| 1. |
|
|
| 2. |
- Marouli, Eirini, et al.
(författare)
-
Rare and low-frequency coding variants alter human adult height
- 2017
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
-
Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
|
|
| 3. |
- Turcot, Valerie, et al.
(författare)
-
Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
|
|
| 4. |
- Justice, Anne E., et al.
(författare)
-
Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
-
Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
|
|
| 5. |
- Manning, Alisa, et al.
(författare)
-
A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
- 2017
-
Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
-
Tidskriftsartikel (refereegranskat)abstract
- To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
|
|
| 6. |
- Sodergren, Erica, et al.
(författare)
-
The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
-
Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
|
|
| 7. |
- Wessel, Jennifer, et al.
(författare)
-
Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
|
|
| 8. |
- Scott, Robert A., et al.
(författare)
-
A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease
- 2016
-
Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:341
-
Tidskriftsartikel (refereegranskat)abstract
- Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.
|
|
| 9. |
- Bridel, Claire, et al.
(författare)
-
Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
-
Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
-
Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
|
|
| 10. |
|
|
| 11. |
- Kersten, CM, et al.
(författare)
-
The Management of Asymptomatic Congenital Pulmonary Airway Malformation: Results of a European Delphi Survey
- 2022
-
Ingår i: Children (Basel, Switzerland). - : MDPI AG. - 2227-9067. ; 9:8
-
Tidskriftsartikel (refereegranskat)abstract
- Consensus on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM) is lacking, and comparison between studies remains difficult due to a large variety in outcome measures. We aimed to define a core outcome set (COS) for pediatric patients with an asymptomatic CPAM. An online, three-round Delphi survey was conducted in two stakeholder groups of specialized caregivers (surgeons and non-surgeons) in various European centers. Proposed outcome parameters were scored according to level of importance, and the final COS was established through consensus. A total of 55 participants (33 surgeons, 22 non-surgeons) from 28 centers in 13 European countries completed the three rounds and rated 43 outcome parameters. The final COS comprises seven outcome parameters: respiratory insufficiency, surgical complications, mass effect/mediastinal shift (at three time-points) and multifocal disease (at two time-points). The seven outcome parameters included in the final COS reflect the diversity in priorities among this large group of European participants. However, we recommend the incorporation of these outcome parameters in the design of future studies, as they describe measurable and validated outcomes as well as the accepted age at measurement.
|
|
| 12. |
|
|
| 13. |
- Mahajan, Anubha, et al.
(författare)
-
Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
-
Tidskriftsartikel (refereegranskat)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
|
|
| 14. |
- Snoek, KG, et al.
(författare)
-
Standardized Postnatal Management of Infants with Congenital Diaphragmatic Hernia in Europe: The CDH EURO Consortium Consensus - 2015 Update
- 2016
-
Ingår i: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 110:1, s. 66-74
-
Tidskriftsartikel (refereegranskat)abstract
- In 2010, the congenital diaphragmatic hernia (CDH) EURO Consortium published a standardized neonatal treatment protocol. Five years later, the number of participating centers has been raised from 13 to 22. In this article the relevant literature is updated, and consensus has been reached between the members of the CDH EURO Consortium. Key updated recommendations are: (1) planned delivery after a gestational age of 39 weeks in a high-volume tertiary center; (2) neuromuscular blocking agents to be avoided during initial treatment in the delivery room; (3) adapt treatment to reach a preductal saturation of between 80 and 95% and postductal saturation >70%; (4) target PaCO<sub>2</sub> to be between 50 and 70 mm Hg; (5) conventional mechanical ventilation to be the optimal <i>initial</i> ventilation strategy, and (6) intravenous sildenafil to be considered in CDH patients with severe pulmonary hypertension. This article represents the current opinion of all consortium members in Europe for the optimal neonatal treatment of CDH.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
- Hirai, T., et al.
(författare)
-
Characterization and heat flux testing of beryllium coatings on Inconel for JET ITER-like wall project
- 2007
-
Ingår i: Physica Scripta. - 0031-8949 .- 1402-4896. ; T128, s. 166-170
-
Tidskriftsartikel (refereegranskat)abstract
- In order to perform a fully integrated material test, JET has launched the ITER-like wall project with the aim of installing a full metal wall during the next major shutdown. The material foreseen for the main chamber wall is bulk Be at the limiters and Be coatings on inconel tiles elsewhere. R&D process comprises global characterization ( structure, purity etc) of the evaporated films and testing of their performance under heat loads. The major results are (i) the layers have survived energy loads of 20 MJ m(-2) which is significantly above the required level of 5 - 10 MJ m(-2), (ii) melting limit of beryllium coating would be at the energy level of 30 MJ m(-2), (iii) cyclic thermal load of 10 MJ m(-2) for up to 50 cycles have not induced any noticeable damage such as flaking or detachment.
|
|
| 22. |
|
|
| 23. |
- Johansson, Anna L., V, et al.
(författare)
-
Were cancer patients worse off than the general population during the COVID-19 pandemic? : A population-based study from Norway, Denmark and Iceland during the pre-vaccination era
- 2023
-
Ingår i: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 31
-
Tidskriftsartikel (refereegranskat)abstract
- Background In a population-based setting, we investigated the risks of testing positive for SARS-CoV-2 and developing severe COVID-19 outcomes among cancer patients compared with the general population.Methods In nationwide cohorts, we identified all individuals in Norway, Denmark and Iceland who tested positive for SARS-CoV-2 or had a severe COVID-19 outcome (hospitalisation, intensive care, and death) from March until December 2020, using data from national health registries. We estimated standardised incidence ratios (SIRs) with 95% confidence intervals (CIs) comparing cancer patients with the general population.Findings During the first wave of the pandemic, cancer patients in Norway and Denmark had higher risks of testing SARS-CoV-2 positive compared to the general population. Throughout 2020, recently treated cancer patients were more likely to test SARS-CoV-2 positive. In Iceland, cancer patients experienced no increased risk of testing positive. The risk of COVID-19-related hospitalisation was higher among cancer patients diagnosed within one year of hospitalisation (Norway: SIR = 2.43, 95% CI 1.89-3.09; Denmark: 2.23, 1.96-2.54) and within five years (Norway: 1.58, 1.35-1.83; Denmark: 1.54, 1.42-1.66). Risks were higher in recently treated cancer patients and in those diagnosed with haematologic malignancies, colorectal or lung cancer. Risks of COVID-19-related intensive care and death were higher among cancer patients. Interpretation Cancer patients were at increased risk of testing positive for SARS-CoV-2 during the first pandemic wave when testing availability was limited, while relative risks of severe COVID-19 outcomes remained increased in cancer patients throughout 2020. Recent cancer treatment and haematologic malignancy were the strongest risk factors.
|
|
| 24. |
- Klyushina, E. S., et al.
(författare)
-
Signatures for Berezinskii-Kosterlitz-Thouless critical behavior in the planar antiferromagnet BaNi2V2O8
- 2021
-
Ingår i: Physical Review B. - : American Physical Society (APS). - 2469-9950 .- 2469-9969. ; 104:6
-
Tidskriftsartikel (refereegranskat)abstract
- We investigate the critical properties of the spin-1 honeycomb antiferromagnet BaNi2V2O8, both below and above the ordering temperature T-N using neutron diffraction and muon spin rotation measurements. Our results characterize BaNi2V2O8 as a two-dimensional (2D) antiferromagnet across the entire temperature range, displaying a series of crossovers from 2D XY to 2D XXZ and then to 2D Heisenberg behavior with increasing temperature. In particular, the extracted critical exponent of the order parameter reveals a narrow temperature regime close to T-N, in which the system behaves as a 2D XY antiferromagnet. Above T-N, evidence for Berezinskii-Kosterlitz-Thouless behavior driven by vortex excitations is obtained from the scaling of the correlation length. Our experimental results are in agreement with classical and quantum Monte Carlo simulations performed using microscopic magnetic model Hamiltonians for BaNi2V2O8.
|
|
| 25. |
- Lubenow, Norbert, et al.
(författare)
-
Results of a systematic evaluation of treatment outcomes for heparin-induced thrombocytopenia in patients receiving danaparoid, ancrod, and/or coumarin explain the rapid shift in clinical practice during the 1990s.
- 2006
-
Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 117:5, s. 507-15
-
Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Randomized controlled trials evaluating treatment of acute, transient, but uncommon diseases are difficult to perform. The prothrombotic adverse drug reaction, heparin-induced thrombocytopenia (HIT), is such an example. During the mid-1980s, the defibrinogenating snake venom, ancrod (+/-warfarin, Canada), or coumarin (warfarin, Canada; phenprocoumon, Germany) alone, were often used to treat HIT. During the 1990s, danaparoid+/-coumarin began to replace ancrod (+/-coumarin), or coumarin alone, for treating HIT, despite danaparoid not being approved for treatment of HIT. METHODS: We performed a retrospective evaluation of treatment outcomes from 1986 to 1999, comparing danaparoid+/-coumarin (n=62) versus ancrod+/-coumarin or coumarin alone (controls, n=56). RESULTS: The predefined composite endpoint of adjudicated new, progressive, or recurrent thrombosis (including thrombotic death), or limb amputation, at day 7 (maximum, one event per patient) was significantly lower in danaparoid-treated patients, compared with controls: 8/62=12.9% (95% CI, 4.3-21.5) vs. 22/56=39.3% (95% CI, 26.1-52.5); p=0.0014. We also found a lower frequency of the composite endpoint at end of study (day 35) in danaparoid-treated patients: 12/62=19.4% vs. 24/56=42.9% (p=0.0088). Major bleeding (by day 7) occurred in 7/62 (11.3%) and 16/56 (28.6%) of danaparoid-treated and control patients, respectively (p=0.0211). CONCLUSIONS: The replacement of ancrod+/-coumarin, or coumarin alone, by danaparoid (+/-coumarin) in the mid-1990s for the treatment of HIT was justified by improved efficacy and safety.
|
|
| 26. |
- Makitie, AA, et al.
(författare)
-
Head and neck cancer management in the Nordic countries: an effort to harmonize treatment
- 2017
-
Ingår i: European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. - : Springer Science and Business Media LLC. - 1434-4726. ; 274:5, s. 2363-2365
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 27. |
- Moldan, Filip, et al.
(författare)
-
The long-term fate of deposited nitrogen in temperate forest soils.
- 2020
-
Ingår i: Biogeochemistry. - : Springer Science and Business Media LLC. - 0168-2563 .- 1573-515X. ; 150, s. 1-15
-
Tidskriftsartikel (refereegranskat)abstract
- Increased anthropogenic nitrogen (N) inputs can alter the N cycle and affect forest ecosystem functions. The impact of increased N deposition depends among others on the ultimate fate of N in plant and soil N pools. Short-term studies (3–18 months) have shown that the organic soil layer was the dominant sink for N. However, longer time scales are needed to investigate the long-term fate of N. Therefore, the soils of four experimental forest sites across Europe were re-sampled ~ 2 decades after labelling with 15N. The sites covered a wide range of ambient N deposition varying from 13 to 58 kg N ha−1 year−1. To investigate the effects of different N loads on 15N recovery, ambient N levels were experimentally increased or decreased. We hypothesized that: (1) the mineral soil would become the dominant 15N sink after 2 decades, (2) long-term increased N deposition would lead to lower 15N recovery levels in the soil and (3) variables related to C dynamics would have the largest impact on 15N recovery in the soil. The results show that large amounts of the added 15N remain in the soil after 2 decades and at 2 out of 4 sites the 15N recovery levels are higher in the mineral soil than in the organic soil. The results show no clear responses of the isotopic signature to the changes in N deposition. Several environmental drivers are identified as controlling factors for long-term 15N recovery. Most drivers that significantly contribute to 15N recovery are strongly related to the soil organic matter (SOM) content. These findings are consistent with the idea that much of the added 15N is immobilized in the SOM. In the organic soil layer, we identify C stock, thickness of the organic layer, N-status and mean annual temperature of the forest sites as most important controlling factors. In the mineral soil we identify C stock, C content, pH, moisture content, bulk density, temperature, precipitation and forest stand age as most important controlling factors. Overall, our results show that these temperate forests are capable of retaining long-term increased N inputs preferably when SOM availability is high and SOM turnover and N availability are low.
|
|
| 28. |
|
|
| 29. |
- Simon, Marie-Christine, et al.
(författare)
-
Distinct alterations of gut morphology and microbiota characterize accelerated diabetes onset in nonobese diabetic mice
- 2020
-
Ingår i: Journal of Biological Chemistry. - 0021-9258. ; 295:4, s. 969-980
-
Tidskriftsartikel (refereegranskat)abstract
- The rising prevalence of type 1 diabetes (T1D) over the past decades has been linked to lifestyle changes, but the underlying mechanisms are largely unknown. Recent findings point to gut-associated mechanisms in the control of T1D pathogenesis. In nonobese diabetic (NOD) mice, a model of T1D, diabetes development accelerates after deletion of the Toll-like receptor 4 (TLR4). We hypothesized that altered intestinal functions contribute to metabolic alterations, which favor accelerated diabetes development in TLR4-deficient (TLR4(?/?)) NOD mice. In 70?90-day-old normoglycemic (prediabetic) female NOD TLR4(+/+) and NOD TLR4(?/?) mice, gut morphology and microbiome composition were analyzed. Parameters of lipid metabolism, glucose homeostasis, and mitochondrial respiratory activity were measured in vivo and ex vivo. Compared with NOD TLR4(+/+) mice, NOD TLR4(?/?) animals showed lower muscle mass of the small intestine, higher abundance of Bacteroidetes, and lower Firmicutes in the large intestine, along with lower levels of circulating short-chain fatty acids (SCFA). These changes are associated with higher body weight, hyperlipidemia, and severe insulin and glucose intolerance, all occurring before the onset of diabetes. These mice also exhibited insulin resistance?related abnormalities of energy metabolism, such as lower total respiratory exchange rates and higher hepatic oxidative capacity. Distinct alterations of gut morphology and microbiota composition associated with reduction of circulating SCFA may contribute to metabolic disorders promoting the progression of insulin-deficient diabetes/T1D development.
|
|
| 30. |
- Song, Jia L, et al.
(författare)
-
Select microRNAs are essential for early development in the sea urchin
- 2012
-
Ingår i: Developmental Biology. - : Elsevier. - 0012-1606 .- 1095-564X. ; 362:1
-
Tidskriftsartikel (refereegranskat)abstract
- microRNAs (miRNAs) are small noncoding RNAs that mediate post-transcriptional gene regulation and have emerged as essential regulators of many developmental events. The transcriptional network during early embryogenesis of the purple sea urchin, Strongylocentrotus purpuratus, is well described and can serve as an excellent model to test functional contributions of miRNAs in embryogenesis. We examined the loss of function phenotypes of major components of the miRNA biogenesis pathway. Inhibition of de novo synthesis of Drosha and Dicer in the embryo led to consistent developmental defects, a failure to gastrulate, and embryonic lethality, including changes in the steady state levels of transcription factors and signaling molecules involved in germ layer specification. We annotated and profiled small RNA expression from the ovary and several early embryonic stages by deep sequencing followed by computational analysis. miRNAs as well as a large population of putative piRNAs (piwi-interacting RNAs) had dynamic accumulation profiles through early development. Defects in morphogenesis caused by loss of Drosha could be rescued with four miRNAs. Taken together our results indicate that post-transcriptional gene regulation directed by miRNAs is functionally important for early embryogenesis and is an integral part of the early embryonic gene regulatory network in S. purpuratus.
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
|
|
