1,215 research outputs found
The application of self-limiting transgenic insects in managing resistance in experimental metapopulations
This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.Data sharing: raw data for this study are available as supplementary data files.1. The mass release of transgenic insects carrying female lethal self-limiting genes can
reduce pest insect populations. Theoretically, substantial releases can be a novel
resistance management tool, since wild type alleles conferring susceptibility to
pesticides can dilute resistance alleles in target populations. A potential barrier to the
deployment of this technology is the need for large-scale area wide releases. Here we
address whether localized releases of transgenic insects could provide an alternative,
means of population suppression and resistance management, without serious loss of
efficacy.
2. We used experimental mesocosms constituting insect metapopulations to explore the
evolution of resistance to the Bacillus thuringiensis toxin Cry1Ac in a high-dose/refugia
landscape in the insect Plutella xylostella. We ran two selection experiments, the first
compared the efficacy of ‘everywhere’ releases and negative controls to a spatially
density-dependent or ‘whack-a-mole’ strategy that concentrated release of transgenic
insects in sub-populations with high levels of resistance. The second experiment tested
the relative efficacy of whack-a-mole and everywhere releases under spatially
homogenous and heterogeneous selection pressure.
3. The whack-a-mole releases were less effective than everywhere releases in terms of
slowing the evolution of resistance, which in the first experiment, largely prevented the
evolution of resistance. In contrast to predictions, heterogeneous whack-a-mole releases
were not more effective under heterogeneous selection pressure. Heterogeneous
selection pressure did, however, reduce total insect population sizes
4. Whack-a-mole releases provided early population suppression that was
indistinguishable from homogeneous everywhere releases. However, insect population
densities tracked the evolution of resistance in this system, as phenotypic resistance
provides access to the 90% of experimental diet containing the toxin Cry1Ac. Thus, as
resistance levels diverged between treatments, carrying capacities diverged and
population sizes increased under the whack- a-mole approach.
Synthesis and Applications Spatially density-dependent releases of transgenic insects,
particularly those targeting source populations at landscape level, could suppress pest
populations in the absence of blanket area-wide management. The resistance
management benefits of self-limiting transgenic insects are, however, reduced in
spatially localized releases, suggesting that they are not best suited for spatially
restricted ‘spot’ treatment of problematic resistance. Nevertheless, area-wide and
spatially heterogeneous releases could be used to support other resistance management
interventions.This work was supported by the Biotechnology and Biological Sciences Research Council
[grant numbers BB/L00948X/1 to MBB and NA, and BB/L00819X/1&2 to BR]
Combining the high-dose/refuge strategy and self-limiting transgenic insects in resistance management - a test in experimental mesocosms
This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.The high-dose/refuge strategy has been the primary approach for resistance management in transgenic crops engineered with Bacillus thuringiensis toxins. However, there are continuing pressures from growers to reduce the size of Bt toxin-free refugia, which typically suffer higher damage from pests. One complementary approach is to release male transgenic insects with a female-specific self-limiting gene. This technology can reduce population sizes and slow the evolution of resistance by introgressing susceptible genes through males. Theory predicts that it could be used to facilitate smaller refugia or reverse the evolution of resistance. In this study, we used experimental evolution with caged insect populations to investigate the compatibility of the self-limiting system and the high-dose/refuge strategy in mitigating the evolution of resistance in diamondback moth, Plutella xylostella. The benefits of the self-limiting system were clearer at smaller refuge size, particularly when refugia were inadequate to prevent the evolution of resistance. We found that transgenic males in caged mesocosms could suppress population size and delay resistance development with 10% refugia and 4% - 15% initial resistance allele frequency. Fitness costs in hemizygous transgenic insects are particularly important for introgressing susceptible alleles into target populations. Fitness costs of the self-limiting gene in this study (P. xylostella OX4139 line L) were incompletely dominant, and reduced fecundity and male mating competitiveness. The experimental evolution approach used here illustrates some of the benefits and pitfalls of combining mass-release of self-limiting insects and the high dose/refuge strategy, but does indicate that they can be complementary.This work was supported by the Biotechnology and Biological Sciences Research Council [grant numbers BB/L00948X/1 to MBB and NA, and BB/L00819X/1&2 to BR]
Properties of layer-by-layer vector stochastic models of force fluctuations in granular materials
We attempt to describe the stress distributions of granular packings using
lattice-based layer-by-layer stochastic models that satisfy the constraints of
force and torque balance and non-tensile forces at each site. The inherent
asymmetry in the layer-by-layer approach appears to lead to an asymmetric force
distribution, in disagreement with both experiments and general symmetry
considerations. The vertical force component probability distribution is robust
and in agreement with predictions of the scalar q model while the distribution
of horizontal force components is qualitatively different and depends on the
details of implementation.Comment: 18 pages, 12 figures (with subfigures), 1 table. Uses revtex,
epsfig,subfigure, and cite. Submitted to PRE. Plots have been bitmapped.
High-resolution version is available. Email [email protected] or
download from http://rainbow.uchicago.edu/~mbnguyen/research/vm.htm
Age before stage: insulin resistance rises before the onset of puberty: a 9-year longitudinal study (EarlyBird 26).
OBJECTIVE: Insulin resistance (IR) is associated with diabetes. IR is higher during puberty in both sexes, with some studies showing the increase to be independent of changes in adiposity. Few longitudinal studies have reported on children, and it remains unclear when the rise in IR that is often attributed to puberty really begins. We sought to establish from longitudinal data its relationship to pubertal onset, and interactions with age, sex, adiposity, and IGF-1. RESEARCH DESIGN AND METHODS: The EarlyBird Diabetes study is a longitudinal prospective cohort study of healthy children aged 5-14 years. Homeostasis model assessment (HOMA-IR), skinfolds (SSF), adiposity (percent fat, measured by dual-energy X-ray absorptiometry), serum leptin, and IGF-1 were measured annually in 235 children (134 boys). Pubertal onset was adduced from Tanner stage (TS) and from the age at which luteinizing hormone (LH) first became serially detectable (≥0.2 international units/L). RESULTS: IR rose progressively from age 7 years, 3-4 years before TS2 was reached or LH became detectable. Rising adiposity and IGF-1 together explained 34% of the variance in IR in boys and 35% in girls (both P < 0.001) over the 3 years preceding pubertal onset. The contribution of IGF-1 to IR was greater in boys, despite their comparatively lower IGF-1 levels. CONCLUSIONS: IR starts to rise in mid-childhood, some years before puberty. Its emergence relates more to the age of the child than to pubertal onset. More than 60% of the variation in IR prior to puberty was unexplained. The demography of childhood diabetes is changing, and prepubertal IR may be important
Models of stress fluctuations in granular media
We investigate in detail two models describing how stresses propagate and
fluctuate in granular media. The first one is a scalar model where only the
vertical component of the stress tensor is considered. In the continuum limit,
this model is equivalent to a diffusion equation (where the r\^ole of time is
played by the vertical coordinate) plus a randomly varying convection term. We
calculate the response and correlation function of this model, and discuss
several properties, in particular related to the stress distribution function.
We then turn to the tensorial model, where the basic starting point is a wave
equation which, in the absence of disorder, leads to a ray-like propagation of
stress. In the presence of disorder, the rays acquire a diffusive width and the
angle of propagation is shifted. A striking feature is that the response
function becomes negative, which suggests that the contact network is
mechanically unstable to very weak perturbations. The stress correlation
function reveals characteristic features related to the ray-like propagation,
which are absent in the scalar description. Our analytical calculations are
confirmed and extended by a numerical analysis of the stochastic wave equation.Comment: 32 pages, latex, 18 figures and 6 diagram
DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair.
XRCC4 and XLF are two structurally related proteins that function in DNA double-strand break (DSB) repair. Here, we identify human PAXX (PAralog of XRCC4 and XLF, also called C9orf142) as a new XRCC4 superfamily member and show that its crystal structure resembles that of XRCC4. PAXX interacts directly with the DSB-repair protein Ku and is recruited to DNA-damage sites in cells. Using RNA interference and CRISPR-Cas9 to generate PAXX(-/-) cells, we demonstrate that PAXX functions with XRCC4 and XLF to mediate DSB repair and cell survival in response to DSB-inducing agents. Finally, we reveal that PAXX promotes Ku-dependent DNA ligation in vitro and assembly of core nonhomologous end-joining (NHEJ) factors on damaged chromatin in cells. These findings identify PAXX as a new component of the NHEJ machinery.T.O. and T.L.B. are supported by the Wellcome Trust. The Jackson lab is funded by Cancer
Research UK (CRUK) program grant C6/A11224, the European Research Council and the
European Community Seventh Framework Programme grant agreement no. HEALTH-F2-2010-
259893 (DDResponse). Core infrastructure funding to the Jackson lab is provided by CRUK
(C6946/A14492) and the Wellcome Trust (WT092096). S.P.J. receives his salary from the
University of Cambridge, supplemented by CRUK. V.M.D. is a CRUK Career Development Fellow. The Draviam lab is funded by a CRUK CDA (C28598/A9787).This is the accepted manuscript version. The final version is available from AAAS at http://www.sciencemag.org/content/347/6218/185.full
Hidden geometric correlations in real multiplex networks
Real networks often form interacting parts of larger and more complex
systems. Examples can be found in different domains, ranging from the Internet
to structural and functional brain networks. Here, we show that these multiplex
systems are not random combinations of single network layers. Instead, they are
organized in specific ways dictated by hidden geometric correlations between
the individual layers. We find that these correlations are strong in different
real multiplexes, and form a key framework for answering many important
questions. Specifically, we show that these geometric correlations facilitate:
(i) the definition and detection of multidimensional communities, which are
sets of nodes that are simultaneously similar in multiple layers; (ii) accurate
trans-layer link prediction, where connections in one layer can be predicted by
observing the hidden geometric space of another layer; and (iii) efficient
targeted navigation in the multilayer system using only local knowledge, which
outperforms navigation in the single layers only if the geometric correlations
are sufficiently strong. Our findings uncover fundamental organizing principles
behind real multiplexes and can have important applications in diverse domains.Comment: Supplementary Materials available at
http://www.nature.com/nphys/journal/v12/n11/extref/nphys3812-s1.pd
Helical Chirality: a Link between Local Interactions and Global Topology in DNA
DNA supercoiling plays a major role in many cellular functions. The global DNA conformation is however intimately linked to local DNA-DNA interactions influencing both the physical properties and the biological functions of the supercoiled molecule. Juxtaposition of DNA double helices in ubiquitous crossover arrangements participates in multiple functions such as recombination, gene regulation and DNA packaging. However, little is currently known about how the structure and stability of direct DNA-DNA interactions influence the topological state of DNA. Here, a crystallographic analysis shows that due to the intrinsic helical chirality of DNA, crossovers of opposite handedness exhibit markedly different geometries. While right-handed crossovers are self-fitted by sequence-specific groove-backbone interaction and bridging Mg2+ sites, left-handed crossovers are juxtaposed by groove-groove interaction. Our previous calculations have shown that the different geometries result in differential stabilisation in solution, in the presence of divalent cations. The present study reveals that the various topological states of the cell are associated with different inter-segmental interactions. While the unstable left-handed crossovers are exclusively formed in negatively supercoiled DNA, stable right-handed crossovers constitute the local signature of an unusual topological state in the cell, such as the positively supercoiled or relaxed DNA. These findings not only provide a simple mechanism for locally sensing the DNA topology but also lead to the prediction that, due to their different tertiary intra-molecular interactions, supercoiled molecules of opposite signs must display markedly different physical properties. Sticky inter-segmental interactions in positively supercoiled or relaxed DNA are expected to greatly slow down the slithering dynamics of DNA. We therefore suggest that the intrinsic helical chirality of DNA may have oriented the early evolutionary choices for DNA topology
The subjective world of home care workers in dementia: an “order of worth” analysis
The perspective of domiciliary workers is needed to recruit a high-quality workforce and meet growing demand. An English ethnographic study yielded extensive insights. To structure analysis of the study data, we apply a method developed by political theorists Boltanski and Thévenot that identifies key variables in different values systems. This “orders of worth” framework is used to map out the distinctive features of the subjective world of home carers. The results can be drawn on to formulate recruitment and retention policies, to design reward strategies or to ensure that training and education opportunities engage effectively with the workforce
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