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The eastern oyster (Crassostrea virginica), has experienced dramatic declines throughout its range, and most U.S. states along the Atlantic and Gulf of Mexico coasts have restoration programs. Oyster restoration in the Hudson River Estuary has been a focus of management agencies for over two decades. The present project was initiated in 2013 after sampling for replacement of the Tappan Zee bridge determined live oysters would be lost during bridge construction, thus requiring mitigation measures. Preliminary studies identified three areas for pilot studies to inform the design of full‐scale efforts. A pilot study involving deployment of oyster shell‐filled gabions and two styles of Reef Balls, found all substrates supported oyster recruitment and growth but there were higher oyster densities on gabions. Some of the gabions, however, failed structurally necessitating a need for new design. For full‐scale restoration, a total of 422 modified gabions and 881 Mini‐Bay style Reef Balls were deployed across three sites which totaled approximately 2.4 ha (6 ac) in seafloor area. Both substrate types were heavily colonized by oysters and several other species at all three sites, essentially duplicating the findings of the pilot study. The final monitoring event in 2020 indicated a total of approximately 5.8 million live oysters were on the substrates deployed in 2018. This mitigation effort was the largest oyster habitat restoration project in, or north of, the New York Harbor region in recent decades based on restoration area and several oyster metrics of early success. [ABSTRACT FROM AUTHOR]

Angiopoietins Ang1 and Ang2 are secreted ligands for the endothelial receptor tyrosine kinase Tie2 essential for vascular development and maintenance. Ang1 acts as an agonist to maintain normal vessel function, whereas Ang2 acts as a Tie2 antagonist. Ang2 is increased in macular edema, sepsis, and other conditions, in which it blocks Ang1-mediated signaling, causing vascular dysfunction and contributing to disease pathology. Therefore, Ang2 is an attractive therapeutic target. Previously, we reported a Tie2 ectodomain variant that selectively binds Ang2 and acts as soluble ligand trap to sequester Ang2; however, the mechanism of Ang2-binding selectivity is unknown. In the present study, we used directed protein evolution to enhance Ang2-binding affinity of this Tie2 ectodomain trap. We examined contributions of individual residues in the ligand-binding interface of Tie2 to Ang1 and Ang2 binding. Surprisingly, different combinations of Tie2 residues were found to bind each ligand, with hydrophobic residues binding both ligands and polar residues contributing selectively to either Ang1 or Ang2 binding. Our analysis also identified a single Tie2 residue, His168, with a pivotal role in both Ang1 and Ang2 binding, enabling competition between binding ligands. In summary, this study reports an enhanced-affinity Ang2-selective ligand trap with potential for therapeutic development and reveals the mechanism behind its selectivity. It also provides the first analysis of contributions of individual Tie2 residues to Ang1 and Ang2 binding and identifies selectivity-determining residues that could be targeted in the future design of small molecule and other inhibitors of Ang2 for the treatment of vascular dysfunction. [ABSTRACT FROM AUTHOR]

Reports on the significance of the economic consequences of inefficient work processes in clinical trials. Citation of Virtual Research Organization (VRO) as an organizational and technology model designed with the goal of achieving effective work process; Areas of emerging technology that will offer technical currencies for moving data more quickly and authoritatively; Benefits of strategic decision-making for VRO.

Focuses on the effect of environmental pollutants on the damage of materials. Reaction of metals and structural stone on sulfur dioxide; Importance of meteorological conditions in determining the concentration of pollutants; Application of kinetics technique in determining chemical reactions.

Presents a letter to the editor concerning the need for the transportation industry to provide the public with highest expectations for safety in the United States.

Activation of MrgX2, an orphan G protein-coupled receptor expressed on mast cells, leads to degranulation and histamine release. Human MrgX2 binds promiscuously to structurally diverse peptides and small molecules that tend to have basic properties (basic secretagogues), resulting in acute histamine-like adverse drug reactions of injected therapeutic agents. We set out to identify MrgX2 orthologues from other mammalian species used in nonclinical stages of drug development. Previously, the only known orthologue of human MrgX2 was from mouse, encoded by Mrgprb2. MrgX2 genes of rat, dog (beagle), minipig, pig, and Rhesus and cynomolgus monkey were identified by bioinformatic approaches and verified by their ability to mediate calcium mobilization in transfected cells in response to the classical MrgX2 agonist, compound 48/80. The peptide GSK3212448 is an inhibitor of the PRC2 epigenetic regulator that caused profound anaphylactoid reactions upon intravenous infusion to rat. We showed GSK3212448 to be a potent MrgX2 agonist particularly at rat MrgX2. We screened sets of drug-like molecules and peptides to confirm the highly promiscuous nature of MrgX2. Approximately 20% of drug-like molecules activated MrgX2 (pEC50 ranging from 4.5 to 6), with the principle determinant being basicity. All peptides tested of net charge +3 or greater exhibited agonist activity, including the cell penetrating peptides polyarginine (acetyl-Arg9-amide) and TAT (49-60), a fragment of HIV-1 TAT protein. Finally, we showed that the glycopeptide antibiotic vancomycin, which is associated with clinical pseudo-allergic reactions known as red man syndrome, is an agonist of MrgX2. [ABSTRACT FROM AUTHOR]