Mechanisms and Geochemical Models of Core Formation

The formation of the Earth's core is a consequence of planetary accretion and processes in the Earth's interior. The mechanical process of planetary differentiation is likely to occur in large, if not global, magma oceans created by the collisions of planetary embryos. Metal-silicate segregation in magma oceans occurs rapidly and efficiently unlike grain scale percolation according to laboratory experiments and calculations. Geochemical models of the core formation process as planetary accretion proceeds are becoming increasingly realistic. Single stage and continuous core formation models have evolved into multi-stage models that are couple to the output of dynamical models of the giant impact phase of planet formation. The models that are most successful in matching the chemical composition of the Earth's mantle, based on experimentally-derived element partition coefficients, show that the temperature and pressure of metal-silicate equilibration must increase as a function of time and mass accreted and so must the oxygen fugacity of the equilibrating material. The latter can occur if silicon partitions into the core and through the late delivery of oxidized material. Coupled dynamical accretion and multi-stage core formation models predict the evolving mantle and core compositions of all the terrestrial planets simultaneously and also place strong constraints on the bulk compositions and oxidation states of primitive bodies in the protoplanetary disk.Comment: Accepted in Fischer, R., Terasaki, H. (eds), Deep Earth: Physics and Chemistry of the Lower Mantle and Core, AGU Monograp

High heterotrophic CO2 emissions from a Malaysian oil palm plantations during dry-season

Background Tropical peatlands are currently being rapidly cleared and drained for the establishment of oil palm plantations, which threatens their globally significant carbon sequestration capacity. Large-scale land conversion of tropical peatlands is important in the context of greenhouse gas emission factors and sustainable land management. At present, quantification of carbon dioxide losses from tropical peatlands is limited by our understanding of the relative contribution of heterotrophic and autotrophic respiration to net peat surface CO2 emissions. Methods In this study we separated heterotrophic and autotrophic components of peat CO2 losses from two oil palm plantations (one established in ‘2000’ and the other in 1978, then replanted in ‘2006’) using chamber-based emissions sampling along a transect from the rooting to non-rooting zones on a peatland in Selangor, Peninsular Malaysia over the course of three months (June-August, 2014). Collar CO2 measurements were compared with soil temperature and moisture at site and also accompanied by depth profiles assessing peat C and bulk density. Results The soil respiration decreased exponentially with distance from the palm trunks with the sharpest decline found for the plantation with the younger palms. The mean heterotrophic flux was 1244.7 ± SE 149.2 mg m-2h-1 and 663.8 ± SE 102.2 mg m-2h-1 at the 2000 and 2006 plantations, respectively. Autotrophic emissions adjacent to the palm trunks were 944 ± SE 99.7 mg m-2h-1 and 1962 ± SE 246 mg m-2h-1 at the 2000 and 2006 plantations, respectively. Heterotrophic CO2 flux was positively related to peat soil moisture, but not temperature. Total peat C stocks were 60 kg m-2 (down to 1 m depth) and did not vary among plantations of different ages but SOC concentrations declined significantly with depth at both plantations but the decline was sharper in the second generation 2006 plantation. Conclusions The CO2 flux values reported in this study suggest a potential for very high carbon (C) loss from drained tropical peats during the dry season. This is particularly concerning given that more intense dry periods related to climate change are predicted for SE Asia. Taken together, this study highlights the need for careful management of tropical peatlands, and the vulnerability of their carbon storage capability under conditions of drainage

GHG emission under different cropping systems in some Histosols of Malaysia

Oil palm is the fastest expanding equatorial crop, and is one of the biggest threats to carbon-rich tropical peatlands in Malaysia. Smallholder plantations cover a vast area of peatlands in Peninsular Malaysia and follow varied cropping systems. Here we analyse the impacts of specific crops and the effects of proximity to such crops, upon GHG emissions from the soil, and the soil microbial community phenotype. We found that only mature oil palm plants in 1st generation oil palm mono-cropping potentially had significant autotrophic contributions to total CO2 emissions with 33.5% increase in locations closer to mature oil palm stems. The sampling locations closer to younger oil palms and other crops did not significantly increase total CO2 emissions. CH4 emissions were significantly greater for sampling locations near plants with adventitious root system such as yam and pineapple crops. However CH4 emissions were very low in comparison to CO2 emissions, and their contribution to carbon loss was limited in these sites. Surface peat microbial community structure was unaffected by proximity to different crops within each cropping system, possibly due to a lack of influence of rhizosphere in the surface peat layers (0–5 cm). The results suggest that most of the total CO2 emissions from these agro-ecosystems contribute to C loss due to microbial decomposition of the peat soil, unlike greater autotrophic contributions to total emissions in forested peatlands reported in other studies. Hence without appropriate above-ground vegetation or hydrology conducive to peat formation, ancient carbon stored in these peatlands is gradually lost into the atmosphere via greater heterotrophic respiration under agricultural management on such peat-based ecosystems

Integrated nuclear proteomics and transcriptomics identifies S100A4 as a therapeutic target in acute myeloid leukemia

Inappropriate localization of proteins can interfere with normal cellular function and drive tumor development. To understand how this contributes to the development of acute myeloid leukemia (AML), we compared the nuclear proteome and transcriptome of AML blasts with normal human CD34+ cells. Analysis of the proteome identified networks and processes that significantly affected transcription regulation including misexpression of 11 transcription factors with seven proteins not previously implicated in AML. Transcriptome analysis identified changes in 40 transcription factors but none of these were predictive of changes at the protein level. The highest differentially expressed protein in AML nuclei compared with normal CD34+ nuclei (not previously implicated in AML) was S100A4. In an extended cohort, we found that over-expression of nuclear S100A4 was highly prevalent in AML (83%; 20/24 AML patients). Knock down of S100A4 in AML cell lines strongly impacted their survival whilst normal hemopoietic stem progenitor cells were unaffected. These data are the first analysis of the nuclear proteome in AML and have identified changes in transcription factor expression or regulation of transcription that would not have been seen at the mRNA level. These data also suggest that S100A4 is essential for AML survival and could be a therapeutic target in AML

Computationally designed Spike antigens induce neutralising responses against the breadth of SARS-COV-2 variants

Updates of SARS-CoV-2 vaccines are required to generate immunity in the population against constantly evolving SARS-CoV-2 variants of concerns (VOCs). Here we describe three novel in-silico designed spike-based antigens capable of inducing neutralising antibodies across a spectrum of SARS-CoV-2 VOCs. Three sets of antigens utilising pre-Delta (T2_32), and post-Gamma sequence data (T2_35 and T2_36) were designed. T2_32 elicited superior neutralising responses against VOCs compared to the Wuhan-1 spike antigen in DNA prime-boost immunisation regime in guinea pigs. Heterologous boosting with the attenuated poxvirus - Modified vaccinia Ankara expressing T2_32 induced broader neutralising immune responses in all primed animals. T2_32, T2_35 and T2_36 elicited broader neutralising capacity compared to the Omicron BA.1 spike antigen administered by mRNA immunisation in mice. These findings demonstrate the utility of structure-informed computationally derived modifications of spike-based antigens for inducing broad immune responses covering more than 2 years of evolved SARS-CoV-2 variants

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca