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The West African monsoon has a clear diurnal cycle in boundary layer properties, synoptic flow, and moist convection. A nocturnal low-level jet (LLJ) brings cool, moist air into the continent and we hypothesize that it may support storms by providing vertical wind shear and a source of moisture. We use idealized simulations to investigate how the mean diurnal cycle in temperature and humidity compared with that of the wind shear impacts on mature squall lines. Thermodynamic diurnal changes dominate those of the winds, although when isolated the LLJ wind is favorable for more intense systems. Bulk characteristics of the storms, including in-cloud upward mass flux and—if precipitation evaporation is accounted for—total surface rain rates, correlate well with the system-relative inflow of convectively unstable air and moisture into the storms. Mean updraft speeds and mean rainfall rates over the storms do not correlate as well with system-relative inflows due to variations in storm morphology such as cold pool intensity. We note that storms tend to move near the speed of the African easterly jet and so maximize the inflow of convectively unstable air. Our results explain the observed diurnal cycle in organized moist convection, with the hours from 1800 to 0000 UTC being the most favorable. Storms are more likely to die after this, despite the LLJ supporting them, with the environment becoming more favorable again by midday. Significance Statement Large organized storms dominate rainfall in the West African Sahel, but models struggle to predict them at the correct time of day and the underlying mechanisms that control their timings are not well understood. Using idealized simulations, we show that the temperature and humidity of the late evening are favorable for such storms whereas inflow from the low-level jet supports storms overnight. Storm inflows of available energy and moisture predict upward mass transport and total rainfall rates, whereas the strength of the storm’s cold pool is important for storm structure and intensity. Our results demonstrate how the environmental wind profile (which varies throughout the day) interacts with internal storm dynamics, posing a major challenge to parameterized models.

Cancer cells can switch between signaling pathways to regulate growth under different conditions. In the tumor microenvironment, this likely helps them evade therapies that target specific pathways. We must identify all possible states and utilize them in drug screening programs. One such state is characterized by expression of the transcription factor Hairy and Enhancer of Split 3 (HES3) and sensitivity to HES3 knockdown, and it can be modeled in vitro. Here, we cultured 3 primary human brain cancer cell lines under 3 different culture conditions that maintain low, medium, and high HES3 expression and characterized gene regulation and mechanical phenotype in these states. We assessed gene expression regulation following HES3 knockdown in the HES3-high conditions. We then employed a commonly used human brain tumor cell line to screen Food and Drug Administration (FDA)-approved compounds that specifically target the HES3-high state. We report that cells from multiple patients behave similarly when placed under distinct culture conditions. We identified 37 FDA-approved compounds that specifically kill cancer cells in the high-HES3–expression conditions. Our work reveals a novel signaling state in cancer, biomarkers, a strategy to identify treatments against it, and a set of putative drugs for potential repurposing.—Poser, S. W., Otto, O., Arps-Forker, C., Ge, Y., Herbig, M., Andree, C., Gruetzmann, K., Adasme, M. F., Stodolak, S., Nikolakopoulou, P., Park, D. M., Mcintyre, A., Lesche, M., Dahl, A., Lennig, P., Bornstein, S. R., Schroeck, E., Klink, B., Leker, R. R., Bickle, M., Chrousos, G. P., Schroeder, M., Cannistraci, C. V., Guck, J., Androutsellis-Theotokis, A. Controlling distinct signaling states in cultured cancer cells provides a new platform for drug discovery. FASEB J. 33, 9235–9249 (2019). www.fasebj.org. © FASEB

α-synuclein-induced neurotoxicity is a core pathogenic event in neurodegenerative synucleinopathies such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. There is currently no disease-modifying therapy available for these diseases. We screened 1,600 FDA-approved drugs for their efficacy to protect LUHMES cells from degeneration induced by wild-type α-synuclein and identified dipyridamole, a non-selective phosphodiesterase inhibitor, as top hit. Systematic analysis of other phosphodiesterase inhibitors identified a specific phosphodiesterase 1 inhibitor as most potent to rescue from α-synuclein toxicity. Protection was mediated by an increase of cGMP and associated with the reduction of a specific α-synuclein oligomeric species. RNA interference experiments confirmed PDE1A and to a smaller extent PDE1C as molecular targets accounting for the protective efficacy. PDE1 inhibition also rescued dopaminergic neurons from wild-type α-synuclein induced degeneration in the substantia nigra of mice. In conclusion, this work identifies inhibition of PDE1A in particular as promising target for neuroprotective treatment of synucleinopathies.

Storage of anthropogenic CO2 in geological formations relies on a caprock as the primary seal preventing buoyant super-critical CO2 escaping. Although natural CO2 reservoirs demonstrate that CO2 may be stored safely for millions of years, uncertainty remains in predicting how caprocks will react with CO2-bearing brines. This uncertainty poses a significant challenge to the risk assessment of geological carbon storage. Here we describe mineral reaction fronts in a CO2 reservoir-caprock system exposed to CO2 over a timescale comparable with that needed for geological carbon storage. The propagation of the reaction front is retarded by redox-sensitive mineral dissolution reactions and carbonate precipitation, which reduces its penetration into the caprock to ∼7 cm in ∼105 years. This distance is an order-of-magnitude smaller than previous predictions. The results attest to the significance of transport-limited reactions to the long-term integrity of sealing behaviour in caprocks exposed to CO2., Anthropogenic CO2 storage, where CO2 is injected into saline geological resevoirs, relies on an impermeable caprock to seal in the CO2, but caprock reaction rates to CO2 acid brines are unclear. Here, Kampman et al. show that mineral reaction front alteration in caprocks takes place over 100,000 years.

The dissolution of silicate minerals by CO2–rich fluids and the subsequent precipitation of CO2 as carbonate minerals represent a means of permanently storing anthropogenic CO2 waste products in a solid and secure form. Modelling the progression of these reactions is hindered by our poor understanding of the rates of mineral dissolution-precipitation reactions and mineral surface properties in natural systems. This study evaluates the chemical evolution of groundwater flowing through a basalt aquifer, which forms part of the leaking CO2-charged system of the Blackfoot Volcanic Field in south-eastern Idaho, USA. Reaction progress is modelled using changes in groundwater chemistry by inverse mass balance techniques. The CO2-promoted fluid-mineral reactions include the dissolution of primary plagioclase, orthoclase, pyroxene and gypsum which is balanced by the precipitation of secondary albite, calcite, zeolite, kaolinite and silica. Mineral mole transfers and groundwater flow rates estimated from hydraulic head data are used to determine the kinetics of plagioclase and orthoclase feldspar dissolution. Plagioclase surface area measurements were determined using the evolution of the U-series isotope ratios in the groundwater and are compared to published surface area measurements. Calculated rates of dissolution for plagioclase range from 2.4 x 10-12 to 4.6 x 10-16 mol/m2/s and orthoclase from 2.0 x 10-13 to 6.8 x 10-16 mol/m2/s respectively. These feldspar reaction rates, correlate with the degree of mineral-fluid disequilibrium and are similar to the dissolution rates for these mineral measured in other natural CO2-charged groundwater systems.

Understanding the long-term response of CO2 injected into porous reservoirs is one of the most important aspects to demonstrate safe and permanent storage. In order to provide quantitative constraints on the long-term impacts of CO2-charged fluids on the integrity of reservoir-caprock systems we recovered some 300m of core from a scientific drill hole through a natural CO2 reservoir, near Green River, Utah. We obtained geomechanical, mineralogical, geochemical, petrophysical and mineralogical laboratory data along the entire length of the core and from non CO2-charged control samples. Furthermore, we performed more detailed studies through portions of low permeability layers in direct contact with CO2-charged layers. This was done to constrain the nature and penetration depths of CO2-promoted fluid-mineral reaction fronts. The major reactions identified include the dissolution of diagenetic dolomite cements and hematite grain coatings, and the precipitation of ankerite and pyrite and have been used as input for geochemical 1D reactive transport modelling, to constrain the magnitude and velocity of the mineral-fluid reaction front. In addition, we compared geomechanical data from the CO2-exposed core and related unreacted control samples to assess the mechanical stability of reservoir and seal rocks in a CO2 storage complex following mineral dissolution and precipitation for thousands of years. The obtained mechanical parameters were coupled to mineralogy and porosity. Key aim of this work was to better quantify the effect of long-term chemical CO2/brine/rock interactions on the mechanical strength and elastic properties of the studied formations.

This research presents the first multitechnique provenance study of the Siwalik Group in the Himalayan foreland basin in India, using the Jawalamukhi section, magnetostratigraphically dated at 13–5 Ma. Combined with provenance data from a Dharamsala Formation sedimentary section (21–13 Ma) located close by, it forms the longest temporally continuous record of Himalayan erosion in the Indian foreland basin. Sandstone petrography and heavy mineral analysis, conglomerate clast composition, Ar-Ar dating of detrital white micas, and Sm-Nd analyses on siltstones, conglomerate matrix and conglomerate clasts was undertaken to determine (1) shifts in source region through time and (2) changes in detrital lag times related to exhumation rates in the hinterland, together interpreted in the light of thrusting events. We interpret the data to show a slow down in exhumation rate of the Higher Himalaya by 16–17 Ma, after which time the locus of thrusting propagated south of the Main Central Thrust, and erosion of the low grade Haimanta Formation to the south became significant. The nonmetamorphosed Inner Lesser Himalaya breached its Haimanta cover by 9 Ma with the metamorphosed Inner Lesser Himalaya (Lesser Himalayan Crystalline Series) exhuming to surface by 6 Ma. This event caused sufficient disruption to established drainage patterns that all Higher Himalayan material was diverted from this location at this time.

International audience; 40Ar–39Ar dating of detrital white micas, petrography and heavy mineral analysis and whole-rock geochemistry has been applied to three time-equivalent sections through the Siwalik Group molasse in SW Nepal [Tinau Khola section (12–6 Ma), Surai Khola section (12–1 Ma) and Karnali section (16–5 Ma)]. 40Ar–39Ar ages from 1415 single detrital white micas show a peak of ages between 20 and 15 Ma for all the three sections, corresponding to the period of most extensive exhumation of the Greater Himalaya. Lag times of less than 5 Myr persist until 10 Ma, indicating Greater Himalayan exhumation rates of up to 2.6 mm year−1, using one-dimensional thermal modelling. There are few micas younger than 12 Ma, no lag times of less than 6 Myr after 10 Ma and whole-rock geochemistry and petrography show a significant provenance change at 12 Ma indicating erosion from the Lesser Himalaya at this time. These changes suggest a switch in the dynamics of the orogen that took place during the 12–10 Ma period whereby most strain began to be accommodated by structures within the Lesser Himalaya as opposed to the Greater Himalaya. Consistent data from all three Siwalik sections suggest a lateral continuity in tectonic evolution for the central Himalayas.

A scientific borehole, CO2W55, was drilled into an onshore anticline, near the town of Green River, Utah for the purposes of studying a series of natural CO2 reservoirs. The objective of this research project is to recover core and fluids from natural CO2 accumulations in order to study and understand the long-term consequences of exposure of supercritical CO2, CO2-gas and CO2-charged fluids on geological materials. This will improve our ability to predict the security of future geological CO2 storage sites and the behaviour of CO2 during migration through the overburden. The Green River anticline is thought to contain supercritical reservoirs of CO2 in Permian sandstone and Mississippian-Pennsylvanian carbonate and evaporite formations at depths > 800 m. Migration of CO2 and CO2-charged brine from these deep formations, through the damage zone of two major normal faults in the overburden, feeds a stacked series of shallow reservoirs in Jurassic sandstones from 500 m depth to near surface. The drill-hole was spudded into the footwall of the Little Grand Wash normal fault at the apex of the Green River anticline, near the site of Crystal Geyser, a CO2-driven cold water geyser. The hole was drilled using a CS4002 Truck Mounted Core Drill to a total depth of 322 m and DOSECC’s hybrid coring system was used to continuously recover core. CO2-charged fluids were first encountered at ~ 35 m depth, in the basal sandstones of the Entrada Sandstone, which is open to surface, the fluids being effectively sealed by thin siltstone layers within the sandstone unit. The well penetrated a ~ 17 m thick fault zone within the Carmel Formation, the footwall damage zone of which hosted CO2-charged fluids in open fractures. CO2-rich fluids were encountered throughout the thickness of the Navajo Sandstone. The originally red sandstone and siltstone units, where they are in contact with the CO2-charged fluids, have been bleached by dissolution of hematite grain coatings. Fluid samples were collected from the Navajo Sandstone at formation pressures using a positive displacement wireline sampler, and fluid CO2 content and pH were measured at surface using high pressure apparatus. The results from the fluid sampling show that the Navajo Sandstone is being fed by active inflow of CO2-saturated brines through the fault damage zone; that these brines mix with meteoric fluid flowing laterally into the fault zone; and that the downhole fluid sampling whilst drilling successfully captures this dynamic process.\ud