Direct interaction between the Gulf Stream and the shelfbreak south of New England

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 2 (2012): 553, doi:10.1038/srep00553.Sea surface temperature imagery, satellite altimetry, and a surface drifter track reveal an unusual tilt in the Gulf Stream path that brought the Gulf Stream to 39.9°N near the Middle Atlantic Bight shelfbreak—200 km north of its mean position—in October 2011, while a large meander brought Gulf Stream water within 12 km of the shelfbreak in December 2011. Near-bottom temperature measurements from lobster traps on the outer continental shelf south of New England show distinct warming events (temperature increases exceeding 6°C) in November and December 2011. Moored profiler measurements over the continental slope show high salinities and temperatures, suggesting that the warm water on the continental shelf originated in the Gulf Stream. The combination of unusual water properties over the shelf and slope in late fall and the subsequent mild winter may affect seasonal stratification and habitat selection for marine life over the continental shelf in 2012.Profiler data were made available by the Ocean Observatory Initiative (OOI) during the construction phase of the project. The OOI is funded by the National Science Foundation and managed by the Consortium for Ocean Leadership. Drifter data were provided by Tim Shaw and David Calhoun at Cape Fear Community College.GGGwas supported by NSFGrant OCE-1129125. RET was supported by the Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution, with funding provided by the Cooperative Institute for the North Atlantic Region. MA was supported by the Penzance Endowed Fund in Support of Assistant Scientists

Chemosensitization by phenothiazines in human lung cancer cells: impaired resolution of γH2AX and increased oxidative stress elicit apoptosis associated with lysosomal expansion and intense vacuolation

Chemotherapy resistance poses severe limitations on the efficacy of anti-cancer medications. Recently, the notion of using novel combinations of ‘old' drugs for new indications has garnered significant interest. The potential of using phenothiazines as chemosensitizers has been suggested earlier but so far our understanding of their molecular targets remains scant. The current study was designed to better define phenothiazine-sensitive cellular processes in relation to chemosensitivity. We found that phenothiazines shared the ability to delay γH2AX resolution in DNA-damaged human lung cancer cells. Accordingly, cells co-treated with chemotherapy and phenothiazines underwent protracted cell-cycle arrest followed by checkpoint escape that led to abnormal mitoses, secondary arrest and/or a form of apoptosis associated with increased endogenous oxidative stress and intense vacuolation. We provide evidence implicating lysosomal dysfunction as a key component of cell death in phenothiazine co-treated cells, which also exhibited more typical hallmarks of apoptosis including the activation of both caspase-dependent and -independent pathways. Finally, we demonstrated that vacuolation in phenothiazine co-treated cells could be reduced by ROS scavengers or the vacuolar ATPase inhibitor bafilomycin, leading to increased cell viability. Our data highlight the potential benefit of using phenothiazines as chemosensitizers in tumors that acquire molecular alterations rendering them insensitive to caspase-mediated apoptosis

A Predictive Model of Intein Insertion Site for Use in the Engineering of Molecular Switches

Inteins are intervening protein domains with self-splicing ability that can be used as molecular switches to control activity of their host protein. Successfully engineering an intein into a host protein requires identifying an insertion site that permits intein insertion and splicing while allowing for proper folding of the mature protein post-splicing. By analyzing sequence and structure based properties of native intein insertion sites we have identified four features that showed significant correlation with the location of the intein insertion sites, and therefore may be useful in predicting insertion sites in other proteins that provide native-like intein function. Three of these properties, the distance to the active site and dimer interface site, the SVM score of the splice site cassette, and the sequence conservation of the site showed statistically significant correlation and strong predictive power, with area under the curve (AUC) values of 0.79, 0.76, and 0.73 respectively, while the distance to secondary structure/loop junction showed significance but with less predictive power (AUC of 0.54). In a case study of 20 insertion sites in the XynB xylanase, two features of native insertion sites showed correlation with the splice sites and demonstrated predictive value in selecting non-native splice sites. Structural modeling of intein insertions at two sites highlighted the role that the insertion site location could play on the ability of the intein to modulate activity of the host protein. These findings can be used to enrich the selection of insertion sites capable of supporting intein splicing and hosting an intein switch