Autochthonous outer ramp sedimentation: The Alamogordo Member of the Lake Valley Formation,New Mexico

Summary Paleozoic carbonate ramp sedimentation has generally been described in terms of downlapping clinoforms composed of allochthonous sediment derived from shallower environments. However, during transgressive episodes when carbonate sediment production is low and down slope sediment transport by gravity becomes inactive, autochthonous carbonate sediment accumulates in vertical stacks of essentially in situ sediment. Autochthonous outer ramp deposition is probably a part of many Paleozoic ramp strata, but has heretofore not been recognized because of the general absence of adequate exposures. Evidence of autochthonous, in situ deposition and preservation of sediments in a starved setting is well displayed in the Alamogordo Member of the Lake Valley Formation in south central New Mexico. This evidence includes: 1) beds and bed sets that are individually continuous and traceable along ramp slope for 32 km, 2) down-ramp sequential distributions of depth-sensitive organisms and assemblages but patchy distribution of rock types, 3) lack of sedimentary structures indicative of transport, 4) well preserved, unabraded fossils, 5) the common occurrence of fossils in life position, 6) beds traceable into and through mounds 7) bed thickness trends ascribed to biotic productivity, and 8) geopetal structures in original position. Integrated paleontologic, sedimentologic, and stratigraphic data provide information about depositional processes and setting. The depositional slope was approximately 0.5^o based on the distribution of fossil algae; this is comparable to dips reported for other Mississippian homoclinal ramps. An oxygen minimum zone may have impinged on the ramp during a major flooding event. Shifts in biotic gradients from bed to bed reveal transgressive-regressive patterns that would not be resolvable without detailed paleontological evidence. The Alamogordo Member formed as a result of transgressive and early highstand starved carbonate sedimentation along a narrow, homoclinal outer ramp. The surface of maximum flooding and the boundary between the TST and HST are within the Alamogordo Member.     

A novel potent metal-binding NDM-1 inhibitor was identified by fragment virtual,SPR and NMR screening

NDM-1 can hydrolyze nearly all available β-lactam antibiotics, including carbapenems. NDM-1 producing bacterial strains are worldwide threats. It is still very challenging to find a potent NDM-1 inhibitor for clinical use. In our study, we used a metal-binding pharmacophore (MBP) enriched virtual fragment library to screen NDM-1 hits. SPR screening helped to verify the MBP virtual hits and identified a new NDM-1 binder and weak inhibitor A1. A solution NMR study of ¹⁵N-labeled NDM-1 showed that A1 disturbed all three residues coordinating the second zinc ion (Zn2) in the active pocket of NDM-1. The perturbation only happened in the presence of zinc ion, indicating that A1 bound to Zn2. Based on the scaffold of A1, we designed and synthesized a series of NDM-1 inhibitors. Several compounds showed synergistic antibacterial activity with meropenem against NDM-1 producing K. pneumoniae.