The significance of soils and soil science towards realization of the United Nations sustainable development goals

Peer reviewedPublisher PD

Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers

Amyloid-beta 42 (A beta 42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for A beta 42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple A beta 42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.Peer reviewe

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Distribution of glyphosate and aminomethylphosphonic acid (AMPA) in agricultural topsoils of the European Union

Approval for glyphosate-based herbicides in the European Union (EU) is under intense debate due to concern about their effects on the environment and human health. The occurrence of glyphosate residues in European water bodies is rather well documented whereas only few, fragmented and outdated information is available for European soils. We provide the first large-scale assessment of distribution (occurrence and concentrations) of glyphosate and its main metabolite aminomethylphosphonic acid (AMPA) in EU agricultural topsoils, and estimate their potential spreading by wind and water erosion. Glyphosate and/or AMPA were present in 45% of the topsoils collected, originating from eleven countries and six crop systems, with a maximum concentration of 2 mg kg−1. Several glyphosate and AMPA hotspots were identified across the EU. Soil loss rates (obtained from recently derived European maps) were used to estimate the potential export of glyphosate and AMPA by wind and water erosion. The estimated exports, result of a conceptually simple model, clearly indicate that particulate transport can contribute to human and environmental exposure to herbicide residues. Residue threshold values in soils are urgently needed to define potential risks for soil health and off site effects related to export by wind and water erosion.JRC.D.3-Land Resource

Moderate cholecalciferol supplementation depresses intestinal calcium absorption in growing dogs

Hormonal regulation of calcium (Ca) absorption was investigated in a cholecalciferol (vitamin D3)supplemented group (hVitD) vs. a control group (cVitD) of growing Great Danes (100 vs. 12.5 μg vitamin D3/kg diet). Although Ca intakes did not differ, fractional Ca absorption was significantly lower in the hVitD group than in the cVitD group. There were no differences in plasma concentrations of Ca, inorganic phosphate, parathyroid hormone, growth hormone or insulin-like growth factor I between groups. Plasma 25-hydroxycholecalciferol [25(OH)D3] concentrations were maintained in the hVitD dogs at the same levels as in the cVitD dogs due to increased turnover of 25(OH)D3 into 24,25-dihydroxycholecalciferol [24,25(OH)2D3] and 1,25-dihydroxycholecalciferol [1,25(OH)2D3]. In hVitD dogs, the greater plasma 24,25(OH)2D3 concentration and the enhanced metabolic clearance rate (MCR) of 1,25(OH)2D3 indicated upregulated 24-hydroxylase activity. The increased MCR of 1,25(OH)2D3 decreased plasma 1,25(OH)2D3 concentrations. In hVitD dogs, the greater production rate of 1,25(OH)2D3 was consistent with the 12.9-fold greater renal 1 α-hydroxylase gene expression compared with cVitD dogs and compensated to a certain extent for the accelerated MCR of 1,25(OH)2D3. The moderately decreased plasma 1,25(OH)2D3 concentration can only partially explain the decreased Ca absorption in the hVitD dogs. Intestinal vitamin D receptor concentrations did not differ between groups and did not account for the decreased Ca absorption. We suggest that 24,25(OH)2D3 may downregulate Ca absorption. Chemicals/CAS: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase, EC 1.14.-; Calcitriol, 32222-06-3; Calcium Radioisotopes; Calcium, 7440-70-2; Calcium, Dietary; Cholecalciferol, 67-97-0; Cytochrome P-450 Enzyme System, 9035-51-2; Phosphates; Receptors, Calcitriol; Steroid Hydroxylases, EC 1.14.-; vitamin D 24-hydroxylase, EC 1.14.

Automatic detection, localization, and volume estimation of ischemic infarcts in noncontrast computed tomographic scans : method and preliminary results

Sensitivity of noncontrast computed tomography (NCCT) in detecting hyperacute ( 8 hours), whereas the expert detection accuracy for these cases is 100\%. Moreover, the method detected all 21 early infarcts, of which 15 were missed by the stroke experts and 14 of 15 were missed by a general radiologist. The method performs automatic analysis in approximately 7 seconds.The results demonstrate potential benefits of our method for enhancing expert's performance because it quickly localizes the infarct and detects cases missed by experts, and it is to be considered as an aid in the emergency department because it substantially outperforms novice readers (100\% vs 27\%) in infarct detection on NCCT