Sound channel propagation through eddies southeast of the Gulf Stream

Also published as: Journal of the Acoustical Society of America 68 (1980): 1750-1767Acoustical signals at 270 Hz from SOFAR floats drifting in the region southeast of the Gulf Stream were recorded during most of 1975 from a near axis sound channel hydrophone near Bermuda. The amplitude levels received exhibit a large increase (12–18 dB) commencing about 24 July, following a long period (March to July) of relatively lower peak level amplitudes. A major part of the increase can be attributed to the influence of a large cyclonic eddy (Gulf Stream ring) that passed slowly between the SOFAR floats and Bermuda. Such an eddy produces a large sound speed anomaly that extends to depths below the axis of the sound channel. On 24 July, two SOFAR floats were known to have approximately the same sound transmission path through the edge of the large eddy. The sound transmission peaks occur when no ocean eddy is between the SOFAR floats and the receiver. Their spacing shows they occur at regular refraction caustics in the sound channel. When the sound transmission path passes through an eddy, these transmission focal distances are shifted to greater range and the signal level may be greatly enhanced. The decrease of caustic peak intensities with range is 5 dB per double distance, and this agrees with theory. Several different levels of peak acoustic intensity occur and these result from two float depths and oceanic thermocline oscillations.Prepared for the Office of Naval Research under Contract N00014-74-C-0262; NR 083-004·

The integrin effector PINCH regulates JNK activity and epithelial migration in concert with Ras suppressor 1

Cell adhesion and migration are dynamic processes requiring the coordinated action of multiple signaling pathways, but the mechanisms underlying signal integration have remained elusive. Drosophila embryonic dorsal closure (DC) requires both integrin function and c-Jun amino-terminal kinase (JNK) signaling for opposed epithelial sheets to migrate, meet, and suture. Here, we show that PINCH, a protein required for integrin-dependent cell adhesion and actin–membrane anchorage, is present at the leading edge of these migrating epithelia and is required for DC. By analysis of native protein complexes, we identify RSU-1, a regulator of Ras signaling in mammalian cells, as a novel PINCH binding partner that contributes to PINCH stability. Mutation of the gene encoding RSU-1 results in wing blistering in Drosophila, demonstrating its role in integrin-dependent cell adhesion. Genetic interaction analyses reveal that both PINCH and RSU-1 antagonize JNK signaling during DC. Our results suggest that PINCH and RSU-1 contribute to the integration of JNK and integrin functions during Drosophila development

The actin regulator zyxin reinforces airway smooth muscle and accumulates in airways of fatal asthmatics

Bronchospasm induced in non-asthmatic human subjects can be easily reversed by a deep inspiration (DI) whereas bronchospasm that occurs spontaneously in asthmatic subjects cannot. This physiological effect of a DI has been attributed to the manner in which a DI causes airway smooth muscle (ASM) cells to stretch, but underlying molecular mechanisms–and their failure in asthma–remain obscure. Using cells and tissues from wild type and zyxin-/- mice we report responses to a transient stretch of physiologic magnitude and duration. At the level of the cytoskeleton, zyxin facilitated repair at sites of stress fiber fragmentation. At the level of the isolated ASM cell, zyxin facilitated recovery of contractile force. Finally, at the level of the small airway embedded with a precision cut lung slice, zyxin slowed airway dilation. Thus, at each level zyxin stabilized ASM structure and contractile properties at current muscle length. Furthermore, when we examined tissue samples from humans who died as the result of an asthma attack, we found increased accumulation of zyxin compared with non-asthmatics and asthmatics who died of other causes. Together, these data suggest a biophysical role for zyxin in fatal asthma

EWS/FLI utilizes NKX2-2 to repress mesenchymal features of Ewing sarcoma

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. In Ewing sarcoma, NKX2-2 is a critical activated target of the oncogenic transcription factor EWS/FLI that is required for transformation. However, its biological function in this malignancy is unknown. Here we provide evidence that NKX2-2 mediates the EWS/FLI-controlled block of mesenchymal features. Transcriptome-wide RNA sequencing revealed that NKX2-2 represses cell adhesion and extracellular matrix organization genes. NKX2-2-depleted cells form more focal adhesions and organized actin stress fibers, and spread over a wider area—hallmarks of mesenchymally derived cells. Furthermore, NKX2-2 represses the actin-stabilizing protein zyxin, suggesting that these morphological changes are attributable to zyxin de-repression. In addition, NKX2-2-knockdown cells display marked increases in migration and substrate adhesion. However, only part of the EWS/FLI phenotype is NKX2-2-dependent; consequently, NKX2-2 is insufficient to rescue EWS/FL

Quantification of zyxin protein expression in the airways of asthmatic and non-asthmatic bronchi.

<p>A) Representative image of zyxin IHC staining. Black arrow indicates ASM bands and black star indicates epithelial layer. Scale bar is 100um. B) Comparison of the percent positivity for zyxin in the ASM layer of asthmatics and non-asthmatics expressed as a fraction of the positive control. C) Comparison of percent positivity for zyxin in the ASM of non-asthmatic controls (n = 27), non-fatal asthmatics (n = 21) and fatal asthmatics (n = 22) in the replication cohort expressed as a fraction of the positive control. p<0.05 denotes significance.</p

Zyxin is recruited to sites of actin stress fiber strain following single isotropic stretch, and is responsible for decreasing the cytoskeleton remodeling rate.

<p>(A) Kymographic analysis of zyxin and actin on a representative stress fiber following a single isotropic stretch. The kymograph is a time lapse montage of images of an actin SF captured in a zyxin^-/- MEF rescued with zyxin-GFP and also expressing actin-mApple Zyxin localizes to sites of stress fiber fragmentation and facilitates stress fiber repair. (B) Quantification of actin and zyxin intensity on a representative stress fiber following a single isotropic stretch showing zyxin’s localization to a site of stress fiber fragmentation and the subsequent recovery of the stress fiber. Kymograph (C) and intensity analysis (D) of zyxin recruitment to an actin strain site in a HASM cells. (E) Mean square displacements (MSD) of microbeads adherent to the cytoskeleton in zyxin^-/- and GFP-zyxin-rescued MEFs. Zyxin^-/- cells have an increased rate of remodeling, as evidenced by the upward shift of the MSD curve. (F) qPCR shows successful knockdown of zyxin in HASM cells of approximately 90% by 48 hours. (G) Western blot shows large reduction in zyxin in HASM cells by 72 hours post-transfection. Two replicates of this knockdown are shown as the two lanes for each condition in the western blot. (H) Cytoskeletal remodeling rate in HASM cells is increased after zyxin knockdown as indicated by the upward shift of the MSD curve.</p

Subject characteristics for both initial discovery cohort and replication cohort. Age is expressed in years ± SD.

<p>Subject characteristics for both initial discovery cohort and replication cohort. Age is expressed in years ± SD.</p

Zyxin mediates post-fluidization resolidification in MASM.

<p>(A) Representative traction maps of wild type and zyxin^-/- primary ASM cells at baseline and 10, 50 and 300 seconds after a single transient isotropic stretch. Maps show colorized distribution of forces. The legend shows the color values in KPa. (B) Net contractile moment is similar in both zyxin^-/- and wild type primary MASM cells in isometric conditions. (C) Normalized changes in net contractile moment in wild type (n = 25) and zyxin^-/- (n = 26) primary MASM cells following a transient 5–10% stretch at time = 0 seconds. (D) Normalized changes in net contractile moment in wild type (n = 22) and zyxin^-/- (n = 23) primary ASM cells following a series of three transient 5–10% stretches at 0, 310 and 620 seconds.</p