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Elevated expression of artemis in human fibroblast cells is associated with cellular radiosensitivity and increased apoptosis

2013-02-11T14:46:19Z

Title: Elevated expression of artemis in human fibroblast cells is associated with cellular radiosensitivity and increased apoptosis Authors: Ulus-Senguloglu, G; Arlett, CF; Plowman, PN; Parnell, J; Patel, N; Bourton, EC; Parris, CN Abstract: Background: The objective of this study was to determine the molecular mechanism(s) responsible for cellular radiosensitivity in two human fibroblast cell lines 84BR and 175BR derived from two cancer patients. Methods: Clonogenic assays were performed following exposure to increasing doses of gamma radiation to confirm radiosensitivity. γ-H2AX foci assays were used to determine the efficiency of DNA double strand break (DSB) repair in cells. Quantitative-PCR (Q-PCR) established the expression levels of key DNA DSB repair proteins. Imaging flow cytometry using Annexin V-FITC was used to compare artemis expression and apoptosis in cells. Results: Clonogenic cellular hypersensitivity in the 84BR and 175BR cell lines was associated with a defect in DNA DSB repair measured by the γ-H2AX foci assay. Q-PCR analysis and imaging flow cytometry revealed a two-fold overexpression of the artemis DNA repair gene which was associated with an increased level of apoptosis in the cells before and after radiation exposure. Over-expression of normal artemis protein in a normal immortalised fibroblast cell line NB1-Tert resulted in increased radiosensitivity and apoptosis. Conclusion: We conclude elevated expression of artemis is associated with higher levels of DNA DSB, radiosensitivity and elevated apoptosis in two radio-hypersensitive cell lines. These data reveal a potentially novel mechanism responsible for radiosensitivity and show that increased artemis expression in cells can result in either radiation resistance or enhanced sensitivity. Description: Copyright @ 2012 Nature Publishing Group

The role of the North Atlantic Oscillation in controlling U.K. butterfly population size and phenology

2013-02-11T14:41:05Z

Title: The role of the North Atlantic Oscillation in controlling U.K. butterfly population size and phenology Authors: Westgarth-Smith, A; Roy, DB; Scholze, M; Tucker, A; Sumpter, JP Abstract: 1. The North Atlantic Oscillation (NAO) exerts considerable control on U.K. weather. This study investigates the impact of the NAO on butterfly abundance and phenology using 34 years of data from the U.K. Butterfly Monitoring Scheme (UKBMS). 2. The study uses a multi-species indicator to show that the NAO does not affect overall U.K. butterfly population size. However, the abundance of bivoltine butterfly species, which have longer flight seasons, were found to be more likely to respond positively to the NAO compared with univoltine species, which show little or a negative response. 3. A positive winter NAO index is associated with warmer weather and earlier flight dates for Anthocharis cardamines (Lepidoptera: Pieridae), Melanargia galathea (Lepidoptera: Nymphalidae), Aphantopus hyperantus (Lepidoptera: Nymphalidae), Pyronia tithonus (Lepidoptera: Nymphalidae), Lasiommata megera (Lepidoptera: Nymphalidae) and Polyommatus icarus (Lepidoptera: Lycaenidae). In bivoltine species, the NAO affects the phenology of the first generation, the timing of which indirectly controls the timing of the second generation. 4. The NAO influences the timing of U.K. butterfly flight seasons more strongly than it influences population size. Description: Copyright @ 2012 The Authors. This article can be accessed from the links below.

What values do the public want their health care systems to use in evaluating technologies?

2013-02-11T14:33:43Z

Title: What values do the public want their health care systems to use in evaluating technologies? Authors: Buxton, MJ; Chambers, JD Description: Copyright @ 2011 The Authors. This article can be accessed from the links below.

Supraspinal fatigue after normoxic and hypoxic exercise in humans

2013-02-11T14:24:29Z

Title: Supraspinal fatigue after normoxic and hypoxic exercise in humans Authors: Goodall, S; Gonzalez-Alonso, J; Ali, L; Ross, EZ; Romer, LM Abstract: Inadequate cerebral O₂ availability has been proposed to be an important contributing factor to the development of central fatigue during strenuous exercise. Here we tested the hypothesis that supraspinal processes of fatigue would be increased after locomotor exercise in acute hypoxia compared to normoxia, and that such change would be related to reductions in cerebral O₂ delivery and tissue oxygenation. Nine endurance-trained cyclists completed three constant-load cycling exercise trials at ∼80% of maximal work rate: (1) to the limit of tolerance in acute hypoxia; (2) for the same duration but in normoxia (control); and (3) to the limit of tolerance in normoxia. Throughout each trial, prefrontal cortex tissue oxygenation and middle cerebral artery blood velocity (MCAV) were assessed using near-infrared spectroscopy and trans-cranial Doppler sonography, respectively. Cerebral O₂ delivery was calculated as the product of arterial O₂ content and MCAV. Before and immediately after each trial, twitch responses to supramaximal femoral nerve stimulation and transcranial magnetic stimulation were obtained to assess neuromuscular and cortical function, respectively. Exercise time was reduced by 54%in hypoxia compared to normoxia (3.6 ± 1.3 vs. 8.1 ± 2.9 min; P<0.001). Cerebral O₂ delivery,cerebral oxygenation and maximum O₂ uptake were reduced whereas muscle electromyographic activity was increased in hypoxia compared to control (P <0.05).Maximum voluntary force and potentiated quadriceps twitch force were decreased below baseline after exercise in each trial;the decreases were greater in hypoxia compared to control (P<0.001), but were not different in the exhaustive trials (P>0.05). Cortical voluntary activation was also decreased after exercise in all trials, but the decline in hypoxia (Δ18%) was greater than in the normoxic trials (Δ5-9%)(P <0.05). The reductions in cortical voluntary activation were paralleled by reductions in cerebral O₂ delivery. The results suggest that curtailment of exercise performance in acute severe hypoxia is due, in part, to failure of drive from the motor cortex, possibly as a consequence of diminished O₂ availability in the brain. Description: Copyright @ 2012 The Authors. This article can be accessed from the links below.