1,033 research outputs found
Oostra, Saastamoinen, Zwaan and Wheat 2018. "Strong phenotypic plasticity limits potential for evolutionary responses to climate change". Transcriptome assembly and gene expression data.
No full textSequence data, gene expression data, and R script for Oostra et al. 2018. Results and methods are described in Oostra et al. 2018 Nature Communications (https://www.nature.com/articles/s41467-018-03384-9). Raw sequencing reads are deposited at NCBI / SRA (BioProject PRJNA376691).This fileset containsa) The transcriptome assembly (fasta format)b) raw counts for expression analyses (two separate .cvs files for abdomen and thorax)c) R script for gene expression analyses (text file)For any questions or additional data requests please contact Vicencio Oostra at [email protected]<br
Fragile X syndrome: From protein function to therapy
No full textFragile X syndrome (FXS) is the leading monogenic cause of intellectual disability and autism. The FMR1 gene contains a CGG repeat present in the 5'-untranslated region which can be unstable upon transmission to the next generation. The repeat is up to 55 CGGs long in the normal population. In patients with fragile X syndrome (FXS), a repeat length exceeding 200 CGGs generally leads to methylation of the repeat and the promoter region, which is accompanied by silencing of the FMR1 gene. The disease is a result of lack of expression of the fragile X mental retardation protein leading to severe symptoms, including intellectual disability, hyperactivity, and autistic-like behavior. The FMR1 protein (FMRP) has a number of functions. The translational dysregulation of a subset of mRNAs targeted by FMRP is probably the major contribution to FXS. FMRP is also involved in mRNA transport to synapses where protein synthesis occurs. For some FMRP-bound mRNAs, FMRP is a direct modulator of mRNA stability either by sustaining or preventing mRNA decay. Increased knowledge about the role of FMRP has led to the identification of potential treatments for fragile X syndrome that were often tested first in the different animal models. This review gives an overview about the present knowledge of the function of FMRP and the therapeutic strategies in mouse and man.status: Publishe
RELATIONSHIP BETWEEN FMRP EXPRESSION IN CELL FROM HAIR ROOTS AND BLOOD SMEARS WITH COGNITIVE FUNCTIONING IN FRAGILE X FULL MUTATION FEMALE
No full textIntroduction: Fragile X syndrome is the most common form of inherited mental
retardation in humans, caused by an expansion of the (CGG) repeat in the FMR1 gene
located on X chromosome. Males carrying a full mutation are always mentally
retarded, whereas females carrying a full mutation show mild to moderate mental
impairment in only approximately 60% of cases, due to the X-inactivation process.
The absence of the FMR1 gene product, FMRP, in the brain is hypothesized as
causative for the observed mental retardation in fragile X patients. Antibody tests
have been developed to identify fragile X patients, based on the presence or absence
of FMRP in both lymphocytes and hair roots. It has been proposed that FMRP
expression in hair roots from females carrying a full mutation may be used as a
prognostic value for the mental capacities. Hair roots originate from the ectoderm,
like brain tissue, and may therefore show a better correlation between FMRP
expression and cognitive functioning than FMRP expression in lymphocytes, which
originate from the mesoderm.
Objectives: This study focussed on the relationship of the antibody test for cognitive
functioning in females carrying a full mutation using either hair roots or bloodsmears.
Method: Thirty samples from females carrying either a normal, premutation or full
mutation were included in this study. All subjects were selected from an Indonesian
fragile X family. The analyses were performed in a blind fashion. All subjects were
tested for FMRP expression in lymphocytes and hair roots using the antibody test.
Classification of the genotypes of the subjects was obtained by Southern blot
analysis. IQ equivalent were determined using Standard Progressive Matrices (SPM)
from Raven, a non-verbal IQ-test. Statistical analysis to show the correlation of
FMRP expression and IQ equivalent was developed using Pearson correlation.
Result: We report a significant relationship between FMRP expression in hair roots
and cognitive functioning in female carriers of the fragile X full mutation (r=0.64,
p=0.015) whereas in lymphocytes no significant relationship could be established
(r=0.31, p= 0.281). We also reported that FMRP expression in blood smear was
relatively higher than hair roots. We also demonstrated in our study group that IQ
equivalents were about 14 % in normal range, 7 % in the borderline range and 79 %
in mild mental impairment range.
Conclusion: Although the size of our study group was limited the results suggest that
FMRP expression in cell of hair roots has stronger correlation for cognitive
functioning in females carrying a full mutation than FMRP expression in
bloodsmears.
Keywords: fragile X syndrome, females full mutation, FMRP, cognitive functionin
Optical determination of thermophoretic velocity
No full textThis graduation work describes the design and implementation of an apparatus for direct measurement of thermophoretic velocity. For particles larger than the mean free path of the suspension gas, there are two theories concerning this velocity, presented by Brock (1962) and Derjaguin and Yalamov (1965). To be able to develop promising future applications, especially in the field of micro-chip manufacture, there is a need for experimental data that can determine which theory is the correct one. The experimental setup used in this work is based on the detection of scattered light from moving particles. Particles are injected in a Millikan cell, where a controlled temperature gradient is present. The scattered light from a laser is magnified and detected by a CCD-camera. Images of moving particles are recorded on videotape. The velocity of an individual particle is determined by cross-correlation of time-separated images. The design of the optics is discussed extensively as well as a modification of the Millikan cell, necessary because of convection flows in the original cell. The cross-correlation is made with a computer programme especially designed for this experiment. It enables measurements of many individual velocities from a single experiment. The evaluation procedure is discussed thoroughly, both theoretical and practical. Measurements of settling velocities have shown that the experimental procedure can distinguish between particles, with a size difference less than 1 gm. Thermophoretic velocities have been determined for sodium chloride, titanium dioxide and PSL spheres at different temperature gradients. The results are compared to theoretical values. The size distribution of the aerosol is shown to have a large effect on the results in these experiments. The preliminary results indicate the superiority of the Brock theory
Possible techniques for particle size analysis in a SiH4-NH3 flame
No full textRecent interest in high temperature structural ceramics has led to the development of chemical vapour phase techniques for the formation of a variety of high quality ceramic powders. Silicon nitride, Si3N4, is one of the most promising materials of these structural ceramics, because of its high temperature strength, thermal shock resistance and corrosion resistance. Si3N4 powders have been prepared by several techniques such as direct nitridation of silicon, decomposition of silicon diimide and vapour phase synthesis. Although, relatively small particles can be produced by using vapour phase synthesis initiated by convective heat [Lit.1], smaller and less agglomerated powders have been prepared using a sophisticated technique, Laser-Chemical Vapour phase Precipitation (L-CVP), developed by Haggerty and Danforth [Lit.2]. Characteristic of this laser-driven gas phase process is a well defined reaction zone which should facilitate a considerable degree of control over composition, size and size distribution of the produced powders. This report gives the results of a literature study performed to investigate the possible techniques for particle size analyses in this reaction zone. The aim of this research is to get a better understanding of the processes taking place in this zone. This particle size analysis is to be performed in a flame of SiH4 and NH3 which is used in the production of Si3N4. The ideal technique measures a particle size distribution in-situ, in the submicron range, is cheap, easy to handle, fast and does not influence our process. The second chapter handles on techniques which use a form of light to determine the psd and are non-intrusive. The third chapter deals with techniques which require sampling, and some possible ways of sampling are reported. Chapter 4 deals with techniques which do not belong to the first two groups. Since thermophoresis can become an important phenomenon in our setup the last chapter deals with this phenomenon.Applied SciencesProcess TechnologyParticle technology and Risk managemen
The synthesis of Si3N4 using a laser-heated reactor
No full textIt was proved that in the newly developed reactor it is possible to produce Si and Si3N4 powders. The yield varied between 0.2 and 2 g. In 1 hour the theoretical yield (100 % SiH4 conversion, 100 sccm) is 13.7 g Si3N4. It could not be determined whether this low yield was due to low SiH4 conversion or to a low Electrostatic precipitator efficiency. The produced powders were analysed by means of TEM-photography, BET-surface determination and a N-content determination…Applied SciencesParticle Technolog
Coated Particles Experiments and Preparation
No full textThe aim of this master project was to prepare coated particles for experiments with the time-of-flight mass spectrometer and for thermophoresis experiments. Firstly, a coated particle was modeled in the computer program SEPRAN to simulate heat conducting behaviour of particle and layer. This yielded particle characteristics for the thermophoretic experiment: a highly conducting core with a low conducting layer. Following experiments involved the preparation of polystyrene particles with different silica layers. A coated particle was made in three reaction steps: the preparation of a core particle of polystyrene, adsorption of small silica particles on the surface of the core and as last a chemical seeding with TEOS, to achieve a smooth silica layer around the particle. A quantitative recipe for the preparation of a smooth silica layer around a polystyrene particle was yielded. These prepared particles in suspension, were used for aerosol experiments. The suspensions were atomized in a nebulizer, the produced airosol stream was used for measurements with the time-of-flight mass spectrometer. Experiments for different particles and different intensities of the excimer laser were performed. The aerosol stream was also used for experiments to show thermophoresis. The last experiment involved the modeling of a nebulizer, this resulted in mathematical model describing concentration as function of time.Applied SciencesChemical Engineering and Materials Scienc
Absence of CYCS mutations in a large Italian cohort of patients with inherited thrombocytopenias of unknown origin.
No full textno abstrac
The Fragile X syndrome protein FMRP associates with BC1 RNA and regulates the translation of specific mRNAs at synapses
No full textThe Fragile X syndrome, which results from the absence of functional FMRP protein, is the most common heritable form of mental retardation. Here, we show that FMRP acts as a translational repressor of specific mRNAs at synapses. Interestingly, FMRP associates not only with these target mRNAs, but also with the dendritic, non-translatable RNA BC1. Blocking of BC1 inhibits the interaction of FMRP with its target mRNAs. Furthermore, BC1 binds directly to FMRP and can also associate, in the absence of any protein, with the mRNAs regulated by FMRP. This suggests a mechanism where BC1 could determine the specificity of FMRP function by linking the regulated mRNAs and FMRP. Thus, when FMRP is not present, loss of translational repression of specific mRNAs at synapses could result in synaptic dysfunction phenotype of Fragile X patients
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