Nighttime Radical NOx Chemistry by CRD

The following work presents measurements of NO2, NO3, N2O5, and organic nitrates (ΣPNs (R(O)O2NO2; and ΣANs (RONO2)) made by 3 years of measurements by a 5-channel cavity ringdown spectroscopy (5- CRD) instrument over the course of two field campaigns and multiple laboratory experiments. The results of these two campaigns are discussed within. The 2017 AQABA ship campaign reports measurements of NO2, NO3 and N2O5 from a mixture of highlypolluted and clean marine environments around the Arabian Peninsula and eastern Mediterranean Sea. NO3 and N2O5 mixing ratios over the detection limits seen over 30 of a possible 60 nights during the nights, with mixing ratios of 12 ± 18 ppt for NO3 (max: 146 ppt) and 23 ± 35 ppt (max: 295 ppt) for N2O5, respectively. This corresponds to a median NO3 lifetime of 65.5 seconds (~0.0153 s-1 reactivity) across the entire campaign, although this was found to be highly variable according to the region. DMS was found to be the single largest contributor (20 – 25%) in each region to controlling the lifetime of NO3, though reactions with anthropogenic VOCs, while generally negligible were a regionally important sink in the Persian Gulf. Heterogeneous uptake onto the surface of particles was limited by high temperatures and contributed only a small fraction to reactivity (~5%). Most reactivity (40 – 80%, depending on region) could not be accounted for in the measurements made during AQABA, though an analysis within suggests that ship emissions may contribute strongly to this and shows that SO2 can be used marker to estimate reactivity. Results further suggest that nighttime removal of NOx was considerably more efficient (factor 2 – 3) than during the day in 4 out of 5 of the AQABA regions, despite longer days, high [OH] concentrations and approximately similar NO2 loss rates with OH and O3. The 2018 SAPHIR campaign reports measurements of NO2, NO3, N2O5, ΣPNs and ΣANs from a series of chamber experiments studying the reaction of NO3 + isoprene. Measurements of NO2, NO3 and N2O5 are presented in a statistical intercomparison against other instruments. NO2 measurements from three instruments, including the 5-CRD, report strong agreement in linear regression analysis with high slopes (> 0.9), high R2 values (> 0.9) and generally insignificant intercepts. NO3 and N2O5 comparisons report high levels of agreement with slopes within instrument uncertainties (1.0 and 0.95); high R2 (> 0.9) and intercepts generally consistent with limits of detection. ΣPNs and ΣANs data show possibility of thermal dissociation of isoprene nitrates at temperatures far lower than previously expected (beginning at 430 K), the implications of which are discussed. Gas phase yields of RONO2 from the reaction of NO3 + isoprene were determined as 0.81 ± 0.17 when taken all together but yields from individual experiments were found to be highly variable with significant uncertainty.168 Seite

A conserved domain for glycogen binding in protein phosphatase-1 targeting subunits

AbstractThe skeletal muscle glycogen-binding subunit (GM) of protein phosphatase-1 (PP1) is the founding member of a family of proteins that tether the PP1 catalytic subunit (PP1C) to glycogen and promote the dephosphorylation of glycogen synthase. A hydrophobic sequence (called here the VFV motif) is conserved among GM, the liver subunit GL, and the widely expressed subunits, PTG, R5 and U5. This study analyzed the role of this VFV motif in binding to glycogen and PP1C. Glutathione S-transferase (GST) fusions with the N-terminal domain of GM (GST-GM(1–240)) and with the full length R5 protein (GST-R5) both bound to glycogen in a co-sedimentation assay. In contrast, GST itself did not bind to glycogen. A single residue substitution in GST-GM(1–240), F155A, reduced glycogen binding by 40%. Double residue substitutions V150A/F155A and F155A/V159A resulted in greater reductions (60–70%) in glycogen binding, showing these hydrophobic residues influenced the protein-glycogen interaction. The wild type and V150A/F155A fusion proteins were digested by trypsin into the same sized fragments at the same rate. Furthermore, the wild type and mutated GST-GM proteins as well as GST-R5 bound equivalent amounts of PP1C, in either pull-down or far-Western assays. These results demonstrated retention of overall tertiary structure by the mutated fusion proteins, and indicated that glycogen and PP1C binding are independent of one another. A 68 residue segment of R5 encompassing the VFV motif was sufficient to produce glycogen binding when fused to GST. This motif, that is in bacterial and fungal starch metabolizing enzymes, probably has been conserved during evolution as a functional domain for binding glycogen and starch

Binding to Na(+) /H(+) exchanger regulatory factor 2 (NHERF2) affects trafficking and function of the enteropathogenic Escherichia coli type III secretion system effectors Map, EspI and NleH.

Enteropathogenic Escherichia coli (EPEC) strains are diarrhoeal pathogens that use a type III secretion system to translocate effector proteins into host cells in order to colonize and multiply in the human gut. Map, EspI and NleH1 are conserved EPEC effectors that possess a C-terminal class I PSD-95/Disc Large/ZO-1 (PDZ)-binding motif. Using a PDZ array screen we identified Na(+)/H(+) exchanger regulatory factor 2 (NHERF2), a scaffold protein involved in tethering and recycling ion channels in polarized epithelia that contains two PDZ domains, as a common target of Map, EspI and NleH1. Using recombinant proteins and co-immunoprecipitation we confirmed that NHERF2 binds each of the effectors. We generated a HeLa cell line stably expressing HA-tagged NHERF2 and found that Map, EspI and NleH1 colocalize and interact with intracellular NHERF2 via their C-terminal PDZ-binding motif. Overexpression of NHERF2 enhanced the formation and persistence of Map-induced filopodia, accelerated the trafficking of EspI to the Golgi and diminished the anti-apoptotic activity of NleH1. The binding of multiple T3SS effectors to a single scaffold protein is unique. Our data suggest that NHERF2 may act as a plasma membrane sorting site, providing a novel regulatory mechanism to control the intracellular spatial and temporal effector protein activity

Relationship between Medication Use and Cardiovascular Disease Health Outcomes in the Jackson Heart Study

Even though some medications have the potential to slow the progress of atherosclerosis and development of CVD, there are many at-risk individuals who continue to resist the benefits that are available by not following the advice of medical professionals. Non-adherence to prescribed drug regimens is a pervasive medical problem that negatively affects treatment outcomes. Information from standardized interviews of 5301 African Americans participating in the Jackson Heart Study was examined to determine the association between demographic parameters, behavior including adherence to prescribed medical regimens, and health outcomes. Data were also collected at Annual Follow-Up and Surveillance visits. During the two weeks prior to the examination visit, almost 52% of the participants reported taking blood pressure medication, 14% took cholesterol medication, 16% took medication for diabetes, and 19% took blood thinning medication. Of those who did not take the prescribed medications, the reasons given were the following: 47% were in a hurry, too busy, or forgot to take medications; 23% were trying to do without medications; 18% had no money to purchase medications; 19% indicated that the medications made them feel bad; 17% felt that they could not carry out daily functions when taking medications. The African American population can benefit from heightened awareness of the risk factors that are associated with CVD and the benefits of following a prescribed treatment regimen. Unacceptable secondary effects of prescribed medication comprised an important cause of non-compliance. Encouragement of this population to communicate with their healthcare providers to ensure that medication regimens are better tolerated could increase compliance and improve health outcomes

Cost-effectiveness of initiating extrafine- or standard size-particle inhaled corticosteroid for asthma in two health-care systems: a retrospective matched cohort study

Data acquisition and analyses were funded by Teva Pharmaceuticals