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PLoS ONE (2)
Briefings in Functional Genomics (1)
The Open Ophthalmology Journal (1)
Chen, Kevin C. (3)
Aizman, Alexander (1)
Cai, Yujie (1)
Chen, Kevin C (1)
Gould, David W. (1)
Hedges, Dale J. (1)
Jung, Jesse J (1)
Kumar, M. Senthil (1)
Lukic, Sergio (1)
Xiao, Jingfa (1)
Xie, Honglin (1)
Year of Publication
Modes of Action of ADP-Ribosylated Elongation Factor 2 in Inhibiting the Polypeptide Elongation Cycle: A Modeling Study
Despite the fact that ADP-ribosylation of eukaryotic elongation factor 2 (EF2) leads to inhibition of protein synthesis, the mechanism by which ADP-ribosylated EF2 (ADPR•EF2) causes this inhibition remains controversial. Here, we applied modeling approaches to investigate the consequences of various modes of ADPR•EF2 inhibitory actions on the two coupled processes, the polypeptide chain elongation and ADP-ribosylation of EF2. Modeling of experimental data indicates that ADPR•EF2 fully blocks the late-phase translocation of tRNAs; but the impairment in the translocation upstream process, mainly the GTP-dependent factor binding with the pretranslocation ribosome and/or the guanine nucleotide exchange in EF2, is responsible for the overall inhibition kinetics. The reduced ADPR•EF2-ribosome association spares the ribosome to bind and shield native EF2 against toxin attack, thereby deferring the inhibition of protein synthesis inhibition and inactivation of EF2. Minimum association with the ribosome also keeps ADPR•EF2 in an accessible state for toxins to catalyze the reverse reaction when nicotinamide becomes available. Our work underscores the importance of unveiling the interactions between ADPR•EF2 and the ribosome, and argues against that toxins inhibit protein synthesis through converting native EF2 to a competitive inhibitor to actively disable the ribosome.
Evolution of animal Piwi-interacting RNAs and prokaryotic CRISPRs
Kumar, M. Senthil
Briefings in Functional Genomics
Piwi-interacting RNAs (piRNAs) and CRISPR RNAs (crRNAs) are two recently discovered classes of small noncoding RNA that are found in animals and prokaryotes, respectively. Both of these novel RNA species function as components of adaptive immune systems that protect their hosts from foreign nucleic acids—piRNAs repress transposable elements in animal germlines, whereas crRNAs protect their bacterial hosts from phage and plasmids. The piRNA and CRISPR systems are nonhomologous but rather have independently evolved into logically similar defense mechanisms based on the specificity of targeting via nucleic acid base complementarity. Here we review what is known about the piRNA and CRISPR systems with a focus on comparing their evolutionary properties. In particular, we highlight the importance of several factors on the pattern of piRNA and CRISPR evolution, including the population genetic environment, the role of alternate defense systems and the mechanisms of acquisition of new piRNAs and CRISPRs.
piRNA; CRISPR; co-evolution; transposable elements; phage; plasmids
Selective Constraint on Copy Number Variation in Human Piwi-Interacting RNA Loci
Gould, David W.
Hedges, Dale J.
Piwi-interacting RNAs (piRNAs) are a recently discovered class of small non-coding RNA found in animals. PiRNAs are primarily expressed in the germline where their best understood function is to repress transposable elements. Unlike previous studies that investigated the evolution of piRNA-generating loci at the level of nucleotide substitutions, here we studied the evolution of piRNA-generating loci at the level of copy number variation (i.e. duplications and deletions) using genome-wide copy number variation data from three human populations. Our analysis shows that at the level of copy number variation there is strong selective constraint and a very high mutation rate in human piRNA-generating loci. Our results differ from a model of positive selection on copy number variation in piRNA-generating loci previously proposed in rodents. We discuss possible reasons for this difference based on the transposable element insertion histories in the rodent and primate lineages.
High Definition Spectral Domain Optical Coherence Tomography Findings in Three Patients with Solar Retinopathy and Review of the Literature
Jung, Jesse J
The Open Ophthalmology Journal
To describe ocular findings in 3 cases of solar retinopathy using high definition, spectral domain optical coherence tomography (SD-OCT) and review the literature for optical coherence tomography (OCT) characteristics associated with worse vision.
Case series and retrospective review of clinical features and Spectralis SD-OCT (Heidelberg Engineering, Vista, California, United States of America). A literature review of OCT findings in cases of solar retinopathy reported on MEDLINE was also performed and analyzed.
Six eyes of 3 patients with solar retinopathy revealed significant foveal pathology. Visual acuity ranged from Snellen 20/30 to 20/50. High definition SD-OCT demonstrated defects at the level of the inner and outer segment junction of the photoreceptors as well as in the inner high reflective layer. There was a significant correlation between chronic disruption of the inner photoreceptor junction with worse vision based on the current case series and literature review.
Screening patients with exposure to central foveal damage from solar retinopathy with high definition SD-OCT improves diagnosis and assessment of photoreceptor damage and vision loss.
Solar retinopathy; fovea; spectral domain optical coherence tomography; Spectralis SD-OCT.
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