| 1. |
- Mishra, A., et al.
(author)
-
Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
-
Journal article (peer-reviewed)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
|
|
| 2. |
- Wightman, D. P., et al.
(author)
-
A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
- 2021
-
In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:9, s. 1276-1282
-
Journal article (peer-reviewed)abstract
- Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology.
|
|
| 3. |
- Hale, S. E., et al.
(author)
-
The sorption and desorption of phosphate-P, ammonium-N and nitrate-N in cacao shell and corn cob biochars
- 2013
-
In: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 91:11, s. 1612-1619
-
Journal article (peer-reviewed)abstract
- The sorption of PO4-P, NH4-N and NO3-N to cacao shell and corn cob biochars produced at 300-350 degrees C was quantified. The biochars were used; (i) as received (unwashed), (ii) after rinsing with Millipore water and (iii) following leaching with Millipore water. In addition to sorption, desorption of PO4-P from the unwashed biochars was quantified. There was no sorption of PO4-P to either washed or rinsed biochars, but following leaching, both biochars adsorbed PO4-P and distribution coefficients (K-d L kg(-1)) were very similar for both materials (10(1.1 +/- 0.5) for cacao shell biochar and 10(1.0 +/- 0.2) for corn cob biochar). The BET surface area and micropore volume increased 80% and 60% for the cacao shell and corn cob biochars following leaching. After 60 d, 1483 +/- 45 mg kg(-1) and 172 +/- 1 mg kg PO4-P was released from the cacao shell and corn cob biochars. NH4-N was sorbed by both unwashed biochars, albeit weakly with K-d values around 10(2) L kg(-1). We speculate that NH4-N could bind via an electrostatic exchange with other cationic species on the surface of the biochar. There was no significant release or sorption of NO3-N from or to either of the biochars.
|
|
| 4. |
- Martinsen, V., et al.
(author)
-
pH effects of the addition of three biochars to acidic Indonesian mineral soils
- 2015
-
In: Soil science and plant nutrition (Tokyo). - : Informa UK Limited. - 0038-0768 .- 1747-0765. ; 61:5, s. 821-834
-
Journal article (peer-reviewed)abstract
- Soil acidity may severely reduce crop production. Biochar (BC) may increase soil pH and cation exchange capacity (CEC) but reported effects differ substantially. In a systematic approach, using a standardized protocol on a uniquely large number set of 31 acidic soils, we quantified the effect of increasing amounts (0-30%; weight:weight) of three types of field-produced BCs (from cacao (Theobroma cacao. L.) shell, oil palm (Elaeis guineensis. Jacq.) shell and rice (Oryza sativa. L.) husk) on soil pH and CEC. Soils were sampled from croplands at Java, Sumatra and Kalimantan, Indonesia. All BCs caused a significant increase in mean soil pH with a stronger response and a greater maximum increase for the cacao shell BC addition, due to a greater acid neutralizing capacity (ANC) and larger amounts of extractable base cations. At 1% BC addition, corresponding to about 30tonsha(-1), the estimated increase in soil pH from the initial mean pH of 4.7 was about 0.5 units for the cacao shell BC, whereas this was only 0.05 and 0.04 units for the oil palm shell and rice husk BC, respectively. Besides depending on BC type, the increase in soil pH upon the addition of each of the three BCs was mainly dependent on soil CEC (low CEC resulting in stronger pH increase), and to a lesser extent on initial soil pH (higher initial pH resulting in stronger pH increase). Addition of BC also increased the amount of exchangeable base cations (cacao shell >> oil palm and rice husk) and CEC. Through this systematic screening of the effect of BC on pH and CEC of acidic soils, we show that a small addition of BC, in particular if made of cacao shell, to acidic agricultural soils increases soil pH and CEC. However, the response is highly dependent on the type, quality and amount of the added BC as well as on intrinsic soil properties, mainly CEC.
|
|
| 5. |
- Jorgensen, E. H., et al.
(author)
-
Long-term fasting in the anadromous Arctic charr is associated with downregulation of metabolic enzyme activity and upregulation of leptin A1 and SOCS expression in the liver
- 2013
-
In: Journal of Experimental Biology. - : The Company of Biologists. - 0022-0949 .- 1477-9145. ; 216:17, s. 3222-3230
-
Journal article (peer-reviewed)abstract
- The life strategy of the anadromous Arctic charr (Salvelinus alpinus) includes several months of voluntary fasting during overwintering in freshwater, leading to emaciation prior to seawater migration in spring. In this study we compared changes in condition, substrate utilization and liver metabolism between captive anadromous charr subjected to food deprivation during late winter and spring, and conspecifics fed in excess. In March, nine out of the 10 sampled fed fish had not eaten, indicating that they were in a voluntary anorexic state. In June, the fed fish were eating and all had higher body mass, condition factor and adiposity than in March. In fasted fish there were only small decreases in body mass, condition factor and adiposity between March and May, but all these parameters decreased markedly from May to June. The fasted fish were depleted in fat and glycogen in June, had suppressed activity of hepatic enzymes involved in lipid metabolism (G6PDH and HOAD) and seemed to rely on protein-derived glucose as a major energy source. This was associated with upregulated liver gene expression of leptin A1, leptin A2, SOCS1, SOCS2 and SOCS3, and reduced IGF-I expression. In an in vitro study with liver slices it was shown that recombinant rainbow trout leptin stimulated SOCS1 and SOCS3 expression, but not SOCS2, IGF-I or genes of enzymes involved in lipid (G6PDH) and amino acid (AspAT) metabolism. It is concluded that liver leptin interacts with SOCS in a paracrine fashion to suppress lipolytic pathways and depress metabolism when fat stores are depleted.
|
|
| 6. |
|
|
| 7. |
- Vekic, T. T., et al.
(author)
-
Effect of calcareous and siliceous amendments on N2O emissions of a grassland soil
- 2023
-
In: Soil Use and Management. - 0266-0032. ; 39:3, s. 1082-1095
-
Journal article (peer-reviewed)abstract
- Liming of acidic agricultural soils has been proposed as a strategy to mitigate nitrous oxide (N2O) emissions, as increased soil pH reduces the N2O/N-2 product ratio of denitrification. The capacity of different calcareous (calcite and dolomite) and siliceous minerals to increase soil pH and reduce N2O emissions was assessed in a 2-year grassland field experiment. An associated pot experiment was conducted using homogenized field soils for controlling spatial soil variability. Nitrous oxide emissions were highly episodic with emission peaks in response to freezing-thawing and application of NPK fertilizer. Liming with dolomite caused a pH increase from 5.1 to 6.2 and reduced N2O emissions by 30% and 60% after application of NPK fertilizer and freezing-thawing events, respectively. Over the course of the 2-year field trial, N2O emissions were significantly lower in dolomite-limed than non-limed soil (p < .05), although this effect was variable over time. Unexpectedly, no significant reduction of N2O emission was found in the calcite treatment, despite the largest pH increase in all tested minerals. We tentatively attribute this to increased N2O production by overall increase in nitrogen turnover rates (both nitrification and denitrification) following rapid pH increase in the first year after liming. Siliceous materials showed little pH effect and had no significant effect on N2O emissions probably because of their lower buffering capacity and lower cation content. In the pot experiment using soils taken from the field plots 3 years after liming and exposing them to natural freezing-thawing, both calcite (p < .01) and dolomite (p < .05) significantly reduced cumulative N2O emission by 50% and 30%, respectively, relative to the non-limed control. These results demonstrate that the overall effect of liming is to reduce N2O emission, although high lime doses may lead to a transiently enhanced emission.
|
|
