| 1. |
- Friedman, James S., et al.
(author)
-
Mutations in a BTB-Kelch Protein, KLHL7, Cause Autosomal-Dominant Retinitis Pigmentosa
- 2009
-
In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 84:6, s. 792-800
-
Journal article (peer-reviewed)abstract
- Retinitis pigmentosa (RP) refers to a genetically heterogeneous group of progressive neurodegenerative diseases that result in dysfunction and/or death of rod and cone photoreceptors in the retina. So far, 18 genes have been identified for autosomal-dominant (ad) RP. Here, we describe an adRP locus (RP42) at chromosome 7p15 through linkage analysis in a six-generation Scandinavian family and identify a disease-causing mutation, c.449G -> A (p.S150N), in exon 6 of the KLHL7 gene. Mutation screening of KLHL7 in 502 retinopathy probands has revealed three different missense mutations in six independent families. KLHL7 is widely expressed, including expression in rod photoreceptors, and encodes a 75 kDa protein of the BTB-Kelch Subfamily within the BTB superfamily. BTB-Kelch proteins have been implicated in ubiquitination through Cullin E3 ligases. Notably, all three putative disease-causing KLHL7 mutations are within a conserved BACK domain; homology modeling suggests that mutant amino acid side chains can potentially fill the cleft between two helices, thereby affecting the ubiquitination complexes. Mutations in an identical region of another BTB-Kelch protein, gigaxonin, have previously been associated with giant axonal neuropathy. Our studies suggest an additional role of the ubiquitin-proteasome protein-degradation pathway in maintaining neuronal health and in disease.
|
|
| 2. |
- Nelson, A. J., et al.
(author)
-
Soft x-ray free electron laser microfocus for exploring matter under extreme conditions
- 2009
-
In: Optics Express. - 1094-4087. ; 17:20, s. 18271-18278
-
Journal article (peer-reviewed)abstract
- We have focused a beam (BL3) of FLASH (Free-electron LASer in Hamburg: lambda = 13.5 nm, pulse length 15 fs, pulse energy 10-40 mu J, 5Hz) using a fine polished off-axis parabola having a focal length of 270 mm and coated with a Mo/Si multilayer with an initial reflectivity of 67% at 13.5 nm. The OAP was mounted and aligned with a picomotor controlled six-axis gimbal. Beam imprints on poly(methyl methacrylate) -PMMA were used to measure focus and the focused beam was used to create isochoric heating of various slab targets. Results show the focal spot has a diameter of <= 1 mu m. Observations were correlated with simulations of best focus to provide further relevant information.
|
|
| 3. |
- Andreasson, Joakim, 1973, et al.
(author)
-
A molecule-based 1 : 2 digital demultiplexer
- 2007
-
In: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 111:38, s. 14274-14278
-
Journal article (peer-reviewed)abstract
- A trichromophoric molecule consisting of a porphyrin linked to both a dihydropyrene and a dihydroindolizine-type photochrome, in combination with a third harmonic generating crystal, functions as a 1:2 digital demultiplexer with photonic inputs and outputs. Each of the two photochromes may be cycled independently between two metastable forms, leading to four photoisomers, three of which are used in the demultiplexer. These isomers interact photochemically with the porphyrin in order to yield the demultiplexer function. With the address input (1064-nm light) turned off, one Output of the device (porphyrin fluorescence) tracks the state of the data input (532-nm light). When the address input is turned on, the second output (absorbance at 572 nm) tracks the state of the data input, while the first output remains off. The demultiplexer does not require chemical or electrical inputs, and can cycle through its operational sequences multiple times.
|
|
| 4. |
- Andreasson, Joakim, 1973, et al.
(author)
-
Molecular 2 : 1 digital multiplexer
- 2007
-
In: Angewandte Chemie - International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 46:6, s. 958-961
-
Journal article (peer-reviewed)abstract
- (Chemical Equation Presented) Two into one: A porphyrin linked to two photochromic moieties performs as a 2:1 digital multiplexer (MUX). It takes heat and red light as the two inputs (in 1 and in 2), and a third switchable input (green light, sel) selects whether the output (porphyrin fluorescence) reports the state of in 1 or in 2. Each photochromic moiety may be independently photoisomerized to isomers that quench the porphyrin fluorescence. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.
|
|
| 5. |
- Appelgren, Patrik, et al.
(author)
-
Modelling of a small helical magnetic flux compression generator
- 2007
-
In: PPPS-2007 - Pulsed Power Plasma Science 2007. - 1424409144 - 9781424409143 ; , s. 1155-1158
-
Conference paper (peer-reviewed)abstract
- Helical flux-compression generators convert the chemical energy bond in explosives into electric energy. This paper briefly presents a model of, implemented in Matlab-Simulink, and simulation results for such a device. The simulation results are compared to experimental data from two experiments with identical generators but with different seed currents, influencing the resistive losses and thus the current amplification. The model is used to analyse the performance of the generator.
|
|
| 6. |
|
|
| 7. |
- Friedman, James S., et al.
(author)
-
Premature truncation of a novel protein, RD3, exhibiting subnuclear localization is associated with retinal degeneration
- 2006
-
In: American Journal of Human Genetics. - 0002-9297. ; 79:6, s. 1059-1070
-
Journal article (peer-reviewed)abstract
- The rd3 mouse is one of the oldest identified models of early-onset retinal degeneration. Using the positional candidate approach, we have identified a C -> T substitution in a novel gene, Rd3, that encodes an evolutionarily conserved protein of 195 amino acids. The rd3 mutation results in a predicted stop codon after residue 106. This change is observed in four rd3 lines derived from the original collected mice but not in the nine wild-type mouse strains that were examined. Rd3 is preferentially expressed in the retina and exhibits increasing expression through early postnatal development. In transiently transfected COS-1 cells, the RD3-fusion protein shows subnuclear localization adjacent to promyelocytic leukemia-gene-product bodies. The truncated mutant RD3 protein is detectable in COS-1 cells but appears to get degraded rapidly. To explore potential association of the human RD3 gene at chromosome 1q32 with retinopathies, we performed a mutation screen of 881 probands from North America, India, and Europe. In addition to several alterations of uncertain significance, we identified a homozygous alteration in the invariant G nucleotide of the RD3 exon 2 donor splice site in two siblings with Leber congenital amaurosis. This mutation is predicted to result in premature truncation of the RD3 protein, segregates with the disease, and is not detected in 121 ethnically matched control individuals. We suggest that the retinopathy-associated RD3 protein is part of subnuclear protein complexes involved in diverse processes, such as transcription and splicing.
|
|
| 8. |
- He, J., et al.
(author)
-
Switching of a photochromic molecule on gold electrodes: single-molecule measurements
- 2005
-
In: Nanotechnology. - : IOP Publishing. - 1361-6528 .- 0957-4484. ; 16:6, s. 695-702
-
Journal article (peer-reviewed)abstract
- We have studied the electronic changes caused by light-induced isomerization of a photochromic molecule between an open state (that absorbs in the UV to become closed) and a closed state (that absorbs in the visible to become open). Data obtained using a newly developed repetitive break junction method are interpreted in terms of single-molecule resistances of 526 +/- 90 M Omega in the open form and 4 +/- 1 M Omega in the closed form when the molecule is bound between two gold contacts via dithiol linkages. The corresponding ratio of open to closed resistance is in close agreement with the results of ab initio calculations, though the measured resistances are about half of the calculated values. Optical spectroscopy indicates that the photoisomerization occurs in both directions on small gold particles, evaporated thin gold films, and in the break junction experiments.
|
|
| 9. |
- Kohl, S, et al.
(author)
-
CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia
- 2005
-
In: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 13:3, s. 302-308
-
Journal article (peer-reviewed)abstract
- Achromatopsia is a congenital, autosomal recessively inherited disorder characterized by a lack of color discrimination, low visual acuity (<0.2), photophobia, and nystagmus. Mutations in the genes for CNGA3, CNGB3, and GNAT2 have been associated with this disorder. Here, we analyzed the spectrum and prevalence of CNGB3 gene mutations in a cohort of 341 independent patients with achromatopsia. In 163 patients, CNGB3 mutations could be identified. A total of 105 achromats carried apparent homozygous mutations, 44 were compound (double) heterozygotes, and 14 patients had only a single mutant allele. The derived CNGB3 mutation spectrum comprises 28 different mutations including 12 nonsense mutations, eight insertions and/or deletions, five putative splice site mutations, and three missense mutations. Thus, the majority of mutations in the CNGB3 gene result in significantly altered and/or truncated polypeptides. Several mutations were found recurrently, in particular a 1 bp deletion, c.1148delC, which accounts for over 70% of all CNGB3 mutant alleles. In conclusion, mutations in the CNGB3 gene are responsible for approximately 50% of all patients with achromatopsia. This indicates that the CNGB3/ACHM3 locus on chromosome 8q21 is the major locus for achromatopsia in patients of European origin or descent.
|
|
| 10. |
- Mattsson, Niklas, 1979, et al.
(author)
-
Reduced cerebrospinal fluid BACE1 activity in multiple sclerosis.
- 2009
-
In: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 15:4, s. 448-54
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Cell and animal experiments have shown that beta-site APP-cleaving enzyme 1 (BACE1) may be involved in myelination. OBJECTIVE: Here, we assess the association of cerebrospinal fluid (CSF) BACE1 activity with multiple sclerosis (MS). METHODS: BACE1 activity and levels of secreted amyloid precursor protein (APP) and amyloid-beta (Abeta) isoforms were analyzed in CSF from 100 patients with MS and 114 neurologically healthy controls. Patients with systemic lupus erythematosus (SLE), 26 with and 41 without cerebral engagement, were also included to enable comparisons with regards to another autoimmune disease. A subset of patients with MS and controls underwent a second lumbar puncture after 10 years. RESULTS: MS patients had lower CSF BACE1 activity than controls (P = 0.03) and patients with cerebral SLE (P < 0.001). Patients with cerebral SLE had higher BACE1 activity than any other group (P < 0.05 for all comparisons). BACE1 activity correlated with the different amyloid markers in all study groups. BACE1 activity decreased over 10 years in the MS group (P = 0.039) and correlated weakly with clinical disease severity scores in an inverse manner. CONCLUSIONS: These results suggest an involvement of BACE1 in the MS disease process.
|
|
