Amyloid-associated increases in soluble tau is a key driver in accumulation of tau aggregates and cognitive decline in early Alzheimer

For optimal design of anti-amyloid-β (Aβ) and anti-tau clinical trials, it is important to understand how Aβ and soluble phosphorylated tau (p-tau) relate to the accumulation of tau aggregates assessed with PET and subsequent cognitive decline across the Alzheimer's disease (AD) continuum. In early stages of AD, increased concentration of soluble CSF p-tau was the main driver of accumulation of insoluble tau aggregates across the brain, and mediated the effect of Aβ on tau aggregation. Further, higher soluble p-tau concentrations were mainly related to faster accumulation of tau aggregates in the regions with strong functional connectivity to individual tau epicenters. In this early stage, higher soluble p-tau concentrations were associated with cognitive decline, which was mediated by faster increase of tau aggregates. In AD dementia, when Aβ fibrils and soluble p-tau levels have plateaued, cognitive decline was driven by the accumulation rate of insoluble tau aggregates. Our data suggest that therapeutic approaches reducing soluble p-tau levels might be most favorable in early AD.

Appropriate Use of Local Phosphate Rock Increases Phosphorus Use Efficiency and Grain Yield of Sorghum and Cowpea in the Sudan Savanna

Development of local P fertilizers using low-grade phosphate rock (PR) is expected to overcome the low-stagnated crop yield in Sub-Saharan Africa. Calcination and partial acidulation methods have been proposed to increase the phosphate (P) solubility of PRs. However, the effects of fertilization with calcinated PR (CPR) and partially acidulated PR (PAPR) on sorghum [Sorghum bicolor (L.)] and cowpea [Vigna unguiculata (L.) Walp.] cultivation are poorly understood. Therefore, we conducted a 2-year field experiment in Burkina Faso to identify the differences in sorghum and cowpea responses to CPR and PAPR application. The following eight treatments were applied with six replicates using a complete randomized block design: control without P fertilization, two types of CP (CPs), triple superphosphate (TSP) as a positive control for CPs, three types of PAPR with different degrees of acidulation (PAPRs), and single superphosphate (SSP) as a positive control for PAPRs. SSP mostly comprised of water-soluble P fraction (WP), TSP and PAPRs of WP and alkaline ammonium citrate-soluble P fraction (SP), and CPRs of SP and 2% citric acid-soluble P fraction (CP). Their solubility was in the order WP > SP > CP. The fertilization effects were evaluated by P use efficiency (PUE). In 2019, the biomass and P uptake of sorghum was decreased by the low available soil water at the early growth stage. On the contrary, cowpea survived the low available soil water because of its shorter growing period compared to sorghum. P fertilization significantly increased the grain yields. However, the effect size differed according to the crop and fertilizer types. The SP, along with WP, significantly contributed to the PUE and grain yield of sorghum, whereas only WP contributed to the PUE of cowpea. Therefore, CPs, mainly consisting of SP and CP, had a disadvantage compared to TSP, especially for cowpea. We thus concluded that PAPRs are effective for sorghum and would be effective for cowpea when the acidulation level is sufficiently high. We also conclude that the long growing period of sorghum is favorable for absorbing slow-release P, but is unfavorable for the variable rainfall often observed in this region.

Effect of long term fertilization on phosphorus dynamics in root zone environment under finger millet - Maize cropping sequence

In an agro-ecosystem, phosphorus (P) is found in organic and an inorganic form which includes soluble P, sorbed P and mineral bounded P. In soil, added P sources undergo various soil processes like mineralization, immobilization, precipitation, weathering, dissolution, sorption and desorption. For understanding the P dynamics in clay loam (Vertic Ustropept) soil, the present study was undertaken in P dynamics under rhizosphere and non-rhizosphere environment of maize in Long Term Fertilizer Experiment at Tamil Nadu Agricultural University, Coimbatore. The results revealed that the fractions of various pools of inorganic NaOH extractable Fe - P, H2SO4 extractable Ca- P, NH4F extractable Al- P, NH4Cl extractable Saloid P and Na citrate - Dithionate extractable Reductant soluble P were dominant in the non-rhizospheric soil than rhizospheric environment. The order of inorganic P fractions in the non-rhizospheric and rhizospheric region of the soil was found as Ca-P > Fe-P > Al-P > Reductant soluble-P > Saloid P and the knee-high stage of the non - rhizosphere soil recorded the highest inorganic as well organic P fractions. Irrespective of P fractions, Ca – P was recorded high (192.5 & 186.7 mg kg-1 ) followed by Fe - P (40.8& 34.9 mg kg-1) at a knee-high stage in non-rhizosphere and rhizosphere, respectively. Practising various nutrient management systems, application of 100% recommended dose of fertilizer along with FYM @ 10 t ha-1 (T8) recorded significant changes in all inorganic (Ca-P, Fe-P, Al-P, Reductant soluble-P, Saloid P), organic fractions and also Total P followed by 150% NPK (T3) in sandy clay loam soil. Nowadays, increasing demand for P fertilizer in India, judicious use of P fertilizer is important. Despite that, intensively cultivated soils have a lot of P reserves like organic and inorganic P pools and effective way of P transformation management could reduce the quantum of P fertilization in soil.

Increased vegetation ground cover reduces water, sediment and phosphorus losses in Cambisol treated with swine slurry

This study aims to evaluate the influence of the ground cover rate by crop residues and the rain time elapsed after the application of liquid swine slurry (LSS) under losses of water, sediments, and phosphorus (P). The study was carried out under a Humic Cambisols. Two areas were delimited: with and without the application of LSS. Each area was subdivided into four levels of crop residues: 5%, 35%, 65%, and 95%. Vegetable residues present in the area, from corn and black oat, were used. Three collecting gutters of 0.60 m² were installed in each subplot. Simulated rain was carried out on these, and the runoff volume collected for quantification and determination of losses. With LSS application, increase in the cover rate by crop residues reduces 0.3 mm h-1 the runoff volume and 1.67 mg m-2 reactive soluble P (H2O-P). The sediment losses in the first collection after the beginning of the rain were 23 times lower in the soil with 95% ground cover than in the soil with 5% ground cover. The loss of total P (total-P) decreases with the increase of the ground cover of the soil and increases in the same way with the increase of the time.

Abstract P357: Induction Of Soluble P-selectin And CD40 Ligand And, FXIII Deficiency Promote Aberrant Coagulation And Thromboembolism In Severe COVID-19

Coagulation dysfunction and thromboembolism emerge as strong comorbidity factors in severe COVID-19. However, the underlying pathomechanisms are largely undefined. Here, we sought to identify the potential underlying molecular mechanisms of SARS-CoV-2 mediated coagulopathy and thromboembolism. In this series, 30 hospitalized COVID-19 patients presenting elevated D-dimer with (severe cases that required intensive care) or without pneumonia (moderate cases) were included in the study. Patients with anticoagulant/ antiplatelet therapy or with a history of cardiovascular diseases were excluded. Phenotypic and molecular characterizations were carried out employing basic coagulation tests, flow cytometry-based multiplex assays, and ELISA. The findings revealed slightly higher prothrombin and activated partial thromboplastin times (aPTT) with normal platelet counts. Elevated levels of plasma P-selectin and CD40 ligand (CD40L), markers of platelet activation, were observed in the moderate COVID-19 cases which were significantly abolished with the progression of COVID-19 severity. Moreover, analysis of the coagulation pathways revealed comparable FIX, prothrombin, and anti-thrombin levels, and a significantly higher level of fibrinogen was observed in both the moderate and severe patients vs. control group. Interestingly, the levels of plasma tissue factor pathway inhibitor (TFPI) and FXIII, a regulator of stable thrombus formation, were significantly lower particularly in the severe COVID-19 cases. Moreover, a dysregulated fibrinolysis was indicated by elevated tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI), and D-dimer levels in COVID-19 cases. In summary, SARS-CoV-2 infection-mediated endothelial cell lining damage potentially enhances soluble P-selectin and CD40L levels inducing platelet activation. Furthermore, in severe COVID-19, a decreased level of TFPI possibly contributes to additional thrombin generation through activation of the TF pathway and provides positive feedback to platelet activation and thrombus formation. FXIII deficiency plays a key role in thrombus instability which most likely promotes thromboembolism in the severe COVID-19.

Soluble P-selectin and correlation with Prothrombin Fragment 1 + 2 in myeloid malignancies in Cipto Mangunkusumo general hospital

Background Myeloid cells express microparticles that could increase the expression of adhesion molecules including P-selectin. We aimed to evaluate the level of soluble P-selectin (sP-selectin) and prothrombin fragment 1 + 2 (F1 + 2), and to determine correlation of sP-selectin with leukocyte count and F1 + 2 levels in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) patients. Methods Patients with newly diagnosed AML (n = 25), CML (n = 13), and controls (n = 17) were recruited in this study. The diagnosis of AML and CML is based on 2001 WHO and/or FAB criteria. Levels of sP-selectin and F1 + 2 were determined using enzyme-linked immunosorbent assay kits (Behring ELISA Processor-III® and Behring Enzygnost F1 + 2). Results sP-selectin was significantly elevated in CML patients compared to AML patients (p = 0.001). Levels of F1 + 2 in AML and CML patients were significantly increased in comparison to controls (p < 0.001 and p = 0.043). Levels of sP-selectin were significantly correlated to leukocyte count (r = 0.437; p = 0.029) and F1 + 2 (r = 0.436; p = 0.029) in AML patients. Conclusions AML and CML patients had an increased tendency to thrombosis. While CML patients had higher platelet and/or endothelial activation, hypercoagulable state are more pronounced in AML patients.

Urinary soluble (pro)renin receptor excretion is associated with urine pH in humans

The (pro)renin receptor [(P)RR] binds to renin and its precursor prorenin to activate the tissue renin-angiotensin system. It is cleaved to generate soluble (P)RR and M8–9, a residual hydrophobic truncated protein. The (pro)renin receptor also functions as an intracellular accessory protein of vacuolar-type H+-ATPase, which plays an essential role in controlling the intracellular vesicular acid environment. Thus, in the kidney, (P)RR may play a role in transporting H+ to urine in the collecting duct. Although blood soluble (P)RR has been recognized as a biomarker reflecting the status of the tissue renin-angiotensin system and/or tissue (P)RR, the significance of urinary soluble (P)RR excretion has not been determined. Therefore, this study aimed to investigate the characteristics of urinary soluble (P)RR excretion. Urinary soluble (P)RR excretion was measured, and its association with background factors was investigated in 441 patients. Relationships between changes in urine pH due to vitamin C treatment, which reduce urine pH, and urinary soluble (P)RR excretion were investigated in 10 healthy volunteers. Urinary soluble (P)RR excretion was 1.46 (0.44–2.92) ng/gCre. Urine pH showed a significantly positive association with urinary soluble (P)RR excretion, independent of other factors. Changes in urine pH and urinary soluble (P)RR excretion due to vitamin C treatment were significantly and positively correlated (ρ = 0.8182, p = 0.0038). These data showed an association between urinary soluble (P)RR excretion and urine pH in humans, suggesting that (P)RR in the kidney might play a role in urine pH regulation.