| 1. |
|
|
| 2. |
- Bravo, L, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 3. |
- Tabiri, S, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 4. |
|
|
| 5. |
- Glasbey, JC, et al.
(författare)
-
- 2021
-
swepub:Mat__t
|
|
| 6. |
|
|
| 7. |
- Deo, R., et al.
(författare)
-
Common genetic variation near the connexin-43 gene is associated with resting heart rate in African Americans: A genome-wide association study of 13,372 participants
- 2013
-
Ingår i: Heart Rhythm. - : Elsevier BV. - 1547-5271. ; 10:3, s. 401-408
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans. OBJECTIVE To identify novel genetic variants associated with resting heart rate in African Americans. METHODS Ten cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of singe nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (P <= 2.5 x 10(-8)). RESULTS Fourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98 x 10(-15)). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans. CONCLUSIONS An intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin.
|
|
| 8. |
|
|
| 9. |
- Faulx, M. D., et al.
(författare)
-
Obstructive sleep apnea and its management in patients with atrial fibrillation: An International Collaboration of Sleep Apnea Cardiovascular Trialists (INCOSACT) global survey of practicing cardiologists
- 2022
-
Ingår i: International journal of cardiology: Heart and Vasculature (IJCHA). - : Elsevier BV. - 2352-9067. ; 42
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Among international cardiologists it is unclear whether equipoise exists regarding the benefit of diagnosing and managing obstructive sleep apnea (OSA) to improve atrial fibrillation (AF) outcomes and whether clinical practice and equipoise are linked. Methods: Between January 2019 and June 2020 we distributed a web-based 12-question survey regarding OSA and AF management to practicing cardiologists in 16 countries. Results: The United States, Japan, Sweden, and Turkey accounted for two-thirds of responses. 863 cardiologists responded; half were general cardiologists, a quarter electrophysiologists. Responses regarding treating OSA with CPAP to improve AF endpoints were mixed. 33% of respondents referred AF patients for OSA screening. OSA was diagnosed in 48% of referred patients and continuous positive airway pressure (CPAP) was prescribed for 59% of them. Nearly 70% of respondents believed randomized controlled trials (RCTs) of OSA treatment in AF patients were necessary and indicated willingness to contribute to such trials. Conclusions: There was no clinical equipoise among surveyed cardiologists; a majority expressed certainty that combined OSA and AF treatment is superior to AF treatment alone for improving AF outcomes. However, a minority of surveyed cardiologists referred AF patients for OSA testing, and while half of screened AF patients had OSA, CPAP was prescribed in little more than half of them, reflecting the view that better clinical trial evidence is needed to support this practice. Our results underscore the need for larger, multi-national prospective studies of OSA treatment and AF outcomes to inform more uniform society guideline recommendations.
|
|
| 10. |
- Nikpay, Majid, et al.
(författare)
-
A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease
- 2015
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:10, s. 1121-1121
-
Tidskriftsartikel (refereegranskat)abstract
- Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of similar to 185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
|
|
| 11. |
- Mehra, Archit, et al.
(författare)
-
Evaluation of the chemical composition of gas- and particle-phase products of aromatic oxidation
- 2020
-
Ingår i: ATMOSPHERIC CHEMISTRY AND PHYSICS. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 20:16, s. 9783-9803
-
Tidskriftsartikel (refereegranskat)abstract
- Aromatic volatile organic compounds (VOCs) are key anthropogenic pollutants emitted to the atmosphere and are important for both ozone and secondary organic aerosol (SOA) formation in urban areas. Recent studies have indicated that aromatic hydrocarbons may follow previously unknown oxidation chemistry pathways, including autoxidation that can lead to the formation of highly oxidised products. In this study we evaluate the gas- and particle-phase ions measured by online mass spectrometry during the hydroxyl radical oxidation of substituted C-9-aromatic isomers (1,3,5-trimethylbenzene, 1,2,4-trimethylbenzene, propylbenzene and isopropylbenzene) and a substituted polyaromatic hydrocarbon (1-methylnaphthalene) under low- and medium-NO x conditions. A time-of-flight chemical ionisation mass spectrometer (ToF-CIMS) with iodide-anion ionisation was used with a filter inlet for gases and aerosols (FIGAERO) for the detection of products in the particle phase, while a Vocus protontransfer-reaction mass spectrometer (Vocus-PTR-MS) was used for the detection of products in the gas phase. The signal of product ions observed in the mass spectra were compared for the different precursors and experimental conditions. The majority of mass spectral product signal in both the gas and particle phases comes from ions which are common to all precursors, though signal distributions are distinct for different VOCs. Gas- and particle-phase composition are distinct from one another. Ions corresponding to products contained in the near-explicit gas phase Master Chemical Mechanism (MCM version 3.3.1) are utilised as a benchmark of current scientific understanding, and a comparison of these with observations shows that the MCM is missing a range of highly oxidised products from its mechanism. In the particle phase, the bulk of the product signal from all precursors comes from ring scission ions, a large proportion of which are more oxidised than previously reported and have undergone further oxidation to form highly oxygenated organic molecules (HOMs). Under the perturbation of OH oxidation with increased NOx, the contribution of HOM-ion signals to the particle-phase signal remains elevated for more substituted aromatic precursors. Up to 43% of product signal comes from ring-retaining ions including HOMs; this is most important for the more substituted aromatics. Unique products are a minor component in these systems, and many of the dominant ions have ion formulae concurrent with other systems, highlighting the challenges in utilising marker ions for SOA.
|
|
| 12. |
|
|
| 13. |
- Smith, Gustav, et al.
(författare)
-
The Impact of Ancestry and Common Genetic Variants on QT Interval in African Americans.
- 2012
-
Ingår i: Circulation: Cardiovascular Genetics. - 1942-325X. ; 5:6, s. 647-655
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: -Ethnic differences in cardiac arrhythmia incidence have been reported, with a particularly high incidence of sudden cardiac death (SCD) and low incidence of atrial fibrillation in individuals of African ancestry. We tested the hypotheses that African ancestry and common genetic variants are associated with prolonged duration of cardiac repolarization, a central pathophysiological determinant of arrhythmia, as measured by the electrocardiographic QT interval. METHODS AND RESULTS: -First, individual estimates of African and European ancestry were inferred from genome-wide single nucleotide polymorphism (SNP) data in seven population-based cohorts of African Americans (n=12 097) and regressed on measured QT interval from electrocardiograms. Second, imputation was performed for 2.8 million SNPs and a genome-wide association (GWA) study of QT interval performed in ten cohorts (n=13 105). There was no evidence of association between genetic ancestry and QT interval (p=0.94). Genome-wide significant associations (p<2.5x10(-8)) were identified with SNPs at two loci, upstream of the genes NOS1AP (rs12143842, p=2x10(-15)) and ATP1B1 (rs1320976, p=2x10(-10)). The most significant SNP in NOS1AP was the same as the strongest SNP previously associated with QT interval in individuals of European ancestry. Low p-values (p<10(-5)) were observed for SNPs at several other loci previously identified in GWA studies in individuals of European ancestry, including KCNQ1, KCNH2, LITAF and PLN. CONCLUSIONS: -We observed no difference in duration of cardiac repolarization with global genetic indices of African ancestry. In addition, our GWA study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include African Americans.
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Akgul, M, et al.
(författare)
-
Diagnostic approach in TFE3-rearranged renal cell carcinoma: a multi-institutional international survey
- 2021
-
Ingår i: Journal of clinical pathology. - : BMJ. - 1472-4146 .- 0021-9746. ; 74:5, s. 291-299
-
Tidskriftsartikel (refereegranskat)abstract
- Transcription factor E3-rearranged renal cell carcinoma (TFE3-RCC) has heterogenous morphologic and immunohistochemical (IHC) features.131 pathologists with genitourinary expertise were invited in an online survey containing 23 questions assessing their experience on TFE3-RCC diagnostic work-up.Fifty (38%) participants completed the survey. 46 of 50 participants reported multiple patterns, most commonly papillary pattern (almost always 9/46, 19.5%; frequently 29/46, 63%). Large epithelioid cells with abundant cytoplasm were the most encountered cytologic feature, with either clear (almost always 10/50, 20%; frequently 34/50, 68%) or eosinophilic (almost always 4/49, 8%; frequently 28/49, 57%) cytology. Strong (3+) or diffuse (>75% of tumour cells) nuclear TFE3 IHC expression was considered diagnostic by 13/46 (28%) and 12/47 (26%) participants, respectively. Main TFE3 IHC issues were the low specificity (16/42, 38%), unreliable staining performance (15/42, 36%) and background staining (12/42, 29%). Most preferred IHC assays other than TFE3, cathepsin K and pancytokeratin were melan A (44/50, 88%), HMB45 (43/50, 86%), carbonic anhydrase IX (41/50, 82%) and CK7 (32/50, 64%). Cut-off for positive TFE3 fluorescent in situ hybridisation (FISH) was preferably 10% (9/50, 18%), although significant variation in cut-off values was present. 23/48 (48%) participants required TFE3 FISH testing to confirm TFE3-RCC regardless of the histomorphologic and IHC assessment. 28/50 (56%) participants would request additional molecular studies other than FISH assay in selected cases, whereas 3/50 participants use additional molecular cases in all cases when TFE3-RCC is in the differential.Optimal diagnostic approach on TFE3-RCC is impacted by IHC and/or FISH assay preferences as well as their conflicting interpretation methods.
|
|
| 17. |
|
|
| 18. |
- Butler, Anne M., et al.
(författare)
-
Novel Loci Associated With PR Interval in a Genome-Wide Association Study of 10 African American Cohorts
- 2012
-
Ingår i: Circulation: Cardiovascular Genetics. - 1942-325X. ; 5:6, s. 639-646
-
Tidskriftsartikel (refereegranskat)abstract
- Background-The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans. Methods and Results-We present results from the largest genome-wide association study to date of PR in 13 415 adults of African descent from 10 cohorts. We tested for association between PR (ms) and approximate to 2.8 million genotyped and imputed single-nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (lambda range: 0.9-1.1), although not after genomic control correction was applied to the overall meta-analysis (lambda: 1.008). In addition to generalizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1, and TBX5 to African American populations at the genome-wide significance level (P<5.0x10(-8)), we also identified a novel locus: ITGA9, located in a region previously implicated in SCN5A expression. The 3p21 region harboring SCN5A also contained 2 additional independent secondary signals influencing PR (P<5.0x10-8). Conclusions-This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European, and Asian descent. (Circ Cardiovasc Genet. 2012;5:639-646.)
|
|
| 19. |
|
|
| 20. |
- Harms, H. J., et al.
(författare)
-
Cardiopulmonary transit time : A novel PET imaging biomarker of in vivo physiology for risk stratification of heart transplant recipients
- 2022
-
Ingår i: Journal of Nuclear Cardiology. - : Springer Nature. - 1071-3581 .- 1532-6551. ; 29, s. 1234-1244
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Myocardial blood flow (MBF) can be quantified using dynamic PET studies. These studies also inherently contain tomographic images of early bolus displacement, which can provide cardiopulmonary transit times (CPTT) as measure of cardiopulmonary physiology. The aim of this study was to assess the incremental prognostic value of CPTT in heart transplant (OHT) recipients.Methods: 94 patients (age 56 +/- 16 years, 78% male) undergoing dynamic N-13-ammonia stress/rest studies were included, of which 68 underwent right-heart catherization. A recently validated cardiac allograft vasculopathy (CAV) score based on PET measures of regional perfusion, peak MBF and left-ventricular (LV) ejection fraction (LVEF) was used to identify patients with no, mild or moderate-severe CAV. Time-activity curves of the LV and right ventricular (RV) cavities were obtained and used to calculate the difference between the LV and RV bolus midpoint times, which represents the CPTT and is expressed in heartbeats. Patients were followed for a median of 2.5 years for the occurrence of major adverse cardiac events (MACE), including cardiovascular death, hospitalization for heart failure or acute coronary syndrome, or re-transplantation.Results: CPTT was significantly correlated with cardiac filling pressures (r = .434, P = .0002 and r = .439, P = .0002 for right atrial and pulmonary wedge pressure), cardiac output (r = - .315, P = .01) and LVEF (r = - .513, P < .0001). CPTT was prolonged in patients with MACE (19.4 +/- 6.0 vs 14.5 +/- 3.0 heartbeats, P < .001, N = 15) with CPTT >= 17.75 beats showing optimal discriminatory value in ROC analysis. CPTT >= 17.75 heartbeats was associated with a 10.1-fold increased risk (P < .001) of MACE and a 7.3-fold increased risk (P < .001) after adjusting for PET-CAV, age, sex and time since transplant.Conclusion: Measurements of cardiopulmonary transit time provide incremental risk stratification in OHT recipients and enhance the value of multiparametric dynamic PET imaging, particularly in identifying high-risk patients.
|
|
| 21. |
- In ’t Veld, Sjors G.J.G., et al.
(författare)
-
Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
-
Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
|
|
| 22. |
- Smith, Gustav, et al.
(författare)
-
Genome-Wide Association Studies of the PR Interval in African Americans.
- 2011
-
Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 7:2
-
Tidskriftsartikel (refereegranskat)abstract
- The PR interval on the electrocardiogram reflects atrial and atrioventricular nodal conduction time. The PR interval is heritable, provides important information about arrhythmia risk, and has been suggested to differ among human races. Genome-wide association (GWA) studies have identified common genetic determinants of the PR interval in individuals of European and Asian ancestry, but there is a general paucity of GWA studies in individuals of African ancestry. We performed GWA studies in African American individuals from four cohorts (n = 6,247) to identify genetic variants associated with PR interval duration. Genotyping was performed using the Affymetrix 6.0 microarray. Imputation was performed for 2.8 million single nucleotide polymorphisms (SNPs) using combined YRI and CEU HapMap phase II panels. We observed a strong signal (rs3922844) within the gene encoding the cardiac sodium channel (SCN5A) with genome-wide significant association (p<2.5×10(-8)) in two of the four cohorts and in the meta-analysis. The signal explained 2% of PR interval variability in African Americans (beta = 5.1 msec per minor allele, 95% CI = 4.1-6.1, p = 3×10(-23)). This SNP was also associated with PR interval (beta = 2.4 msec per minor allele, 95% CI = 1.8-3.0, p = 3×10(-16)) in individuals of European ancestry (n = 14,042), but with a smaller effect size (p for heterogeneity <0.001) and variability explained (0.5%). Further meta-analysis of the four cohorts identified genome-wide significant associations with SNPs in SCN10A (rs6798015), MEIS1 (rs10865355), and TBX5 (rs7312625) that were highly correlated with SNPs identified in European and Asian GWA studies. African ancestry was associated with increased PR duration (13.3 msec, p = 0.009) in one but not the other three cohorts. Our findings demonstrate the relevance of common variants to African Americans at four loci previously associated with PR interval in European and Asian samples and identify an association signal at one of these loci that is more strongly associated with PR interval in African Americans than in Europeans.
|
|
| 23. |
- Adamopoulos, Stamatis, et al.
(författare)
-
Right heart failure with left ventricular assist devices: Preoperative, perioperative and postoperative management strategies. A clinical consensus statement of the Heart Failure Association (HFA) of the ESC
- 2024
-
Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844.
-
Tidskriftsartikel (refereegranskat)abstract
- Right heart failure (RHF) following implantation of a left ventricular assist device (LVAD) is a common and potentially serious condition with a wide spectrum of clinical presentations with an unfavourable effect on patient outcomes. Clinical scores that predict the occurrence of right ventricular (RV) failure have included multiple clinical, biochemical, imaging and haemodynamic parameters. However, unless the right ventricle is overtly dysfunctional with end-organ involvement, prediction of RHF post-LVAD implantation is, in most cases, difficult and inaccurate. For these reasons optimization of RV function in every patient is a reasonable practice aiming at preparing the right ventricle for a new and challenging haemodynamic environment after LVAD implantation. To this end, the institution of diuretics, inotropes and even temporary mechanical circulatory support may improve RV function, thereby preparing it for a better adaptation post-LVAD implantation. Furthermore, meticulous management of patients during the perioperative and immediate postoperative period should facilitate identification of RV failure refractory to medication. When RHF occurs late during chronic LVAD support, this is associated with worse long-term outcomes. Careful monitoring of RV function and characterization of the origination deficit should therefore continue throughout the patient's entire follow-up. Despite the useful information provided by the echocardiogram with respect to RV function, right heart catheterization frequently offers additional support for the assessment and optimization of RV function in LVAD-supported patients. In any patient candidate for LVAD therapy, evaluation and treatment of RV function and failure should be assessed in a multidimensional and multidisciplinary manner.
|
|
| 24. |
- Bannan, T. J., et al.
(författare)
-
A method for extracting calibrated volatility information from the FIGAERO-HR-ToF-CIMS and its experimental application
- 2019
-
Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 12:3, s. 1429-1439
-
Tidskriftsartikel (refereegranskat)abstract
- The Filter Inlet for Gases and AEROsols (FIGAERO) is an inlet specifically designed to be coupled with the Aerodyne High-Resolution Time-of-Flight Chemical Ionization Mass Spectrometer (HR-ToF-CIMS). The FIGAERO-HR-ToF-CIMS provides simultaneous molecular information relating to both the gas- and particle-phase samples and has been used to extract vapour pressures (VPs) of the compounds desorbing from the filter whilst giving quantitative concentrations in the particle phase. However, such extraction of vapour pressures of the measured particle-phase components requires use of appropriate, well-defined, reference compounds. Vapour pressures for the homologous series of polyethylene glycols (PEG) ((H-(O-CH 2 CH 2 ) n -OH) for n = 3 to n = 8), covering a range of vapour pressures (VP) (10 -1 to 10 -7 Pa) that are atmospherically relevant, have been shown to be reproduced well by a range of different techniques, including Knudsen Effusion Mass Spectrometry (KEMS). This is the first homologous series of compounds for which a number of vapour pressure measurement techniques have been found to be in agreement, indicating the utility as a calibration standard, providing an ideal set of benchmark compounds for accurate characterization of the FIGAERO for extracting vapour pressure of measured compounds in chambers and the real atmosphere. To demonstrate this, single-component and mixture vapour pressure measurements are made using two FIGAERO-HR-ToF-CIMS instruments based on a new calibration determined from the PEG series. VP values extracted from both instruments agree well with those measured by KEMS and reported values from literature, validating this approach for extracting VP data from the FIGAERO. This method is then applied to chamber measurements, and the vapour pressures of known products are estimated. © 2019 Author(s).
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
- Dans, Madeline G., et al.
(författare)
-
Aryl amino acetamides prevent Plasmodium falciparum ring development via targeting the lipid-transfer protein PfSTART1
- 2024
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- With resistance to most antimalarials increasing, it is imperative that new drugs are developed. We previously identified an aryl acetamide compound, MMV006833 (M-833), that inhibited the ring-stage development of newly invaded merozoites. Here, we select parasites resistant to M-833 and identify mutations in the START lipid transfer protein (PF3D7_0104200, PfSTART1). Introducing PfSTART1 mutations into wildtype parasites reproduces resistance to M-833 as well as to more potent analogues. PfSTART1 binding to the analogues is validated using organic solvent-based Proteome Integral Solubility Alteration (Solvent PISA) assays. Imaging of invading merozoites shows the inhibitors prevent the development of ring-stage parasites potentially by inhibiting the expansion of the encasing parasitophorous vacuole membrane. The PfSTART1-targeting compounds also block transmission to mosquitoes and with multiple stages of the parasite’s lifecycle being affected, PfSTART1 represents a drug target with a new mechanism of action.
|
|
| 29. |
- Gupta, Rajeev Kumar, et al.
(författare)
-
Biochar influences nitrogen and phosphorus dynamics in two texturally different soils
- 2024
-
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14
-
Tidskriftsartikel (refereegranskat)abstract
- Nitrogen (N) and phosphorus (P) are vital for crop growth. However, most agricultural systems have limited inherent ability to supply N and P to crops. Biochars (BCs) are strongly advocated in agrosystems and are known to improve the availability of N and P in crops through different chemical transformations. Herein, a soil-biochar incubation experiment was carried out to investigate the transformations of N and P in two different textured soils, namely clay loam and loamy sand, on mixing with rice straw biochar (RSB) and acacia wood biochar (ACB) at each level (0, 0.5, and 1.0% w/w). Ammonium N (NH4-N) decreased continuously with the increasing incubation period. The ammonium N content disappeared rapidly in both the soils incubated with biochars compared to the unamended soil. RSB increased the nitrate N (NO3–N) content significantly compared to ACB for the entire study period in both texturally divergent soils. The nitrate N content increased with the enhanced biochar addition rate in clay loam soil until 15 days after incubation; however, it was reduced for the biochar addition rate of 1% compared to 0.5% at 30 and 60 days after incubation in loamy sand soil. With ACB, the net increase in nitrate N content with the biochar addition rate of 1% remained higher than the 0.5% rate for 60 days in clay loam and 30 days in loamy sand soil. The phosphorus content remained consistently higher in both the soils amended with two types of biochars till the completion of the experiment.
|
|
| 30. |
|
|
| 31. |
- Lau, Heather H. C., et al.
(författare)
-
The G51D SNCA mutation generates a slowly progressive alpha-synuclein strain in early-onset Parkinson's disease
- 2023
-
Ingår i: Acta neuropathologica communications. - : BioMed Central (BMC). - 2051-5960. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Unique strains of a-synuclein aggregates have been postulated to underlie the spectrum of clinical and pathological presentations seen across the synucleinopathies. Whereas multiple system atrophy (MSA) is associated with a predominance of oligodendroglial a-synuclein inclusions, a-synuclein aggregates in Parkinson's disease (PD) preferentially accumulate in neurons. The G51D mutation in the SNCA gene encoding a-synuclein causes an aggressive, early-onset form of PD that exhibits clinical and neuropathological traits reminiscent of both PD and MSA. To assess the strain characteristics of G51D PD a-synuclein aggregates, we performed propagation studies in M83 transgenic mice by intracerebrally inoculating patient brain extracts. The properties of the induced a-synuclein aggregates in the brains of injected mice were examined using immunohistochemistry, a conformational stability assay, and by performing a-synuclein seed amplification assays. Unlike MSA-injected mice, which developed a progressive motor phenotype, G51D PD-inoculated animals remained free of overt neurological illness for up to 18 months post-inoculation. However, a subclinical synucleinopathy was present in G51D PD-inoculated mice, characterized by the accumulation of a-synuclein aggregates in restricted regions of the brain. The induced a-synuclein aggregates in G51D PD-injected mice exhibited distinct properties in a seed amplification assay and were much more stable than those present in mice injected with MSA extract, which mirrored the differences observed between human MSA and G51D PD brain samples. These results suggest that the G51D SNCA mutation specifies the formation of a slowly propagating a-synuclein strain that more closely resembles a-synuclein aggregates associated with PD than MSA.
|
|
| 32. |
- Mancini, G. B. J., et al.
(författare)
-
Pharmacologic Options for the Management of Systolic Heart Failure: Examining Underlying Mechanisms
- 2015
-
Ingår i: Canadian Journal of Cardiology. - : Pulsus Group Inc.. - 0828-282X. ; 31:10, s. 1282-1292
-
Forskningsöversikt (refereegranskat)abstract
- The optimal management of systolic heart failure includes combination therapy to influence myocardial remodelling favourably by affecting neurohormonal activation and underlying maladaptive pathophysiological pathways. These medications include modulators of the renin-angiotensin-aldosterone system (eg, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists) and β-adrenergic receptor blockers. In addition, an agent with a distinct and complementary mechanism of bradycardic action, the selective pacemaker-current (If) inhibitor ivabradine, provides further reduction of heart rate. Also, a new drug that incorporates neprilysin inhibition combined with angiotensin receptor blockade shows incremental effectiveness. The primary goal of this review is to provide a mechanistic explanation of the complementary role of therapeutic interventions in modulating pathways leading to progressive systolic heart failure. A secondary goal is to summarize the key findings of the pivotal clinical trials that have demonstrated the efficacy of these agents in this population. © 2015 Canadian Cardiovascular Society.
|
|
| 33. |
- Mehra, A., et al.
(författare)
-
The persistence of a proxy for cooking emissions in megacities: a kinetic study of the ozonolysis of self-assembled films by simultaneous small and wide angle X-ray scattering (SAXS/WAXS) and Raman microscopy
- 2021
-
Ingår i: Faraday Discussions. - 1359-6640. ; 226, s. 382-408
-
Tidskriftsartikel (refereegranskat)abstract
- Cooking emissions account for a significant proportion of the organic aerosols emitted into the urban environment and high pollution events have been linked to an increased organic content on urban particulate matter surfaces. We present a kinetic study on surface coatings of self-assembled (semi-solid) oleic acid-sodium oleate cooking aerosol proxies undergoing ozonolysis. We found clear film thickness-dependent kinetic behaviour and measured the effect of the organic phase on the kinetics for this system. In addition to the thickness-dependent kinetics, we show that significant fractions of unreacted proxy remain after extensive ozone exposure and that this effect scales approximately linearly with film thickness, suggesting that a late-stage inert reaction product may form and inhibit reaction progress - effectively building up an inert crust. We determine this by using a range of simultaneous analytical techniques; most notably Small-Angle X-ray Scattering (SAXS) has been used for the first time to measure the reaction kinetics of films of a wide range of thicknesses from ca. 0.59 to 73 mu m with films <10 mu m thick being of potential atmospheric relevance. These observations have implications for the evolution of particulate matter in the urban environment, potentially extending the atmospheric lifetimes of harmful aerosol components and affecting the local urban air quality and climate.
|
|
| 34. |
- Mehra, A., et al.
(författare)
-
Using highly time-resolved online mass spectrometry to examine biogenic and anthropogenic contributions to organic aerosol in Beijing
- 2021
-
Ingår i: Faraday Discussions. - 1359-6640. ; 226, s. 382-408
-
Tidskriftsartikel (refereegranskat)abstract
- Organic aerosols, a major constituent of fine particulate mass in megacities, can be directly emitted or formed from secondary processing of biogenic and anthropogenic volatile organic compound emissions. The complexity of volatile organic compound emission sources, speciation and oxidation pathways leads to uncertainties in the key sources and chemistry leading to formation of organic aerosol in urban areas. Historically, online measurements of organic aerosol composition have been unable to resolve specific markers of volatile organic compound oxidation, while offline analysis of markers focus on a small proportion of organic aerosol and lack the time resolution to carry out detailed statistical analysis required to study the dynamic changes in aerosol sources and chemistry. Here we use data collected as part of the joint UK-China Air Pollution and Human Health (APHH-Beijing) collaboration during a field campaign in urban Beijing in the summer of 2017 alongside laboratory measurements of secondary organic aerosol from oxidation of key aromatic precursors (1,3,5-trimethyl benzene, 1,2,4-trimethyl benzene, propyl benzene, isopropyl benzene and 1-methyl naphthalene) to study the anthropogenic and biogenic contributions to organic aerosol. For the first time in Beijing, this study applies positive matrix factorisation to online measurements of organic aerosol composition from a time-of-flight iodide chemical ionisation mass spectrometer fitted with a filter inlet for gases and aerosols (FIGAERO-ToF-I-CIMS). This approach identifies the real-time variations in sources and oxidation processes influencing aerosol composition at a near-molecular level. We identify eight factors with distinct temporal variability, highlighting episodic differences in OA composition attributed to regional influences and in situ formation. These have average carbon numbers ranging from C-5-C-9 and can be associated with oxidation of anthropogenic aromatic hydrocarbons alongside biogenic emissions of isoprene, alpha -pinene and sesquiterpenes.
|
|
| 35. |
|
|
| 36. |
- Priestley, Michael, et al.
(författare)
-
Chemical characterisation of benzene oxidation products under high- and low-NOx conditions using chemical ionisation mass spectrometry
- 2021
-
Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 21:5, s. 3473-3490
-
Tidskriftsartikel (refereegranskat)abstract
- Aromatic hydrocarbons are a class of volatile organic compounds associated with anthropogenic activity and make up a significant fraction of urban volatile organic compound (VOC) emissions that contribute to the formation of secondary organic aerosol (SOA). Benzene is one of the most abundant species emitted from vehicles, biomass burning and industry. An iodide time-of-flight chemical ionisation mass spectrometer (ToF-CIMS) and nitrate ToF-CIMS were deployed at the Julich Plant Atmosphere Chamber as part of a series of experiments examining benzene oxidation by OH under high- and low-NOx conditions, where a range of organic oxidation products were detected. The nitrate scheme detects many oxidation products with high masses, ranging from intermediate volatile organic compounds (IVOCs) to extremely low volatile organic compounds (ELVOCs), including C-12 dimers. In comparison, very few species with C->= 6 and O-> 8 were detected with the iodide scheme, which detected many more IVOCs and semi-volatile organic compounds (SVOCs) but very few ELVOCs and low volatile organic compounds (LVOCs). A total of 132 and 195 CHO
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
- Testor, Pierre, et al.
(författare)
-
OceanGliders: A component of the integrated GOOS
- 2019
-
Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6
-
Forskningsöversikt (refereegranskat)abstract
- The OceanGliders program started in 2016 to support active coordination and enhancement of global glider activity. OceanGliders contributes to the international efforts of the Global Ocean Observation System (GOOS) for Climate, Ocean Health and Operational Services. It brings together marine scientists and engineers operating gliders around the world: (1) to observe the long-term physical, biogeochemical, and biological ocean processes and phenomena that are relevant for societal applications; and, (2) to contribute to the GOOS through real-time and delayed mode data dissemination. The OceanGliders program is distributed across national and regional observing systems and significantly contributes to integrated, multi-scale and multi-platform sampling strategies. OceanGliders shares best practices, requirements, and scientific knowledge needed for glider operations, data collection and analysis. It also monitors global glider activity and supports the dissemination of glider data through regional and global databases, in real-time and delayed modes, facilitating data access to the wider community. OceanGliders currently supports national, regional and global initiatives to maintian and expand the capabilities and application of gliders to meet key global challenges such as improved measurement of ocean boundary currents, water transformation and storm forecast.
|
|
| 42. |
- Tomlins, Scott A., et al.
(författare)
-
The role of SPINK1 in ETS rearrangement-negative prostate cancers
- 2008
-
Ingår i: Cancer Cell. - Amsterdam : Elsevier. - 1535-6108 .- 1878-3686. ; 13:6, s. 519-28
-
Tidskriftsartikel (refereegranskat)abstract
- ETS gene fusions have been characterized in a majority of prostate cancers; however, the key molecular alterations in ETS-negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier expression exclusively in a subset of ETS rearrangement-negative cancers ( approximately 10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier expression can be detected noninvasively in urine, and observed that SPINK1 outlier expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier expression model and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement-negative prostate cancers.
|
|
| 43. |
|
|
| 44. |
- Walsh, Daniel J., et al.
(författare)
-
Anti-prion drugs do not improve survival in novel knock-in models of inherited prion disease
- 2024
-
Ingår i: PLoS Pathogens. - : PUBLIC LIBRARY SCIENCE. - 1553-7366 .- 1553-7374. ; 20:4
-
Tidskriftsartikel (refereegranskat)abstract
- Prion diseases uniquely manifest in three distinct forms: inherited, sporadic, and infectious. Wild-type prions are responsible for the sporadic and infectious versions, while mutant prions cause inherited variants like fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). Although some drugs can prolong prion incubation times up to four-fold in rodent models of infectious prion diseases, no effective treatments for FFI and fCJD have been found. In this study, we evaluated the efficacy of various anti-prion drugs on newly-developed knock-in mouse models for FFI and fCJD. These models express bank vole prion protein (PrP) with the pathogenic D178N and E200K mutations. We applied various drug regimens known to be highly effective against wild-type prions in vivo as well as a brain-penetrant compound that inhibits mutant PrPSc propagation in vitro. None of the regimens tested (Anle138b, IND24, Anle138b + IND24, cellulose ether, and PSCMA) significantly extended disease-free survival or prevented mutant PrPSc accumulation in either knock-in mouse model, despite their ability to induce strain adaptation of mutant prions. Our results show that anti-prion drugs originally developed to treat infectious prion diseases do not necessarily work for inherited prion diseases, and that the recombinant sPMCA is not a reliable platform for identifying compounds that target mutant prions. This work underscores the need to develop therapies and validate screening assays specifically for mutant prions, as well as anti-prion strategies that are not strain-dependent. We treated two mouse models of inherited prion disease with a variety of drug treatments, including several which have been previously shown to be highly effective against infectious prion diseases and another that biochemically inhibits the formation of mutant prion proteins in a test tube assay. Surprisingly none of the treatments improved lifespans in the either mouse model even though several treatments changed the distribution pattern of prion pathology in the brains of treated mice. Our results show that alternative strategies are needed to develop treatments for inherited prion diseases.
|
|
| 45. |
|
|
