Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells

Poly(ADP-ribose) polymerase [PARP; NAD+ ADP-ribosyltransferase; NAD+: poly(adenosine-diphosphate-d-ribosyl)-acceptor ADP-d-ribosyltransferase, EC 2.4.2.30] is a zinc-finger DNA-binding protein that detects specifically DNA strand breaks generated by genotoxic agents. To determine its biological function, we have inactivated both alleles by gene targeting in mice. Treatment of PARP−/− mice either by the alkylating agent N-methyl-N-nitrosourea (MNU) or by γ-irradiation revealed an extreme sensitivity and a high genomic instability to both agents. Following whole body γ-irradiation (8 Gy) mutant mice died rapidly from acute radiation toxicity to the small intestine. Mice-derived PARP−/− cells displayed a high sensitivity to MNU exposure: a G2/M arrest in mouse embryonic fibroblasts and a rapid apoptotic response and a p53 accumulation were observed in splenocytes. Altogether these results demonstrate that PARP is a survival factor playing an essential and positive role during DNA damage recovery.

Long-term recovery patterns of arctic tundra after winter seismic exploration

In response to the increasing global demand for energy, oil exploration and development are expanding into frontier areas of the Arctic, where slow-growing tundra vegetation and the underlying permafrost soils are very sensitive to disturbance. The creation of vehicle trails on the tundra from seismic exploration for oil has accelerated in the past decade, and the cumulative impact represents a geographic footprint that covers a greater extent of Alaska’s North Slope tundra than all other direct human impacts combined. Seismic exploration for oil and gas was conducted on the coastal plain of the Arctic National Wildlife Refuge, Alaska, USA, in the winters of 1984 and 1985. This study documents recovery of vegetation and permafrost soils over a two-decade period after vehicle traffic on snow-covered tundra. Paired permanent vegetation plots (disturbed vs. reference) were monitored six times from 1984 to 2002. Data were collected on percent vegetative cover by plant species and on soil and ground ice characteristics. We developed Bayesian hierarchical models, with temporally and spatially autocorrelated errors, to analyze the effects of vegetation type and initial disturbance levels on recovery patterns of the different plant growth forms as well as soil thaw depth. Plant community composition was altered on the trails by species-specific responses to initial disturbance and subsequent changes in substrate. Long-term changes included increased cover of graminoids and decreased cover of evergreen shrubs and mosses. Trails with low levels of initial disturbance usually improved well over time, whereas those with medium to high levels of initial disturbance recovered slowly. Trails on ice-poor, gravel substrates of riparian areas recovered better than those on ice-rich loamy soils of the uplands, even after severe initial damage. Recovery to pre-disturbance communities was not possible where trail subsidence occurred due to thawing of ground ice. Previous studies of disturbance from winter seismic vehicles in the Arctic predicted short-term and mostly aesthetic impacts, but we found that severe impacts to tundra vegetation persisted for two decades after disturbance under some conditions. We recommend management approaches that should be used to prevent persistent tundra damage.

Structure and photoluminescence studies of Pr-implanted GaN

The structure and photoluminscence (PL) properties of Pr-implanted GaN thin films have been studied. RBS/channeling technique was used to explore the damage recovery at high annealing temperature and study the dependence of the radiation damage with ion implantation direction. A complete recovery of the ion implantation damage cannot be achieved at annealing temperatures up to 1050degreesC. It is found that the channeling implantation results in the decrease of the damage. The PL experimental results indicate that the PL efficiency increases exponentially with annealing temperature up to the maximum temperature of 1050degreesC. Moreover, the PL intensity is also seriously affected by ion implantation geometries. The PL intensity for the sample implanted along channeled direction is nearly 2 times more intense than that observed from the sample implanted along random direction. The thermal quenching of PL intensity from 10 to 300K for sample annealed at 1050degreesC is only 30%. (C) 2004 Elsevier B.V. All rights reserved.

RBS/channeling study and photoluminscence properties of Er-implanted GaN

The Raman back scattering/channeling technique was used to analyze the damage recovery at different annealing temperatures and to determine the lattice location of the Er-implanted GaN samples. A better damage recovery was observed with increasing annealing temperature below 1000degreesC, but a complete recovery of the implantation damage cannot be achieved. For a sample annealed for at 900degreesC 30 min the Er and Ga angular scans across the <0001> axis was measured indicating that about 76% of Er ions occupies substitutional sites. Moreover, the photoluminscence (PL) properties of Er-implanted GaN thin films have been also studied. The experimental results indicate that those samples annealed at a higher temperature below 1000degreesC had a stronger 1539nm PL intensity. The thermal quenching of PL intensity for samples annealed at 900degreesC measured at temperatures from 15K to 300K is 30%.

A novel self-healing supramolecular polymer system

Utilising supramolecular pi-pi stacking interactions to drive miscibility in two-component polymer blends offers a novel approach to producing materials with unique properties. We report in this paper the preparation of a supramolecular polymer network that exploits this principle. A low molecular weight polydiimide which contains multiple pi-electron-poor receptor sites along its backbone forms homogeneous films with a siloxane polymer that features pi-electron-rich pyrenyl end-groups. Compatibility results from a complexation process that involves chain-folding of the polydiimide to create an optimum binding site for the pi-electron-rich chain ends of the polysiloxane. These complementary pi-electron-rich and -poor receptors exhibit rapid and reversible complexation behaviour in solution, and healable characteristics in the solid state in response to temperature. A mechanism is proposed for this thermoreversible healing behaviour that involves disruption of the intermolecular pi-pi stacking cross-links as the temperature of the supramolecular film is increased. The low T-g siloxane component can then flow and as the temperature of the blend is decreased, pi-pi stacking interactions drive formation of a new network and so lead to good damage-recovery characteristics of the two-component blend.

Responsabilidade civil concorrencial: a busca pela efetiva reparação de danos

Esta monografia analisa as decisões dos tribunais brasileiros sobre responsabilização civil dos agentes que acarretaram danos decorrentes de condutas anticompetitivas, com o objetivo de verificar se a reparação dos referidos danos demonstra-se efetiva. Para a introdução do tema da responsabilidade civil concorrencial, foram apresentados os elementos da responsabilização civil, procurando focar a aplicação destes elementos em matéria concorrencial. Em seguida, de maneira a averiguar se os danos decorrentes de práticas anticompetitivas estão sendo efetivamente reparados, foi realizada uma análise dos casos que discutem esta matéria nos principais tribunais brasileiros. Essa análise conta com a exposição dos principais problemas enfrentados pelo Poder Judiciário refletidos nas decisões proferidas. Dentre os problemas elencados, foi destacada e aprofundada a análise da quantificação de danos, tendo sido proposto um método de quantificação dos danos morais coletivos. Por fim, foram tecidos alguns comentários acerca do pré-projeto de alteração do artigo da Lei 8.884/94 que versa sobre a matéria. A conclusão deste estudo demonstra que não há efetividade na reparação dos danos acarretados por práticas contrárias ao direito antitruste.

Genotoxic responses of juvenile tilapia (Oreochromis niloticus) exposed to florfenicol and oxytetracycline

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Thermal stability of ion-implanted ZnO

Zinc oxide single crystals implanted at room temperature with high-dose (1.4x10(17) cm(-2)) 300 keV As+ ions are annealed at 1000-1200 degrees C. Damage recovery is studied by a combination of Rutherford backscattering/channeling spectrometry (RBS/C), cross-sectional transmission electron microscopy (XTEM), and atomic force microscopy. Results show that such a thermal treatment leads to the decomposition and evaporation of the heavily damaged layer instead of apparent defect recovery and recrystallization that could be inferred from RBS/C and XTEM data alone. This study shows that heavily damaged ZnO has relatively poor thermal stability compared to as-grown ZnO which is a significant result and has implications for understanding results on thermal annealing of ion-implanted ZnO. (c) 2005 Americian Institute of Physics.

Fijian coral reef damage and recovery from Cyclone Kina

EXTRACT (SEE PDF FOR FULL ABSTRACT): Early in 1993, Cyclone Kina struck the Fiji Islands, causing more than $100 million in property damage and damaging the coral environment as well. A few days after the cyclone, the most damaged reef was studied. The same reef had been studied 6 months before. This reef crest is dominated by Acropora. Comparison showed that 80-90% of the Acropora was torn from the outer reef and deposited in the inner lagoon. ... It is estimated that it will take a few years to 30 years for the reef to recover to pre-Kina conditions.

The role of corticospinal tract damage in chronic motor recovery and neurorehabilitation: a pilot study

Background. With diffusion-tensor imaging (DTi) it is possible to estimate the structural characteristics of fiber bundles in vivo. This study used DTi to infer damage to the corticospinal tract (CST) and relates this parameter to (a) the level of residual motor ability at least 1 year poststroke and (b) the outcome of intensive motor rehabilitation with constraint-induced movement therapy (CIMT). Objective. To explore the role of CST damage in recovery and CIMT efficacy. Methods. Ten patients with low-functioning hemiparesis were scanned and tested at baseline, before and after CIMT. Lesion overlap with the CST was indexed as reduced anisotropy compared with a CST variability map derived from 26 controls. Residual motor ability was measured through the Wolf Motor Function Test (WMFT) and the Motor Activity Log (MAL) acquired at baseline. CIMT benefit was assessed through the pre—post treatment comparison of WMFT and MAL performance. Results. Lesion overlap with the CST correlated with residual motor ability at baseline, with greater deficits observed in patients with more extended CST damage. Infarct volume showed no systematic association with residual motor ability. CIMT led to significant improvements in motor function but outcome was not associated with the extent of CST damage or infarct volume. Conclusion. The study gives in vivo support for the proposition that structural CST damage, not infarct volume, is a major predictor for residual functional ability in the chronic state. The results provide initial evidence for positive effects of CIMT in patients with varying, including more severe, CST damage.

A dominant-negative mutant of human poly(ADP-ribose) polymerase affects cell recovery, apoptosis, and sister chromatid exchange following DNA damage.

Poly(ADP-ribose) polymerase [PARP; NAD+ ADP-ribosyltransferase; NAD+:poly(adenosine-diphosphate-D-ribosyl)-acceptor ADP-D-ribosyltransferase, EC 2.4.2.30] is a zinc-dependent eukaryotic DNA-binding protein that specifically recognizes DNA strand breaks produced by various genotoxic agents. To study the biological function of this enzyme, we have established stable HeLa cell lines that constitutively produce the 46-kDa DNA-binding domain of human PARP (PARP-DBD), leading to the trans-dominant inhibition of resident PARP activity. As a control, a cell line was constructed, producing a point-mutated version of the DBD, which has no affinity for DNA in vitro. Expression of the PARP-DBD had only a slight effect on undamaged cells but had drastic consequences for cells treated with genotoxic agents. Exposure of cell lines expressing the wild-type (wt) or the mutated PARP-DBD, with low doses of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) resulted in an increase in their doubling time, a G2 + M accumulation, and a marked reduction in cell survival. However, UVC irradiation had no preferential effect on the cell growth or viability of cell lines expressing the PARP-DBD. These PARP-DBD-expressing cells treated with MNNG presented the characteristic nucleosomal DNA ladder, one of the hallmarks of cell death by apoptosis. Moreover, these cells exhibited chromosomal instability as demonstrated by higher frequencies of both spontaneous and MNNG-induced sister chromatid exchanges. Surprisingly, the line producing the mutated DBD had the same behavior as those producing the wt DBD, indicating that the mechanism of action of the dominant-negative mutant involves more than its DNA-binding function. Altogether, these results strongly suggest that PARP is an element of the G2 checkpoint in mammalian cells.

Load on osseointegrated fixation of a transfemoral amputee during a fall : loading, descent, impact and recovery analysis

Falling represents a health risk for lower limb amputees fitted with an osseointegrated fixation mainly because of the potential damage to the fixation. The purpose of this study was to characterise a real forward fall that occurred inadvertently to a transfemoral amputee fitted with an osseointegrated fixation while attending a gait measurement session to assess the load applied on the residuum. The objective was to analyse the load applied on the fixation with an emphasis on the sequence of events, the pattern and the magnitude of the forces and moments. The load was measured directly at 200 Hz using a six-channel transducer. Complementary video footage was also studied. The fall was divided into four phases: loading (240 ms), descent (620 ms), impact (365 ms) and recovery (2495 ms). The main impact forces and moments occurred 870 ms and 915 ms after the heel contact, and corresponded to 133 %BW and 17 %BWm, or 1.2 and 11.2 times the maximum forces and moments applied during the previous steps of the participant, respectively. This study provided key information to engineers and clinicians facing the challenge to design equipment, and rehabilitation and exercise programs to restore safely the locomotion of lower limb amputees.

Attenuation of muscle damage by preconditioning with muscle hyperthermia

This study investigated the hypothesis that muscle damage would be attenuated in muscles subjected to passive hyperthermia 1 day prior to exercise. Fifteen male students performed 24 maximal eccentric actions of the elbow flexors with one arm; the opposite arm performed the same exercise 2-4 weeks later. The elbow flexors of one arm received a microwave diathermy treatment that increased muscle temperature to over 40°C, 16-20 h prior to the exercise. The contralateral arm acted as an untreated control. Maximal voluntary isometric contraction strength (MVC), range of motion (ROM), upper arm circumference, muscle soreness, plasma creatine kinase activity and myoglobin concentration were measured 1 day prior to exercise, immediately before and after exercise, and daily for 4 days following exercise. Changes in the criterion measures were compared between conditions (treatment vs. control) using a two-way repeated measures ANOVA with a significance level of P < 0.05. All measures changed significantly following exercise, but the treatment arm showed a significantly faster recovery of MVC, a smaller change in ROM, and less muscle soreness compared with the control arm. However, the protective effect conferred by the diathermy treatment was significantly less effective compared with that seen in the second bout performed 4-6 weeks after the initial bout by a subgroup of the subjects (n = 11) using the control arm. These results suggest that passive hyperthermia treatment 1 day prior to eccentric exercise-induced muscle damage has a prophylactic effect, but the effect is not as strong as the repeated bout effect. © Springer-Verlag 2006.