| 951. |
- Bujakowska, Kinga, et al.
(författare)
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Study of Gene-Targeted Mouse Models of Splicing Factor Gene Prpf31 Implicated in Human Autosomal Dominant Retinitis Pigmentosa (RP)
- 2009
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 50:12, s. 5927-5933
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. Pre-mRNA processing factor 31 (PRPF31) is a ubiquitous protein needed for the assembly of the pre-mRNA splicing machinery. It has been shown that mutations in this gene cause autosomal dominant retinitis pigmentosa 11 (RP11), which is characterized by rod-cell degeneration. Interestingly, mutations in this ubiquitously expressed gene do not lead to phenotypes other than retinal malfunction. Furthermore, the dominant inheritance pattern has shown incomplete penetrance, which poses interesting questions about the disease mechanism of RP11. METHODS. To characterize PRPF31 function in the rod cells, two animal models have been generated. One was a heterozygous knock-in mouse (Prpf31(A216P/+)) carrying a point mutation p.A216P, which has previously been identified in RP11 patients. The second was a heterozygous knockout mouse (Prpf31(+/-)). Retinal degeneration in RP11 mouse models was monitored by electroretinography and histology. RESULTS. Generation of the mouse models is presented, as are results of ERGs and retinal morphology. No degenerative phenotype on fundus examination was found in Prpf31(A216P/+) and Prpf31(+/-) mice. Prpf31(A216P/A216P) and Prpf31(-/-) genotypes were embryonic lethal. CONCLUSIONS. The results imply that Prpf31 is necessary for survival, and there is no compensation mechanism in mouse for the lack of this splicing factor. The authors suggest that p.A216P mutation in Prpf31 does not exert a dominant negative effect and that one Prpf31 wild-type allele is sufficient for maintenance of the healthy retina in mice.
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| 952. |
- Butcher, LM, et al.
(författare)
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Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells
- 2016
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 10458-
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Tidskriftsartikel (refereegranskat)abstract
- Non-CG methylation is an unexplored epigenetic hallmark of pluripotent stem cells. Here we report that a reduction in non-CG methylation is associated with impaired differentiation capacity into endodermal lineages. Genome-wide analysis of 2,670 non-CG sites in a discovery cohort of 25 phenotyped human induced pluripotent stem cell (hiPSC) lines revealed unidirectional loss (Δβ=13%, P<7.4 × 10−4) of non-CG methylation that correctly identifies endodermal differentiation capacity in 23 out of 25 (92%) hiPSC lines. Translation into a simplified assay of only nine non-CG sites maintains predictive power in the discovery cohort (Δβ=23%, P<9.1 × 10−6) and correctly identifies endodermal differentiation capacity in nine out of ten pluripotent stem cell lines in an independent replication cohort consisting of hiPSCs reprogrammed from different cell types and different delivery systems, as well as human embryonic stem cell (hESC) lines. This finding infers non-CG methylation at these sites as a biomarker when assessing endodermal differentiation capacity as a readout.
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| 953. |
- Carlberg, Patrick, et al.
(författare)
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Nanoimprint - a tool for realizing nano-bio research
- 2004
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Ingår i: 2004 4th IEEE Conference on Nanotechnology. - 0780385365 ; , s. 199-200
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Konferensbidrag (refereegranskat)abstract
- In this paper, we present a status report on how implementation of nanoimprint lithography has advanced our research. Contact guidance nerve growth experiments have so far primarily been done on micrometer-structured surfaces. We have made a stamp with 17 areas of different, submicron, line width and spacing covering a total 2.6 mm
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| 954. |
- Cernicharo, J., et al.
(författare)
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A high-resolution line survey of IRC+10216 with Herschel/HIFI First results: Detection of warm silicon dicarbide (SiC2)
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521:1, s. Article Number: L8-
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Tidskriftsartikel (refereegranskat)abstract
- We present the first results of a high-spectral-resolution survey of the carbon-rich evolved star IRC+10216 that was carried out with the HIFI spectrometer onboard Herschel. This survey covers all HIFI bands, with a spectral range from 488 to 1901 GHz. In this letter we focus on the band-1b spectrum, in a spectral range 554.5-636.5 GHz, where we identified 130 spectral features with intensities above 0.03 K and a signal-to-noise ratio >5. Detected lines arise from HCN, SiO, SiS, CS, CO, metal-bearing species and, surprisingly, silicon dicarbide (SiC2). We identified 55 SiC2 transitions involving energy levels between 300 and 900 K. By analysing these rotational lines, we conclude that SiC2 is produced in the inner dust formation zone, with an abundance of similar to 2 x 10(-7) relative to molecular hydrogen. These SiC2 lines have been observed for the first time in space and have been used to derive an SiC2 rotational temperature of similar to 204 K and a source-averaged column density of similar to 6.4 x 10(15) cm(-2). Furthermore, the high quality of the HIFI data set was used to improve the spectroscopic rotational constants of SiC2.
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| 955. |
- Cook, Lola, et al.
(författare)
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The commercial genetic testing landscape for Parkinson's disease
- 2021
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1353-8020 .- 1873-5126. ; 92, s. 107-111
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThere have been no specific guidelines regarding which genes should be tested in the clinical setting for Parkinson's disease (PD) or parkinsonism. We evaluated the types of clinical genetic testing offered for PD as the first step of our gene curation.MethodsThe National Institutes of Health (NIH) Genetic Testing Registry (GTR) was queried on 12/7/2020 to identify current commercial PD genetic test offerings by clinical laboratories, internationally.ResultsWe identified 502 unique clinical genetic tests for PD, from 28 Clinical Laboratory Improvement Amendments (CLIA)-approved clinical laboratories. These included 11 diagnostic PD panels. The panels were notable for their differences in size, ranging from 5 to 62 genes. Five genes for variant query were included in all panels (SNCA, PRKN, PINK-1, PARK7 (DJ1), and LRRK2). Notably, the addition of the VPS35 and GBA genes was variable. Panel size differences stemmed from inclusion of genes linked to atypical parkinsonism and dystonia disorders, and genes in which the link to PD causation is controversial.ConclusionThere is an urgent need for expert opinion regarding which genes should be included in a commercial laboratory multi-gene panel for PD.
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| 956. |
- Danilovich, T., et al.
(författare)
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Sulphur-bearing molecules in AGB stars. Part 2. II. Abundances and distributions of CS and SiS
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 617
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Tidskriftsartikel (refereegranskat)abstract
- Context. Sulphur has long been known to form different molecules depending on the chemical composition of its environment. More recently, the sulphur-bearing molecules SO and H2S have been shown to behave differently in oxygen-rich asymptotic giant branch (AGB) circumstellar envelopes of different densities. Aims. By surveying a diverse sample of AGB stars for CS and SiS emission, we aim to determine in which environments these sulphur bearing molecules most readily occur. We include sources with a range of mass-loss rates and carbon-rich, oxygen-rich, and mixed S-type chemistries. Where these molecules are detected, we aim to determine their CS and SiS abundances. Methods. We surveyed 20 AGB stars of different chemical types using the APEX telescope, and combined this with an IRAM 30 m and APEX survey of CS and SiS emission towards over 30 S-type stars. For those stars with detections, we performed radiative transfer modelling to determine abundances and abundance distributions. Results. We detect CS towards all the surveyed carbon stars, some S-type stars, and the highest mass-loss rate oxygen-rich stars, (M > 5 x 10(-6) M-circle dot yr(-1)). SiS is detected towards the highest mass-loss rate sources of all chemical types (M >= similar to 8 x 10(-7) M-circle dot yr(-1)). We find CS peak fractional abundances ranging from similar to 4 x 10(-7) to similar to 2 x 10(-5) for the carbon stars, from similar to 3 x 10(-8) to similar to 1 x 10(-7) for the oxygen-rich stars, and from similar to 1 x 10(-7) to similar to 8 x 10(-6) for the S-type stars. We find SiS peak fractional abundances ranging from similar to 9 x 10(-6) to similar to 2 x 10(-5) for the carbon stars, from similar to 5 x 10(-7) to similar to 2 x 10(-6) for the oxygen-rich stars, and from similar to 2 x 10(-7) to similar to 2 x 10(-6) for the S-type stars. Conclusions. Overall, we find that wind density plays an important role in determining the chemical composition of AGB circumstellar envelopes. It is seen that for oxygen-rich AGB stars both CS and SiS are detected only in the highest density circumstellar envelopes and their abundances are generally lower than for carbon-rich AGB stars by around an order of magnitude. For carbon-rich and S-type stars SiS was also only detected in the highest density circumstellar envelopes, while CS was detected consistently in all surveyed carbon stars and sporadically among the S-type stars.
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| 957. |
- Danilovich, Taissa, 1987, et al.
(författare)
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Sulphur-bearing molecules in AGB stars. Part I. The occurrence of hydrogen sulphide
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 606
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Tidskriftsartikel (refereegranskat)abstract
- Context. Sulphur is a relatively abundant element in the local Galaxy that is known to form a variety of molecules in the circumstellar envelopes of AGB stars. The abundances of these molecules vary based on the chemical types and mass-loss rates of AGB stars. Aims. Through a survey of (sub-) millimetre emission lines of various sulphur-bearing molecules, we aim to determine which molecules are the primary carriers of sulphur in different types of AGB stars. In this paper, the first in a series, we investigate the occurrence of H2S in AGB circumstellar envelopes and determine its abundance, where possible. Methods. We surveyed 20 AGB stars with a range of mass-loss rates and different chemical types using the Atacama Pathfinder Experiment (APEX) telescope to search for rotational transition lines of five key sulphur-bearing molecules: CS, SiS, SO, SO2, and H2S. Here we present our results for H2S, including detections, non-detections, and detailed radiative transfer modelling of the detected lines. We compared results based on various descriptions of the molecular excitation of H2S and different abundance distributions, including Gaussian abundances, where possible, and two different abundance distributions derived from chemical modelling results. Results. We detected H2S towards five AGB stars, all of which have high mass-loss rates of. M >= 5 x 10(-6) M-circle dot yr(-1) and are oxygen rich. H2S was not detected towards the carbon or S-type stars that fall in a similar mass-loss range. For the stars in our sample with detections, we find peak o-H2S abundances relative to H-2 between 4 x 10(-7) and 2.5 x 10(-5). Conclusions. Overall, we conclude that H2S can play a significant role in oxygen-rich AGB stars with higher mass-loss rates, but is unlikely to play a key role in stars of other chemical types or in lower mass-loss rate oxygen-rich stars. For two sources, V1300 Aql and GX Mon, H2S is most likely the dominant sulphur-bearing molecule in the circumstellar envelope.
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| 958. |
- Davstad, I, et al.
(författare)
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Patterns of illicit drug use and retention in a methadone program: a longitudinal study
- 2007
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Ingår i: Journal of opioid management. - : Weston Medical Publishing. - 1551-7489. ; 3:1, s. 27-34
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to analyze illicit drug use of participants in a methadone treatment program in relation to methadone dose, counseling, and retention.Methods: This was a longitudinal study of a cohort of 204 heroin-dependent subjects admitted for the first time to a methadone program in Stockholm. The patients were admitted between 1995 and mid-2000 and were followed until December 2000 or discharge. Up to June 11, 1998, individual psychosocial counseling was provided; after this date individual counseling was replaced with group counseling. Clinical data were collected from patient records and from a laboratory database. Rates of drugpositive urine analyses during different time periods were measured.Results: The mean observation time was 2.5 years for all patients. The one-year retention rate was 84 percent, and the two-year rate was 65 percent, with no major differences between the two counseling groups. Almost all patients relapsed to illicit drug use. Discharged patients had a significantly higher rate of positive urine samples (21 percent versus 9 percent) than patients who remained in treatment. Also, low methadone dose and younger age predicted discharge from treatment.Conclusion: The frequent urine monitoring showed that illicit drug use was rather common, even in a program with structured psychosocial interventions, although it was lower than in other studies. This testing policy can be used for early identification of patients at risk for drop-out or discharge who should be offered complementary interventions.
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| 959. |
- De Beck, Elvire, 1985, et al.
(författare)
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ALMA observations of TiO2 around VY Canis Majoris
- 2015
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 580
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Tidskriftsartikel (refereegranskat)abstract
- Context. Titanium dioxide, TiO2, is a refractory species that could play a crucial role in the dust-condensation sequence around oxygen-rich evolved stars. To date, gas phase TiO2 has been detected only in the complex environment of the red supergiant VY CMa. Aims. We aim to constrain the distribution and excitation of TiO2 around VY CMa in order to clarify its role in dust formation. Methods. We analyse spectra and channel maps for TiO2 extracted from ALMA science verification data. Results. We detect 15 transitions of TiO2, and spatially resolve the emission for the first time. The maps demonstrate a highly clumpy, anisotropic outflow in which the TiO2 emission likely traces gas exposed to the stellar radiation field. An accelerating bipolar-like structure is found, oriented roughly east-west, of which the blue component runs into and breaks up around a solid continuum component. A distinct tail to the south-west is seen for some transitions, consistent with features seen in the optical and near-infrared. Conclusions. We find that a significant fraction of TiO2 remains in the gas phase outside the dust-formation zone and suggest that this species might play only a minor role in the dust-condensation process around extreme oxygen-rich evolved stars like VY CMa.
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| 960. |
- De Beck, Elvire, 1985, et al.
(författare)
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ALMA observations of TiO2 around VY CMa
- 2016
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 728:2, s. Art. no. UNSP 022009-
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Konferensbidrag (refereegranskat)abstract
- Titanium dioxide, TiO2, is a refractory species that could play a crucial role in the dust-condensation sequence around oxygen-rich evolved stars. We present and discuss the detections of 15 emission lines of TiO2 with ALMA in the complex environment of the red supergiant VY CMa. The observations reveal a highly clumpy, anisotropic outflow in which the TiO2 emission likely traces gas exposed to the stellar radiation field. We find evidence for a roughly east-west oriented, accelerating bipolar-like structure, of which the blue component runs into and breaks up around a solid continuum component. We see a distinct tail to the south-west for some transitions, consistent with features seen in the optical and near-infrared. We find that a significant fraction of TiO2 remains in the gas phase outside the dust-formation zone and suggest that this species might play only a minor role in the dust-condensation process around extreme oxygen-rich evolved stars like VY CMa.
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