Removal of the Northern Paleo-Teton Range along the Yellowstone Hotspot Track

Classically held mechanisms for removing mountain topography (e.g., erosion and gravitational collapse) require 10-100 Myr or more to completely remove tectonically generated relief. Here, we propose that mountain ranges can be completely and rapidly (\u3c 2 Myr) removed by a migrating hotspot. In western North America, multiple mountain ranges, including the Teton Range, terminate at the boundary with the relatively low relief track of the Yellowstone hotspot. This abrupt transition leads to a previously untested hypothesis that preexisting mountainous topography along the track has been erased. We integrate thermochronologic data collected from the footwall of the Teton fault with flexural-kinematic modeling and length-displacement scaling to show that the paleo-Teton fault and associated Teton Range was much longer (min. original length 190-210 km) than the present topographic expression of the range front (~65 km) and extended across the modern-day Yellowstone hotspot track. These analyses also indicate that the majority of fault displacement (min. 11.4-12.6 km) and the associated footwall mountain range growth had accumulated prior to Yellowstone encroachment at ~2 Ma, leading us to interpret that eastward migration of the Yellowstone hotspot relative to stable North America led to removal of the paleo-Teton mountain topography via posteruptive collapse of the range following multiple supercaldera (VEI 8) eruptions from 2.0 Ma to 600 ka and/or an isostatic collapse response, similar to ranges north of the Snake River plain. While this extremely rapid removal of mountain ranges and adjoining basins is probably relatively infrequent in the geologic record, it has important implications for continental physiography and topography over very short time spans

Tectonic Transport Directions, Shear Senses and Deformation Temperatures Indicated by Quartz c‐Axis Fabrics and Microstructures in a NW‐SE Transect across the Moine and Sgurr Beag Thrust Sheets, Caledonian Orogen of Northern Scotland

Moine metasedimentary rocks of northern Scotland are characterized by arcuate map patterns of mineral lineations that swing progressively clockwise from orogen‐perpendicular E‐trend-ing lineations in greenschist facies mylonites above the Moine thrust on the foreland edge of the Caledonian Orogen, to S‐trending lineations at higher structural levels and metamorphic grades in the hinterland. Quartz c‐axis fabrics measured on a west to east coast transect demonstrate that the lineations developed parallel to the maximum principal extension direction and therefore track the local tectonic transport direction. Microstructures and c‐axis fabrics document a progressive change from top to the N shearing in the hinterland to top to the W shearing on the foreland edge. Field relationships indicate that the domain of top to the N shearing was at least 55 km wide before later horizontal shortening on km‐scale W‐vergent folds that detach on the underlying Moine thrust. Previously published data from the Moine thrust mylonites demonstrate that top to the W shearing had largely ceased by 430 Ma, while preliminary isotopic age data suggest top to the N shearing occurred at ~470–450 Ma. In addition, data from the east coast end of our transect indicate normal-sense top down‐SE shearing at close to peak temperatures at ~420 Ma that may be related to the closing stages of Scandian deformation, metamorphism and cooling/exhumation

Lithologic Controls on Focused Erosion and Intraplate Earthquakes in the Eastern Tennessee Seismic Zone

We present a new geomorphic model for the intraplate eastern Tennessee seismic zone (ETSZ). Previous studies document that the Upper Tennessee drainage basin is in a transient state of adjustment to ~150 m of base level fall that occurred in the Late Miocene. Using quantitative geomorphology, we demonstrate that base level fall resulted in the erosion of ~3,500 km3 of highly erodibility rock in an ~70 km wide by ~350‐km‐long corridor in the Paleozoic fold‐thrust belt above the ETSZ. Models of modern incision rates show a NE‐SW trending swath of elevated erosion ~30 km southeast of the center of the ETSZ. Stress modeling shows that lithologically focused erosion has affected fault clamping stress on preexisting, favorably oriented faults. We argue that the lithologically controlled transient erosional response to base level fall in the Upper Tennessee basin has given rise to and is sustaining earthquake activity in the ETSZ

Effect of Dam Emplacement and Water Level Changes on Sublacustrine Geomorphology and Recent Sedimentation in Jackson Lake, Grand Teton National Park (Wyoming, United States)

Dam installation on a deep hydrologically open lake provides the experimental framework necessary to study the influence of outlet engineering and changing base levels on limnogeological processes. Here, high-resolution seismic reflection profiles, sediment cores, and historical water level elevation datasets were employed to assess the recent depositional history of Jackson Lake, a dammed glacial lake located adjacent to the Teton fault in western Wyoming (USA). Prograding clinoforms imaged in the shallow stratigraphy indicate a recent lake-wide episode of delta abandonment. Submerged ∼11–12 m below the lake surface, these Gilbert-type paleo-deltas represent extensive submerged coarse-grained deposits along the axial and lateral margins of Jackson Lake that resulted from shoreline transgression following dam construction in the early 20th century. Other paleo-lake margin environments, including delta plain, shoreline, and glacial (drumlins, moraines) landforms were likewise inundated following dam installation, and now form prominent features on the lake floor. In deepwater, a detailed chronology was established using 137Cs, 210Pb, and reservoir-corrected 14C for a sediment core that spans ∼1654–2019 Common Era (CE). Dam emplacement (1908–1916 CE) correlates with a nearly five-fold acceleration in accumulation rates and a depositional shift towards carbonaceous sediments. Interbedded organic-rich black diatomaceous oozes and tan silts track changes in reservoir water level elevation, which oscillated in response to regional climate and downstream water needs between 1908 and 2019 CE. Chemostratigraphic patterns of carbon, phosphorus, and sulfur are consistent with a change in nutrient status and productivity, controlled initially by transgression-driven flooding of supralittoral soils and vegetation, and subsequently with water level changes. A thin gravity flow deposit punctuates the deepwater strata and provides a benchmark for turbidite characterization driven by hydroclimate change. Because the Teton fault is a major seismic hazard, end-member characterization of turbidites is a critical first step for accurate discrimination of mass transport deposits controlled by earthquakes in more ancient Jackson Lake strata. Results from this study illustrate the influence of dam installation on sublacustrine geomorphology and sedimentation, which has implications for lake management and ecosystem services. Further, this study demonstrates that Jackson Lake contains an expanded, untapped sedimentary archive recording environmental changes in the American West

The Use of Steroid Sulfatase Inhibitors as a Novel Therapeutic Strategy Against Hormone-Dependent Endometrial Cancer

The past few years have seen an increase in the reported incidence of endometrial carcinoma, one of the most frequently diagnosed malignancies of the female genital tract. Estrogen production is vital for the mitogenesis of endometrial tumors. Inhibition of steroid sulfatase (STS), an enzyme responsible for the synthesis of steroids with estrogenic properties, may represent a novel therapeutic target for this type of cancer. This study investigates the effects of STX64 (also known as 667Coumate and BN83495) and STX213, two potent STS inhibitors, on hormone-dependent endometrial cancer cell growth in vivo. When tested in intact mice with endometrial cancer xenografts, STX64 had limited effect on tumor growth. In contrast, the microtubule disruptor STX140 reduced tumor growth by 55%. In a hormone-dependent endometrial xenograft model in ovariectomized mice, both STX64 and STX213 given orally, daily at 1 mg/kg significantly inhibited tumor growth by 48 and 67%, respectively. However, when given orally at 1 mg/kg once weekly, only STX213 still inhibited tumor proliferation. At a higher dose of STX64 (10 mg/kg, orally, daily), a greater tumor growth inhibition of 59% was observed. Liver and tumor STS activity was completely inhibited in all daily treatment groups. Plasma estradiol (E2) levels were also significantly decreased. A significant correlation was observed between plasma E2 concentrations and STS activity, indicating the importance of circulating E2 on tumor growth. This novel study demonstrates for the first time that STS inhibitors are potent inhibitors of endometrial cancer growth in nude mice

The Regulation and Function of the Forkhead Transcription Factor, Forkhead Box O1, Is Dependent on the Progesterone Receptor in Endometrial Carcinoma

In many type I endometrial cancers, the PTEN gene is inactivated, which ultimately leads to constitutively active Akt and the inhibition of Forkhead box O1 (FOXO1), a member of the FOXO subfamily of Forkhead/winged helix family of transcription factors. The expression, regulation, and function of FOXO1 in endometrial cancer were investigated in this study. Immunohistochemical analysis of 49 endometrial tumor tissues revealed a decrease of FOXO1 expression in 95.9% of the cases compared with the expression in normal endometrium. In four different endometrial cancer cell lines (ECC1, Hec1B, Ishikawa, and RL95), FOXO1 mRNA was expressed at similar levels; however, protein levels were low or undetectable in Ecc1, Ishikawa, and RL95 cells. Using small interfering RNA technology, we demonstrated that the low levels of FOXO1 protein were due to the involvement of Skp2, an oncogenic subunit of the Skp1/Cul1/F-box protein ubiquitin complex, given that silencing Skp2 increased FOXO1 protein expression in Ishikawa cells. Inhibition of Akt in Ishikawa cells also increased nuclear FOXO1 protein levels. Additionally, progestins increased FOXO1 protein levels, specifically through progesterone receptor B (PRB) as determined by using stably transfected PRA-specific and PRB-specific Ishikawa cell lines. Finally, overexpression of triple mutant (Tm) FOXO1 in the PR-specific Ishikawa cell lines caused cell cycle arrest and significantly decreased proliferation in the presence and absence of the progestin, R5020. Furthermore, TmFOXO1 overexpression induced apoptosis in PRB-specific cells in the presence and absence of ligand. Taken together, these data provide insight into the phosphoinositide-3-kinase/Akt/FOXO pathway for the determination of progestin responsiveness and the development of alternate therapies for endometrial cancer