1,701 research outputs found
Mild recessive epidermolytic hyperkeratosis associated with a novel keratin 10 donor splice-site mutation in a family of Norfolk terrier dogs
Background  Epidermolytic hyperkeratosis in humans is caused by dominant-negative mutations in suprabasal epidermal keratins 1 and 10. However, spontaneous keratin mutations have not been confirmed in a species other than human. Objectives  To describe an autosomal recessive, mild, nonpalmar/plantar epidermolytic ichthyosis segregating in an extended pedigree of Norfolk terrier dogs due to a splice-site mutation in the gene encoding keratin 10 (KRT10). Methods  Dogs were evaluated clinically, and skin samples were examined by light and electron microscopy. Genomic DNA samples and cDNA from skin RNA were sequenced and defined a mutation in KRT10. Consequences of the mutation were evaluated by assessing protein expression with immunohistochemistry and Western blotting and gene expression with real-time RT-PCR (reverse transcriptase-polymerase chain reaction). Results  Adult dogs with the disease had generalized, pigmented hyperkeratosis with epidermal fragility. Light microscopic examination defined epidermolysis with hyperkeratosis; ultrastructural changes included a decrease in tonofilaments and abnormal filament aggregation in upper spinous and granular layer keratinocytes. Affected dogs were homozygous for a single base GT→TT change in the consensus donor splice site of intron 5 in KRT10. Keratin 10 protein was not detected with immunoblotting in affected dogs. Heterozygous dogs were normal based on clinical and histological appearance and keratin 10 protein expression. The mutation caused activation of at least three cryptic or alternative splice sites. Use of the cryptic sites resulted in transcripts containing premature termination codons. One transcript could result in shortening of the proximal portion of the 2B domain before the stutter region. Quantitative real-time PCR indicated a significant decrease in KRT10 mRNA levels in affected dogs compared with wild-type dogs. Conclusions  This disease is the first confirmed spontaneous keratin mutation in a nonhuman species and is the first reported recessive form of epidermolytic hyperkeratosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74670/1/j.1365-2133.2005.06735.x.pd
Data Platforms and Cities
This section offers a series of joint reflections on (open) data platform
from a variety of cases, from cycling, traffic and mapping to activism,
environment and data brokering. Data platforms play a key role in contemporary
urban governance. Linked to open data initiatives, such platforms are often
proposed as both mechanisms for enhancing the accountability of administrations
and performing as sites for 'bottom-up' digital invention. Such promises
of smooth flows of data, however, rarely materialise unproblematically.
The development of data platforms is always situated in legal and administrative
cultures, databases are often built according to the standards of existing
digital ecologies, access always involves processes of social negotiation, and
interfaces (such as sensors) may become objects of public contestation. The
following contributions explore the contested and mutable character of open
data platforms as part of heterogeneous publics and trace the pathways of data
through different knowledge, skills, public and private configurations. They
also reflect on the value of STS approaches to highlight issues and tensions as
well as to shape design and governance
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Development of a design basis tornado and structural design criteria for Lawrence Livermore Laboratory's Site 300
Criteria are prescribed and guidance is provided for professional personnel who are involved with the evaluation of existing buildings and facilities at Site 300 near Livermore, California to resist the possible effects of extreme winds and tornadoes. The development of parameters for the effects of tornadoes and extreme winds and guidelines for evaluation and design of structures are presented. The investigations conducted are summarized and the techniques used for arriving at the combined tornado and extreme wind risk model are discussed. The guidelines for structural design methods for calculating pressure distributions on walls and roofs of structures and methods for accommodating impact loads from missiles are also presented. (auth
Development of a design basis tornado and structural design criteria for the Nevada Test Site, Nevada. Final report
In order to evaluate the ability of critical facilities at the Nevada Test Site to withstand the possible damaging effects of extreme winds and tornadoes, parameters for the effects of tornadoes and extreme winds and structural design criteria for the design and evaluation of structures were developed. The meteorological investigations conducted are summarized, and techniques used for developing the combined tornado and extreme wind risk model are discussed. The guidelines for structural design include methods for calculating pressure distributions on walls and roofs of structures and methods for accommodating impact loads from wind-driven missiles. Calculations for determining the design loads for an example structure are included. (LCL
Canine NAPEPLD-associated models of human myelin disorders
Canine leukoencephalomyelopathy (LEMP) is a juvenile-onset neurodegenerative disorder of the CNS white matter currently described in Rottweiler and Leonberger dogs. Genome-wide association study (GWAS) allowed us to map LEMP in a Leonberger cohort to dog chromosome 18. Subsequent whole genome re-sequencing of a Leonberger case enabled the identification of a single private homozygous non-synonymous missense variant located in the highly conserved metallo-beta-lactamase domain of the N-acyl phosphatidylethanolamine phospholipase D (NAPEPLD) gene, encoding an enzyme of the endocannabinoid system. We then sequenced this gene in LEMP-affected Rottweilers and identified a different frameshift variant, which is predicted to replace the C-terminal metallo-beta-lactamase domain of the wild type protein. Haplotype analysis of SNP array genotypes revealed that the frameshift variant was present in diverse haplotypes in Rottweilers, and also in Great Danes, indicating an old origin of this second NAPEPLD variant. The identification of different NAPEPLD variants in dog breeds affected by leukoencephalopathies with heterogeneous pathological features, implicates the NAPEPLD enzyme as important in myelin homeostasis, and suggests a novel candidate gene for myelination disorders in people
Classical heisenberg antiferromagnet away from the pyrochlore lattice limit: entropic versus energetic selection
The stability of the disordered ground state of the classical Heisenberg
pyrochlore antiferromagnet is studied within extensive Monte Carlo simulations
by introducing an additional exchange interaction that interpolates
between the pyrochlore lattice () and the face-centered cubic lattice
(). It is found that for as low as , the system is
long range ordered : the disordered ground state of the pyrochlore
antiferromagnet is unstable when introducing very small deviations from the
pure limit. Furthermore, it is found that the selected phase is a
collinear state energetically greater than the incommensurate phase suggested
by a mean field analysis. To our knowledge this is the first example where
entropic selection prevails over the energetic one.Comment: 5 (two-column revtex4) pages, 1 table, 7 ps/eps figures. Submitted to
Phys. Rev.
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