Constraints upon water advection in sediments of the Mariana Trough

Thermal gradient measurements, consolidation tests, and pore water compositions from the Mariana Trough imply that water is moving through the sediments in areas with less than about 100 m of sediment cover. The maximum advection rates implied by the thermal measurements and consolidation tests may be as high as 10−5 cm s−1 but are most commonly in the range of 1 to 5×10−6 cm s−1. Theoretical calculations of the effect of the highest advection rates upon carbonate dissolution indicate that dissolution may be impeded or enhanced (depending upon the direction of flow) by a factor of 2 to 5 times the rate for diffusion alone. The average percentage of carbonate is consistently higher in two cores from the area with no advection or upward advection than the average percentage of carbonate in three cores from the area with downward advection. This increase in average amount of carbonate in cores with upward moving water or no movement cannot be attributed solely to differences in water depth or in amount of terrigenous dilution. If the sediment column acts as a passive boundary layer, then the water velocities necessary to affect chemical gradients of silica are in the range 10−9 to 10−10 cm s−l. However, if dissolution of silica occurs within the sediment column, then the advection velocities needed to affect chemical gradients are at least 3×10−8 cm s−l and may be as high as 3×10−6 cm s−l. This order of magnitude increase in advection velocities when chemical reactions occur within the sediments is probably applicable to other cations in addition to silica. If so, then the advection velocities needed to affect heat flow ( >10−8 cm s−1) and pore water chemical gradients are much nearer in magnitude than previously assumed

An empirical thermal history of the Earth's upper mantle

We have compiled petrological and geochemical data from 71 ophiolite suites and greenstone belts, which range in age from 15 to 3760 Ma. We have selected those rocks whose compositions indicate that they are either normal mid-ocean ridge basalts (MORBs) or hotspot-type MORBs. Then we used the data base to calculate the most primitive liquidus temperature for each rock suite. The results show that the liquidus temperature of the Phanerozoic ophiolites ranges from a low of 1212°C to a high of 1417°C. Using these data and two exponential curves bracketing the maximum and minimum temperatures versus time, we infer that the Phanerozoic suites had a mean liquidus temperature of 1272±7°C and a mean temperature range of 1218° to 1425°C. The liquidus temperatures of Archean MORBlike greenstones range from 1305° to 1576°C. Using these data and two exponential curves bracketing the maximum and minimum temperatures versus time, we infer that Archean melts at 2.8 Ga had a mean liquidus temperature of 1399±13°C and a temperature range from 1301° to 1533°C. Using two different methods, we show that the change in the mean liquidus temperature since the late Archean is from 96±13°C (from temperature ranges) to 127±20°C (from temperature means). When we convert these liquidus temperatures to potential temperature of the mantle, we find that the change in the mean upper mantle potential temperature since the late Archean is from 137±8°C (from temperature ranges) to 187±42°C (from temperature means). This change is less than that which was previously thought to have occurred. We compared the liquidus temperatures calculated from our data set with an independent data set from the modern day Pacific plate. The resulting histograms have the same shape and the same temperature range, showing that our method for calculating mantle temperatures from MORBlike rocks in ophiolite suites is valid. When our calculated liquidus temperatures for all time intervals are plotted in histograms, the resulting distributions are not bimodal, but skewed unimodal. That is, the distributions show a high-T tail which results from the presence of hotspot magmas in the data set. The Archean temperature distribution is also skewed unimodal, and the high-temperature Archean rocks, such as komatiites, plot in the hotspot area of the distribution. This strongly supports the contention that komatiites do not represent “normal” Archean mantle but rather were probably erupted by hotspots. Our data suggest that the relative proportion of hotspot magmas in oceanic lithosphere has remained nearly constant over geologic time

Evidence for excess pore pressures in southwest Indian Ocean sediments

Brown clay cores from the Madagascar and Crozet basins show the following evidence of excess pore pressures: large amounts of flow-in, increasing average sedimentation rate with age, and nonlinear temperature gradients. Additionally, many hilltops in these basins have no visible sediment cover. The bare hilltops may result from periodic slumping caused by excess pore pressures. Calculated excess pore pressures which equal or exceed the overburden pressure were inferred from water fluxes predicted by nonlinear temperature gradients and laboratory permeability measurements by using Darcy's law. Since pore pressures which exceed the overburden pressure are unreasonable, we attribute this discrepancy to laboratory measurements which underestimate the in situ permeability. The widespread presence of overpressured sediments in areas of irregular topography provides a process for resuspension of clay-sized particles. This mechanism does not require high current velocities for the erosion of clay and therefore can be applied to many areas where no strong currents are evident. Carbonate-rich sediments from the Madagascar Ridge, the Mozambique Ridge, and the Agulhas Plateau had almost no flow-in and occurred in areas where all topography was thickly draped with sediment. Since the age and tectonic location of the ridges and plateaus preclude water circulation in the basement, we attribute these differences between the brown clay and the carbonate-rich material to an absence of significant excess pore pressures in the plateau and ridge sediments

Correlated sediment thickness, temperature gradient and excess pore pressure in a marine fault block basin

Measurements of temperature gradient and excess pore pressure in the surficial sediment of a fault block basin in the Guatemala Basin correlate with sediment thickness. The temperature gradient is smaller and the excess pore pressure gradient is more negative in areas of thinner sediment. This correlation is explained by postulating downward pore water advection within the sediments, with flow velocities on the order of 10−9 to 10−8 m/s in the thinnest sediments and much less flow in the thickest sediments. Sediment physical properties and pore water chemistry also support this interpretation. Since the conductive heat flow of the basin as a whole is less than one third that predicted by sea floor spreading models, the oceanic basement may be the site of a vigorous hydrothermal circulation system. The pore water advection in the sediments may be driven by this larger scale circulation

TRPA1- FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p

YesRecent evidence suggests that the ion channel TRPA1 is implicated in lung adenocarcinoma (LUAD) where its role and mechanism of action remain unknown. We have previously established that the membrane receptor FGFR2 drives LUAD progression through aberrant protein-protein interactions mediated via its C-terminal proline rich motif. Here, we report that the N-terminal ankyrin repeats of TRPA1 directly bind to the C-terminal proline rich motif of FGFR2 inducing the constitutive activation of the receptor, thereby prompting LUAD progression and metastasis. Furthermore, we show that upon metastasis to the brain, TRPA1 gets depleted, an effect triggered by the transfer of TRPA1-targeting exosomal microRNA (miRNA-142-3p) from brain astrocytes to cancer cells. This downregulation, in turn, inhibits TRPA1-mediated activation of FGFR2 hindering the metastatic process. Our study reveals a direct binding event and characterizes the role of TRPA1 ankyrin repeats in regulating FGFR2-driven oncogenic process; a mechanism that is hindered by miRNA-142-3p.Faculty of Biological Sciences at the University of Leeds, Wellcome Trust Seed Award, Royal Society Research Grant RG150100, MR/K021303/1, Swedish Research Council (2014-3801) and the Medical Faculty at Lund University

On The Rate and Extent of Drug Delivery to the Brain

To define and differentiate relevant aspects of blood–brain barrier transport and distribution in order to aid research methodology in brain drug delivery. Pharmacokinetic parameters relative to the rate and extent of brain drug delivery are described and illustrated with relevant data, with special emphasis on the unbound, pharmacologically active drug molecule. Drug delivery to the brain can be comprehensively described using three parameters: Kp,uu (concentration ratio of unbound drug in brain to blood), CLin (permeability clearance into the brain), and Vu,brain (intra-brain distribution). The permeability of the blood–brain barrier is less relevant to drug action within the CNS than the extent of drug delivery, as most drugs are administered on a continuous (repeated) basis. Kp,uu can differ between CNS-active drugs by a factor of up to 150-fold. This range is much smaller than that for log BB ratios (Kp), which can differ by up to at least 2,000-fold, or for BBB permeabilities, which span an even larger range (up to at least 20,000-fold difference). Methods that measure the three parameters Kp,uu, CLin, and Vu,brain can give clinically valuable estimates of brain drug delivery in early drug discovery programmes

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research