Background-Sudden infant death syndrome (SIDS) is a leading cause of death during the first 6 months after birth. About 5% to 10% of SIDS may stem from cardiac channelopathies such as long-QT syndrome. We recently implicated mutations in ␣1-syntrophin (SNTA1) as a novel cause of long-QT syndrome, whereby mutant SNTA1 released inhibition of associated neuronal nitric oxide synthase by the plasma membrane Ca-ATPase PMCA4b, causing increased peak and late sodium current (I Na ) via S-nitrosylation of the cardiac sodium channel. This study determined the prevalence and functional properties of SIDS-associated SNTA1 mutations. Methods and Results-Using polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing of SNTA1's open reading frame, 6 rare (absent in 800 reference alleles) missense mutations (G54R, P56S, T262P, S287R, T372M, and G460S) were identified in 8 (Ϸ3%) of 292 SIDS cases. These mutations were engineered using polymerase chain reaction-based overlap extension and were coexpressed heterologously with SCN5A, neuronal nitric oxide synthase, and PMCA4b in HEK293 cells. I Na was recorded using the whole-cell method. A significant 1.4-to 1.5-fold increase in peak I Na and 2.3-to 2.7-fold increase in late I Na compared with controls was evident for S287R-, T372M-, and G460S-SNTA1 and was reversed by a neuronal nitric oxide synthase inhibitor. These 3 mutations also caused a significant depolarizing shift in channel inactivation, thereby increasing the overlap of the activation and inactivation curves to increase window current. Conclusions-Abnormal biophysical phenotypes implicate mutations in SNTA1 as a novel pathogenic mechanism for the subset of channelopathic SIDS. Functional studies are essential to distinguish pathogenic perturbations in channel interacting proteins such as ␣1-syntrophin from similarly rare but innocuous ones. (Circ Arrhythm Electrophysiol. 2009;2:667-676.)

[1] We derive the correlation patterns over the global latitudes and from the stratosphere to lower thermosphere (broadly referred to as teleconnection) using temperature data measured by the Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) from 2002 to 2010, and using 54 years of simulations of temperatures and winds by the Whole Atmosphere Community Climate Model (WACCM). We also analyze the possible mechanisms of teleconnection by investigating the correlations between the temperature and residual circulation. The correlation patterns show that teleconnection exists globally over the equatorial, mid-and high-latitudes, and temperature anomalies correspond well to the anomalies of the residual circulations through adiabatic heating/cooling. A main new finding of this study is that the teleconnection extends well into the lower thermosphere, the thermospheric anomalies are consistent with the corresponding changes of the winter-to-summer lower-thermospheric branch of the residual circulation, and the winter stratosphere perturbations influence the thermosphere globally. Using a reference point chosen in the northern winter stratosphere, we find that the teleconnection structures for time periods with and without Sudden Stratospheric Warmings (SSWs) display similar patterns in SABER, and teleconnection patterns in WACCM are nearly identical for days with major SSWs, minor SSWs and without SSWs. WACCM results show strong inter-annual and intra-annual altitude variations of the teleconnection patterns in the southern polar region but stable altitudes of correlation regions in the equatorial and northern latitudes. The altitude variations are likely responsible for the weak correlations poleward of 60 S when multiyear or multimonth data are used.Citation: Tan, B., X. Chu, H.-L. Liu, C. Yamashita, and J. M. Russell III (2012), Zonal-mean global teleconnection from 15 to 110 km derived from SABER and WACCM,