Molecular dynamics study of accelerated ion-induced shock waves in biological media

We present a molecular dynamics study of the effects of carbon- and iron-ion induced shock waves in DNA duplexes in liquid water. We use the CHARMM force field implemented within the MBN Explorer simulation package to optimize and equilibrate DNA duplexes in liquid water boxes of different sizes and shapes. The translational and vibrational degrees of freedom of water molecules are excited according to the energy deposited by the ions and the subsequent shock waves in liquid water are simulated. The pressure waves generated are studied and compared with an analytical hydrodynamics model which serves as a benchmark for evaluating the suitability of the simulation boxes. The energy deposition in the DNA backbone bonds is also monitored as an estimation of biological damage, something which is not possible with the analytical model

Temozolomide-mediated radiation enhancement in glioblastoma: a report on underlying mechanisms.

PURPOSE: In this study, we investigated the mechanisms by which temozolomide enhances radiation response in glioblastoma cells. EXPERIMENTAL DESIGN: Using a panel of four primary human glioblastoma cell lines with heterogeneous O(6)-methylguanine-DNA methyltransferase (MGMT) protein expression, normal human astrocytes, and U87 xenografts, we investigated (a) the relationship of MGMT status with efficacy of temozolomide-based chemoradiation using a panel of in vitro and in vivo assays; (b) underlying mechanisms by which temozolomide enhances radiation effect in glioblastoma cells; and (c) strategies to overcome resistance to radiation + temozolomide. RESULTS: Temozolomide enhances radiation response most effectively in glioblastomas without detectable MGMT expression. On concurrent radiation + temozolomide administration in MGMT-negative glioblastomas, there seems to be decreased double-strand DNA (dsDNA) repair capacity and enhanced dsDNA damage compared either with radiation alone or with sequentially administered temozolomide. Our data suggest that O(6)-benzylguanine can enhance the antitumor effects of concurrent radiation + temozolomide in MGMT-positive cells by enhancing apoptosis and the degree of dsDNA damage. O(6)-Benzylguanine was most effective when administered concurrently with radiation + temozolomide and had less of an effect when administered with temozolomide in the absence of radiation or when administered sequentially with radiation. Our in vivo data using U87 xenografts confirmed our in vitro findings. CONCLUSIONS: The present study shows that temozolomide enhances radiation response most effectively in MGMT-negative glioblastomas by increasing the degree of radiation-induced double-strand DNA damage. In MGMT-positive glioblastomas, depletion of MGMT by the addition of O(6)-benzylguanine significantly enhances the antitumor effect of concurrent radiation + temozolomide. These are among the first data showing mechanisms of synergy between radiation and temozolomide and the effect of MGMT

Outcome and Toxicity of Proton Therapy for Vestibular Schwannoma: A Cohort Study

Objective: To assess the efficacy and toxicity of proton radiotherapy in vestibular schwannoma. Study Design: Retrospective chart review and volumetric MRI-analyses. Setting: Tertiary referral center. Patients: Vestibular schwannoma patients treated with protons between 2003 and 2018. Intervention: Proton radiotherapy. Main Outcome Measures: Tumor control was defined as not requiring salvage treatment. Progressive hearing loss was defined as a decrease in maximum speech discrimination score below the 95% critical difference in reference to the pretreatment score. Hearing assessment includes contralateral hearing and duration of follow-up. Dizziness and/or unsteadiness and facial and trigeminal nerve function were scored. Patients who had surgery prior to proton radiotherapy were separately assessed. Results: Of 221 included patients, 136 received single fraction and 85 fractionated proton radiotherapy. Actuarial 5-year local control rate was 96% (95% CI 90-98%). The median radiological follow-up was 4.5 years. Progressive postirradiation speech discrimination score loss occurred in 42% of patients with audiometric follow-up within a year. Facial paresis was found in 5% (usually mild), severe dizziness in 5%, and trigeminal neuralgia in 5% of patients receiving protons as primary treatment. Conclusions: Proton radiotherapy achieves high tumor control with modest side effects aside from hearing loss in vestibular schwannoma patients. Limited and heterogeneous outcome reporting hamper comparisons to the literature. Potential sequelae of radiation therapy impacting vestibular function, cognitive function, and quality of life warrant further evaluation. Subgroups that benefit most from proton radiotherapy should be identified to optimize allocation and counterbalance its costs.Otorhinolaryngolog

Métodos alternativos do teste de frio para avaliação do vigor de sementes de milho Alternative methods of the cold test for evaluation of corn seed vigor

O presente trabalho teve como objetivo básico estudar comparativamente quatro métodos para a condução do teste de frio, visando a avaliação do potencial fisiológico das sementes de milho. Para tanto, foram utilizados dois cultivares de milho (AG 3010 e AG 5011), cada um representado por 5 lotes com potenciais fisiológicos distintos. Amostras de sementes de todos os lotes foram submetidas a quatro procedimentos do teste de frio, a saber: "terra" (mistura de terra e areia) em caixas empilhadas (método tradicional); "terra" em caixas dispostas lado a lado; bandeja com "terra"; bandeja com "terra" + papel toalha. Estes procedimentos foram comparados com os testes de germinação padrão, envelhecimento acelerado e emergência das plântulas em campo. O teste de frio em bandeja oferece maior facilidade para padronização e permite a obtenção de resultados mais consistentes do que o teste de frio utilizando-se "terra" em caixas, inclusive quanto à relação com a emergência das plântulas em campo.<br>This research was conducted with the objective of comparing different procedures of the cold test to evaluate corn seed vigor. Two cultivars (AG 3010 and AG 5011) represented by 5 lots each were used. Seed samples of all lots were submitted to four procedures of the cold test: stacked deep-box (Brazilian traditional method), deep-box disposed side by side, tray with soil and tray with soil + paper towel, in cold chamber at 10°C for seven days followed by germination at 25°C. Those procedures were also compared with germination, accelerated aging and seedling field emergence tests. The cold test in tray exhibited a great level of standardization than the procedure known as deep-box, allowing for more consistent results and a closer relationship to seedling field emergence

[Album de photographies du Canada et des États-Unis] / [divers photographes]

Appartient à l’ensemble documentaire : PhoGéo