1,259 research outputs found
Somatic Mutation of the Cd95 Gene in Human B Cells as a Side-Effect of the Germinal Center Reaction
Somatic hypermutation specifically modifies rearranged immunoglobulin (Ig) genes in germinal center (GC) B cells. However, the bcl-6 gene can also acquire somatic mutations during the GC reaction, indicating that certain non-Ig genes can be targeted by the somatic hypermutation machinery. The CD95 gene, implicated in negative selection of B lymphocytes in GCs, is specifically expressed by GC B cells and was recently identified as a tumor suppressor gene being frequently mutated in (post) GC B cell lymphomas. In this study, the 5′ region (5′R) and/or the last exon coding for the death domain (DD) of the CD95 gene were investigated in naive, GC, and memory B cells from seven healthy donors. About 15% of GC and memory, but not naive, B cells carried mutations within the 5′R (mutation frequency 2.5 × 10−4 per basepair). Mutations within the DD were very rare but could be efficiently selected by inducing CD95-mediated apoptosis: in 22 apoptosis-resistant cells, 12 DD mutations were found. These results indicate that human B cells can acquire somatic mutations of the CD95 gene during the GC reaction, which potentially confers apoptosis resistance and may counteract negative selection through the CD95 pathway
Exploration of the Eucalyptus globulus gene pool
The first Europeans to discover Eucalyptus
globulus were French explorers in 1792. Its seed
was rapidly spread throughout the world in the
19th century and this was the species by which
much of the world first knew the genus.
However, it was in the industrial forests of the
20th century that this species, once considered
the ‘Prince of Eucalypts’, achieved greatest
prominence due to its fast growth and superior
pulp qualities. Formal breeding first commenced
in 1966 in Portugal and in the late 1980’s large
base population trials from open-pollinated seed
collections from native stands were established
in many countries. These trials have provided
unprecedented insights into the quantitative
genetic control of numerous traits of economic
and ecological importance and how this variation
is spatially distributed in the native range of the
species. However with large, fully pedigreed
breeding populations becoming available for
quantitative analysis and the rapidly expanding
knowledge of DNA sequence variation, we are
now at the threshold of a new understanding of
this important eucalypt gene pool. Indications of
the significance of non-additive genetic effects
are becoming available. The E. globulus
chloroplast genome has now been sequenced
and several genome maps have been published.
Studies of the variation in nuclear microsatellites
and the lignin biosynthesis gene CCR confirm
the complex, spatially structured nature of the
native gene pool. Strong spatial structuring of
the chloroplast genome has provided a tool for
tracking seed migration and the geographic
origin of exotic landraces. Highly divergent
lineages of chloroplast DNA have been
discovered and studies of the hypervariable JLA+
region argue that some components of the E.
globulus gene pool have been assimilated from
other species following hybridisation
Structure formation in active networks
Structure formation and constant reorganization of the actin cytoskeleton are
key requirements for the function of living cells. Here we show that a minimal
reconstituted system consisting of actin filaments, crosslinking molecules and
molecular-motor filaments exhibits a generic mechanism of structure formation,
characterized by a broad distribution of cluster sizes. We demonstrate that the
growth of the structures depends on the intricate balance between
crosslinker-induced stabilization and simultaneous destabilization by molecular
motors, a mechanism analogous to nucleation and growth in passive systems. We
also show that the intricate interplay between force generation, coarsening and
connectivity is responsible for the highly dynamic process of structure
formation in this heterogeneous active gel, and that these competing mechanisms
result in anomalous transport, reminiscent of intracellular dynamics
Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus.
Nuclear myosin I (NM1) is a nuclear isoform of the well-known "cytoplasmic" Myosin 1c protein (Myo1c). Located on the 11(th) chromosome in mice, NM1 results from an alternative start of transcription of the Myo1c gene adding an extra 16 amino acids at the N-terminus. Previous studies revealed its roles in RNA Polymerase I and RNA Polymerase II transcription, chromatin remodeling, and chromosomal movements. Its nuclear localization signal is localized in the middle of the molecule and therefore directs both Myosin 1c isoforms to the nucleus. In order to trace specific functions of the NM1 isoform, we generated mice lacking the NM1 start codon without affecting the cytoplasmic Myo1c protein. Mutant mice were analyzed in a comprehensive phenotypic screen in cooperation with the German Mouse Clinic. Strikingly, no obvious phenotype related to previously described functions has been observed. However, we found minor changes in bone mineral density and the number and size of red blood cells in knock-out mice, which are most probably not related to previously described functions of NM1 in the nucleus. In Myo1c/NM1 depleted U2OS cells, the level of Pol I transcription was restored by overexpression of shRNA-resistant mouse Myo1c. Moreover, we found Myo1c interacting with Pol II. The ratio between Myo1c and NM1 proteins were similar in the nucleus and deletion of NM1 did not cause any compensatory overexpression of Myo1c protein. We observed that Myo1c can replace NM1 in its nuclear functions. Amount of both proteins is nearly equal and NM1 knock-out does not cause any compensatory overexpression of Myo1c. We therefore suggest that both isoforms can substitute each other in nuclear processes
Collective dynamics of active cytoskeletal networks
Self organization mechanisms are essential for the cytoskeleton to adapt to
the requirements of living cells. They rely on the intricate interplay of
cytoskeletal filaments, crosslinking proteins and molecular motors. Here we
present an in vitro minimal model system consisting of actin filaments, fascin
and myosin-II filaments exhibiting pulsative collective long range dynamics.
The reorganizations in the highly dynamic steady state of the active gel are
characterized by alternating periods of runs and stalls resulting in a
superdiffusive dynamics of the network's constituents. They are dominated by
the complex competition of crosslinking molecules and motor filaments in the
network: Collective dynamics are only observed if the relative strength of the
binding of myosin-II filaments to the actin network allows exerting high enough
forces to unbind actin/fascin crosslinks. The feedback between structure
formation and dynamics can be resolved by combining these experiments with
phenomenological simulations based on simple interaction rules
Search for gravitational wave bursts in LIGO's third science run
We report on a search for gravitational wave bursts in data from the three
LIGO interferometric detectors during their third science run. The search
targets subsecond bursts in the frequency range 100-1100 Hz for which no
waveform model is assumed, and has a sensitivity in terms of the
root-sum-square (rss) strain amplitude of hrss ~ 10^{-20} / sqrt(Hz). No
gravitational wave signals were detected in the 8 days of analyzed data.Comment: 12 pages, 6 figures. Amaldi-6 conference proceedings to be published
in Classical and Quantum Gravit
Searching for a Stochastic Background of Gravitational Waves with LIGO
The Laser Interferometer Gravitational-wave Observatory (LIGO) has performed
the fourth science run, S4, with significantly improved interferometer
sensitivities with respect to previous runs. Using data acquired during this
science run, we place a limit on the amplitude of a stochastic background of
gravitational waves. For a frequency independent spectrum, the new limit is
. This is currently the most sensitive
result in the frequency range 51-150 Hz, with a factor of 13 improvement over
the previous LIGO result. We discuss complementarity of the new result with
other constraints on a stochastic background of gravitational waves, and we
investigate implications of the new result for different models of this
background.Comment: 37 pages, 16 figure
Housing Arrangement and Location Determine the Likelihood of Housing Loss Due to Wildfire
Surging wildfires across the globe are contributing to escalating residential losses and have major social, economic, and ecological consequences. The highest losses in the U.S. occur in southern California, where nearly 1000 homes per year have been destroyed by wildfires since 2000. Wildfire risk reduction efforts focus primarily on fuel reduction and, to a lesser degree, on house characteristics and homeowner responsibility. However, the extent to which land use planning could alleviate wildfire risk has been largely missing from the debate despite large numbers of homes being placed in the most hazardous parts of the landscape. Our goal was to examine how housing location and arrangement affects the likelihood that a home will be lost when a wildfire occurs. We developed an extensive geographic dataset of structure locations, including more than 5500 structures that were destroyed or damaged by wildfire since 2001, and identified the main contributors to property loss in two extensive, fire-prone regions in southern California. The arrangement and location of structures strongly affected their susceptibility to wildfire, with property loss most likely at low to intermediate structure densities and in areas with a history of frequent fire. Rates of structure loss were higher when structures were surrounded by wildland vegetation, but were generally higher in herbaceous fuel types than in higher fuel-volume woody types. Empirically based maps developed using housing pattern and location performed better in distinguishing hazardous from non-hazardous areas than maps based on fuel distribution. The strong importance of housing arrangement and location indicate that land use planning may be a critical tool for reducing fire risk, but it will require reliable delineations of the most hazardous locations
Genetic parameters for growth, wood density and pulp yield in Eucalyptus globulus
Genetic variation and co-variation among the key
pulpwood selection traits for Eucalyptus globulus were
estimated for a range of sites in Portugal, with the aim of
improving genetic parameters used to predict breeding
values and correlated response to selection. The trials
comprised clonally replicated full-sib families (eight trials)
and unrelated clones (17 trials), and exhibited varying
levels of pedigree connectivity. The traits studied were stem
diameter at breast height, Pilodyn penetration (an indirect
measure of wood basic density) and near infrared reflectance
predicted pulp yield. Univariate and multivariate
linear mixed models were fitted within and across sites, and estimates of additive genetic, total genetic, environmental
and phenotypic variances and covariances were obtained.
All traits studied exhibited significant levels of additive
genetic variation. The average estimated within-site narrowsense
heritability was 0.19±0.03 for diameter and 0.29±
0.03 for Pilodyn penetration, and the pooled estimate for
predicted pulp yield was 0.42±0.14. When they could be
tested, dominance and epistatic effects were generally not
statistically significant, although broad-sense heritability
estimates were slightly higher than narrow-sense heritability
estimates. Averaged across trials, positive additive
(0.64±0.08), total genetic (0.58±0.04), environmental
(0.38±0.03) and phenotypic (0.43±0.02) correlation estimates
were consistently obtained between diameter and
Pilodyn penetration. This data argues for at least some form
of pleiotropic relationship between these two traits and that
selection for fast growth will adversely affect wood density
in this population. Estimates of the across-site genetic
correlations for diameter and Pilodyn penetration were
high, indicating that the genotype by environment interaction
is low across the range of sites tested. This result
supports the use of single aggregated selection criteria for
growth and wood density across planting environments in
Portugal, as opposed to having to select for performance in
different environment
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