Shortening Events Research Articles

Quantum Chemistry Based Battery Electrochemistry: The Effect of Entropy and Anode Surface Structure

Lithium-sulfur (Li-S) battery is a promising battery technology, thanks to their high energy density and the use of inexpensive materials. A Li-S battery typically consists of a Li anode, a sulfur cathode or sulfur-based catholyte, and an organic solvent for lithium polysulfides (Li2S x ). Upon discharge, Li2S x chains accept Li and undergo successive chain shortening events, with the final discharge product being Li2S. Li2S is however insoluble in typical organic solvents and its irreversible precipitation leads to the impairment of Li-S batteries. The addition of phosphorus pentasulfide (P2S5) to a Li2S x catholyte has been experimentally and theoretically shown to form complexes with sulfur chains, which can accommodate Li2S, thus overcome the problem of Li2S precipitation and improving battery cyclability. [1]Quantum chemistry and specifically density functional theory (DFT) calculations have been used to predict molecular structures and electrochemical potentials for Li-S batteries, as well as other electrochemical systems. Here we present a series of DFT calculations (uB3LYP/6-31+G(2df,p)) using the P2S5-Li2S8 system as a case study to highlight considerations critical to reliable electrochemical predictions. Here, we focus on entropy, atomic structure of metal anode surface sites, and the level of DFT theory.The level of theory used throughout this study (uB3LYP/6-31+G(2df,p)) was chosen after careful comparison with other levels of theory, with varying methods and functionals (HF, B3LYP, M06, M11) and basis sets (3-21G, 6-31G(d), 6-31+G(2df,p), 6-311G(d), 6-311+G(2df,p), cc-pVTZ). The B3LYP functional with the 6-31+G(2df,p) or cc-pVTZ basis set performed best in predicting electrochemical potentials in agreement with the cyclic voltammetry experiments, as well as the nuclear magnetic resonance spectra. In addition, different solvents, all with similar dielectric constants, were considered and the resulting impact on E 0 was found to be negligible.The standard electrochemical potential for a full-cell reaction (E 0) is directly related to the Gibbs free energy of the reaction (ΔG 0): ΔG 0 = –nFE 0, where n is the number of electrons transferred and F is the Faraday constant. Gibbs free energy comprises an electronic energy (E elec), a temperature dependent sensible enthalpy (H sens) and a temperature dependent entropy term (–TS). Often, the sensible enthalpy and entropy terms are neglected and reaction Gibbs free energy is approximated as the difference of electronic energy between products and reactants. Our results for reactions involving lithium polysulfide chains and sulfur chains anchored on phosphorus groups indicate that, even at room temperature, the entropy term has a significant contribution to E 0 (of 0.2-0.3 V). Importantly, without considering this contribution, theoretically predicted electrochemical potentials do not match experimental results from cyclic voltammetry.Additionally, atomic structures of different surface sites impact the evaluation of E 0. Several surface sites, as shown in Fig. 1a, were simulated for the atom to be reacted (shown transparent in Fig. 1a), while keeping the rest of the atoms stationary. The Gibbs free energy of reaction was calculated for each site and its effect on E 0 was compared with that of the standard thermodynamic result for bulk Li(s), as shown in Fig. 1b. We found that as pexted, Li atoms in the ‘lone’ or ‘pair’ configuration react more readily. In the case of the ‘lone’ Li, E 0 increases by 0.35 V.In summary, DFT was used to identify the complexation and reaction mechanisms governing P2S5-Li2S8 catholyte batteries. In the calculation of electrochemical potentials for this system, we identified that special care should be taken to the temperature dependence of Gibbs free energy of reactions, the variation of local surface sites for the metal anode, and the level of DFT theory used. These considerations will aid the understanding of Li-S and other battery chemistry.[1] Wang, P., Kateris, N., Li, B., Zhang, Y., Luo, J., Wang, C., Zhang, Y., Jayaraman, A.S., Hu, X., Wang, H. and Li, W., 2023. High-Performance Lithium–Sulfur Batteries via Molecular Complexation. Journal of the American Chemical Society, 145 (2023) 18865–18876. Figure 1

Polyphase formation of a Neoarchean auriferous fault zone network in the Michipicoten greenstone belt, southern Superior craton

Correlating structurally distinctive fault zones for understanding an unknown deformation system at the regional scale remains a challenge for understanding orogenic evolution and gold endowment. The current study deals with this challenge in the southern Michipicoten greenstone belt (MGB) of the Superior craton focusing on a Neoarchean auriferous fault zone network. Three deformation events associated with episodic gold mineralization are revealed in the ca. 2745 Ma host granitoid: (1) NW‒SE shortening recorded by the subvertical Grace and Minto B fault zones and locally the inclined Jubilee and Hornblende fault zones; (2) top-to-NNE strike-slip to oblique faulting indicated primarily by the dominant structures of the Jubilee and Hornblende fault zones; and (3) top-to-NE extension demonstrated by the northeast-dipping Parkhill #4 and Cooper fault zones. Fault zone lithologies and mineral assemblages suggest that the localization of deformation for the formation of these fault zones was controlled by rheological heterogeneities and syn-deformation fluids. The first and second events are correlated with two shortening events in a gold-endowed, structurally and kinematically distinctive deformation zone of the northern MGB. This correlation based on deformation processes suggests a larger footprint of gold mineralization associated with a regional deformation in the MGB and has implications for investigating structural evolution of orogens and orogenic gold mineralization in general.

Alternative Polyadenylation Characterizes Epithelial and Fibroblast Phenotypic Heterogeneity in Pancreatic Ductal Adenocarcinoma

Human tumors are characterized by extensive intratumoral transcriptional variability within the cancer cell and stromal compartments. This variation drives phenotypic heterogeneity, producing cell states with differential pro- and anti-tumorigenic properties. While bulk RNA sequencing cannot achieve cell-type-specific transcriptional granularity, single-cell sequencing has permitted an unprecedented view of these cell states. Despite this knowledge, we lack an understanding of the mechanistic drivers of this transcriptional and phenotypic heterogeneity. 3′ untranslated region alternative polyadenylation (3′ UTR-APA) drives gene expression alterations through regulation of 3′ UTR length. These 3′ UTR alterations modulate mRNA stability, protein expression and protein localization, resulting in cellular phenotypes including differentiation, cell proliferation, and migration. Therefore, we sought to determine whether 3′ UTR-APA events could characterize phenotypic heterogeneity of tumor cell states. Here, we analyze the largest single-cell human pancreatic ductal adenocarcinoma (PDAC) dataset and resolve 3′ UTR-APA patterns across PDAC cell states. We find that increased proximal 3′ UTR-APA is associated with PDAC progression and characterizes a metastatic ductal epithelial subpopulation and an inflammatory fibroblast population. Furthermore, we find significant 3′ UTR shortening events in cell-state-specific marker genes associated with increased expression. Therefore, we propose that 3′ UTR-APA drives phenotypic heterogeneity in cancer.

Migmatite dome as a result of multi-fold interference pattern, in the Damara Belt, Namibia

The western part of the Pan-African Damara Orogen in Namibia is located at the intersection of two highly oblique mobile belts: the coastal NNW-trending Kaoko-Gariep belts and the inland NE-trending Damara Belt. The Namibfontein-Vergenoeg (NV) domes are two, basement-cored, migmatite domes exposed in this orogenic intersection. These domes formed through the superposition of four deformation phases in the presence of melt, giving rise to syn-migmatitic multi-fold interference patterns. Early E-W shortening produced steep N–S striking S1 fabrics linked to km-scale steeply E-inclined F1 folds, likely reflecting the southern continuity of the Kaoko Belt fabrics. The superposition of NE-plunging, NNW-inclined F2 folds formed during NNW-SSE, orogen-perpendicular shortening and produced a Type 1 dome-and-basin fold interference pattern. Progressive with D2, D3 deformation caused localised m-scale folding of steep fabrics into inclined to recumbent, NW-plunging F3 folds, and local top-to-the-S or -SE thrusting. NNW-SSE shortening is correlated with the collision of the Congo and Kalahari cratons during Damara Belt formation. Finally, orogen-parallel NE-SW shortening, produced localised NE-inclined and NE-plunging F4 folds. This weaker shortening phase in the Damara Belt is enigmatic and may reflect tectonic activities further in eastern and western Gondwana. The superposition of F4 folds on F2 folds defines a Type 3 fold interference pattern that established the final 3D architecture of the NV domes. The deformation fabrics at the NV domes document three distinct regional shortening events related to large-scale tectonic switches involved in the western Gondwana Supercontinent assembly.

Structural analysis of the central Tunisian Atlas: Implications for salt-related structures and conjugate strike-slip faults

This scientific study aims to investigate the geological characteristics and tectonic processes of the central Tunisian Atlas region, focusing on the influence of tectonic events related to the Jurassic-Early Cretaceous Tethyan rifting and the subsequent Cenozoic tectonic inversion and uplift. In particular, this research emphasizes the strong control of tectono-sedimentary events on the geology of the central Tunisian Atlas, with specific attention given to the understudied isolated salt-related structures. To gain insights into the relationship between deep-seated faults, salt tectonism, and the conjugate strikes-slip faults, this study is based on subsurface data, including 2D seismic reflection and gravity data. The analysis investigates, the location of salt extrusions in relation to fault intersections. Results derived from subsurface data indicate that diapiric intrusions primarily occur at the junctions of major fault systems likely inherited from the Triassic-Jurassic Tethyan period. Notably, salt migration was remarkably active during the early Cretaceous, as evidenced by halotectonic sequences and salt-related mini-basins. Furthermore, fault blocks display sedimentary infill above tilted blocks, where salt structures appear to occur at their peripheries. During the subsequent tertiary compressions, the structural configurations of the basin (i.e., Z-shape basin) promote the strike-slip movement along pre-existing faults. This new structural interpretation suggests a closely relationship between fault zones inherited from the Jurassic-Early Cretaceous Tethyan Opening and isolated salt-related structures. The subsequent Cenozoic shortening events, including the Atlassic and Alpine events, have led to uplift of the deep-seated faults, facilitating the ascension and deformation of Triassic evaporitic sediments within subcircular isolated structures. Field observations and seismic sections indicate the presence of sedimentary gaps resulting from these processes. The findings of this study contribute to a comprehensive understanding of the deep tectonic framework and shallow salt-related structures in the central Tunisian Atlas.

Late Paleozoic-Jurassic tectonic evolution of the eastern Deseado Massif in central-southern Patagonia

Previous tectonic studies have indicated that the peri-cratonic lithosphere, located away from continental margins, is sensitive to far-field stresses propagating from active plate margins, which induce variable deformation. In order to gain a better understanding of potential intraplate tectonic events associated with the geodynamic evolution of the active margin of southwestern Gondwana, we conducted a tectono-sedimentary study of the Permian-Jurassic volcano-sedimentary record in the Deseado Massif, located in southern Patagonia. Our multidisciplinary analysis includes detailed geological mapping of an area of approximately 150 km2, structural analysis, geoelectric tomography, 2D seismic data, new geochronological dating, petrographic studies, and stratigraphic loggings of the volcano-sedimentary basin record. This comprehensive data set has allowed us to establish the tectonic, sedimentary, and magmatic evolution of the eastern Deseado Massif. Specifically, we have identified major normal faults associated with the syn-extensional deposition of late Permian and Jurassic sedimentary and volcanic rocks, as well as the Late Triassic emplacement of intermediate and felsic intrusive bodies. Additionally, interspersed large-scale shortening events were recognized, which induced positive tectonic inversion events in the region, recording contrasting stress fields during the analyzed lapse. Based on this, six major intraplate tectonomagmatic events were defined: (i) a potential post-Devonian pre-late Permian exhumation of the Neoproterozoic-early Paleozoic igneous-metamorphic basement, which we tentatively link to the Gondwanide orogeny; (ii) intraplate extension in the Late Permian (255 ± 4 Ma) related to the deposition of the Dos Hermanos Member of the La Golondrina Formation; (iii) Late Triassic (231 ± 3 Ma) intrusion of andesitic bodies, tentatively linked to the inland migration of arc magmatism associated with the South Gondwana flat slab; (iv) subsequent Late Triassic positive tectonic inversion of Permian extensional faults caused by a large-scale contractional event linked to the South Gondwana flat slab; (v) the extension-related emplacement and deposition of Early-Middle Jurassic (176 ± 3 Ma; 172 ± 4 Ma) sedimentary (lacustrine and fan deltas-related deposits), pyroclastic rocks (ignimbrites and ash tuffs), and lavas (lava domes and dykes) related to the Chon Aike silicic large igneous province; and (vi) poorly-constrained post-Middle Jurassic positive tectonic inversion of Jurassic faults. Therefore, we suggest that the geological events preserved in the Deseado Massif provide a key deformational record of the distal effects associated with ancient geodynamic processes that occurred along the southwestern active margin of Gondwana.

Differential expression of mRNA 3′-end isoforms in cervical and ovarian cancers

Early diagnosis and therapeutic targeting are continuing challenges for gynecological cancers. Here, we focus on cancer transcriptomes and describe the differential expression of 3′UTR isoforms in patients using an algorithm to detect differential poly(A) site usage. We find primarily 3′UTR shortening cases in cervical cancers compared with the normal cervix. We show differential expression of alternate 3′-end isoforms of FOXP1, VPS4B, and OGT in HPV16-positive patients who develop high-grade cervical lesions compared with the infected but non-progressing group. In contrast, in ovarian cancers, 3′UTR lengthening is more evident compared with normal ovary tissue. Nevertheless, highly malignant ovarian tumors have unique 3′UTR shortening events (e.g., CHRAC1, SLC16A1, and TOP2A), some of which correlate with upregulated protein levels in tumors. Overall, our study shows isoform level deregulation in gynecological cancers and highlights the complexity of the transcriptome. This transcript diversity could help identify novel cancer genes and provide new possibilities for diagnosis and therapy.

40Ar/39Ar muscovite geochronology of Arperos Basin inversion in Southern Mexico: new insights into cretaceous shortening initiation in southernmost North America

ABSTRACT During Cretaceous–Eocene time, North America was involved in a succession of shortening events that produced major orogenic belts. Previous work permitted the characterization of the kinematics and dynamics of some of these orogenic events along various transects. However, the timing of shortening is not well constrained everywhere. This has led to misinterpretation of the tectonic history of some sectors of the North American Pacific margin and to an incomplete understanding of the subduction dynamics. Mexico is one of those sectors in which the shortening history is not completely defined. We present structural and 40Ar/39Ar isotopic data from major shortening structures in southern Mexico, documenting two episodes of shortening: a first one at ~ 118–112 Ma, not considered in previous works, and a second one at ~ 104–90 Ma, which was previously interpreted as the record of shortening initiation. Integrated with previous data, our 40Ar/39Ar results indicate that, in Mexico, the shortening history was developed in two main stages: 1) a Late Aptian–Early Albian stage of localized shortening, during which the oceanic Arperos Basin was closed and the Guerrero terrane arc accreted to nuclear Mexico forming a ~ 80 km-wide suture belt, and 2) a latest Albian–Eocene stage, in which shortening was propagated from the North American trench to the plate interior, producing the development of a critically tapered wedge. Whether these two stages represent two superposed orogenic cycles or two steps within the same orogenic cycle remains to be established. In any case, the Late Aptian–Early Albian stage of deformation, which was not fully recognized in most previous works, is a key for our understanding of the causes that triggered shortening in southern North America after ~ 100 m.y. of extension associated with Pangea break-up

Hindered Trench Migration Due To Slab Steepening Controls the Formation of the Central Andes

AbstractThe formation of the Central Andes dates back to ∼50 Ma, but its most pronounced episode, including the growth of the Altiplano‐Puna Plateau and pulsatile tectonic shortening phases, occurred within the last 25 Ma. The reason for this evolution remains unexplained. Using geodynamic numerical modeling we infer that the primary cause of the pulses of tectonic shortening and growth of the Central Andes is the changing geometry of the subducted Nazca plate, and particularly the steepening of the mid‐mantle slab segment which results in a slowing down of the trench retreat and subsequent increase in shortening of the advancing South America plate. This steepening first happens after the end of the flat slab episode at ∼25 Ma, and later during the buckling and stagnation of the slab in the mantle transition zone. Processes that mechanically weaken the lithosphere of the South America plate, as suggested in previous studies, enhance the intensity of the shortening events. These processes include delamination of the mantle lithosphere and weakening of foreland sediments. Our new modeling results are consistent with the timing and amplitude of the deformation from geological data in the Central Andes at the Altiplano latitude.

CstF64-Induced Shortening of the BID 3'UTR Promotes Esophageal Squamous Cell Carcinoma Progression by Disrupting ceRNA Cross-talk with ZFP36L2.

The majority of human genes have multiple polyadenylation sites, which are differentially used through the process of alternative polyadenylation (APA). Dysregulation of APA contributes to numerous diseases, including cancer. However, specific genes subject to APA that impact oncogenesis have not been well characterized, and many cancer APA landscapes remain underexplored. Here, we used dynamic analyses of APA from RNA-seq (DaPars) to define both the 3'UTR APA profile in esophageal squamous cell carcinoma (ESCC) and to identify 3'UTR shortening events that may drive tumor progression. In four distinct squamous cell carcinoma datasets, BID 3'UTRs were recurrently shortened and BID mRNA levels were significantly upregulated. Moreover, system correlation analysis revealed that CstF64 is a candidate upstream regulator of BID 3'UTR length. Mechanistically, a shortened BID 3'UTR promoted proliferation of ESCC cells by disrupting competing endogenous RNA (ceRNA) cross-talk, resulting in downregulation of the tumor suppressor gene ZFP36L2. These in vitro and in vivo results were supported by human patient data whereby 3'UTR shortening of BID and low expression of ZFP36L2 are prognostic factors of survival in ESCC. Collectively, these findings demonstrate that a key ceRNA network is disrupted through APA and promotes ESCC tumor progression.Significance: High-throughput analysis of alternative polyadenylation in esophageal squamous cell carcinoma identifies recurrent shortening of the BID 3'UTR as a driver of disease progression.

Forced apart: a microtubule-based mechanism for equidistant positioning of multiple nuclei in single cells

Cells can position multiple copies of components like carboxysomes, nucleoids, and nuclei at regular intervals. By controlling positions, cells, for example, ensure equal partitioning of organelles over daughter cells and, in the case of nuclei, control cell sizes during cellularization. Mechanisms that generate regular patterns are as yet poorly understood. We used fission yeast cell cycle mutants to investigate the dispersion of multiple nuclei by microtubule-generated forces in single cells. After removing internuclear attractive forces by microtubule-based molecular motors, we observed the establishment of regular patterns of nuclei. Based on live-cell imaging, we hypothesized that microtubule growth within internuclear spaces pushes neighbouring nuclei apart. In the proposed mechanism, which was validated by stochastic simulations, the repulsive force weakens with increasing separation because stochastic shortening events limit the extent over which microtubules generate forces. Our results, therefore, demonstrate how cells can exploit the dynamics of microtubule growth for the equidistant positioning of organelles.

Palaeoproterozoic foreland fold-thrust belt structures and lateral faults in the West Troms Basement Complex, northern Norway, and their relation to inverted metasedimentary sequences

Palaeoproterozoic fold-thrust belt structures and steep, lateral shear zones characterize the foreland deformation of Neoarchaean basement tonalites in Vanna, West Troms Basement Complex, northern Norway. Low-grade par-autochthonous and allochthonous cover units (2.4–2.2. Ga) with sandstones and calcareous metapelites exist in separate areas of the foreland. They were formed as intracontinental rift- and/or deltaic shelf deposits, and subsequently intruded by a diorite sill at c. 2.2 Ga. The basement and cover units were folded and inverted along low-angle thrusts and steep reverse faults during two late/post Svecofennian (1.77–1.63 Ga) orthogonal shortening events (D1-D2). The D1 event involved NE-SW shortening, folding, ENE-directed thrusting, and dextral lateral shearing, controlled by pre-existing, N-S striking mafic dykes (c. 2.4 Ga) and basin-bounding normal faults. The D2 event involved SE vergent nappe translation, flat-ramp thrust propagation in a frontal duplex above a basement-seated detachment, and sinistral lateral reactivation in a partitioned orogen-parallel, transpressive setting. Hydrothermal fluid circulation affected all the shear zones. New aeromagnetic data show the basement-involved fold-thrust belt architecture well. The orthogonal Vanna Island fold-thrust belt styles of deformation resemble other inverted rift-basin deposits in northern Fennoscandia, deformed during the Svecofennian Orogeny (1.92–1.79 Ga), Alta-Kautokeino and Karasjok greenstone belts in northern Norway, Central Lapland, Peräpohja, Kittilä and Kuusamo belts of Finland, and in the Norrbotten province of Sweden. Westward younging of the orogenic events explain the younger age span of deformation on Vanna Island.

Active north-vergent thrusting in the northern Sicily continental margin in the frame of the quaternary evolution of the Sicilian collisional system

A three-stage evolution has characterized the Sicilian Fold and Thrust Belt (SFTB) during the last 15 My: two main thin-skinned shortening events involving mainly Meso-Cenozoic carbonate units, followed by thick-skinned thrusting involving Plio-Pleistocene deposits in the frontal area as well as the crystalline basement in the inner and deeper sector of the chain. We investigated the northern Sicily continental margin, by using differently-penetrative seismic reflection data and new field surveys, which revealed, both offshore and onshore, north-vergent compressional structures that affected the tectonic edifice during Quaternary time. These structures, correlated with the kinematic setting pointed out by seismicity and GPS measurements, could disclose an important change in distribution and orientation of deformation in the frame of the Africa-Europe convergence. Our hypothesis is that the most recent tectonic processes in the northern Sicily continental margin are representative of a jump of the deformation from the frontal area of the SFTB in the Sicily Channel to the inner sector in the Southern Tyrrhenian Sea. This study is in agreement with recent interpretations about a change in the subduction polarity in the central Mediterranean orogenic system, as a consequence of the ongoing collision of the African promontory with the thinned continental to oceanic sectors (Algerian and Tyrrhenian basins) of the European plate.The seismic activity associated with the north-vergent thrust could have implication for the assessment of the seismic risk in the Central Mediterranean and understanding of active structures in marine areas that could be responsible for tsunami hazard.

Structural overprinting criteria determined from regional aeromagnetic data: An example from the Hill End Trough, East Gondwana

Determining overprinting relationships in the geological record has underpinned our understanding of the evolution of the Earth and has provided the context in which to interpret geoscientific datasets. Geological overprinting relationships are generally determined from outcrop relationships. When outcrop is absent or limited, overprinting relationships using geological observations is often ineffective or ambiguous. We show how aeromagnetic data can be used to inform superposition of geological structures using a combination of folded stratigraphy, faults (both high angle and low angle), and plutons from the well-exposed Hill End Trough, in the Phanerozoic eastern Lachlan Orogen. Overprinting relationships reveal episodic inversion of the Late Silurian to Early Devonian back arc basin succession, preserved within the Hill End Trough, occurred during superimposed shortening events. The first event resulted in the development of regional folds associated with the Tabberabberan Orogeny and the second event resulted in the development of overprinting north-south and north-northwest trending faults during the Early Carboniferous Kanimblan Orogeny. Inversion structures are overprinted by a Carboniferous granite, which is overprinted by previously unrecognised northeast- and northwest conjugate faults, which we interpret to be related to the Permo-Triassic Hunter Bowen Orogeny.

Deformation history of the Puna plateau, Central Andes of northwestern Argentina

Two tectonic shortening events created the first-order structural characteristics of the Puna plateau: one in the Paleozoic and a second during the Andean Orogeny in the Cenozoic. To constrain the structural characteristics and timing of Andean deformation in the Puna plateau, we focus on differentiating these two shortening events and provide cooling ages (apatite fission track and apatite (U–Th)/He) to determine the amount of Andean exhumation on the hanging-wall of major Cenozoic faults. Two contrasting expressions of shortening are documented. In Ordovician strata, strain requires four stages: folding, flattening through cleavage formation, low-angle faulting and local distributed shear. In the Mesozoic and Cenozoic strata, shortening is expressed as reverse faults, fault-propagation folds and dipping panels. Dissimilarities reflect different P-T conditions and amount of strain, as structures in the Ordovician rocks require higher temperatures and strain than Andean structures in the Mesozoic and Cenozoic strata. Furthermore, local Cretaceous AFT cooling ages in pervasively cleaved Ordovician rocks reveal these rocks did not reach temperatures compatible with cleavage formation during the Andean event. Lastly, our data show a middle Eocene to Oligocene exhumation history that supports an overall continuous development of the Andean thrust belt in the Puna plateau since the early Cenozoic.

Geophysical interpretation and tectonic synthesis of the Proterozoic southern McArthur Basin, northern Australia

The southern McArthur Basin is highly prospective for sediment-hosted Zn-Pb-Ag mineralisation, and hosts the McArthur River and Teena deposits within the Batten Fault Zone. The basin formed in response to widespread extension and thermal subsidence, and was subsequently deformed during crustal shortening events that affected the North Australian Craton during the Proterozoic. Mineralisation is hosted in structurally controlled sub-basins that formed during deposition of the middle McArthur Group. Recognition of structures controlling these sub-basins has traditionally been challenging because overprinting relationships from several extension and crustal shortening events created a complex fault and depositional architecture. In this work, we interpret and model newly acquired and existing gravity, magnetic and seismic data to better understand the regional structural architecture and evolution of the southern McArthur Basin. Important for base metal exploration, results from this study suggest that the prospective lower Barney Creek Formation was deposited during intermittent, and broadly north–south-directed extension at ca. 1645–1640 Ma. This caused strike-slip movement along major north-northwest-trending faults, and normal movement along east–west to east-northeast-trending faults. Faulting resulted in significant sub-basin deepening in some areas, and uplift and erosion in others. These sub-basins developed in transtensional segments of strike-slip faults, and adjacent to normal faults. Geophysical modelling also identified an anomalously thick pile of mafic volcanics within the early basin fill represented by the Tawallah Group. This is significant because mafic volcanics have previously been interpreted as the source of base metals within the region, and the thick volcanic pile we identified occurs in close proximity to the McArthur River and Teena deposits. Sub-basin bounding faults that were active during mineralization tap into this anomalously thick pile of volcanics, suggesting that they likely represented fluid pathways for ascending metalliferous brines.

Does pulsed Tibetan deformation correlate with Indian plate motion changes?

Models that aim to explain the causes of the significant Indian plate motion acceleration around 70 Ma, and the subsequent deceleration around 52 Ma predict different scenarios regarding crustal shortening of the Tibetan Plateau, which can be tested by precisely determining the timing of regional shortening events in Tibet. Here we attempt to determine this timing by presenting a high-resolution magnetostratigraphy of a ∼3.5 km thick sedimentary sequence in the syn-contractional Gonjo Basin, east-central Tibet. We successfully isolated the primary remanence as confirmed by positive fold and reversal tests. Correlation to the geomagnetic polarity time scale reveals a 69–41.5 Ma age for the Gonjo Basin sedimentary succession. Average sedimentation rates indicate two episodes of enhanced sediment accumulation rate at 69–64 Ma and 52–48 Ma, which coincide with periods of vertical axis rotation recorded in the basin fill. This coincidence suggests a tectonic cause, which given regional structures we interpret as shortening pulses. Our results are similar to those from basins elsewhere in southern, central and northern Tibet, suggesting plateau-wide, synchronous shortening pulses at ∼69–64 Ma and ∼52–48 Ma. These pulses are synchronous with major acceleration and deceleration of India-Asia convergence rate, suggesting that both the acceleration and deceleration of India-Asia convergence may be associated with enhanced crustal deformation in Tibet, which we use to evaluate previous dynamic models explaining the Indian plate motion changes and India-Asia collision processes.

Alternation of back-arc extension and compression in an overriding plate: evidence from Cretaceous structures in the western Liaoning region, eastern China

The dynamic evolution in an overriding plate remains a controversial issue. Cretaceous structures in the western Liaoning (WL) region of the eastern North China Craton (NCC), an overriding plate bordering the Pacific Ocean, provide insights into the dynamic evolution related to Paleo-Pacific Plate subduction. We present structural and fault-slip data from the Jurassic–Cretaceous basins in the WL region, together with previously published isotopic ages, to constrain structural and stress field evolution during the Cretaceous. These data reveal four phases of deformation in the WL region: tectonic shortening (D1) at 137–136 Ma, extension (D2) during 136–97 Ma, another shortening (D3) at the beginning of the Late Cretaceous, and relatively weak extension (D4) during the Late Cretaceous. Inversions of the measured fault-slip data yield NW–SE compression during D1, NW–SE extension during D2, NNW–SSE compression during D3, and N–S extension during D4. Deformation phases D1 and D3 correspond to shortening events B and C of the Yanshan Movement, whereas D2 corresponds to the peak destruction of the NCC in a back-arc extensional setting. The structural evolution indicates that the back-arc extension (D2) of the Early Cretaceous started immediately after the brief shortening event D1 and ended with another shortening event D3. Subsequently, the back-arc region underwent weak extension (D4) during the Late Cretaceous. A slab-driven model could account for the tectonic evolution in the eastern NCC. Periodic changes in the kinematics of the subducting Paleo-Pacific Plate are responsible for the alternation of the back-arc extension and compression in the overriding plate.

Abstract A14: Alternative polyadenylation drives oncogenic gene expression in pancreatic cancer

Abstract Tumors can co-opt the mRNA processing machinery to dysregulate the expression of oncogenes and tumor suppressors. One such altered process, termed alternative polyadenylation (APA), is responsible for regulating 3’-untranslated region (UTR) length. APA is driven by a core set of factors that recognize a series of highly conserved sequences within the 3’-UTR on the pre-mRNA. The pre-mRNA is then cleaved before addition of the poly(A) tail. As most transcripts contain several polyadenylation sequences, the choice of where to cleave is a critical determinant of 3’-UTR length. The 3’-UTR contains regulatory sequences, including miRNA binding sites, that control mRNA stability, function, and subcellular localization. Therefore, altering the length of a 3’-UTR can have dramatic impacts on gene function and cellular phenotype. APA factor expression is altered in a variety of cancer types, resulting in dysregulated gene expression. For example, loss of the APA factor CFIm25 in glioblastoma increases cell proliferation through 3’-UTR shortening and upregulated expression of cyclin D1. Pan-cancer analyses have revealed that hundreds of transcripts undergo APA. How these changes in 3’-UTR length are mechanistically linked to changes in gene expression and function are complex and only now being functionally addressed. Despite recent efforts to interrogate APA events in human tumors, numerous critical gaps in knowledge remain. Several pan-cancer analyses have revealed common APA events across diverse tumor types. However, no large-scale, single tumor-type analysis has been reported. Furthermore, the role of APA in pancreatic ductal adenocarcinoma (PDA) has been largely unaddressed. An understanding of the gene-regulatory mechanisms driving PDA progression may provide novel targets for therapeutic intervention. We have performed a comprehensive analysis of differential APA events in normal pancreas and PDA tumors, and observe widespread 3’-UTR shortening in PDA, correlating with expression changes in known PDA drivers and alterations in cancer signaling networks. Experimental validation of candidate genes reveals APA as a novel mechanism of regulation for the PDA oncogene ALDOA, and other genes implicated in pancreatic cancer cell growth, migration, and invasion. Hierarchical clustering of APA events allowed the development of a prognostic signature, identifying patients with poor prognosis. We find that 3’-UTR shortening events drive a preferential loss of tumor suppressive miRNA binding sites, and validate these findings through experimental manipulation of 3’-UTRs in cultured cells. Finally, we identify the serine/threonine kinase casein kinase 1 alpha (CK1) as an APA-regulated, targetable factor driving pancreatic cancer cell growth; inhibition of CK1 attenuates cell proliferation, colony formation, and migration. Our study reveals new mechanisms of dysregulation for cancer promoting genes, highlights the prognostic value of APA analysis, and identifies new targetable factors for PDA. Citation Format: Swati Venkat, Arwen A Tisdale, Kevin H. Eng, Michael E. Feigin. Alternative polyadenylation drives oncogenic gene expression in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr A14.

Shortening and kinematics of the Late Triassic rocks in the Tolimán area, central Mexico

In the Tolimán area, central Mexico, the Late Triassic rocks (El Chilar Formation; López-Ramos, 1985) record two deformation events. The first event (D1A) is characterized by open chevron folds and incipient axial plane cleavage in the less competent rocks (shale). The second deformation event (D2B) is accommodated through of mesoscopic and kilometric reverse faults that cut the first folding. The first deformation event records approximately 30% of shortening. It was obtained from chevron folds that affected a succession of intercalated layers of sandstone and shale. The folds (class 1B and 1C in Ramsay's classification) are symmetric and asymmetric with a vergence to the NNE, while mesoscopic reverse faults related with this first event have tectonic transport toward NNE. The second deformation event is registered in the Late Triassic rocks through reverse faults with a tectonic transport to the ~E. Based on our observations and the information of other authors, we suggest that the Late Triassic rocks in the study area register two shortening events, the first occurred in Early Jurassic time, related to the start of subduction in the paleo pacific margin of Pangea. While the second is associated with the Late Cretaceous-Paleogene orogenic event that produces the Mexican fold and thrust belt.