583 research outputs found
Scanning detection of mutations in human ornithine transcarbamoylase by chemical mismatch cleavage.
Cloning and expression of a mammalian peptide chain release factor with sequence similarity to tryptophanyl-tRNA synthetases
The termination of protein synthesis is encoded by in-frame nonsense (stop) codons. Most organisms use three nonsense codons: UGA, UAG, and UAA. In contrast to sense codons, which are decoded by specific tRNAs, nonsense codons are decoded by proteins called release factors (RFs). Here we report the cloning of a mammalian RF cDNA by the use of monoclonal antibodies specific for rabbit RF. Functional studies showed that, when expressed in Escherichia coli, the protein encoded by this cDNA has in vitro biochemical characteristics similar to those of previously characterized mammalian RFs. DNA sequencing of this eukaryotic RF cDNA revealed a remarkable sequence similarity to bacterial and mitochondrial tryptophanyl-tRNA synthetases, with the greatest similarity confined to the synthetase active site, and no obvious similarity to bacterial RFs
Polar Smectic Films
We report on a new experimental procedure for forming and studying polar
smectic liquid crystal films. A free standing smectic film is put in contact
with a liquid drop, so that the film has one liquid crystal/liquid interface
and one liquid crystal/air interface. This polar environment results in changes
in the textures observed in the film, including a boojum texture and a
previously unobserved spiral texture in which the winding direction of the
spiral reverses at a finite radius from its center. Some aspects of these
textures are explained by the presence of a Ksb term in the bulk elastic free
energy density that favors a combination of splay and bend deformations.Comment: 4 pages, REVTeX, 3 figures, submitted to PR
Hydrodynamics of topological defects in nematic liquid crystals
We show that back-flow, the coupling between the order parameter and the
velocity fields, has a significant effect on the motion of defects in nematic
liquid crystals. In particular the defect speed can depend strongly on the
topological strength in two dimensions and on the sense of rotation of the
director about the core in three dimensions.Comment: 4 pages including two figure
A Call to Standardize the Definition and Method of Assessing Women for Vaginal Discharge Syndrome in Pregnancy.
Intermittency in Dynamics of Two-Dimensional Vortex-like Defects
We examine high-order dynamical correlations of defects (vortices,
disclinations etc) in thin films starting from the Langevin equation for the
defect motion. We demonstrate that dynamical correlation functions of
vorticity and disclinicity behave as where is the
characteristic scale and is the fugacity. As a consequence, below the
Berezinskii-Kosterlitz-Thouless transition temperature are
characterized by anomalous scaling exponents. The behavior strongly differs
from the normal law occurring for simultaneous correlation
functions, the non-simultaneous correlation functions appear to be much larger.
The phenomenon resembles intermittency in turbulence.Comment: 30 pages, 11 figure
Self-Consistent Model of Annihilation-Diffusion Reaction with Long-Range Interactions
We introduce coarse-grained hydrodynamic equations of motion for
diffusion-annihilation system with a power-law long-range interaction. By
taking into account fluctuations of the conserved order parameter - charge
density - we derive an analytically solvable approximation for the nonconserved
order parameter - total particle density. Asymptotic solutions are obtained for
the case of random Gaussian initial conditions and for system dimensionality . Large-t, intermediate-t and small-t asymptotics were calculated and
compared with existing scaling theories, exact results and simulation data.Comment: 22 pages, RevTEX, 1 PostScript figur
Whole exome sequencing identifies novel genes for fetal hemoglobin response to hydroxyurea in children with sickle cell anemia.
Hydroxyurea has proven efficacy in children and adults with sickle cell anemia (SCA), but with considerable inter-individual variability in the amount of fetal hemoglobin (HbF) produced. Sibling and twin studies indicate that some of that drug response variation is heritable. To test the hypothesis that genetic modifiers influence pharmacological induction of HbF, we investigated phenotype-genotype associations using whole exome sequencing of children with SCA treated prospectively with hydroxyurea to maximum tolerated dose (MTD). We analyzed 171 unrelated patients enrolled in two prospective clinical trials, all treated with dose escalation to MTD. We examined two MTD drug response phenotypes: HbF (final %HbF minus baseline %HbF), and final %HbF. Analyzing individual genetic variants, we identified multiple low frequency and common variants associated with HbF induction by hydroxyurea. A validation cohort of 130 pediatric sickle cell patients treated to MTD with hydroxyurea was genotyped for 13 non-synonymous variants with the strongest association with HbF response to hydroxyurea in the discovery cohort. A coding variant in Spalt-like transcription factor, or SALL2, was associated with higher final HbF in this second independent replication sample and SALL2 represents an outstanding novel candidate gene for further investigation. These findings may help focus future functional studies and provide new insights into the pharmacological HbF upregulation by hydroxyurea in patients with SCA
Gene content evolution in the arthropods
Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception. These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity
- …