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The pathway of hepatitis C virus mRNA recruitment to the human ribosome.
Eukaryotic protein synthesis begins with mRNA positioning in the ribosomal decoding channel in a process typically controlled by translation-initiation factors. Some viruses use an internal ribosome entry site (IRES) in their mRNA to harness ribosomes independently of initiation factors. We show here that a ribosome conformational change that is induced upon hepatitis C viral IRES binding is necessary but not sufficient for correct mRNA positioning. Using directed hydroxyl radical probing to monitor the assembly of IRES-containing translation-initiation complexes, we have defined a crucial step in which mRNA is stabilized upon initiator tRNA binding. Unexpectedly, however, this stabilization occurs independently of the AUG codon, underscoring the importance of initiation factor-mediated interactions that influence the configuration of the decoding channel. These results reveal how an IRES RNA supplants some, but not all, of the functions normally carried out by protein factors during initiation of protein synthesis
FGF23 metabolism, a new paradigm for chronic kidney disease
Introduction: Ā Fibroblast growth factor-23 (FGF23) is a major regulator of phosphate metabolism often elevated in genetic hypophosphataemic disorders and in chronic kidney disease. Recent studies have identified relationships between FGF23 and various markers of iron status including ferritin. New assays measuring the intact form of FGF23 have been released. Ā Objective: Ā To determine the relationship between ferritin and C-terminal and intact FGF23 concentrations in blood. Ā Method: Ā FGF23 concentrations were measured using the 2nd generation, two-site enzyme-linked immunosorbent assay for either C-terminal or intact FGF23 (Immutopics Inc., Ca, USA). Ferritin was measured on a COBAS 6000 (Roche Diagnostics). Assay accuracy and precision were monitored using kit controls supplied by the manufacturers. Ā Results: Ā We observe a weak negative correlation between measurements of C-terminal and intact FGF23 (Pearsonās rho=0.85 p<0.0001). We observed no statistically significant correlation of ferritin concentrations with either FGF23 C-terminal or intact. However high concentrations of ferritin were observed in samples showing low concentrations of C-terminal FGF23 (<140RU/mL) and intact FGF23 (<122pg/mL). Ā Conclusion: Ā Although not statistically significant, we observe a negative relationship between concentrations of ferritin and FGF23. High level of C-terminal FGF23 is found in patients with chronic kidney disease, especially in patients with end-stage renal disease usually regarded as a compensatory response to hyperphosphatemia or phosphate overload. We observed a cluster of patients with retention of both C-terminal and intact FGF23 associated with low levels of ferritin suggesting that metabolism and/or excretion of FGF23 in CDK patients might be an iron dependent mechanism
The Jewish and Hellenistic influences on Paul: A case study of mysterion (Saint Paul).
This study examines how the word mysterion ( mystery ) in the Apostle Paul\u27s writings was influenced by both Jewish and Hellenistic sources. The word mysterion occurs eight times, twice in Romans (11:25 and 16:25), and six times in 1 Corinthians (2:1, 7; 4:1; 13:2; 14:2; and 15:51). This study is divided into two parts. The first section (Part 1) uses an historical methodology to focus on the origin and development of the word mysterion. This section will look not only at the use of the word mysterion within the mystery cults, but also at the way it developed in other areas. By examining these different areas, it will demonstrate not only similarities between the areas\u27 uses of the word mysterion but also the unique characteristics that developed in their use of the word. The second section (Part II) will consist of an exegesis of certain verses in Romans and 1 Corinthians. The main intent of Part II is to examine the word mysterion as it occurs within Romans and 1 Corinthians, to see how the mystery verses relate to each other and how the use of mysterion was influenced by Jewish and Hellenistic sources. (Abstract shortened by UMI.)Dept. of Religious Studies. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis1998 .F72. Source: Masters Abstracts International, Volume: 39-02, page: 0367. Adviser: Dorothy Sly. Thesis (M.A.)--University of Windsor (Canada), 1998
Evolving collective behavior in an artificial ecology
Collective behavior refers to coordinated group motion, common to many animals. The dynamics of a group can be seen as a distributed model, each āanimalā applying the same rule set. This study investigates the use of evolved sensory controllers to produce schooling behavior. A set of artificial creatures āliveā in an artificial world with hazards and food. Each creature has a simple artificial neural network brain that controls movement in different situations. A chromosome encodes the network structure and weights, which may be combined using artificial evolution with another chromosome, if a creature should choose to mate. Prey and predators coevolve without an explicit fitness function for schooling to produce sophisticated, nondeterministic, behavior. The work highlights the role of speciesā physiology in understanding behavior and the role of the environment in encouraging the development of sensory systems
Correspondences Between Cluster Structures.
This thesis introduces quasi-homomorphisms of cluster algebras, a class of maps relating cluster algebras of the same type, but with different coefficients. The definition is given in terms of seed orbits, the smallest equivalence classes of seeds on which the mutation rules for non-normalized seeds are unambiguous. After proving basic structural results, we provide examples of quasi-homomorphisms involving familiar cluster algebras. We construct a quasi-isomorphism between cluster stuctures in Grassmannians and cluster structures in Fock-Goncharov spaces of configurations of affine flags. We explore the related notion of a quasi-automorphism, and compare the resulting group with other groups of symmetries of cluster structures.
For cluster algebras from surfaces, we determine the subgroup of quasi-automorphisms inside the tagged mapping class group of the surface.PhDMathematicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/133477/1/cmfra_1.pd
Phosphorylation stoichiometries of human eukaryotic initiation factors.
Eukaryotic translation initiation factors are the principal molecular effectors regulating the process converting nucleic acid to functional protein. Commonly referred to as eIFs (eukaryotic initiation factors), this suite of proteins is comprised of at least 25 individual subunits that function in a coordinated, regulated, manner during mRNA translation. Multiple facets of eIF regulation have yet to be elucidated; however, many of the necessary protein factors are phosphorylated. Herein, we have isolated, identified and quantified phosphosites from eIF2, eIF3, and eIF4G generated from log phase grown HeLa cell lysates. Our investigation is the first study to globally quantify eIF phosphosites and illustrates differences in abundance of phosphorylation between the residues of each factor. Thus, identification of those phosphosites that exhibit either high or low levels of phosphorylation under log phase growing conditions may aid researchers to concentrate their investigative efforts to specific phosphosites that potentially harbor important regulatory mechanisms germane to mRNA translation
Different strokes for different folks? Revealing the physical characteristics of smartphone users from their swipe gestures
Anthropometrics show that the lengths of many human body segments follow a common proportional relationship. To know the length of one body segment - such as a thumb - potentially provides a predictive route to other physical characteristics, such as overall standing height. In this study, we examined whether it is feasible that the length of a personās thumb could be revealed from the way in which they complete swipe gestures on a touchscreen-based smartphone.From a corpus of approx. 19000 swipe gestures captured from 178 volunteers, we found that people with longer thumbs complete swipe gestures with shorter completion times, higher speeds and with higher accelerations than people with shorter thumbs. These differences were also observed to exist between our male and female volunteers, along with additional differences in the amount of touch pressure applied to the screen.Results are discussed in terms of linking behavioural and physical biometrics. Keywords: Touchscreen gestures, behavioral biometrics, physical biometrics<br/
A comparative analysis of Social Impact Bond and conventional financing approaches to health service commissioning in England: the case of social prescribing
The article compares two social prescribing interventions in Northern England. One was financed through a Social Impact Bond (SIB) and the other was financed in a more conventional way. It utilises a comparative approach to understand the extent to which different methods of financing social prescribing conform to key features of the New Public Management (NPM) or New Public Governance (NPG) in their design and implementation. It finds that a SIB approach tends towards NPM during programme design and implementation and that this creates challenges for social prescribing programmes, the complexity of which appear better suited to an NPG-based relational approach
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