The glucocorticoid-Angptl4-ceramide axis induces insulin resistance through PP2A and PKCζ.

Chronic glucocorticoid exposure is associated with the development of insulin resistance. We showed that glucocorticoid-induced insulin resistance was attenuated upon ablation of Angptl4, a glucocorticoid target gene encoding the secreted protein angiopoietin-like 4, which mediates glucocorticoid-induced lipolysis in white adipose tissue. Through metabolomic profiling, we revealed that glucocorticoid treatment increased hepatic ceramide concentrations by inducing enzymes in the ceramide synthetic pathway in an Angptl4-dependent manner. Angptl4 was also required for glucocorticoids to stimulate the activities of the downstream effectors of ceramide, protein phosphatase 2A (PP2A) and protein kinase Cζ (PKCζ). We further showed that knockdown of PP2A or inhibition of PKCζ or ceramide synthesis prevented glucocorticoid-induced glucose intolerance in wild-type mice. Moreover, the inhibition of PKCζ or ceramide synthesis did not further improve glucose tolerance in Angptl4-/- mice, suggesting that these molecules were major downstream effectors of Angptl4. Overall, our study demonstrates the key role of Angptl4 in glucocorticoid-augmented hepatic ceramide production that induces whole-body insulin resistance

Dextromethorphan in the treatment of early myoclonic encephalopathy evolving into migrating partial seizures in infancy

Epileptic encephalopathy with suppression-burst in electroencephalography (EEG) can evolve into a few types of epileptic syndromes. We present here an unusual case of early myoclonic encephalopathy that evolved into migrating partial seizures in infancy. A female neonate initially had erratic myoclonus movements, hiccups, and a suppression-burst pattern in EEG that was compatible with early myoclonic encephalopathy. The seizures were controlled with dextromethorphan (20 mg/kg), and a suppression-burst pattern in EEG was reverted to relatively normal background activity. However, at 72 days of age, alternating focal tonic seizures, compatible with migrating partial seizures in infancy, were demonstrated by the 24-hour EEG recording. The seizures responded poorly to dextromethorphan. To our knowledge, this is the first reported case of early myoclonic encephalopathy evolving into migrating partial seizure in infancy. Whether it represents another age-dependent epilepsy evolution needs more clinical observation

Composite type A thymoma and diffuse large B-cell lymphoma

AbstractThe concurrent occurrence of thymoma and diffuse large B-cell lymphoma in the thymus has not been previously reported. We describe a 74-year-old man who presented with general weakness, neck lymphadenopathy, night sweats, and body weight loss. A right anterior mediastinal mass was found on computed tomography of the chest. The immunohistochemical stains AE1/AE3, CD20, CD3, and MUM-1 confirmed the different components of the mediastinal tumor. A heavy-chain gene clonality assay and light-chain gene clonality assay confirmed the B-cell clonality of the mediastinal tumor and neck lymph node. The patient had received a complete course of chemotherapy, and the result of positron emission tomography–computed tomography showed complete remission. The pathologic report of this mass revealed composite type A thymoma and diffuse large B-cell lymphoma. If concurrent or composite thymoma and lymphoma are suspected, a thorough examination of the thymoma with a combination of ancillary studies is recommended to rule out the possibility of concurrent lymphoma

Biomechanical investigation of flexor digitorum tendons in trigger finger patients using sonography

Trigger finger (TF) has generally been ascribed to primary changes in the first annular (A1) pulley. Repeated friction between the A1 pulley and flexor digitorum tendons could result in swelling of soft tissues, and thus it has been speculated that TF affects tendons’ biomechanical behaviors. However, the pathology mechanism related to these behaviors remains unclear. The purposes of this study are to understand (1) the variations in the morphologies of the flexor digitorum profundus (FDP) and flexor digitorum superficialis (FDS) between normal fingers and TFs, (2) the differences in the biomechanical behaviors of the FDP and FDS between normal fingers and TFs in various finger flexion positions, and (3) the effect of various finger positions on the biomechanical behaviors of the FDP and FDS

Quantum metastability in a class of moving potentials

In this paper we consider quantum metastability in a class of moving potentials introduced by Berry and Klein. Potential in this class has its height and width scaled in a specific way so that it can be transformed into a stationary one. In deriving the non-decay probability of the system, we argue that the appropriate technique to use is the less known method of scattering states. This method is illustrated through two examples, namely, a moving delta-potential and a moving barrier potential. For expanding potentials, one finds that a small but finite non-decay probability persists at large times. Generalization to scaling potentials of arbitrary shape is briefly indicated.Comment: 10 pages, 1 figure

Observations of the cold wake of Typhoon Fanapi (2010)

Author Posting. © American Geophysical Union, 2013. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 40 (2013): 316–321, doi:10.1029/2012GL054282.Several tens of thousands of temperature profiles are used to investigate the thermal evolution of the cold wake of Typhoon Fanapi, 2010. Typhoon Fanapi formed a cold wake in the Western North Pacific Ocean on 18 September characterized by a mixed layer that was >2.5 °C cooler than the surrounding water, and extending to >80 m, twice as deep as the preexisting mixed layer. The initial cold wake became capped after 4 days as a warm, thin surface layer formed. The thickness of the capped wake, defined as the 26 °C–27 °C layer, decreased, approaching the background thickness of this layer with an e-folding time of 23 days, almost twice the e-folding lifetime of the Sea Surface Temperature (SST) cold wake (12 days). The wake was advected several hundreds of kilometers from the storm track by a preexisting mesoscale eddy. The observations reveal new intricacies of cold wake evolution and demonstrate the challenges of describing the thermal structure of the upper ocean using sea surface information alone.This work is primarily supported by the U.S. Office of Naval Research, with additional support from the National Science Foundation and the National Science Council, Taiwan

Areca Users in Combination with Tobacco and Alcohol Use Are Associated with Younger Age of Diagnosed Esophageal Cancer in Taiwanese Men

BACKGROUND: Whether the habitual use of substances (tobacco, alcohol, or areca nut (seed of the Areca palm)) can affect the age of esophageal squamous cell carcinoma (ESCC) presentation has rarely been examined. METHODS: The study subjects were those who were males and the first time to be diagnosed as ESCC (ICD-9 150) and who visited any of three medical centers in Taiwan between 2000 and 2009. A standardized questionnaire was used to collect substance uses and other variables. RESULTS: Mean age (±SD) at presentation of ESCC was 59.2 (±11.3) years in a total of 668 cases. After adjusting for other covariates, alcohol drinkers were 3.58 years younger to have ESCC than non-drinkers (p = 0.002). A similar result was found among areca chewers, who were 6.34 years younger to have ESCC than non-chewers (p<0.0001), but not among cigarette smokers (p = 0.10). When compared to the group using 0-1 substances, subjects using both cigarettes and alcohol were nearly 3 years younger to contract ESCC. Furthermore, those who use areca plus another substance were 7-8 years younger. Subjects using all three substances had the greatest age difference, 9.20 years younger (p<0.0001), compared to the comparison group. CONCLUSION: Our findings suggest that habitually consuming tobacco, alcohol, and areca nut can influence the age-onset of ESCC. Since the development of ESCC is insidious and life-threatening, our observation is worthy to be reconfirmed in the large-scale and long-term follow-up prospective cohort studies to recommend the screening strategy of this disease

Characterization of traverse slippage experienced by Spirit rover on Husband Hill at Gusev crater

Spirit rover experienced significant slips traversing Husband Hill. This paper analyzes the slippage Spirit experienced from Sol 154 to Sol 737. Slippage with respect to terrain type and slope is computed using data downlinked from the rover, rover position, and orientation estimations from visual odometry (VO) and photogrammetry based bundle adjustment (BA) method. Accumulated slippage reached a maximum of 83.86 m on Sol 648. However, as Spirit descended into the Inner Basin, the direction of slippage reversed, and accumulated slippage approached zero by the end of the entire traverse. Eight local regions with significant slips and nineteen traverse segments have been analyzed. Slippage was found to be highly correlated to slope direction and magnitude; the reverse of slope directions in the ascending and descending portions of the traverse proves to be the main contributor to the observed cancellation of slippage. While the horizontal component of the slippage almost canceled out, the difference in elevation continually accumulated, mainly during the ascent. In general, long traverse segments created more slips than short ones. This is reflected in both the accumulated and individual slippages. In considering the four major Mars terrain types, Spirit performed best on bedrock, managing to drive on slopes close to 30°. Fine-grain surfaces were the most challenging; though progress was made on slopes up to 15°, slippages of over 100% (more slippage than distance traveled) occurred for short segments. The results of this work can be incorporate into a traverse planning framework in which rover slippage is minimized. Results can be employed in landed planetary missions for precision navigation to avoid potentially dangerous regions by considering expected slippage

Examination of effects of GSK3β phosphorylation, β-catenin phosphorylation, and β-catenin degradation on kinetics of Wnt signaling pathway using computational method

<p>Abstract</p> <p>Background</p> <p>Recent experiments have explored effects of activities of kinases other than the well-studied GSK3β, in wnt pathway signaling, particularly at the level of β-catenin. It has also been found that the kinase PKA attenuates β-catenin degradation. However, the effects of these kinases on the level and degradation of β-catenin and the resulting downstream transcription activity remain to be clarified. Furthermore, the effect of GSK3β phosphorylation on the β-catenin level has not been examined computationally. In the present study, the effects of phosphorylation of GSK3β and of phosphorylations and degradation of β-catenin on the kinetics of the wnt signaling pathway were examined computationally.</p> <p>Methods</p> <p>The well-known computational Lee-Heinrich kinetic model of the wnt pathway was modified to include these effects. The rate laws of reactions in the modified model were solved numerically to examine these effects on β-catenin level.</p> <p>Results</p> <p>The computations showed that the β-catenin level is almost linearly proportional to the phosphorylation activity of GSK3β. The dependence of β-catenin level on the phosphorylation and degradation of free β-catenin and downstream TCF activity can be analyzed with an approximate, simple function of kinetic parameters for added reaction steps associated with effects examined, rationalizing the experimental results.</p> <p>Conclusion</p> <p>The phosphorylations of β-catenin by kinases other than GSK3β involve free unphorphorylated β-catenin rather than GSK3β-phosphorylated β-catenin*. In order to account for the observed enhancement of TCF activity, the β-catenin dephosphorylation step is essential, and the kinetic parameters of β-catenin phosphorylation and degradation need to meet a condition described in the main text. These findings should be useful for future experiments.</p