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Hsiao H.-C.,College StationTX | Gonzalez K.L.,College StationTX | Catanese Jr D.J.,Rice University | Catanese Jr D.J.,Baylor College of Medicine | And 4 more authors.
PLoS ONE | Year: 2014

Interactions between structured proteins require a complementary topology and surface chemistry to form sufficient contacts for stable binding. However, approximately one third of protein interactions are estimated to involve intrinsically disordered regions of proteins. The dynamic nature of disordered regions before, in some cases, after binding calls into question the role of partner topology in forming protein interactions. To understand how intrinsically disordered proteins identify the correct interacting partner proteins, we evaluated interactions formed by the Drosophila melanogaster Hox transcription factor Ultrabithorax (Ubx), which contains both structured and disordered regions. Ubx binding proteins are enriched in specific folds: 23 of its 39 partners include one of 7 folds, out of the 1195 folds recognized by SCOP. For the proteins harboring the two most populated folds, DNA-RNA binding 3-helical bundles and α-α superhelices, the regions of the partner proteins that exhibit these preferred folds are sufficient for Ubx binding. Three disorder-containing regions in Ubx are required to bind these partners. These regions are either alternatively spliced or multiply phosphorylated, providing a mechanism for cellular processes to regulate Ubx-partner interactions. Indeed, partner topology correlates with the ability of individual partner proteins to bind Ubx spliceoforms. Partners bind different disordered regions within Ubx to varying extents, creating the potential for competition between partners and cooperative binding by partners. The ability of partners to bind regions of Ubx that activate transcription and regulate DNA binding provides a mechanism for partners to modulate transcription regulation by Ubx, and suggests that one role of disorder in Ubx is to coordinate multiple molecular functions in response to tissue-specific cues. Copyright: © 2014 Hsiao et al.


Driver J.H.,risksciences.net LLC | Price P.S.,Dow Chemical Company | Van Wesenbeeck I.,Dow AgroSciences | Ross J.H.,risksciences.net LLC | And 6 more authors.
Science of the Total Environment | Year: 2016

Dow AgroSciences (DAS) markets and sells 1,3-Dichloropropene (1,3-D), the active ingredient in Telone®, which is used as a pre-plant soil fumigant nematicide in economically important crops in California. 1,3-D has been regulated as a “probable human carcinogen” and the California Department of Pesticide Regulation limits use of 1,3-D based on human health risk assessments for bystanders. This paper presents a risk characterization for bystanders based on advances in the assessment of both exposure and hazard. The revised bystander risk assessment incorporates significant advances: 1) new data on residency duration and mobility in communities where 1,3-D is in high demand; 2) new information on spatial and temporal concentrations of 1,3-D in air based on multi-year modeling using a validated model; and 3) a new stochastic spatial and temporal model of long-term exposures. Predicted distributions of long-term, chronic exposures indicate that current, and anticipated uses of 1,3-D would result in lifetime average daily doses lower than 0.002 mg/kg/d, a dose associated with theoretical lifetime excess cancer risk of < 10− 5 to > 95% of the local population based on a non-threshold risk assessment approach. Additionally, examination of 1,3-D toxicity studies including new chronic toxicity data and mechanism of action supports the use of a non-linear, threshold based risk assessment approach. The estimated maximum annual average daily dose of < 0.0016 mg/kg/d derived from the updated exposure assessment was then compared with a threshold point of departure. The calculated margin of exposure is > 1000-fold, a clear indication of acceptable risk for human health. In summary, the best available science supports 1,3-D's threshold nature of hazard and the revised exposure assessment supports that current agricultural uses of 1,3-D are associated with reasonable certainty of no harm, i.e., estimated long-term exposures pose insignificant health risks to bystanders even when the non-threshold approach is assumed. © 2016 Elsevier B.V.


Suresh M.A.,Texas A&M University | Suresh M.A.,College StationTX | Zhang W.,Texas A&M University | Gong W.,Texas A&M University | And 7 more authors.
ACM Transactions on Sensor Networks | Year: 2015

Monitoring flow-based systems (FBS) (e.g., water distribution systems, oil and gas pipelines, the human cardiovascular system) is of paramount importance considering their economic and health impacts. FBS monitoring typically has been achieved by costly, complex, static sensors that are strategically placed. To reduce the cost of monitoring, we propose a mobile wireless sensor network (WSN) system comprised of mobile sensors (their movement aided by the inherent flow in the FBS) and static beacons that aid in locating sensors. This article presents the first complete architectural design, algorithms, and protocols for optimal monitoring of FBS. Our proposed solution includes sensing and communication models, MAC and group management protocols for sensor and beacon communication, and algorithms for sensor and beacon placement. We compare our proposed solution with the state of the art through extensive simulations and a proof-of-concept system implementation. We demonstrate performance improvements, such as a dramatic reduction (a factor of 91) in the number of sensors when the sensing range is marginally (2.5 times) increased. © 2015 ACM.

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