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| 3. |
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| 4. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 5. |
- Rheinbay, E, et al.
(författare)
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Analyses of non-coding somatic drivers in 2,658 cancer whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 102-
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of drivers of cancer has traditionally focused on protein-coding genes1–4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5′ region of TP53, in the 3′ untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available.
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| 6. |
- Carlevaro-Fita, J, et al.
(författare)
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Cancer LncRNA Census reveals evidence for deep functional conservation of long noncoding RNAs in tumorigenesis
- 2020
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1, s. 56-
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Tidskriftsartikel (refereegranskat)abstract
- Long non-coding RNAs (lncRNAs) are a growing focus of cancer genomics studies, creating the need for a resource of lncRNAs with validated cancer roles. Furthermore, it remains debated whether mutated lncRNAs can drive tumorigenesis, and whether such functions could be conserved during evolution. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we introduce the Cancer LncRNA Census (CLC), a compilation of 122 GENCODE lncRNAs with causal roles in cancer phenotypes. In contrast to existing databases, CLC requires strong functional or genetic evidence. CLC genes are enriched amongst driver genes predicted from somatic mutations, and display characteristic genomic features. Strikingly, CLC genes are enriched for driver mutations from unbiased, genome-wide transposon-mutagenesis screens in mice. We identified 10 tumour-causing mutations in orthologues of 8 lncRNAs, including LINC-PINT and NEAT1, but not MALAT1. Thus CLC represents a dataset of high-confidence cancer lncRNAs. Mutagenesis maps are a novel means for identifying deeply-conserved roles of lncRNAs in tumorigenesis.
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| 7. |
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| 8. |
- Othman, Nor Zalina, et al.
(författare)
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Aeration rate effect on the growth kinetics, phytase production and plasmid stability of recombinant Escherichia coli BL21 (DE3)
- 2014
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Ingår i: Journal of Pure and Applied Microbiology. - 0973-7510. ; 8:4, s. 2721-2728
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Tidskriftsartikel (refereegranskat)abstract
- Phytase production using Escherichia coli BL21 (DE3), a recombinant strain harboring a plasmid encoding thermostable Bacillus phytase, in semi-industrial scale was studied in this work. Among the factors needed to be considered in order to achieve high enzyme yield, aeration rate plays an important role. Suitable aeration is required to supply cells with sufficient amount of air for cell and phytase production. The effect of different aeration rates, (1.0, 2.0 and 3.0 vv-1min-1), on the kinetics of cell growth and phytase production by the recombinant E. coli BL21 (DE3) in 16-L pilot scale stirred tank bioreactor was investigated. The highest cell concentration of 3.81 gL-1 concomitant with the maximal total phytase production of 15.63 UmL-1 were obtained in a bioreactor of aeration rate 3.0vv-1min-1. At this high aeration rate, a maximal specific growth rate (μmax) and the maximal specific phytase production of 0.33 h-1 and 4102Ug-1, respectively, were achieved.
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| 12. |
- El Massry, Abdel Moneim, et al.
(författare)
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Synthesis and structure elucidation of novel fused 1,2,4-triazine derivatives as potent inhibitors targeting CYP1A1 activity
- 2012
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Ingår i: Bioorganic and Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 20:8, s. 2624-2637
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Tidskriftsartikel (refereegranskat)abstract
- Synthesis and structure elucidation of new series of novel fused 1,2,4-triazine derivatives 3a-3f, 4a-4i and 6a-6b and their inhibitory activities are presented. Molecular structures of the synthesized compounds were confirmed by H-1 NMR, C-13 NMR, MS spectra and elemental analyses. X-ray crystallographic analysis was performed on 2-acetyl-8-(N,N-diacetylamino)-6-(4-methoxybenzyl)-3-(4-methoxy-phenyl)- 7-oxo-2,3-dihydro-7H-[1,2,4]triazolo[4,3-b][1,2,4]triazine 3d and 2-acetyl-8-(N-acetyl- amino)-6-benzyl-3-(4-chlorophenyl)-3-methyl-7-oxo-2,3-dihydro-7H-[1,2,4] triazolo[4,3-b][1,2,4]triazine 4e to secure their structures. The inhibitory effect of these compounds toward the CPY1A1 activity was screened to determine their potential as promising anticancer drugs. Our data showed that compounds 4e, 5a, 5b and 6b possess the highest inhibitory effects among all tested compounds. Furthermore, analysis of triazolotriazine derivatives docking showed that these compounds bind only at the interface of substrate recognition site 2 (SRS2) and (SRS6) at the outer surface of the protein. Amino-acids ASN214, SER216 and ILE462 participate in the binding of these compounds through H-bonds.
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| 13. |
- Erfan, Ahmed M., et al.
(författare)
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Chicken anaemia virus enhances and prolongs subsequent avian influenza (H9N2) and infectious bronchitis viral infections
- 2019
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Ingår i: Veterinary Microbiology. - : ELSEVIER SCIENCE BV. - 0378-1135 .- 1873-2542. ; 230, s. 123-129
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Tidskriftsartikel (refereegranskat)abstract
- Immunosuppressive viral diseases have a great economic importance in the poultry industry due to the increased susceptibility to secondary infections. Chicken anaemia virus (CAV) is one of the major immunosuppressive diseases in chickens. In addition, low pathogenic avian influenza (LPAI) of subtype H9N2 and infectious bronchitis (IB) viruses are among the most frequently reported respiratory viral diseases in poultry worldwide. In the present study, specific pathogen free chickens were used to understand the impact of CAV on secondary infection with LPAI-H9N2 or 1B viruses. Clinical outcomes, viral shedding dynamics, and cytokine levels wereassessed. The results exhibit that chickens previously infected with CAV produceconsiderablyhigher titresof LPAI-H9N2 or IB viruses in the oropharyngeal swabs (P < 0.05), tracheas and kidneys. In addition, the immunologic effect of CAV provokedthe development of clinical signs of LPAI-H9N2 and IB virus infections. Moreover, results suggested that pre-infection with CAV directly correlated with elevated levels of IL-6 and IFN gamma. These findings underline the importance of CAV pre-infection on LPAI-H9N2 or IB infection in chickens, and indicate that co-circulation of CAV can contribute to the spread and evolution of LPAI H9N2 and IB viruses.
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| 14. |
- Lauwers, E., et al.
(författare)
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Potential human transmission of amyloid beta pathology: surveillance and risks
- 2020
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Ingår i: Lancet Neurology. - 1474-4422 .- 1474-4465. ; 19:10, s. 872-878
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Tidskriftsartikel (refereegranskat)abstract
- Studies in experimental animals show transmissibility of amyloidogenic proteins associated with prion diseases, Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases. Although these data raise potential concerns for public health, convincing evidence for human iatrogenic transmission only exists for prions and amyloid beta after systemic injections of contaminated growth hormone extracts or dura mater grafts derived from cadavers. Even though these procedures are now obsolete, some reports raise the possibility of iatrogenic transmission of amyloid beta through putatively contaminated neurosurgical equipment. Iatrogenic transmission of amyloid beta might lead to amyloid deposition in the brain parenchyma and blood vessel walls, potentially resulting in cerebral amyloid angiopathy after several decades. Cerebral amyloid angiopathy can cause life-threatening brain haemorrhages; yet, there is no proof that the transmission of amyloid can also lead to Alzheimer's dementia. Large, long-term epidemiological studies and sensitive, cost-efficient tools to detect amyloid are needed to better understand any potential routes of amyloid beta transmission and to clarify whether other similar proteopathic seeds, such as tau or alpha-synuclein, can also be transferred iatrogenically.
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| 15. |
- Roskam, Isabelle, et al.
(författare)
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Parental Burnout Around the Globe : a 42-Country Study
- 2021
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Ingår i: Affective science. - : Springer Science and Business Media LLC. - 2662-205X .- 2662-2041. ; 2, s. 58-79
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Tidskriftsartikel (refereegranskat)abstract
- High levels of stress in the parenting domain can lead to parental burnout, a condition that has severe consequences for both parents and children. It is not yet clear, however, whether parental burnout varies by culture, and if so, why it might do so. In this study, we examined the prevalence of parental burnout in 42 countries (17,409 parents; 71% mothers; Mage = 39.20) and showed that the prevalence of parental burnout varies dramatically across countries. Analyses of cultural values revealed that individualistic cultures, in particular, displayed a noticeably higher prevalence and mean level of parental burnout. Indeed, individualism plays a larger role in parental burnout than either economic inequalities across countries, or any other individual and family characteristic examined so far, including the number and age of children and the number of hours spent with them. These results suggest that cultural values in Western countries may put parents under heightened levels of stress.Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-020-00028-4.
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| 16. |
- Roskam, Isabelle, et al.
(författare)
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Three reasons why parental burnout is more prevalent in individualistic countries : a mediation study in 36 countries
- 2024
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Ingår i: Social Psychiatry and Psychiatric Epidemiology. - : Springer Nature. - 0933-7954 .- 1433-9285. ; 59, s. 681-694
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe prevalence of parental burnout, a condition that has severe consequences for both parents and children, varies dramatically across countries and is highest in Western countries characterized by high individualism.MethodIn this study, we examined the mediators of the relationship between individualism measured at the country level and parental burnout measured at the individual level in 36 countries (16,059 parents).ResultsThe results revealed three mediating mechanisms, that is, self-discrepancies between socially prescribed and actual parental selves, high agency and self-directed socialization goals, and low parental task sharing, by which individualism leads to an increased risk of burnout among parents.ConclusionThe results confrm that the three mediators under consideration are all involved, and that mediation was higher for self-discrepancies between socially prescribed and actual parental selves, then parental task sharing, and lastly selfdi-rected socialization goals. The results provide some important indications of how to prevent parental burnout at the societal level in Western countries.
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| 17. |
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| 18. |
- Stovell, MG, et al.
(författare)
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The effect of succinate on brain NADH/NAD+ redox state and high energy phosphate metabolism in acute traumatic brain injury
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 11140-
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Tidskriftsartikel (refereegranskat)abstract
- A key pathophysiological process and therapeutic target in the critical early post-injury period of traumatic brain injury (TBI) is cell mitochondrial dysfunction; characterised by elevation of brain lactate/pyruvate (L/P) ratio in the absence of hypoxia. We previously showed that succinate can improve brain extracellular chemistry in acute TBI, but it was not clear if this translates to a change in downstream energy metabolism. We studied the effect of microdialysis-delivered succinate on brain energy state (phosphocreatine/ATP ratio (PCr/ATP)) with 31P MRS at 3T, and tissue NADH/NAD+ redox state using microdialysis (L/P ratio) in eight patients with acute major TBI (mean 7 days). Succinate perfusion was associated with increased extracellular pyruvate (+26%, p < 0.0001) and decreased L/P ratio (−13%, p < 0.0001) in patients overall (baseline-vs-supplementation over time), but no clear-cut change in 31P MRS PCr/ATP existed in our cohort (p > 0.4, supplemented-voxel-vs-contralateral voxel). However, the percentage decrease in L/P ratio for each patient following succinate perfusion correlated significantly with their percentage increase in PCr/ATP ratio (Spearman's rank correlation, r = −0.86, p = 0.024). Our findings support the interpretation that L/P ratio is linked to brain energy state, and that succinate may support brain energy metabolism in select TBI patients suffering from mitochondrial dysfunction.
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| 23. |
- El-Seedi, Hesham R., et al.
(författare)
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Anti-schistosomiasis triterpene glycoside from the Egyptian medicinal plant Asparagus stipularis
- 2011
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Ingår i: REV BRAS FARMACOGN. - : SOC BRASILEIRA FARMACOGNOSIA. - 0102-695X. ; 22:2, s. 314-318
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Tidskriftsartikel (refereegranskat)abstract
- Bioassay-guided isolation using an in vitro assay testing for anti-schistosomiasis yielded a novel triterpene saponin, asparagalin A, from the n-butanol extract of the roots of Asparagus stipularis Forssk., Asparagaceae. The structure was elucidated by spectroscopic analysis and chemical transformations. Administration of asparagalin A resulted in a retardation of worm growth and locomotion at the first day and showed a significant activity of egg-laying suppression at 200 mu g/mL concentration.
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| 24. |
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| 26. |
- Hashim, Fatma A., et al.
(författare)
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An efficient adaptive-mutated Coati optimization algorithm for feature selection and global optimization
- 2023
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Ingår i: Alexandria Engineering Journal. - : ELSEVIER. - 1110-0168 .- 2090-2670. ; 85, s. 29-48
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Tidskriftsartikel (refereegranskat)abstract
- The feature selection (FS) problem has occupied a great interest of scientists lately since the highly dimensional datasets might have many redundant and irrelevant features. FS aims to eliminate such features and select the most important ones that affect classification performance. Metaheuristic algorithms are the best choice to solve this combinatorial problem. Recent researchers invented and adapted new algorithms, hybridized many algorithms, or enhanced existing ones by adding some operators to solve the FS problem. In our paper, we added some operators to the Coati optimization algorithm (CoatiOA). The first operator is the adaptive s-best mutation operator to enhance the balance between exploration and exploitation. The second operator is the directional mutation rule that opens the way to discover the search space thoroughly. The final enhancement is controlling the search direction toward the global best. We tested the proposed mCoatiOA algorithm in solving) in solving challenging problems from the CEC'20 test suite. mCoatiOA performance was compared with Dandelion Optimizer (DO), African vultures optimization algorithm (AVOA), Artificial gorilla troops optimizer (GTO), whale optimization algorithm (WOA), Fick's Law Algorithm (FLA), Particle swarm optimization (PSO), Harris hawks optimization (HHO), and Tunicate swarm algorithm (TSA). According to the average fitness, it can be observed that the proposed method, mCoatiOA, performs better than the other optimization algorithms on 8 test functions. It has lower average standard deviation values compared to the competitive algorithms. Wilcoxon test showed that the results obtained by mCoatiOA are significantly different from those of the other rival algorithms. mCoatiOA has been tested as a feature selection algorithm. Fifteen benchmark datasets of various types were collected from the UCI machine-learning repository. Different evaluation criteria are used to determine the effectiveness of the proposed method. The proposed mCoatiOA achieved better results in comparison with other published methods. It achieved the mean best results on 75% of the datasets.
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| 27. |
- Hutchinson, Peter J, et al.
(författare)
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Consensus statement from the 2014 International Microdialysis Forum
- 2015
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 41:9, s. 1517-1528
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Tidskriftsartikel (refereegranskat)abstract
- Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published. Since then, there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.
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| 28. |
- Lindblad, Bo S, et al.
(författare)
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Age and sex are important factors in determining normal retinol levels
- 1998
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Ingår i: Journal of Tropical Pediatrics. - : Oxford University Press (OUP). - 1465-3664 .- 0142-6338. ; 44:2, s. 96-99
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Tidskriftsartikel (refereegranskat)abstract
- Cut-off levels for serum retinol levels of 20 micrograms/dl for marginal and 10 micrograms/dl for definite deficiency have been advocated and extensively used in population studies. However, the blood serum levels of retinol of the newborn are known to be very low and although the age dependency of the retinol binding protein has been described, the normal levels of serum retinol at different ages have not been reported from larger series. While studying poor populations of young infants in Lahore, Pakistan, we thought it necessary to try to achieve appropriate reference values by analysing the levels of serum retinol of expatriates from the Indian subcontinent who live in the affluent United Arab Emirates, where retinol deficiency is not seen either at the hospital or the community levels. We have studied material, cord blood, infantile and adult levels of retinol and found a highly significant age relationship of serum retinol levels. During very early infancy the 'normal' mean is below what has been considered deficiency. This is new information and important in the evaluation of retinol status of individuals as well as populations. In addition, we found lower levels in women, pregnant or non-pregnant, than those in adult men. This sex difference in adults was not seen in infants. We recommend a cut off level for deficiency of 10 micrograms/dl, but only for those above 1 month of postnatal age.
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| 29. |
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| 30. |
- Sayed, Mohammed A., et al.
(författare)
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Analyses of mads‐box genes suggest hvmads56 to regulate lateral spikelet development in barley
- 2021
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Ingår i: Plants. - : MDPI AG. - 2223-7747. ; 10:12
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Tidskriftsartikel (refereegranskat)abstract
- MADS‐box transcription factors are crucial regulators of inflorescence and flower development in plants. Therefore, the recent interest in this family has received much attention in plant breeding programs due to their impact on plant development and inflorescence architecture. The aim of this study was to investigate the role of HvMADS‐box genes in lateral spikelet development in barley (Hordeum vulgare L.). A set of 30 spike‐contrasting barley lines were phenotypically and genotypically investigated under controlled conditions. We detected clear variations in the spike and spikelet development during the developmental stages among the tested lines. The lateral flo-rets in the deficiens and semi‐deficiens lines were more reduced than in two‐rowed cultivars except cv. Kristina. Interestingly, cv. Kristina, int‐h.43 and int‐i.39 exhibited the same behavior as def.5, def.6, semi‐def.1, semi‐def.8 regarding development and showed reduced lateral florets size. In HOR1555, HOR7191 and HOR7041, the lateral florets continued their development, eventually setting seeds. In contrast, lateral florets in two‐rowed barley stopped differentiating after the awn primordia stage giving rise to lateral floret sterility. At harvest, the lines tested showed large variation for all central and lateral spikelet‐related traits. Phylogenetic analysis showed that more than half of the 108 MADS‐box genes identified are highly conserved and are expressed in different barley tissues. Re-sequence analysis of a subset of these genes showed clear polymorphism in either SNPs or in/del. Variation in HvMADS56 correlated with altered lateral spikelet morphology. This suggests that HvMADS56 plays an important role in lateral spikelet development in barley.
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| 31. |
- Sayed, Mohammed A., et al.
(författare)
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Genome-Wide Association Study of Salt Tolerance-Related Traits during Germination and Seedling Development in an Intermedium-Spike Barley Collection
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 23:19
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Tidskriftsartikel (refereegranskat)abstract
- Increased salinity is one of the major consequences of climatic change affecting global crop production. The early stages in the barley (Hordeum vulgare L.) life cycle are considered the most critical phases due to their contributions to final crop yield. Particularly, the germination and seedling development are sensitive to numerous environmental stresses, especially soil salinity. In this study, we aimed to identify SNP markers linked with germination and seedling development at 150 mM NaCl as a salinity treatment. We performed a genome-wide association study (GWAS) using a panel of 208 intermedium-spike barley (H. vulgare convar. intermedium (Körn.) Mansf.) accessions and their genotype data (i.e., 10,323 SNPs) using the genome reference sequence of “Morex”. The phenotypic results showed that the 150 mM NaCl salinity treatment significantly reduced all recorded germination and seedling-related traits compared to the control treatment. Furthermore, six accessions (HOR 11747, HOR 11718, HOR 11640, HOR 11256, HOR 11275 and HOR 11291) were identified as the most salinity tolerant from the intermedium-spike barley collection. GWAS analysis indicated that a total of 38 highly significantly associated SNP markers under control and/or salinity traits were identified. Of these, two SNP markers on chromosome (chr) 1H, two on chr 3H, and one on chr 4H were significantly linked to seedling fresh and dry weight under salinity stress treatment. In addition, two SNP markers on chr 7H were also significantly associated with seedling fresh and dry weight but under control condition. Under salinity stress, one SNP marker on chr 1H, 5H and 7H were detected for more than one phenotypic trait. We found that in most of the accessions exhibiting the highest salinity tolerance, most of the salinity-related QTLs were presented. These results form the basis for detailed studies, leading to improved salt tolerance breeding programs in barley.
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| 32. |
- Stovell, MG, et al.
(författare)
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An overview of clinical cerebral microdialysis in acute brain injury
- 2023
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Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 14, s. 1085540-
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral microdialysis may be used in patients with severe brain injury to monitor their cerebral physiology. In this article we provide a concise synopsis with illustrations and original images of catheter types, their structure, and how they function. Where and how catheters are inserted, their identification on imaging modalities (CT and MRI), together with the roles of glucose, lactate/pyruvate ratio, glutamate, glycerol and urea are summarized in acute brain injury. The research applications of microdialysis including pharmacokinetic studies, retromicrodialysis, and its use as a biomarker for efficacy of potential therapies are outlined. Finally, we explore limitations and pitfalls of the technique, as well as potential improvements and future work that is needed to progress and expand the use of this technology.
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