25 research outputs found
Correcting pervasive errors in RNA crystallography through enumerative structure prediction
Three-dimensional RNA models fitted into crystallographic density maps
exhibit pervasive conformational ambiguities, geometric errors and steric
clashes. To address these problems, we present enumerative real-space
refinement assisted by electron density under Rosetta (ERRASER), coupled to
Python-based hierarchical environment for integrated 'xtallography' (PHENIX)
diffraction-based refinement. On 24 data sets, ERRASER automatically corrects
the majority of MolProbity-assessed errors, improves the average Rfree factor,
resolves functionally important discrepancies in noncanonical structure and
refines low-resolution models to better match higher-resolution models
Tumor Growth Rate Determines the Timing of Optimal Chronomodulated Treatment Schedules
In host and cancer tissues, drug metabolism and susceptibility to drugs vary in a circadian (24 h) manner. In particular, the efficacy of a cell cycle specific (CCS) cytotoxic agent is affected by the daily modulation of cell cycle activity in the target tissues. Anti-cancer chronotherapy, in which treatments are administered at a particular time each day, aims at exploiting these biological rhythms to reduce toxicity and improve efficacy of the treatment. The circadian status, which is the timing of physiological and behavioral activity relative to daily environmental cues, largely determines the best timing of treatments. However, the influence of variations in tumor kinetics has not been considered in determining appropriate treatment schedules. We used a simple model for cell populations under chronomodulated treatment to identify which biological parameters are important for the successful design of a chronotherapy strategy. We show that the duration of the phase of the cell cycle targeted by the treatment and the cell proliferation rate are crucial in determining the best times to administer CCS drugs. Thus, optimal treatment times depend not only on the circadian status of the patient but also on the cell cycle kinetics of the tumor. Then, we developed a theoretical analysis of treatment outcome (TATO) to relate the circadian status and cell cycle kinetic parameters to the treatment outcomes. We show that the best and the worst CCS drug administration schedules are those with 24 h intervals, implying that 24 h chronomodulated treatments can be ineffective or even harmful if administered at wrong circadian times. We show that for certain tumors, administration times at intervals different from 24 h may reduce these risks without compromising overall efficacy
RNA Nanotechnology
Cite this entry as: Yaradoddi J.S. et al. (2019) RNA Nanotechnology. In: MartĂnez L., Kharissova O., Kharisov B. (eds) Handbook of Ecomaterials. Springer, Cham Publisher Name: Springer, Cham DOI: https://doi.org/10.1007/978-3-319-68255-6_193 Print ISBN: 978-3-319-68254-9 Online ISBN: 978-3-319-68255-6 First Online: 14 February 2019DNA, RNA, and proteins are seemed to be immensely substantial tools for nanobiotechnological applications; this is since their exceptional biochemical properties and role. Particularly RNA is categorized over comparatively high-temperature stability, varied organizational pliability, and their performance in natural circumstances. Above properties made, RNA, a valued constituent for bionanotechnology processes and usefulness, especially RNA nanotechnology, could synthesize complex molecules using simple molecules through de nova nanostructures having exceptional utility by the strategy, integration, and manipulations of most predominant processes which are usually based on different RNA structures and because of their vital biochemical properties. The current chapter emphasis on the basic principles inspires the normal design of RNA nanostructures, pronounces the important methods that are used in constructing nanoparticles’ self-assemblages, and further describes the associated challenges and excelled opportunities of RNA nanotechnology in near future.Peer reviewe