaters and the locations and exposure to the risk of communities. For a field site in southern Nepal, we analyse catchment response to a range of simulated rainfall events, which when evaluated collectively can help guide potential flood management solutions. This is achieved through the adoption of SCIMAP-Flood, a decision support framework that works at the catchment-scale to identify critical source areas for floodwaters. The SCIMAP-Flood Fitted inverse modelling approach has been applied to the East Rapti catchment, Nepal. For multiple flood impact locations throughout the catchment, SCIMAP-Flood effectively identifies locations where flood management measures would have the most positive effects on risk reduction. The results show that the spatial targeting of mitigation measures in areas of irrigated and rainfed agriculture and the prevention of deforestation or removal of shrubland would be the most effective approaches. If these actions were in the upper catchment above Hetauda or upstream of Manahari they would have the most effective reduction in the flood peak

The Molonglo Galactic Plane Survey: I. Overview and Images

The first epoch Molonglo Galactic Plane Survey (MGPS1) is a radio continuum survey made using the Molonglo Observatory Synthesis Telescope (MOST) at 843 MHz with a resolution of 43" X 43" cosec |delta|. The region surveyed is 245 deg < l < 355 deg, |b| < 1.5 deg. The thirteen 9 deg X 3 deg mosaic images presented here are the superposition of over 450 complete synthesis observations, each taking 12 h and covering 70' X 70' cosec |delta|. The root-mean-square sensitivity over much of the mosaiced survey is 1-2 mJy/beam (1 sigma), and the positional accuracy is approximately 1" X 1" cosec |delta| for sources brighter than 20 mJy. The dynamic range is no better than 250:1, and this also constrains the sensitivity in some parts of the images. The survey area of 330 sq deg contains well over 12,000 unresolved or barely resolved objects, almost all of which are extra-galactic sources lying in the Zone of Avoidance. In addition a significant fraction of this area is covered by extended, diffuse emission associated with thermal complexes, discrete H II regions, supernova remnants, and other structures in the Galactic interstellar medium.Comment: Paper with 3 figures and 1 table + Table 2 + 7 jpg grayscales for Fig 4. Astrophysical Journal Supplement (in press) see also http://www.astrop.physics.usyd.edu.au/MGP