238 research outputs found

    Acetylation of the HIV-1 Tat protein by p300 is important for its transcriptional activity.

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    AbstractThe human immunodeficiency virus 1 (HIV-1) Tat protein activates transcriptional elongation by recruiting the positive transcription elongation factor (pTEFb) complex to the TAR RNA element, which is located at the 5′ extremity of all viral transcripts [1–3]. Tat also associates in vitro and in vivo with the transcriptional coactivator p300/CBP [4–6]. This association has been proposed to recruit the histone acetyltransferase (HAT) activity of p300 to the integrated HIV-1 promoter. We have observed that the purified p300 HAT domain acetylates recombinant Tat proteins in vitro and that Tat is acetylated in vivo. The major targets of acetylation by p300 are lysine residues (Lys50 and Lys51) in the arginine-rich motif (ARM) used by Tat to bind RNA and for nuclear import. Mutation of these residues in full-length recombinant Tat blocked its acetylation in vitro. Furthermore, mutation of these lysine residues to arginine markedly decreased the synergistic activation of he HIV promoter by Tat and p300 or by Tat and cyclin T1. These results demonstrate that acetylation of Tat by p300/CBP is important for its transcriptional activation of the HIV promoter

    Durability design of reinforced concrete structures: a comparison of the use of durability indexes in the deemed-to-satisfy approach and the full-probabilistic approach

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    Abstract: To show the application of the chloride conductivity index test in service life prediction (SLP) using both the deemed-to-satisfy and probabilistic approaches to performance-based durability design. It is desirable to adopt a performance-based approach with respect to durability design of reinforced concrete (RC) structures. This is based on the perception that the durability of RC is achieved when the limiting value from an established test method is met. In South Africa, the durability index (DI) approach has been developed, which permits performance-based specifications for durability of RC. This approach involves the application of a test method together with a SLP model. This integrated approach links material properties directly with the expected service life of RC structures and environmental conditions. Two DIs are relevant to degradation processes in RC: the chloride conductivity index which is related to chloride ingress, and the oxygen permeability index related to carbonation. The study presented here focuses on the application of the chloride conductivity index as the main input parameter of a SLP model concerned with chloride-induced reinforcement corrosion. The methodology and output of the SLP model as applied in the deemed-to-satisfy approach are compared with those of the probabilistic approach. Both approaches are exemplified using a concrete pier cast in situ in a marine environment. The performance-based durability specifications from the deemed-to-satisfy approach are found to be more conservative compared to those of the probabilistic approach

    Fragmentation processes of ionized 5-fluorouracil in the gas phase and within clusters

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    We have measured mass spectra for positive ions produced from neutral 5-fluorouracil by electron impact at energies from 0 to 100 eV. Fragment ion appearance energies of this (radio-)chemotherapy agent have been determined for the first time and we have identified several new fragment ions of low abundance. The main fragmentations are similar to uracil, involving HNCO loss and subsequent HCN loss, CO loss, or FCCO loss. The features adjacent to these prominent peaks in the mass spectra are attributed to tautomerization preceding the fragmentation and/or the loss of one or two additional hydrogen atoms. A few fragmentions are distinct for 5-fluorouracil compared to uracil, most notably the production of the reactive moiety CF+. Finally, multiphoton ionization mass spectra are compared for 5-fluorouracil from a laser thermal desorption source and from a supersonic expansion source. The detection of a new fragment ion at 114 u in the supersonic expansion experiments provides the first evidence for a clustering effect on the radiation response of 5-fluorouracil. By analogy with previous experiments and calculations on protonated uracil, this is assigned to NH3 loss from protonated 5-fluorouracil

    Modifying patterns of movement in people with low back pain -does it help? A systematic review

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    Background: Physiotherapy for people with low back pain frequently includes assessment and modification of lumbo-pelvic movement. Interventions commonly aim to restore normal movement and thereby reduce pain and improve activity limitation. The objective of this systematic review was to investigate: (i) the effect of movement-based interventions on movement patterns (muscle activation, lumbo-pelvic kinematics or postural patterns) of people with low back pain (LBP), and (ii) the relationship between changes in movement patterns and subsequent changes in pain and activity limitation. Methods. MEDLINE, Cochrane Central, EMBASE, AMI, CINAHL, Scopus, AMED, ISI Web of Science were searched from inception until January 2012. Randomised controlled trials or controlled clinical trials of people with LBP were eligible for inclusion. The intervention must have been designed to influence (i) muscle activity patterns, (ii) lumbo-pelvic kinematic patterns or (iii) postural patterns, and included measurement of such deficits before and after treatment, to allow determination of the success of the intervention on the lumbo-pelvic movement. Twelve trials (25% of retrieved studies) met the inclusion criteria. Two reviewers independently identified, assessed and extracted data. The PEDro scale was used to assess method quality. Intervention effects were described using standardised differences between group means and 95% confidence intervals. Results: The included trials showed inconsistent, mostly small to moderate intervention effects on targeted movement patterns. There was considerable heterogeneity in trial design, intervention type and outcome measures. A relationship between changes to movement patterns and improvements in pain or activity limitation was observed in one of six studies on muscle activation patterns, one of four studies that examined the flexion relaxation response pattern and in two of three studies that assessed lumbo-pelvic kinematics or postural characteristics. Conclusions: Movement-based interventions were infrequently effec tive for changing observable movement patterns. A relationship between changes in movement patterns and improvement in pain or activity limitation was also infrequently observed. No independent studies confirm any observed relationships. Challenges for future research include defining best methods for measuring (i) movement aberrations, (ii) improvements in movements, and (iii) the relationship between changes in how people move and associated changes in other health indicators such as activity limitation
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