| 11. |
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| 12. |
- Nyström, Anna-Maja, et al.
(författare)
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A severe form of Noonan syndrome and autosomal dominant café-au-lait spots : evidence for different genetic origins
- 2009
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 98:4, s. 693-698
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The clinical overlap among Noonan syndrome (NS), cardio-facio-cutaneous (CFC), LEOPARD and Costello syndromes as well as Neurofibromatosis type 1 is extensive, which complicates the process of diagnosis. Further genotype–phenotype correlations are required to facilitate future diagnosis of these patients. Therefore, investigations of the genetic cause of a severe phenotype in a patient with NS and the presence of multiple café-au-lait spots (CAL) spots in the patient and four members of the family were performed. Methods: Mutation analyses of candidate genes, PTPN11, NF1, SPRED1 and SPRED2, associated with these syndromes, were conducted using DNA sequencing. Results: A previously identified de novo mutation, PTPN11 F285L and an inherited NF1 R1809C substitution in the index patient were found. However, neither PTPN11 F285L, NF1 R1809C, SPRED1 nor SPRED2 segregated with CAL spots in the family. The results indicate that the familial CAL spots trait in this family is caused by a mutation in another gene, distinct from previous genes associated with CAL spots in these syndromes. Conclusion: We suggest that the atypical severe symptoms in the index patient may be caused by an additive effect on the F285L mutation in PTPN11 by another mutation, for example the NF1 R1809C or alternatively, the not yet identified gene mutation associated with CAL spots in this family.
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| 13. |
- Nyström, Anna-Maja, et al.
(författare)
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Investigation of gene dosage imbalances in patients with Noonan syndrome using multiplex ligation-dependent probe amplification analysis
- 2010
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Ingår i: European Journal of Medical Genetics. - : Elsevier BV. - 1769-7212 .- 1878-0849. ; 53:3, s. 117-121
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Tidskriftsartikel (refereegranskat)abstract
- The RAS-MAPK syndromes are a group of clinically and genetically related disorders caused by dysregulation of the RAS-MAPK pathway. A member of this group of disorders, Noonan syndrome (NS), is associated with several different genes within the RAS-MAPK pathway. To date, mutations in PTPN11, SOS1, KRAS, RAF1 and SHOC2 are known to cause NS and a small group of patients harbour mutations in BRAF, MEK1 or NRAS. The majority of the mutations are predicted to cause an up-regulation of the pathway; hence they are gain-of-function mutations. Despite recent advances in gene identification in NS, the genetic aetiology is still unknown in about of patients.To investigate the contribution of gene dosage imbalances of RAS-MAPK-related genes to the pathogenesis of NS, a multiplex ligation-dependent probe amplification (MLPA) assaywas developed. Two probe sets were designed for seven RAS-MAPK-syndrome-related candidate genes: PTPN11, SOS1, RAF1, KRAS, BRAF, MEK1 and MEK2. The probe sets were validated in 15 healthy control individuals and in glioma tumour cell lines. Subsequently, 44 NS patients negative for mutations in known NS-associated genes were screened using the two probe sets. The MLPA results for the patients revealed no gene dosage imbalances. In conclusion, the present results exclude copy number variation of PTPN11, SOS1, RAF1, KRAS, BRAF, MEK1 and MEK2 as a common pathogenic mechanism of NS. The validated and optimised RAS-MAPK probe sets presented here enable rapid high throughput screening of further patients with RAS-MAPK syndromes.
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| 14. |
- Phan Xuan, Tuan, 1984, et al.
(författare)
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Aggregation behavior of aqueous cellulose nanocrystals: the effect of inorganic salts
- 2016
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Ingår i: Cellulose. - : Springer Science and Business Media LLC. - 0969-0239 .- 1572-882X. ; 23:6, s. 3653-3663
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Tidskriftsartikel (refereegranskat)abstract
- Natural anisotropic building-blocks such as cellulose nanocrystals (CNCs) have attracted considerable attention due to their biodegradability and nanometer-size. In this work the colloidal behavior of CNCs, obtained from sulfuric acid hydrolysis of microcrystalline cellulose, has been studied in presence of salts of different valences. The influence on the colloidal stability and nature of aggregates has been investigated for monovalent salts (LiCl, NaCl, KCl, CsCl), divalent salts (CaCl2 and MgCl2), and a trivalent salt (AlCl3), both experimentally by means of turbidity and small angle X-ray scattering (SAXS) measurements, as well as by Monte Carlo simulations using a simple coarse-grained model. For the entire salt series, a critical aggregation concentration (CAC) could be determined by turbidity measurements, as a result of the reduction of effective Coulomb repulsions due to the presence of sulfate groups on the CNC surface. The CACs also followed the Schulze-Hardy law, i.e. the critical aggregation concentration decreased with increasing counterion valence. For the monovalent ions, the CACs followed the trend Li+ > Na+ > K+ > Cs+, which could be rationalized in terms of matching affinities between the cation and the sulfate groups present at the surface of CNCs. From the SAXS measurements it was shown that the density of the aggregates increased with increasing salt concentration and ion valence. In addition, these findings were rationalized by means of simulation, which showed a good correlation with experimental data. The combination of the experimental techniques and the simulations offered insight into interaction-aggregation relationship of CNC suspensions, which is of importance for their structural design applications.
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| 15. |
- Schoumans, Jacqueline, et al.
(författare)
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Comprehensive mutational analysis of a cohort of Swedish Cornelia de Lange syndrome patients
- 2007
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 15:2, s. 143-149
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Tidskriftsartikel (refereegranskat)abstract
- Cornelia de Lange syndrome (CdLS; OMIM 122470) is a rare multiple congenital anomaly/mental retardation syndrome characterized by distinctive dysmorphic facial features, severe growth and developmental delay and abnormalities of the upper limbs. About 50% of CdLS patients have been found to have heterozygous mutations in the NIPBL gene and a few cases were recently found to be caused by mutations in the X-linked SMC1L1 gene. We performed a mutation screening of all NIPBL coding exons by direct sequencing in 11 patients (nine sporadic and two familial cases) diagnosed with CdLS in Sweden and detected mutations in seven of the cases. All were de novo, and six of the mutations have not been previously described. Four patients without identifiable NIPBL mutations were subsequently subjected to multiplex ligation-dependent probe amplification analysis to exclude whole exon deletions/duplications of NIPBL. In addition, mutation analysis of the 5' untranslated region (5' UTR) of NIPBL was performed. Tiling resolution array comparative genomic hybridization analysis was carried out on these four patients to detect cryptic chromosome imbalances and in addition the boys were screened for SMC1L1 mutations. We found a de novo 9p duplication with a size of 0.6 Mb in one of the patients with a CdLS-like phenotype but no mutations were detected in SMC1L1. So far, two genes (NIPBL and SMC1L1) have been identified causing CdLS or CdLS-like phenotypes. However, in a considerable proportion of individuals demonstrating the CdLS phenotype, mutations in any of these two genes are not found and other potential loci harboring additional CdLS-causing genes should be considered.
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| 16. |
- Thuresson, Ann-Charlotte, et al.
(författare)
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Whole-genome array-CGH for detection of submicroscopic chromosomal imbalances in children with mental retardation
- 2007
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Ingår i: Cytogenetic and Genome Research. - : S. Karger AG. - 1424-8581 .- 1424-859X. ; 118:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Chromosomal imbalances are the major cause of mental retardation (MR). Many of these imbalances are caused by submicroscopic deletions or duplications not detected by conventional cytogenetic methods. Microarray-based comparative genomic hybridization (array-CGH) is considered to be superior for the investigation of chromosomal aberrations in children with MR, and has been demonstrated to improve the diagnostic detection rate of these small chromosomal abnormalities. In this study we used 1 Mb genome-wide array-CGH to screen 48 children with MR and congenital malformations for submicroscopic chromosomal imbalances, where the underlying cause was unknown. All children were clinically investigated and subtelomere FISH analysis had been performed in all cases. Suspected microdeletion syndromes such as deletion 22q11.2, Williams-Beuren and Angelman syndromes were excluded before array-CGH analysis was performed. We identified de novo interstitial chromosomal imbalances in two patients (4%), and an interstitial deletion inherited from an affected mother in one patient (2%). In another two of the children (4%), suspected imbalances were detected but were also found in one of the non-affected parents. The yield of identified de novo alterations detected in this study is somewhat less than previously described, and might reflect the importance of which selection criterion of patients to be used before array-CGH analysis is performed. However, array-CGH proved to be a high-quality and reliable tool for genome-wide screening of MR patients of unknown etiology.
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| 17. |
- Thuresson, Axel, et al.
(författare)
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Flocculated Laponite-PEG/PEO dispersions with monovalent salt, a SAXS and simulation study.
- 2016
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 1095-7103 .- 0021-9797. ; 466, s. 330-342
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Tidskriftsartikel (refereegranskat)abstract
- It is well-known that clay can form lamellar structures i.e. tactoids, and recently it has been shown that the tactoid formation is dependent on the platelet diameter. To the authors knowledge, no tactoid formation has been observed for montmorillonite platelets with a diameter less than 60nm. In this study, small angle X-ray scattering in combination with coarse-grained modeling and molecular dynamics simulations have been utilized to study the sediment of Laponite-polyethylene glycol/polyethylene oxide (PEG/PEO) at elevated salt concentrations (150mM-1M). Laponite consists of platelets with a diameter of 25nm and it is known to have a relatively monodisperse size-distribution. At pH 10, the face of the platelets has a strong negative charge, whereas the rim is slightly positive. Here we show that it is possible to induce tactoids for Laponite if two constraints are fulfilled: (1) addition of high amount of salt such as NaCl, and (2) addition of a neutral polymer such as PEG. The role of the salt is to screen the repulsive interactions between the platelets and the role of the polymer is to bridge the platelets together: hence the loss in configurational entropy of the polymer is counteracted by the gain in attractive polymer-platelet interaction. As the concentration of NaCl and/or PEG increases, the Bragg peak becomes sharper, which is an indication of that larger tactoids are formed. Comparison between Laponite and montmorillonite shows that the interlayer distance between the platelets increases linearly with an increased Debye screening length for both type of clays, whereas the structure peaks of Laponite are broader compared to the montmorillonite. We argue that the main reason to the latter is due to the size of the platelets: (i) smaller platelets are less rotationally restricted and (ii) the effect of positive edge charges is larger when the platelets are smaller, which results in more irregular aggregates. In absence of the polymer, montmorillonite form tactoids above ∼0.3MNaCl whereas Laponite does not. Even though the model used is simple, we find qualitative agreement between experiments and simulations, which verifies that the underlying physics for tactoid formation is captured.
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| 18. |
- Thuresson, Axel, et al.
(författare)
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Flocculated Laponite-PEG/PEO Dispersions with Multivalent Salt : A SAXS, Cryo-TEM, and Computer Simulation Study
- 2017
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 121:13, s. 7387-7396
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study is to scrutinize the mechanism behind aggregation, i.e., tactoid formation of nanostructures with the shape of a platelet. For that purpose, the clay minerals Laponite and montmorillonite have been used as model systems. More specifically, we are interested in the role of: the platelet size, the electrostatic interactions, and adsorbing polymers. Our hypothesis is that the presence of PEG is crucial for tactoid formation if the system is constituted by small nanometric platelets. For this purpose, SAXS, USAXS, Cryo-TEM, and coarse-grained molecular dynamics simulations have been used to study how the formation and the morphology of the tactoids are affected by the platelet size. The simulations indicate that ion-ion correlations are not enough to induce large tactoids solely if the platelets are small and the absolute charge is too low, i.e., in the size and charge range of Laponite. When a polymer is introduced into the system, the tactoid size grows, and the results can be explained by weak attractive electrostatic correlation forces and polymer bridging. It is shown that when the salt concentration increases the long-ranged electrostatic repulsion is screened, and a free energy minimum appears at short distances due to the ion-ion correlation effects. When a strongly adsorbing polymer is introduced into the system, a second free energy minimum appears at a slightly larger separation. The latter dominates if the polymer is relatively long and/or the polymer concentration is high enough. (Graph Presented).
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| 19. |
- Thuresson, Axel, et al.
(författare)
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Temperature Response of Charged Colloidal Particles by Mixing Counterions Utilizing Ca2+/Na+ Montmorillonite as Model System
- 2017
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Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 121:14, s. 7951-7958
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Tidskriftsartikel (refereegranskat)abstract
- The osmotic pressure and the aggregation of charged colloids as a function of temperature have been investigated using Monte Carlo and molecular dynamics simulations for different ratios of monovalent and divalent counterions. In the simulations the water is treated as a temperature-dependent dielectric continuum, and only the electrostatic interactions are considered. It was found that the temperature response can be controlled, i.e., the osmotic pressure can increase, decrease, or be kept constant, as a function of temperature depending on the monovalent/divalent counterion ratio. The increase in osmotic pressure with temperature, which occurs at low enough surface charge density and/or low fraction of divalent ions, can be understood from the DLVO theory. The origin of the opposite behavior can be explained by the enhanced attractive electrostatic ion-ion correlation interactions with temperature. The constraint is that the absolute value of the surface charge density of the colloids must be above a certain threshold, i.e., high enough such that the attractive ion-ion correlations can dominate the interaction regarding the divalent ions. The current conclusions are supported by the microstructural characterization of Ca2+/Na+-montmorillonite clay using small-angle X-ray scattering. A qualitative agreement is observed between the simulations and the experimental data.
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| 20. |
- Thuresson, Hanna, 1972-
(författare)
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Att läsa bilder med kroppen : En studie om yngre förskolebarns kommunicerande
- 2013
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this study is to examine young pre-school children´s literacy with a focus on their communication about pictures. Based on the ethnographic method and video-recorded observations, this study demonstrates how young children communicate about pictures in various media.The results show that the body language used by young children in combination with various media pictures has a complex structure involving facial expressions, physical gestures and postures, which all contribute to making meaning. The study also focuses on pictures common in the pre-school environment. The results in this area show that the majority of such pictures feature animals, a circumstance that restricts the children’s meaning-making potential. Furthermore, the study pays attention to the variations in the balance of power among the children when they communicate about pictures in a book placed on the floor.The study concludes with a pedagogical discussion of teachers’ use of various media and language stimulation methods to promote literacy in the light of the finding that children use a more bodily-based method of communication.
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