873 research outputs found
The replacement histone H2A.Z in a hyperacetylated form is a feature of active genes in the chicken
The replacement histone H2A.Z is variously reported
as being linked to gene expression and preventing the
spread of heterochromatin in yeast, or concentrated
at heterochromatin in mammals. To resolve this
apparent dichotomy, affinity-purified antibodies
against the N-terminal region of H2A.Z, in both a triacetylatedandnon-
acetylatedstate, areusedin native
chromatin immmuno-precipitation experiments with
mononucleosomes from three chicken cell types. The
hyperacetylated species concentrates at the 50 end of
active genes, both tissue specific and housekeeping
but is absent from inactive genes, while the
unacetylated form is absent from both active and
inactive genes. A concentration of H2A.Z is also
found at insulators under circumstances implying a
link to barrier activity but not to enhancer blocking.
Although acetylated H2A.Z is widespread throughout
the interphase genome, at mitosis its acetylation is
erased, the unmodified form remaining. Thus,
although H2A.Z may operate as an epigenetic marker
for active genes, its N-terminal acetylation does not
The replacement histone H2A.Z in a hyperacetylated form is a feature of active genes in the chicken
The replacement histone H2A.Z is variously reported
as being linked to gene expression and preventing the
spread of heterochromatin in yeast, or concentrated
at heterochromatin in mammals. To resolve this
apparent dichotomy, affinity-purified antibodies
against the N-terminal region of H2A.Z, in both a triacetylatedandnon-
acetylatedstate, areusedin native
chromatin immmuno-precipitation experiments with
mononucleosomes from three chicken cell types. The
hyperacetylated species concentrates at the 50 end of
active genes, both tissue specific and housekeeping
but is absent from inactive genes, while the
unacetylated form is absent from both active and
inactive genes. A concentration of H2A.Z is also
found at insulators under circumstances implying a
link to barrier activity but not to enhancer blocking.
Although acetylated H2A.Z is widespread throughout
the interphase genome, at mitosis its acetylation is
erased, the unmodified form remaining. Thus,
although H2A.Z may operate as an epigenetic marker
for active genes, its N-terminal acetylation does not
Association of FCGR3A and FCGR3B haplotypes with rheumatoid arthritis and primary Sjögren's syndrome [POSTER PRESENTATION]
Background
Rheumatoid arthritis (RA) is an autoimmune disease that is thought to arise from a complex interaction between multiple genetic factors and environmental triggers. We have previously demonstrated an association between a Fc gamma receptor (FcγR) haplotype and RA in a cross-sectional cohort of RA patients. We have sought to confirm this association in an inception cohort of RA patients and matched controls. We also extended our study to investigate a second autoanti-body associated rheumatic disease, primary Sjögren's syndrome (PSS).
Methods
The FCGR3A-158F/V and FCGR3B-NA1/NA2 functional polymorphisms were examined for association in an inception cohort of RA patients (n = 448), and a well-characterised PSS cohort (n = 83) from the United Kingdom. Pairwise disequilibrium coefficients (D') were calculated in 267 Blood Service healthy controls. The EHPlus program was used to estimate haplotype frequencies for patients and controls and to determine whether significant linkage disequilibrium was present. A likelihood ratio test is performed to test for differences between the haplotype frequencies in cases and controls. A permutation procedure implemented in this program enabled 1000 permutations to be performed on all haplotype associations to assess significance.
Results
There was significant linkage disequilibrium between FCGR3A and FCGR3B (D' = -0.445, P = 0.001). There was no significant difference in the FCGR3A or FCGR3B allele or genotype frequencies in the RA or PSS patients compared with controls. However, there was a significant difference in the FCGR3A-FCGR3B haplotype distributions with increased homozygosity for the FCGR3A-FCGR3B 158V-NA2 haplotype in both our inception RA cohort (odds ratio = 2.15, 95% confidence interval = 1.1–4.2 P = 0.027) and PSS (odds ratio = 2.83, 95% confidence interval = 1.0–8.2, P = 0.047) compared with controls. The reference group for these analyses comprised individuals who did not possess a copy of the FCGR3A-FCGR3B 158V-NA2 haplotype.
Conclusions
We have confirmed our original findings of association between the FCGR3A-FCGR3B 158V-NA2 haplotype and RA in a new inception cohort of RA patients. This suggests that there may be an RA-susceptibility gene at this locus. The significant increased frequency of an identical haplotype in PSS suggests the FcγR genetic locus may contribute to the pathogenesis of diverse autoantibody-mediated rheumatic diseases
Replicated analysis of the genetic architecture of quantitative traits in two wild great tit populations
Currently, there is much debate on the genetic architecture of quantitative traits in wild populations. Is trait variation influenced by many genes of small effect or by a few genes of major effect? Where is additive genetic variation located in the genome? Do the same loci cause similar phenotypic variation in different populations? Great tits (Parus major) have been studied extensively in long-term studies across Europe and consequently are considered an ecological ‘model organism’. Recently, genomic resources have been developed for the great tit, including a custom SNP chip and genetic linkage map. In this study, we used a suite of approaches to investigate the genetic architecture of eight quantitative traits in two long-term study populations of great tits—one in the Netherlands and the other in the United Kingdom. Overall, we found little evidence for the presence of genes of large effects in either population. Instead, traits appeared to be influenced by many genes of small effect, with conservative estimates of the number of contributing loci ranging from 31 to 310. Despite concordance between population-specific heritabilities, we found no evidence for the presence of loci having similar effects in both populations. While population-specific genetic architectures are possible, an undetected shared architecture cannot be rejected because of limited power to map loci of small and moderate effects. This study is one of few examples of genetic architecture analysis in replicated wild populations and highlights some of the challenges and limitations researchers will face when attempting similar molecular quantitative genetic studies in free-living populations
Spin density wave dislocation in chromium probed by coherent x-ray diffraction
We report on the study of a magnetic dislocation in pure chromium. Coherent
x-ray diffraction profiles obtained on the incommensurate Spin Density Wave
(SDW) reflection are consistent with the presence of a dislocation of the
magnetic order, embedded at a few micrometers from the surface of the sample.
Beyond the specific case of magnetic dislocations in chromium, this work may
open up a new method for the study of magnetic defects embedded in the bulk.Comment: 8 pages, 7 figure
Gravitational Lensing at Millimeter Wavelengths
With today's millimeter and submillimeter instruments observers use
gravitational lensing mostly as a tool to boost the sensitivity when observing
distant objects. This is evident through the dominance of gravitationally
lensed objects among those detected in CO rotational lines at z>1. It is also
evident in the use of lensing magnification by galaxy clusters in order to
reach faint submm/mm continuum sources. There are, however, a few cases where
millimeter lines have been directly involved in understanding lensing
configurations. Future mm/submm instruments, such as the ALMA interferometer,
will have both the sensitivity and the angular resolution to allow detailed
observations of gravitational lenses. The almost constant sensitivity to dust
emission over the redshift range z=1-10 means that the likelihood for strong
lensing of dust continuum sources is much higher than for optically selected
sources. A large number of new strong lenses are therefore likely to be
discovered with ALMA, allowing a direct assessment of cosmological parameters
through lens statistics. Combined with an angular resolution <0.1", ALMA will
also be efficient for probing the gravitational potential of galaxy clusters,
where we will be able to study both the sources and the lenses themselves, free
of obscuration and extinction corrections, derive rotation curves for the
lenses, their orientation and, thus, greatly constrain lens models.Comment: 69 pages, Review on quasar lensing. Part of a LNP Topical Volume on
"Dark matter and gravitational lensing", eds. F. Courbin, D. Minniti. To be
published by Springer-Verlag 2002. Paper with full resolution figures can be
found at ftp://oden.oso.chalmers.se/pub/tommy/mmviews.ps.g
Horizons, Constraints, and Black Hole Entropy
Black hole entropy appears to be ``universal''--many independent
calculations, involving models with very different microscopic degrees of
freedom, all yield the same density of states. I discuss the proposal that this
universality comes from the behavior of the underlying symmetries of the
classical theory. To impose the condition that a black hole be present, we must
partially break the classical symmetries of general relativity, and the
resulting Goldstone boson-like degrees of freedom may account for the
Bekenstein-Hawking entropy. In particular, I demonstrate that the imposition of
a ``stretched horizon'' constraint modifies the algebra of symmetries at the
horizon, allowing the use of standard conformal field theory techniques to
determine the asymptotic density of states. The results reproduce the
Bekenstein-Hawking entropy without any need for detailed assumptions about the
microscopic theory.Comment: 16 pages, talk given at the "Peyresq Physics 10 Meeting on Micro and
Macro structures of spacetime
Contributions of Riemann invariants to the Entropy of Extremal Black Holes
We use the entropy function formalism introduced by A. Sen to obtain the
entropy of extremal and static black holes in four and
five dimensions, with higher derivative terms of a general type. Starting from
a generalized Einstein--Maxwell action with nonzero cosmological constant, we
examine all possible scalar invariants that can be formed from the complete set
of Riemann invariants (up to order 10 in derivatives). The resulting entropies
show the deviation from the well known Bekenstein--Hawking area law
for Einstein's gravity up to second order derivatives.Comment: 16 pages, revised version, comments and references added, accepted
for publication in JHE
Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS
The chi_b(nP) quarkonium states are produced in proton-proton collisions at
the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS
detector. Using a data sample corresponding to an integrated luminosity of 4.4
fb^-1, these states are reconstructed through their radiative decays to
Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks
corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new
structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is
also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes.
This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table,
corrected author list, matches final version in Physical Review Letter
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