Potentiated L-type Ca2+ Channels Rectify

Strong depolarization and dihydropyridine agonists potentiate inward currents through native L-type Ca2+ channels, but the effect on outward currents is less clear due to the small size of these currents. Here, we examined potentiation of wild-type α1C and two constructs bearing mutations in conserved glutamates in the pore regions of repeats II and IV (E2A/E4A-α1C) or repeat III (E3K-α1C). With 10 mM Ca2+ in the bath and 110 mM Cs+ in the pipette, these mutated channels, expressed in dysgenic myotubes, produced both inward and outward currents of substantial amplitude. For both the wild-type and mutated channels, we observed strong inward rectification of potentiation: strong depolarization had little effect on outward tail currents but caused the inward tail currents to be larger and to decay more slowly. Similarly, exposure to DHP agonist increased the amplitude of inward currents and decreased the amplitude of outward currents through both E2A/E4A-α1C and E3K-α1C. As in the absence of drug, strong depolarization in the presence of dihydropyridine agonist had little effect on outward tail currents but increased the amplitude and slowed the decay of inward tail currents. We tested whether cytoplasmic Mg2+ functions as the blocking particle responsible for the rectification of potentiated L-type Ca2+ channels. However, even after complete removal of cytoplasmic Mg2+, (−)BayK 8644 still potentiated inward current and partially blocked outward current via E2A/E4A-α1C. Although zero Mg2+ did not reveal potentiation of outward current by DHP agonist, it did have two striking effects, (a) a strong suppression of decay of both inward and outward currents via E2A/E4A-α1C and (b) a nearly complete elimination of depolarization-induced potentiation of inward tail currents. These results can be explained by postulating that potentiation exposes a binding site in the pore to which an intracellular blocking particle can bind and produce inward rectification of the potentiated channels

Visualization methods for statistical analysis of microarray clusters

BACKGROUND: The most common method of identifying groups of functionally related genes in microarray data is to apply a clustering algorithm. However, it is impossible to determine which clustering algorithm is most appropriate to apply, and it is difficult to verify the results of any algorithm due to the lack of a gold-standard. Appropriate data visualization tools can aid this analysis process, but existing visualization methods do not specifically address this issue. RESULTS: We present several visualization techniques that incorporate meaningful statistics that are noise-robust for the purpose of analyzing the results of clustering algorithms on microarray data. This includes a rank-based visualization method that is more robust to noise, a difference display method to aid assessments of cluster quality and detection of outliers, and a projection of high dimensional data into a three dimensional space in order to examine relationships between clusters. Our methods are interactive and are dynamically linked together for comprehensive analysis. Further, our approach applies to both protein and gene expression microarrays, and our architecture is scalable for use on both desktop/laptop screens and large-scale display devices. This methodology is implemented in GeneVAnD (Genomic Visual ANalysis of Datasets) and is available at . CONCLUSION: Incorporating relevant statistical information into data visualizations is key for analysis of large biological datasets, particularly because of high levels of noise and the lack of a gold-standard for comparisons. We developed several new visualization techniques and demonstrated their effectiveness for evaluating cluster quality and relationships between clusters

Left Displacement of the Abomasum in 4 Beef Calves

Citation: Oman, R. E., Streeter, R. N., Reppert, E. J., & Chako, C. Z. (2016). Left Displacement of the Abomasum in 4 Beef Calves. Journal of Veterinary Internal Medicine, 30(4), 1376-1380. doi:10.1111/jvim.14353BackgroundLittle is known about the occurrence rate, underlying etiology or treatment of left displacement of the abomasum in beef calves. ObjectiveDescribe the clinical presentation, diagnosis and treatment of left displacement of the abomasum in 4 beef calves. AnimalsFour client-owned beef breed calves with left displaced abomasum (LDA). MethodsRetrospective case series. Hospital medical records were reviewed to identify all beef breed cattle under the age of 6 months diagnosed with LDA. ResultsFour beef calves were treated for left displacement of the abomasum. All four had a history of decreased appetite and left-sided abdominal distention. Two had recently been treated for necrotic laryngitis and one was being treated for clostridial abomasitis. Ultrasonography confirmed the abomasum to be displaced between the rumen and the left body wall in all calves. The calves were initially treated by rolling to correct the abomasal displacement. The abomasum redisplaced in 3 of 4 calves within 1 hour to 6 days; 1 calf developed a mesenteric volvulus. A right paramedian abomasopexy was performed in all cases. Three of 4 calves grew well and remained in the herd 6-18 months later; 1 calf was euthanized because of complications associated with necrotic laryngitis. Conclusions and clinical importanceLeft displacement of the abomasum should be considered as a differential diagnosis for beef calves with abdominal distention. Concurrent necrotic laryngitis can increase the risk of abomasal displacement in beef calves. Treatment should include surgical correction as rolling is not curative and might be associated with mesenteric volvulus

Nuclear spin coherence in a quantum wire

We have observed millisecond-long coherent evolution of nuclear spins in a quantum wire at 1.2 K. Local, all-electrical manipulation of nuclear spins is achieved by dynamic nuclear polarization in the breakdown regime of the Integer Quantum Hall Effect combined with pulsed Nuclear Magnetic Resonance. The excitation thresholds for the breakdown are significantly smaller than what would be expected for our sample and the direction of the nuclear polarization can be controlled by the voltage bias. As a four-level spin system, the device is equivalent to two qubits.Comment: 5 pages, 5 figure

Holocene environment of Central Kamchatka, Russia: Implications from a multi-proxy record of Two-Yurts Lake

© 2015 Elsevier B.V. Within the scope of Russian-German palaeoenvironmental research, Two-Yurts Lake (TYL, Dvuh-Yurtochnoe in Russian) was chosen as the main scientific target area to decipher Holocene climate variability on Kamchatka. The 5. ×. 2 km large and 26 m deep lake is of proglacial origin and situated on the eastern flank of Sredinny Ridge at the northwestern end of the Central Kamchatka Valley, outside the direct influence of active volcanism. Here, we present results of a multi-proxy study on sediment cores, spanning about the last 7000 years. The general tenor of the TYL record is an increase in continentality and winter snow cover in conjunction with a decrease in temperature, humidity, and biological productivity after 5000-4500. cal. yrs. BP, inferred from pollen and diatom data and the isotopic composition of organic carbon. The TYL proxy data also show that the late Holocene was punctuated by two colder spells, roughly between 4500 and 3500 cal. yrs. BP and between 1000 and 200 cal. yrs. BP, as local expressions of the Neoglacial and Little Ice Age, respectively. These environmental changes can be regarded as direct and indirect responses to climate change, as also demonstrated by other records in the regional terrestrial and marine realm. Long-term climate deterioration was driven by decreasing insolation, while the short-term climate excursions are best explained by local climatic processes. The latter affect the configuration of atmospheric pressure systems that control the sources as well as the temperature and moisture of air masses reaching Kamchatka

On the evolution of eccentric and inclined protoplanets embedded in protoplanetary disks

Young planets embedded in their protoplanetary disk interact gravitationally with it leading to energy and angular momentum exchange. This interaction determines the evolution of the planet through changes to the orbital parameters. We investigate changes in the orbital elements of a 20 Earth--mass planet due to the torques from the disk. We focus on the non-linear evolution of initially non-vanishing eccentricity $e$ and/or inclination $i$. We treat the disk as a two- or three-dimensional viscous fluid and perform hydrodynamical simulations with an embedded planet. We find rapid exponential decay of the planet orbital eccentricity and inclination for small initial values of $e$ and $i$, in agreement with linear theory. For larger values of $e > 0.1$ the decay time increases and the decay rate scales as $\dot{e} \propto e^{-2}$, consistent with existing theoretical models. For large inclinations ($i$ > 6 deg) the inclination decay rate shows an identical scaling $di/dt \propto i^{-2}$. We find an interesting dependence of the migration on the eccentricity. In a disk with aspect ratio $H/r=0.05$ the migration rate is enhanced for small non-zero eccentricities ($e < 0.1$), while for larger values we see a significant reduction by a factor of $\sim 4$. We find no indication for a reversal of the migration for large $e$, although the torque experienced by the planet becomes positive when $e \simeq 0.3$. This inward migration is caused by the persisting energy loss of the planet. For non gap forming planets, eccentricity and inclination damping occurs on a time scale that is very much shorter than the migration time scale. The results of non linear hydrodynamic simulations are in very good agreement with linear theory for small $e$ and $i$.Comment: accepted for Astronomy & Astrophysics, 16 pages, 16 figures, animations under: http://www.tat.physik.uni-tuebingen.de/~kley/publ/paper/eccp.htm

High STEAP1 expression is associated with improved outcome of Ewing's sarcoma patients

Background Ewing's sarcoma (ES) is the second most common bone or soft-tissue sarcoma in childhood and adolescence and features a high propensity to metastasize. The six-transmembrane epithelial antigen of the prostate 1 (STEAP1) is a membrane-bound mesenchymal stem cell marker highly expressed in ES. Here, we investigated the role of STEAP1 as an immunohistological marker for outcome prediction in patients with ES. Patients and methods Membranous STEAP1 immunoreactivity was analyzed using immunohistochemistry in 114 primary pre-chemotherapy ES of patients diagnosed from 1983 to 2010 and compared with clinical parameters and patient outcome. Median follow-up was 3.85 years (range 0.43-17.51). Results A total of 62.3% of the ES samples displayed detectable STEAP1 expression with predominant localization of the protein at the plasma membrane. High membranous STEAP1 immunoreactivity was found in 53.5%, which correlated with better overall survival (P=0.021). Accordingly, no or low membranous STEAP1 expression was identified as an independent risk factor in multivariate analysis (hazard ratio 2.65, P=0.036). Conclusion High membranous STEAP1 expression predicts improved outcome and may help to define a specific subgroup of ES patients, who might benefit from adapted therapy regimen