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1.
MOTIVATION: Chromatin breakage by ionizing radiation is relevant to studies of carcinogenesis, tumor radiotherapy, biodosimetry and molecular biology. This article focuses on computer analysis of chromosome irradiation in mammlian cells. METHODS: Polymer physics and Monte Carlo numerical methods are used to develop a coarse-grained computational approach. Chromatin is modeled as a random walk on a cubic lattice, and the radiation tracks hitting the chromatin are modeled as straight lines hitting lattice sites. Each track can make a cluster of DSBs on a chromosome. RESULTS: The results obtained replace conjectured DNA fragment-size distribution functions in the recently developed RLC formalism by more mechanistically motivated distributions. The discrete lattice algorithm reproduces features of current radiation experiments relevant to chromatin on large scales. It approximates the continuous formalism and experimental data with adequate precision. It was also found that assuming either fixed chromatin with correlations among different clusters of DSBs or moving chromatin with no such correlations gives virtually identical numerical predictions. 相似文献
2.
A polymer, random walk model for the size-distribution of large DNA fragments after high linear energy transfer radiation 总被引:2,自引:0,他引:2
Ponomarev AL Brenner D Hlatky LR Sachs RK 《Radiation and environmental biophysics》2000,39(2):111-120
DNA double-strand breaks (DSBs) produced by densely ionizing radiation are not located randomly in the genome: recent data
indicate DSB clustering along chromosomes. Stochastic DSB clustering at large scales, from >100 Mbp down to <0.01 Mbp, is
modeled using computer simulations and analytic equations. A random-walk, coarse-grained polymer model for chromatin is combined
with a simple track structure model in Monte Carlo software called DNAbreak and is applied to data on alpha-particle irradiation
of V-79 cells. The chromatin model neglects molecular details but systematically incorporates an increase in average spatial
separation between two DNA loci as the number of base-pairs between the loci increases. Fragment-size distributions obtained
using DNAbreak match data on large fragments about as well as distributions previously obtained with a less mechanistic approach.
Dose-response relations, linear at small doses of high linear energy transfer (LET) radiation, are obtained. They are found
to be non-linear when the dose becomes so large that there is a significant probability of overlapping or close juxtaposition,
along one chromosome, for different DSB clusters from different tracks. The non-linearity is more evident for large fragments
than for small. The DNAbreak results furnish an example of the RLC (randomly located clusters) analytic formalism, which generalizes
the broken-stick fragment-size distribution of the random-breakage model that is often applied to low-LET data.
Received: 19 July 1999 / Accepted in revised form: 10 December 1999 相似文献
3.
W. Friedland Peter Jacob Herwig G. Paretzke Matteo Merzagora Andrea Ottolenghi 《Radiation and environmental biophysics》1999,38(1):39-47
The Monte Carlo track structure code PARTRAC has been further improved by implementing electron scattering cross-sections
for liquid water and by explicitly modelling the interaction of water radicals with DNA. The model of the genome inside a
human cell nucleus in its interphase is based on the atomic coordinates of the DNA double helix with an additional volume
for the water shell. The DNA helix is wound around histone complexes, and these nucleosomes are folded into chromatin fibres
and further to fibre loops, which are interconnected to build chromosomes with a territorial organisation. Simulations have
been performed for the irradiation of human fibroblast cells with carbon K and aluminium K ultrasoft x-rays, 220 kVp x-rays
and 60Co γ-rays. The ratio single-strand breaks to double-strand breaks (ssb/dsb) for both types of ultrasoft x-rays is lower than for
γ-rays by a factor of 2. The contributions of direct and indirect effects to strand break induction are almost independent
of photon energy. Strand break patterns from indirect effects reflect differences in the susceptibility of the DNA helix to
OH• attack inside the chromatin fibre. Distributions of small DNA fragments (<3 kbp) are determined by the chromatin fibre structure
irrespective of whether direct or indirect effects are causing the breaks. In the calculated fragment size distributions for
larger DNA fragments (>30 kbp), a substantial deviation from random breakage is found only for carbon K irradiation, and is
attributed to its inhomogeneous dose distribution inside the cell nucleus. For the other radiation qualities, the results
for larger fragments can be approximated by random breakage distributions calculated for a yield of dsb which is about 10%
lower than the average for the whole genome. The excess of DNA fragments detected experimentally in the 8–300 kbp region after
x-ray irradiation is not seen in our simulation results.
Received: 19 October 1998 / Accepted in revised form: 14 January 1999 相似文献
4.
In this paper a new form of the solution for the Laplace transform and moments of the distribution of the waiting time for
two genes to coalescence is presented. The two genes are sampled from a subdivided population where migration rates between
populations are constant in time. Equal subpopulation size is not assumed. For the special case of an island model with equal
migration rates between islands, the Laplace transform of the coalescence time and the first and second moments are found
explicitly. The new form of the solutions allows numerical calculation. The connection of how the results relate to a panmictic
population when migration rates are large is illustrated using strong-migration-limit theory.
Received: 19 April 1999 / Revised version: 22 March 2001 / Published online: 19 September 2001 相似文献
5.
In this paper we examine spatio-temporal pattern formation in reaction-diffusion systems on the surface of the unit sphere
in 3D. We first generalise the usual linear stability analysis for a two-chemical system to this geometrical context. Noting
the limitations of this approach (in terms of rigorous prediction of spatially heterogeneous steady-states) leads us to develop,
as an alternative, a novel numerical method which can be applied to systems of any dimension with any reaction kinetics. This
numerical method is based on the method of lines with spherical harmonics and uses fast Fourier transforms to expedite the
computation of the reaction kinetics. Numerical experiments show that this method efficiently computes the evolution of spatial
patterns and yields numerical results which coincide with those predicted by linear stability analysis when the latter is
known. Using these tools, we then investigate the r?le that pre-pattern (Turing) theory may play in the growth and development
of solid tumours. The theoretical steady-state distributions of two chemicals (one a growth activating factor, the other a
growth inhibitory factor) are compared with the experimentally and clinically observed spatial heterogeneity of cancer cells
in small, solid spherical tumours such as multicell spheroids and carcinomas. Moreover, we suggest a number of chemicals which
are known to be produced by tumour cells (autocrine growth factors), and are also known to interact with one another, as possible
growth promoting and growth inhibiting factors respectively. In order to connect more concretely the numerical method to this
application, we compute spatially heterogeneous patterns on the surface of a growing spherical tumour, modelled as a moving-boundary
problem. The numerical results strongly support the theoretical expectations in this case. Finally in an appendix we give
a brief analysis of the numerical method.
Received: 27 July 2000 / Revised version: 15 August 2000 / Published online: 16 February 2001 相似文献
6.
Ionizing radiation produces DNA double strand breaks (DSBs) in chromosomes. For densely ionizing radiation, the DSBs are not spaced randomly along a chromosome: recent data for size distributions of DNA fragments indicate break clustering on kbp-Mbp scales. Different DSB clusters on a chromosome are typically made by different, statistically independent, stochastically structured radiation tracks, and the average number of tracks involved can be small. We therefore model DSB positions along a chromosome as a stationary Poisson cluster process, i.e. a stochastic process consisting of secondary point processes whose locations are determined by a primary point process that is Poisson. Each secondary process represents a break cluster, typically consisting of 1-10 DSBs in a comparatively localized stochastic pattern determined by chromatin geometry and radiation track structure. Using this Poisson cluster process model, which we call the randomly located clusters (RLC) formalism, theorems are derived for how the DNA fragment-size distribution depends on radiation dose. The RLC dose-response relations become non-linear when the dose becomes so high that DSB clusters from different tracks overlap or adjoin closely. The RLC formalism generalizes previous models, fits current data adequately and facilitates mechanistically based extrapolations from high-dose experiments to the much lower doses of interest for most applications. 相似文献
7.
The photomechanic infrared receptor for the detection of forest fires in the beetle Melanophila acuminata (Coleoptera: Buprestidae) 总被引:1,自引:0,他引:1
H. Schmitz H. Bleckmann 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1998,182(5):647-657
We recorded from single units of individual sensilla of the thoracic infrared (IR) pit organs of Melanophila acuminata. When the organ was stimulated with a thermal radiator whose emission spectrum was similar to that of a typical forest fire,
units responded phasically with up to seven spikes within 30–40 ms at a radiation power of 24 mW cm−2. In the experiments all wavelengths shorter than 1.6 μm were excluded by a longpass IR filter. Response latencies were about
4 ms and initial impulse frequencies were up to 250 impulses per second (ips). A single spike could be generated even when
stimulus duration was only 2 ms. Reduction of total radiation power from 24 mW cm−2 to 5 mW cm−2 resulted in increased response latencies of 5–6 ms and the occurrence of only two to three spikes. Initial impulse frequencies
decreased to 125 ips. According to our physiological results and calculations, Melanophila should be able to detect a 10-hectare fire from a distance of 12 km. Mechanical stimuli also evoked responses of the IR sensilla.
All present morphological and physiological findings lead to the conclusion that the IR receptors of Melanophila must function by means of a hitherto undescribed photomechanic mechanism.
Accepted: 1 November 1997 相似文献
8.
Mitsuhiro Takayama 《Ichthyological Research》2002,49(2):165-170
The spawning period of the Far Eastern brook lamprey, Lethenteron reissneri, in the headstream of the Himekawa River is estimated to be between mid-March and late May with the peak of spawning activity
between early April and early May. The sex ratio (female:male) in 1999 ranged from 1 : 2.5 to 1 : 3.0 (mean 1 : 2.8) and in
2000 from 1 : 0.8 to 1 : 4.0 (mean 1 : 2.4). In >90% of the observations of spawning nests, males outnumbered females. The
construction area of spawning nests tended to shift upstream during the spawning period. The nests were constructed at water
depths between 5 and 70 cm, water velocity between 10 and 30 cm/s, and on substrate with pebbles of 5–20 mm in diameter. Lethenteron reissneri constructed nests on substrate similar with Petromyzon marinus, but at shallower points and in areas with a slower water velocity.
Received: April 2, 2001 / Revised: December 12, 2001 / Accepted: December 27, 2001 相似文献
9.
We developed a simple, versatile system for applying a range of biaxial loads to cell–matrix constructs for the study of
mechanobiology. The system consists of porous polyethylene bars that are polymerized into a square fibroblast-populated gel
and loaded by freely hanging weights attached to sutures routed through a custom loading rig. The cost to manufacture each
mold/loading rig pair was less than US $250 and the expected life of the components is up to 10 years. Neonatal and adult
cardiac fibroblasts contracted gels to a decreasing extent as external load was increased (P=0.003) and achieved contraction forces of up to 1.4 mN per million cells. Strain distributions were reasonably homogeneous
in the central region of the gel (25% of gel area), but clearly nonhomogeneous outside that central region. The primary advantages
of this system are simplicity, low cost, biaxial loading, and the ability to test for a dose–response effect of mechanical
load. The current disadvantages are the inability to apply cycling loading and the inhomogeneities introduced by the use of
rigid loading bars.
Received: 15 November 2001 / Accepted: 30 January 2002 相似文献
10.
Qi Wang Monica Pujol-Canadell Maria Taveras Guy Garty Jay Perrier Carlos Bueno-Beti Igor Shuryak David J. Brenner Helen C. Turner 《Radiation and environmental biophysics》2020,59(1):89-98
Environmental contamination and ingestion of the radionuclide Cesium-137 (137Cs) is a large concern in fallout from a nuclear reactor accident or improvised nuclear device, and highlights the need to develop biological assays for low-dose rate, internal emitter radiation. To mimic low-dose rates attributable to fallout, we have developed a VAriable Dose-rate External 137Cs irradiatoR (VADER), which can provide arbitrarily varying and progressive low-dose rate irradiations in the range of 0.1–1.2 Gy/day, while circumventing the complexities of dealing with radioactively contaminated biomaterials. We investigated the kinetics of mouse peripheral leukocytes DNA damage response in vivo after variable, low-dose rate 137Cs exposure. C57BL/6 mice were placed in the VADER over 7 days with total accumulated dose up to 2.7 Gy. Peripheral blood response including the leukocyte depletion, apoptosis as well as its signal protein p53 and DNA repair biomarker γ-H2AX was measured. The results illustrated that blood leukocyte numbers had significantly dropped by day 7. P53 levels peaked at day 2 (total dose = 0.91 Gy) and then declined; whereas, γ-H2AX fluorescence intensity (MFI) and foci number generally increased with accumulated dose and peaked at day 5 (total dose = 2.08 Gy). ROC curve analysis for γ-H2AX provided a good discrimination of accumulated dose < 2 Gy and ≥ 2 Gy, highlighting the potential of γ-H2AX MFI as a biomarker for dosimetry in a protracted, environmental exposure scenario. 相似文献
11.
H. Schmitz M. Mürtz H. Bleckmann 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2000,186(6):543-549
The pit organs of the beetle Melanophilaacuminata were stimulated with monochromatic infrared radiation using a continuous wave CO overtone infrared laser. Best sensitivity
was in the wavelength range 2.8–3.5 μm. In this range a stimulus intensity of 14.7 mW cm−2 was sufficient to generate single action potentials. At a wavelength of 5 μm receptor performance significantly decreased.
An increase in stimulus intensity caused a decrease in response latency and an increase in the number of action potentials
elicited. At a given wavelength (3.4 μm) the dynamic amplitude range of action potential responses covered 12 dB. At high
stimulus intensities (94.2 mW cm−2) a stimulus duration of 4 ms was sufficient to generate one to two action potentials and a stimulus duration of 60 ms already
caused response saturation (with up to nine action potentials). In a repetitive stimulus regime distinct receptor potentials
were visible up to a frequency of 600 Hz.
Accepted: 18 March 2000 相似文献
12.
A new liparid, Careproctus
parvidiscus, is described on the basis of a single specimen (177 mm in standard length) collected from the southern Okhotsk Sea, off
Shiretoko Point, Hokkaido, Japan, at 400–700 m depth. It is distinguished from other congeners by the following combination
of the characters: 50 dorsal fin rays, 44 anal fin rays, 10 + 47 = 57 vertebrae, 2 pleural ribs, 14 pyloric caeca being slender
and pointed, 2 suprabranchial pores, narrower gill opening, longer lower lobe of pectoral fin, base of uppermost pectoral
fin ray almost on a level with center of eye, rudimentary disk, dusky peritoneum, and black stomach.
Received: June 13, 2001 / Revised: December 7, 2001 / Accepted: December 22, 2001 相似文献
13.
Ponomarev AL Belli M Hahnfeldt PJ Hlatky L Sachs RK Cucinotta FA 《Radiation research》2006,166(6):908-916
The non-random distribution of DNA breakage in PFGE (pulsed-field gel electrophoresis) experiments poses a problem of proper subtraction of the background DNA damage to obtain a fragment-size distribution due to radiation only. A naive bin-to-bin subtraction of the background signal will not result in the right DNA mass distribution histogram. This problem could become more pronounced for high-LET (linear energy transfer) radiation, because the fragment-size distribution manifests a higher frequency of smaller fragments. Previous systematic subtraction methods have been based on random breakage, appropriate for low-LET radiation. Moreover, an investigation is needed to determine whether the background breakage is itself random or non-random. We consider two limiting cases: (1) the background damage is present in all cells, and (2) it is present in only a small subset of cells, while other cells are not contributing to the background DNA fragmentation. We give a generalized formalism based on stochastic processes for the subtraction of the background damage in PFGE experiments for any LET and apply it to two sets of PFGE data for iron ions. 相似文献
14.
Upeneus australiae sp. nov. is described on the basis of 14 specimens collected from Australian waters. Although it belongs to the seven-spined
group of Upeneus, now comprising five species, U. australiae is distinguished from its congeners by the combination of the following characters: 6–7 + 16–18 (modally 7 + 17) gill rakers,
ectopterygoids without teeth, five and six black oblique bars on upper and lower caudal lobes, respectively, and peritoneum
transparent with small black spots.
Received: July 26, 2001 / Revised: November 2, 2001 / Accepted: December 4, 2001 相似文献
15.
David Vermijlen Christopher J. Froelich Dianzhong Luo Nathalie Suarez-Huerta Bernard Robaye Eddie Wisse 《Cancer immunology, immunotherapy : CII》2001,50(4):212-217
Cytotoxic lymphocytes may induce apoptosis in their target cells by the FasL (Fas ligand) pathway or the perforin/granzyme
B pathway. It has been shown that Fas-expressing colon carcinoma (CC) cells are resistant to FasL-mediated apoptosis. The
aims of this study were to determine whether CC cells are also resistant to perforin/granzyme B and whether the FasL resistance
lies upstream of caspase-3 activation. The resistance of the Fas-expressing rat CC531s cells to the FasL pathway was confirmed
by treating them with recombinant human soluble FasL, using rat hepatocytes as a positive control. The intracellular delivery
of granzyme B by sublytic concentrations of perforin, on the other hand, resulted in many features of apoptosis (chromatin
condensation, nucleus fragmentation, loss of microvilli and internucleosomal DNA fragmentation) within 3 h. Since both the
FasL and perforin/granzyme B pathways converge at caspase-3, we measured caspase-3 activity to learn whether the FasL resistance
was due to failure to activate this crucial executioner. Caspase-3 activation occurred in CC531s cells after perforin/granzyme
B treatment, but not after the addition of recombinant FasL. Furthermore, we showed that caspase-3 activity is involved in
the execution of perforin/granzyme-B-induced apoptosis in CC531s cells, since the cell-permeable caspase-3 inhibitor Z-DEVD-FMK
abrogated DNA fragmentation. Together, these results suggest that CC cells are sensitive to perforin/granzyme-B-induced apoptosis
by activating caspase-3 and FasL resistance lies upstream of this executioner caspase.
Received: 20 November 2000 / Accepted: 8 March 2001 相似文献
16.
Atsushi Fukui Miyuki Suzuki Yachiyo Suzuki Itsuro Uotani 《Ichthyological Research》2002,49(2):159-164
The early ontogeny of Lophonectes gallus (Bothidae) is described based on 83 specimens (1.9–17.5 mm BL), collected from the Tasman Sea off southeastern Australia.
The larvae are diagnosed by the following array of characters: vertebrae 10 + 30–31 = 40–41; one elongated dorsal fin ray
and several melanophores present on gut in preflexion stage (1.9–4.7 mm BL); and spines on posterior basipterygial process,
and urohyal, cleithrum, and epiotic without spines after postflexion stage (8.0–17.5 mm BL). The larvae are relatively small
at metamorphosis (15–18 mm BL) compared with other bothid larvae.
Received: March 22, 2001 / Revised: December 12, 2001 / Accepted: December 26, 2001 相似文献
17.
Spawning grounds and nests of Trachidermus fasciatus (Cottidae) in the Kashima and Shiota estuaries system facing Ariake Bay, Japan 总被引:1,自引:1,他引:0
Norio Onikura Naohiko Takeshita Seiichi Matsui Seiro Kimura 《Ichthyological Research》2002,49(2):198-201
The spawning grounds of a cottid fish, Trachidermus fasciatus, were investigated off the mouth of the Kashima River in Ariake Bay from January to March, 1996–1999. The nests were found
about 1.1–2.3 km off the mouth of the river, where the bottom salinity was 8‰–21‰ at low tides. Oyster shells were mainly
found to be used as nests. A male, a pair, a male and egg clusters, a pair and egg clusters, or a female were found inside
shells. The average number of guarded egg clusters per male in shells was 1.3 ± 0.4.
Received: March 2, 2001 / Revised: September 17, 2001 / Accepted: November 13, 2001 相似文献
18.
In some species of hagfish, the phenomenon of chromosome elimination occurs during embryogenesis. However, only two repetitive
DNA families are known to be represented in chromosomes that are eliminated from somatic cells of the Japanese hagfish Eptatretus okinoseanus. Using molecular analyses, another germ line-restricted, highly repetitive DNA family has been detected in another Japanese
hagfish, Paramyxine atami. The repeat unit of this family, which is 83 bp long, has been designated “EEPa1”, for Eliminated Element of P. atami 1. DNA filter hybridization using EEPa1 as a probe revealed that this family is shared among several species and is conserved
in the germline DNA. Although eliminated, repetitive DNA that is shared interspecifically has not been reported in hagfish
species, cases of chromatin diminution and chromosome elimination processes have been described previously in other organisms.The
patterns and intensities of hybridization signals suggest that members of the repetitive DNA family defined by EEPa1 have
undergone concerted molecular evolution.
Received: 7 January 1997 / Accepted: 13 May 1997 相似文献
19.
Rich dynamics of a ratio-dependent one-prey two-predators model 总被引:3,自引:0,他引:3
The objective of this paper is to systematically study the qualitative properties of a ratio-dependent one-prey two-predator
model. We show that the dynamics outcome of the interactions are very sensitive to parameter values and initial data. Specifically,
we show the interactions can lead to all the following possible outcomes: 1) competitive exclusion; 2) total extinction, i.e.,
collapse of the whole system; 3) coexistence in the form of positive steady state; 4) coexistence in the form of oscillatory
solutions; and 5) introducing a friendly and better competitor can save a otherwise doomed prey species. These results reveal
far richer dynamics compared to similar prey dependent models. Biological implications of these results are discussed.
Received: 14 November 2000 / Revised version: 18 February 2001 / Published online: 19 September 2001 相似文献
20.
We present an analysis of X-ray-induced damage in ΦX174 plasmid DNA, applying doses between D = 250 and 1,500 Gy. To analyse this damage in detail, the distribution of plasmid fragments after irradiation have been determined
by scanning force microscopy. The results show that even for the lowest dose of D = 250 Gy, a significant amount of double-strand breaks are observed. For increasing dose, the percentage of small fragments
increases and is accompanied by a shortening of the average fragment length from < L> = 1,400 nm for a dose of D = 250 Gy to < L> = 1,080 nm after irradiation with D = 1,500 Gy. The most crucial parameter, the average number of double-strand breaks per broken plasmid (<DSBb> ) has been determined for the first time for the applied doses. The results show that the average number of DSBs per broken
plasmid <DSBb> increases almost linearly from a value of <DSBb> = 1.3 after irradiation with D = 250 Gy to <DSBb> = 1.7 after exposure to D = 1,500 Gy. The presented results show that the amount of DSBs induced by X-ray radiation in plasmid DNA can be calculated
with high accuracy by means of scanning force microscopy, providing relevant information regarding the interaction of X-rays
with DNA molecules.
相似文献
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