Disposition of Federally Owned Surpluses

PDZ domains are scaffolding modules in protein-protein interactions that mediate numerous physiological functions by interacting canonically with the C-terminus or non-canonically with an internal motif of protein ligands. A conserved carboxylate-binding site in the PDZ domain facilitates binding via backbone hydrogen bonds; however, little is known about the role of these hydrogen bonds due to experimental challenges with backbone mutations. Here we address this interaction by generating semisynthetic PDZ domains containing backbone amide-to-ester mutations and evaluating the importance of individual hydrogen bonds for ligand binding. We observe substantial and differential effects upon amide-to-ester mutation in PDZ2 of postsynaptic density protein 95 and other PDZ domains, suggesting that hydrogen bonding at the carboxylate-binding site contributes to both affinity and selectivity. In particular, the hydrogen-bonding pattern is surprisingly different between the non-canonical and canonical interaction. Our data provide a detailed understanding of the role of hydrogen bonds in protein-protein interactions

Feasibility and Safety of Multicenter Tissue and Biofluid Sampling for α-Synuclein in Parkinson's Disease: The Systemic Synuclein Sampling Study (S4)

BACKGROUND: α-synuclein is a lead Parkinson's disease (PD) biomarker. There are conflicting reports regarding accuracy of α-synuclein in different tissues and biofluids as a PD biomarker, and the within-subject anatomical distribution of α-synuclein is not well described. The Systemic Synuclein Sampling Study (S4) aims to address these gaps in knowledge. The S4 is a multicenter, cross-sectional, observational study evaluating α-synuclein in multiple tissues and biofluids in PD and healthy controls (HC). OBJECTIVE: To describe the baseline characteristics of the S4 cohort and safety and feasibility of this study. METHODS: Participants underwent motor and non-motor clinical assessments, dopamine transporter SPECT, biofluid collection (cerebrospinal fluid, saliva, and blood), and tissue biopsies (skin, sigmoid colon, and submandibular gland). Biopsy adequacy was determined based on presence of adequate target tissue. Tissue sections were stained with the 5C12 monoclonal antibody against unmodified α-synuclein. All specimens were acquired and processed in a standardized manner. Adverse events were systematically recorded. RESULTS: The final cohort consists of 82 participants (61 PD, 21 HC). In 68 subjects (83%), all types of specimens were obtained but only 50 (61%) of subjects had all specimens both collected and evaluable for α-synuclein. Mild adverse events were common, especially for submandibular gland biopsy, but only 1 severe adverse event occurred. CONCLUSION: Multicenter tissue and biofluid sampling for α-synuclein is feasible and generally safe. S4 will inform understanding of the concurrent distribution of α-synuclein pathology and biomarkers in biofluids and peripheral nervous system in PD

Provenance of Cretaceous through Eocene strata of the Four Corners region: Insights from detrital zircons in the San Juan Basin, New Mexico and Colorado

Cretaceous through Eocene strata of the Four Corners region provide an excellent record of changes in sediment provenance from Sevier thin-skinned thrusting through the formation of Laramide block uplifts and intra-foreland basins. During the ca. 125–50 Ma timespan, the San Juan Basin was flanked by the Sevier thrust belt to the west, the Mogollon highlands rift shoulder to the southwest, and was influenced by (ca. 75–50 Ma) Laramide tectonism, ultimately preserving a >6000 ft (>2000 m) sequence of continental, marginal-marine, and offshore marine sediments. In order to decipher the influences of these tectonic features on sediment delivery to the area, we evaluated 3228 U-Pb laser analyses from 32 detrital-zircon samples from across the entire San Juan Basin, of which 1520 analyses from 16 samples are newly reported herein. The detrital-zircon results indicate four stratigraphic intervals with internally consistent age peaks: (1) Lower Cretaceous Burro Canyon Formation, (2) Turonian (93.9–89.8 Ma) Gallup Sandstone through Campanian (83.6–72.1 Ma) Lewis Shale, (3) Campanian Pictured Cliffs Sandstone through Campanian Fruitland Formation, and (4) Campanian Kirtland Sandstone through Lower Eocene (56.0–47.8 Ma) San Jose Formation. Statistical analysis of the detrital-zircon results, in conjunction with paleocurrent data, reveals three distinct changes in sediment provenance. The first transition, between the Burro Canyon Formation and the Gallup Sandstone, reflects a change from predominantly reworked sediment from the Sevier thrust front, including uplifted Paleozoic sediments and Mesozoic eolian sandstones, to a mixed signature indicating both Sevier and Mogollon derivation. Deposition of the Pictured Cliffs Sandstone at ca. 75 Ma marks the beginning of the second transition and is indicated by the spate of near-depositional-age zircons, likely derived from the Laramide porphyry copper province of southern Arizona and southwestern New Mexico. Paleoflow indicators suggest the third change in provenance was complete by 65 Ma as recorded by the deposition of the Paleocene Ojo Alamo Sandstone. However, our new U-Pb detrital-zircon results indicate this transition initiated ∼8 m.y. earlier during deposition of the Campanian Kirtland Formation beginning ca. 73 Ma. This final change in provenance is interpreted to reflect the unroofing of surrounding Laramide basement blocks and a switch to local derivation. At this time, sediment entering the San Juan Basin was largely being generated from the nearby San Juan Mountains to the north-northwest, including uplift associated with early phases of Colorado mineral belt magmatism. Thus, the detrital-zircon spectra in the San Juan Basin document the transition from initial reworking of the Paleozoic and Mesozoic cratonal blanket to unroofing of distant basement-cored uplifts and Laramide plutonic rocks, then to more local Laramide uplifts.National Science Foundation (NSF grant EAR-1649254

Exploring for structurally concealed Carlin-type mineralization: A case study from the northern Shoshone Range, Nevada, USA

This study integrates results from previous studies with new reconnaissance-scale mapping of rock types, structures, and hydrothermal alteration at Goat Ridge and Tenabo to provide a district-scale cross section and palinspastic restoration of an area in Nevada with high potential for Carlin-type mineralization in the footwall of a dismembered thrust fault. Reinterpretation of legacy drill data in light of recent advances in the understanding of Cenozoic normal faulting in the area with the expected stratigraphy of the Roberts Mountains autochthon allows for deciphering whether previous drill holes piercements of faults are the Roberts Mountains thrust or are tilted normal faults that down-dropped the deep-water siliciclastic rocks of Roberts Mountains allochthon onto the coeval carbonate rocks of the Roberts Mountains autochthon. A cross-sectional reconstruction shows that ∼11.1 km (120 %) of extension was accomplished along one set of faults that initiated at 60-70°and tilted 40°E. Previously underappreciated Mesozoic folds are present, which likely formed with horizontal fold hinges. Because of Cenozoic normal faulting and associated tilting, the hinge lines currently plunge at moderate angles and are offset as they step across each crosscutting fault. The anticlinal fold hinges produced the modern exposures of lower plate rocks in the range. The Eocene paleogeologic map that results from a plan-view structural restoration shows that the hinge lines of the original folds trended northwest-southeast in the southern half of the range but turned northward toward the northern end of the range. Mineralization in the range includes silver-dominated polymetallic veins/lodes, weak porphyry-type, Carlin-type, and siliciclastic-hosted gold deposits of uncertain origin. Porphyry-style and silver-dominated polymetallic vein mineralization is associated with ∼39–40 Ma granodiorites, with the silver-dominated polymetallic veins interpreted as the distal veins around weakly mineralized and/or deeply buried porphyry system(s), probably of the quartz monzonitic-granitic porphyry Mo-Cu subclass of porphyry molybdenum deposits. Crosscutting relationships demonstrate that at least one of “upper plate” gold deposits is Eocene, but a Miocene age cannot be ruled out for the other gold deposits. © 2023 The Author(s)Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Coarse muscovite veins and alteration deep in the Yerington batholith, Nevada: insights into fluid exsolution in the roots of porphyry copper systems

Veins and pervasive wall-rock alteration composed of coarse muscovite +/- quartz +/- pyrite are documented for the first time in a porphyritic granite at Luhr Hill in the Yerington District, Nevada. Coarse muscovite at Luhr Hill occurs at paleodepths of similar to 6-7 km in the roots of a porphyry copper system and crops out on the scale of tens to hundreds of meters, surrounded by rock that is unaltered or variably altered to sodic-calcic assemblages. Coarse muscovite veins exhibit a consistent orientation, subvertical and N-S striking, which structurally restores to subhorizontal at the time of formation. Along strike, coarse muscovite veins swell from distal, millimeter-thick muscovite-only veinlets to proximal, centimeter-thick quartz-sulfide-bearing muscovite veins. Crosscutting relationships between coarse muscovite veins, pegmatite dikes, and sodic-calcic veins indicate that muscovite veins are late-stage magmatic-hydrothermal features predating final solidification of the Luhr Hill porphyritic granite. Fluid inclusions in the muscovite-quartz veins are high-density aqueous inclusions of similar to 3-9 wt% NaCl eq. and < 1 mol% CO2 that homogenize between similar to 150 and 200 A degrees C, similar to fluid inclusions from greisen veins in Sn-W-Mo vein systems. Our results indicate that muscovite-forming fluids at Luhr Hill were mildly acidic, of low to moderate salinity and sulfur content and low CO2 content, and that muscovite in deep veins and alteration differs in texture, composition, and process of formation from sericite at shallower levels of the hydrothermal system. Although the definition of greisen is controversial, we suggest that coarse muscovite alteration is more similar to alteration in greisen-type Sn-W-Mo districts worldwide than to sericitic alteration at higher levels of porphyry copper systems. The fluids that form coarse muscovite veins and alteration in the roots of porphyry copper systems are distinct from fluids that formed copper ore or widespread, shallower, acidic alteration. We propose that this style of veins and alteration at Luhr Hill represents degassing of moderate volumes of overpressured hydrothermal fluid during late crystallization of deep levels of the Yerington batholith.Geological Society of America; Society of Economic Geologists12 month embargo; Published Online: 27 February 2017.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]