Stereociliary Myosin-1c Receptors Are Sensitive to Calcium Chelation and Absent from Cadherin 23 Mutant Mice

The identities of some of the constituents of the hair-cell transduction apparatus have been elucidated only recently. The molecular motor myosin-1c (Myo1c) functions in adaptation of the hair-cell response to sustained mechanical stimuli and is therefore an integral part of the transduction complex. Recent data indicate that Myo1c interacts in vitro with two other molecules proposed to be important for transduction: cadherin 23 (Cdh23), a candidate for the stereociliary tip link, and phosphatidylinositol 4,5-bisphosphate (PIP2), which is abundant in the membranes of hair-cell stereocilia. It is not known, however, whether these interactions occur in hair cells. Using an in situ binding assay on saccular hair cells, we demonstrated previously that Myo1c interacts with molecules at stereociliary tips, the site of transduction, through sequences contained within its calmodulin (CaM)-binding neck domain, which can bind up to four CaM molecules. In the current study, we identify the second CaM-binding IQ domain as a region of Myo1c that mediates CaM-sensitive binding to stereociliary tips and to PIP2 immobilized on a solid support. Binding of Myo1c to stereociliary tips of cochlear and vestibular hair cells is disrupted by treatments that break tip links. In addition, Myo1c does not bind to stereocilia from mice whose hair cells lack Cdh23 protein despite the presence of PIP2 in the stereociliary membranes. Collectively, our data suggest that Myo1c and Cdh23 interact at the tips of hair-cell stereocilia and that this interaction is modulated by CaM

Neglecting plant–microbe symbioses leads to underestimation of modeled climate impacts

The extent to which terrestrial ecosystems slow climate change by sequestering carbon hinges in part on nutrient limitation. We used a coupled carbon–climate model that accounts for the carbon cost to plants of supporting nitrogen-acquiring microbial symbionts to explore how nitrogen limitation affects global climate. To do this, we first calculated the reduction in net primary production due to the carbon cost of nitrogen acquisition. We then used a climate model to estimate the impacts of the resulting increase in atmospheric CO2 on temperature and precipitation regimes. The carbon costs of supporting symbiotic nitrogen uptake reduced net primary production by 8.1 Pg C yr−1, with the largest absolute effects occurring in tropical forest biomes and the largest relative changes occurring in boreal and alpine biomes. Globally, our model predicted relatively small changes in climate due to the carbon cost of nitrogen acquisition with temperature increasing by 0.1 ∘C and precipitation decreasing by 6 mm yr−1. However, there were strong regional impacts, with the largest impact occurring in boreal and alpine ecosystems, where such costs were estimated to increase temperature by 1.0 ∘C and precipitation by 9 mm yr−1. As such, our results suggest that carbon expenditures to support nitrogen-acquiring microbial symbionts have critical consequences for Earth\u27s climate, and that carbon–climate models that omit these processes will overpredict the land carbon sink and underpredict climate change

Macrostructural analysis : unravelling polyphase glacitectonic histories

Many Pleistocene glacial profiles look extremely simple, comprising till, or glacitectonite, overlying older sediments or bedrock (Figure 4.1). In more complex sequences the till may itself be overlain by younger sediments laid down as the ice retreated or during a completely separate, later phase of advance. Macroscopically, subglacial traction tills (Evans et al., 2007) are typically massive, unstructured deposits suggesting that it should be relatively straightforward to unravel the glacitectonic deformation history recorded by the sequence. Many reconstructions do indeed look very simple, slabs of sediment have been tilted and stacked and then overridden by the glacier to cap the structure with till. Added to this is the use of vertical exaggeration which makes the whole structure look like alpine tectonics (for an example see fig. 5 in van Gijssel, 1987). Dropping the exaggeration led to the recognition that actually we were looking at much more horizontal structures, i.e. overriding nappes and not imbricated slabs (van der Wateren, 1987). Traditionally (van der Meer, 1987) glaciotectonics was thought to relate to large structures like big push moraines and not to smaller structures like drag structures underneath tills (Figure 4.2), let alone to the tills themselves. With the notion that deforming bed tills are tectonically and not sedimentologically structured and could be regarded as tectomicts (Menzies et al., 2006), comes the realisation that glacitectonics happens across a wide range of scales, from the microscopic to tens of kilometres. Only by realising the full range of glaciotectonic scales can we hope to understand the processes

Evolution of the Near-Infrared Tully-Fisher Relation: Constraints on the Relationship Between the Stellar and Total Masses of Disk Galaxies since z=1

Using a combination of Keck spectroscopy and near-infrared imaging, we investigate the K-band and stellar mass Tully-Fisher relation for 101 disk galaxies at 0.2 < z < 1.2, with the goal of placing the first observational constraints on the assembly history of halo and stellar mass. Our main result is a lack of evolution in either the K-band or stellar mass Tully-Fisher relation from z = 0 - 1.2. Furthermore, although our sample is not statistically complete, we consider it suitable for an initial investigation of how the fraction of total mass that has condensed into stars is distributed with both redshift and total halo mass. We calculate stellar masses from optical and near-infrared photometry and total masses from maximum rotational velocities and disk scale lengths, utilizing a range of model relationships derived analytically and from simulations. We find that the stellar/total mass distribution and stellar-mass Tully-Fisher relation for z > 0.7 disks is similar to that at lower redshift, suggesting that baryonic mass is accreted by disks along with dark matter at z < 1, and that disk galaxy formation at z < 1 is hierarchical in nature. We briefly discuss the evolutionary trends expected in conventional structure formation models and the implications of extending such a study to much larger samples.Comment: ApJ, in press, 9 page

Limits from the Hubble Space Telescope on a Point Source in SN 1987A

We observed supernova 1987A (SN 1987A) with the Space Telescope Imaging Spectrograph (STIS) on the Hubble Space Telescope (HST) in 1999 September, and again with the Advanced Camera for Surveys (ACS) on the HST in 2003 November. No point source is observed in the remnant. We obtain a limiting flux of F_opt < 1.6 x 10^{-14} ergs/s/cm^2 in the wavelength range 2900-9650 Angstroms for any continuum emitter at the center of the supernova remnant (SNR). It is likely that the SNR contains opaque dust that absorbs UV and optical emission, resulting in an attenuation of ~35% due to dust absorption in the SNR. Taking into account dust absorption in the remnant, we find a limit of L_opt < 8 x 10^{33} ergs/s. We compare this upper bound with empirical evidence from point sources in other supernova remnants, and with theoretical models for possible compact sources. Bright young pulsars such as Kes 75 or the Crab pulsar are excluded by optical and X-ray limits on SN 1987A. Of the young pulsars known to be associated with SNRs, those with ages < 5000 years are all too bright in X-rays to be compatible with the limits on SN 1987A. Examining theoretical models for accretion onto a compact object, we find that spherical accretion onto a neutron star is firmly ruled out, and that spherical accretion onto a black hole is possible only if there is a larger amount of dust absorption in the remnant than predicted. In the case of thin-disk accretion, our flux limit requires a small disk, no larger than 10^{10} cm, with an accretion rate no more than 0.3 times the Eddington accretion rate. Possible ways to hide a surviving compact object include the removal of all surrounding material at early times by a photon-driven wind, a small accretion disk, or very high levels of dust absorption in the remnant.Comment: 40 pages, 5 figures. AAStex. Accepted, ApJ 04/28/200

Costs of reproduction and carry-over effects in breeding albatrosses

We investigated the physiology of two closely related albatross species relative to their breeding strategy: black-browed albatrosses (Thalassarche melanophris) breed annually, while grey-headed albatrosses (T. chrysostoma) breed biennially. From observations of breeding fate and blood samples collected at the end of breeding in one season and feather corticosterone levels (fCort) sampled at the beginning of the next breeding season, we found that in both species some post-breeding physiological parameters differed according to breeding outcome (successful, failed, deferred). Correlations between post-breeding physiology and fCort, and links to future breeding decisions, were examined. In black-browed albatrosses, post-breeding physiology and fCort were not significantly correlated, but fCort independently predicted breeding decision the next year, which we interpret as a possible migratory carry-over effect. In grey-headed albatrosses, post-breeding triglyceride levels were negatively correlated with fCort, but only in females, which we interpret as a potential cost of reproduction. However, this potential cost did not carry-over to future breeding in the grey-headed albatrosses. None of the variables predicted future breeding decisions. We suggest that biennial breeding in the grey-headed albatrosses may have evolved as a strategy to buffer against the apparent susceptibility of females to negative physiological costs of reproduction. Future studies are needed to confirm this

Randomized controlled trial of computerized cognitive behavioural therapy for depressive symptoms: effectiveness and costs of a workplace intervention

Background Depression and anxiety are major causes of absence from work and underperformance in the workplace. Cognitive behavioural therapy (CBT) can be effective in treating such problems and online versions offer many practical advantages. The aim of the study was to investigate the effectiveness of a computerized CBT intervention (MoodGYM) in a workplace context.Method The study was a phase III two-arm, parallel randomized controlled trial whose main outcome was total score on the Work and Social Adjustment Scale (WSAS). Depression, anxiety, psychological functioning, costs and acceptability of the online process were also measured. Most data were collected online for 637 participants at baseline, 359 at 6 weeks marking the end of the intervention and 251 participants at 12 weeks post-baseline.Results In both experimental and control groups depression scores improved over 6 weeks but attrition was high. There was no evidence for a difference in the average treatment effect of MoodGYM on the WSAS, nor for a difference in any of the secondary outcomes.Conclusions This study found no evidence that MoodGYM was superior to informational websites in terms of psychological outcomes or service use, although improvement to subthreshold levels of depression was seen in nearly half the patients in both groups

918-7 Limitations of Percutaneous Interventions in the Treatment of Bifurcation Lesions Involving the Left Anterior Descending Coronary Artery

Serious complications may occur when intervention is unsuccessful in bifurcation lesions involving the left anterior descending (LAD) and first major diagonal (D), because of the large amount of involved myocardium. To determine this complication rate, we reviewed 82 consecutive cases, over a 3 year period, in which these lesions were attempted. Sixty-six percent of the subjects were male, and 37% had unstable angina. The mean age was 59 and the mean ejection fraction was 56%. Digital calipers were used to measure vessel minimum lumen (MLD) and reference diameters. For the LAD the final MLD was 1.81mm and for the 0 1.32mm. The final percent mean diameter stenoses for the LAD and D were 41% and 45%, respectively. There were no significant differences in the rates of success or complication between groups treated with angioplasty only (N=68) or directional atherectomy (N=14). The in-hospital event-free success rate was 55%. The in-hospital complication rates were:Recurrent Ischemia16%Ventricular Tachycardia2%Myocardial Infarction14%Stroke2%Bypass Surgery12%Death1%Repeat Procedure4%Composite34%ConclusionLAD bifurcation lesion intervention is associated with a high in-hospital complication rate. Since these lesions are not amenable to stent placement or atherectomy with simultaneous protection of both vessels, these cases should be carefully evaluated before intervention, and bypass surgery should be considered as a treatment option

Genetic Diversity of PCR-Positive, Culture-Negative and Culture-Positive Mycobacterium ulcerans Isolated from Buruli Ulcer Patients in Ghana.

Culture of Mycobacterium ulcerans from Buruli ulcer patients has very low sensitivity. Thus confirmation of M. ulcerans infection is primarily based on PCR directed against IS2404. In this study we compare the genotypes obtained by variable number of tandem repeat analysis of DNA from IS2404-PCR positive cultures with that obtained from IS2404 positive, culture-negative tissue. A significantly greater genetic heterogeneity was found among culture-negative samples compared with that found in cultured strains but a single genotype is over-represented in both sample sets. This study provides evidence that both the focal location of bacteria in a lesion as well as differences in the ability to culture a particular genotype may underlie the low sensitivity of culture. Though preliminary, data from this work also suggests that mycobacteria previously associated with fish disease (M. pseudoshottsii) may be pathogenic for humans

Eulerian simulation of the fluid dynamics of helicopter brownout

A computational model is presented that can be used to simulate the development of the dust cloud that can be entrained into the air when a helicopter is operated close to the ground in desert or dusty conditions. The physics of this problem, and the associated pathological condition known as ‘brownout’ where the pilot loses situational awareness as a result of his vision being occluded by dust suspended in the flow around the helicopter, is acknowledged to be very complex. The approach advocated here involves an approximation to the full dynamics of the coupled particulate-air system. Away from the ground, the model assumes that the suspended particles remain in near equilibrium under the action of aerodynamic forces. Close to the ground, this model is replaced by an algebraic sublayer model for the saltation and entrainment process. The origin of the model in the statistical mechanics of a distribution of particles governed by aerodynamic forces allows the validity of the method to be evaluated in context by comparing the physical properties of the suspended particulates to the local properties of the flow field surrounding the helicopter. The model applies in the Eulerian frame of reference of most conventional Computational Fluid Dynamics codes and has been coupled with Brown’s Vorticity Transport Model. Verification of the predictions of the coupled model against experimental data for particulate entrainment and transport in the flow around a model rotor are encouraging. An application of the coupled model to analyzing the differences in the geometry and extent of the dust clouds that are produced by single main rotor and tandem-rotor configurations as they decelerate to land has shown that the location of the ground vortex and the size of any regions of recirculatory flow, should they exist, play a primary role in governing the extent of the dust cloud that is created by the helicopter