ATP mediates both activation and inhibition of K(ATP) channel activity via cAMP-dependent protein kinase in insulin-secreting cell lines.

The single-channel recording technique was employed to investigate the mechanism conferring ATP sensitivity to a metabolite-sensitive K channel in insulin-secreting cells. ATP stimulated channel activity in the 0-10 microM range, but depressed it at higher concentrations. In inside-out patches, addition of the cAMP-dependent protein kinase inhibitor (PKI) reduced channel activity, suggesting that the stimulatory effect of ATP occurs via cAMP-dependent protein kinase-mediated phosphorylation. Raising ATP between 10 and 500 microM in the presence of exogenous PKI progressively reduced the channel activity; it is proposed that this inactivation results from a reduction in kinase activity owing to an ATP-dependent binding of PKI or a protein with similar inhibitory properties to the kinase. A model describing the effects of ATP was developed, incorporating these two separate roles for the nucleotide. Assuming that the efficacy of ATP in controlling the channel activity depends upon the relative concentrations of inhibitor and catalytic subunit associated with the membrane, our model predicts that the channel sensitivity to ATP will vary when the ratio of these two modulators is altered. Based upon this, it is shown that the apparent discrepancy existing between the sensitivity of the channel to low ATP concentrations in the excised patch and the elevated intracellular level of ATP may be explained by postulating a change in the inhibitor/kinase ratio from 1:1 to 3:2 owing to the loss of protein kinase after patch excision. At a low concentration of ATP (10-20 microM), a nonhydrolyzable ATP analogue, AMP-PNP, enhanced the channel activity when present below 10 microM, whereas the analogue blocked the channel activity at higher concentrations. It is postulated that AMP-PNP inhibits the formation of the kinase-inhibitor complex in the former case, and prevents phosphate transfer in the latter. A similar mechanism would explain the interaction between ATP and ADP which is characterized by enhanced activity at low ADP concentrations and blocking at higher concentrations

On the Solved Turbulent Scales in Turbulent Plume Fires

Plume fires are characterized by a turbulent nature with a large number of different scales. LES is often used to solve the largest structures and to model the smallest ones. Grid size and time steps become decisive to place the limit between resolved and modelled turbulence. Significant information on this limit and its placement can be obtained with spectral analyses of the specific turbulent kinetic energy. While frequency analysis is relatively easy, an analysis in the wavenumber domain is more challenging. The IWC method, typically used in structures and acoustics, is used here for this purpose. IWC method allows to obtain wavenumber spectra with a better resolution than those obtained with a direct approach. Furthermore, in this paper the IWC method is also used in its reverse form to obtain frequency spectra. Although rather dense grids have been chosen, the number of nodes along the plume and their spacing is not such as to guarantee detailed wavenumber spectra with the direct approach and consequently with the reverse IWC. On the contrary, the IWC method provides wavenumber spectra in agreement with those obtained directly, but of much higher quality

Torsion pendulum facility for direct force measurements of LISA GRS related disturbances

A four mass torsion pendulum facility for testing of the LISA GRS is under development in Trento. With a LISA-like test mass suspended off-axis with respect to the pendulum fiber, the facility allows for a direct measurement of surface force disturbances arising in the GRS. We present here results with a prototype pendulum integrated with very large-gap sensors, which allows an estimate of the intrinsic pendulum noise floor in the absence of sensor related force noise. The apparatus has shown a torque noise near to its mechanical thermal noise limit, and would allow to place upper limits on GRS related disturbances with a best sensitivity of 300 fN/Hz^(1/2) at 1mHz, a factor 50 from the LISA goal. Also, we discuss the characterization of the gravity gradient noise, one environmental noise source that could limit the apparatus performances, and report on the status of development of the facility.Comment: Submitted to Proceedings of the 6th International LISA Symposium, AIP Conference Proceedings 200

Genome- wide analyses reveal population structure and identify candidate genes associated with tail fatness in local sheep from a semi- arid area

Under a climate change perspective, the genetic make-up of local livestock breeds showing adaptive traits should be explored and preserved as a priority. We used genotype data from the ovine 50 k Illumina BeadChip for assessing breed autozygosity based on runs of homozygosity (ROH) and fine-scale genetic structure and for detecting genomic regions under selection in 63 Tunis ia n sheep samples. The average genomic inbreeding coefficients based on ROH were estimated at 0.017, 0.021, and 0.024 for Barbarine (BAR, n = 26), Noire de Thibar (NDT, n = 23), and Queue fine de l'Ouest (QFO, n = 14) breeds, respectively. The genomic relationships among individuals based on identity by state (IBS) distance matrix highlighted a recent introgression of QFO into the BAR and a genetic differentiation of NDT samples, possibly explained by past introgression of Europe an gene pools. Genome-wide scan for ROH across breeds and within the BAR sample set identified an outstanding signal on chromosome 13 (46.58–49.61 Mbp). These results were confirmed using FST index, differentiating fat vs. thin-tailed individuals. Candidate genes under selection pressure (CDS2, PROKR1, and BMP2) were associated to lipid storage and probably preferentially selected in fat-tailed BAR animals. Our findings suggest paying more attention to preserve the genetic integrity and adaptive alleles of local sheep breeds

Corneal Cross-Linking for the Treatment of Keratoconus in a Patient with Ipsilateral Myelinated Retinal Nerve Fiber Layer

Keratoconus associated with myelinated retinal nerve fibers is not frequent and the relationship between the two pathologies is difficult to explain, therefore studies and further investigation are required. The etiology of each condition may suggest the role of genetic factors. Follow-up is important to evaluate the progression of keratoconus and myelination. Here we describe the unusual coexistence of keratoconus and ipsilateral myelinated retinal nerve fiber layer and, for the first time, the corneal cross-linking treatment in this condition

Upper limits to surface force disturbances on LISA proof masses and the possibility of observing galactic binaries

We report on the measurement of parasitic surface force noise on a hollow replica of a LISA (Laser Interferometer Space Antenna for the observation of gravitational waves) proof mass surrounded by a faithful representation of its in flight surroundings, namely the capacitive sensor used to detect proof-mass motion. Parasitic forces are detected through the corresponding torque exerted on the proof mass and measured with a torsion pendulum in the frequency range 0.1 30 mHz. The sensor electrodes, electrode housing and associated readout electronics have the same nominal design as for the flight hardware, including 4 mm gaps around the proof mass along the sensitive laser interferometry axis. We show that the measured upper limit for surface forces would allow detection of a number of galactic binaries signals with signal to noise ratio up to approximately 40 for 1 year integration. We also discuss how the flight test under development, LISA Pathfinder, will substantially improve this limit, approaching the performance required for LISA.Comment: 3 Figures. Submitted to Physical Review Letter

Surrogate endpoints in trials-a call for better reporting

Better reporting of RCTs with primary surrogate endpoints