A Peptide Core Motif for Binding to Heterotrimeric G Protein α Subunits

Recently, in vitro selection using mRNA display was used to identify a novel peptide sequence that binds with high affinity to G{alpha}i1. The peptide was minimized to a 9-residue sequence (R6A-1) that retains high affinity and specificity for the GDP-bound state of G{alpha}i1 and acts as a guanine nucleotide dissociation inhibitor (GDI). Here we demonstrate that the R6A-1 peptide interacts with G{alpha} subunits representing all four G protein classes, acting as a core motif for G{alpha} interaction. This contrasts with the consensus G protein regulatory(GPR) sequence, a 28-mer peptide GDI derived from the GoLoco (G{alpha}i/0-Loco interaction)/GPR motif that shares no homology with R6A-1 and binds only to G{alpha}i1-3 in this assay. Binding of R6A-1 is generally specific to the GDP-bound state of the G{alpha} subunits and excludes association with G{beta}{gamma}. R6A-G{alpha}i1 complexes are resistant to trypsin digestion and exhibit distinct stability in the presence of Mg2+, suggesting that the R6A and GPR peptides exert their activities using different mechanisms. Studies using G{alpha}i1/G{alpha}s chimeras identify two regions of G{alpha}i1 (residues 1–35 and 57–88) as determinants for strong R6A-Gi{alpha}1 interaction. Residues flanking the R6A-1 peptide confer unique binding properties, indicating that the core motif could be used as a starting point for the development of peptides exhibiting novel activities and/or specificity for particular G protein subclasses or nucleotide-bound states

The prognostic significance of the mixed lineage leukaemia partial tandem duplication in acute myeloid leukaemia

This study concerns a specific molecular genetic mutation, the mixed lineage leukaemia partial tandem duplication ( MLL PTD). MLL is a transcriptional regulator that known to be instrumental in both normal haematopoiesis and in leukaemogenesis. This study aimed to evaluate the prognostic importance of this abnormality through investigation of its influence on clinical outcome, its utility as a marker of minimal residual disease (MRD) and the downstream effects of its expression. A qualitative PCR assay was established and determined the frequency of MLL PTD to be 5.2% in de novo AML. MLL PTD was found to be a useful independent marker being associated with a greater risk of relapse and a reduction of relapse free survival and overall survival. A quantitative PCR (QPCR) assay was developed that reliably distinguished AML-related MLL PTDs from the low level of background MLL PTDs occurring normally. Despite a high rate of cytogenetic clonal evolution MLL PTD expression remained stabled between diagnosis and relapse, making it a suitable marker for MRD. Results also suggested the QPCR assay could determine onset of remission and prediction of relapse. Gene expression profiling was used to identify a gene signature unique to the MLL PTD and was found to be distinct from that associated with MLL translocation. Analysis of the gene signature also identified three candidate chemotherapy compounds predicted to antagonise the effects of the MLL PTD. The results of this study could prove instrumental in improving the treatment of MLL PTD patients.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Two- and three-dimensional simulations of core-collapse supernovae with CHIMERA

Ascertaining the core-collapse supernova mechanism is a complex, and yet unsolved, problem dependent on the interaction of general relativity, hydrodynamics, neutrino transport, neutrino-matter interactions, and nuclear equations of state and reaction kinetics. Ab initio modeling of core-collapse supernovae and their nucleosynthetic outcomes requires care in the coupling and approximations of the physical components. We have built our multi-physics CHIMERA code for supernova modeling in 1-, 2-, and 3-D, using ray-by-ray neutrino transport, approximate general relativity, and detailed neutrino and nuclear physics. We discuss some early results from our current series of exploding 2D simulations and our work to perform computationally tractable simulations in 3D using the "Yin-Yang" grid.Comment: Proceedings of the 12th Symposium on Nuclei in the Cosmos. 5-12 August 2012. Cairns, Australia. Published online at http://pos.sissa.it/archive/conferences/146/208/NIC%20XII_208.pdf Corrected typ

Preliminary Understanding of Complexities in Swimming Performance of Common Minnow (Cyprinidae) Taxa

Understanding swimming performance of native freshwater fishes has implications for ecology, conservation, and management. In particular, this type of information has practical importance for improving the understanding of fish dispersal, occurrence, migration, and invasive potential. The objective of this study was to characterize swimming performance of 2 taxa from the comparatively understudied minnow family (Cyprinidae) and test for potential drivers as a function of total length, sex, habitat, morphology, or some combination. The study assessed Spotfin Shiner (Cyprinella spiloptera; n = 66) and Bluntnose Minnow (Pimephales notatus; n = 24) populations from an ontogenic range of male and female individuals from lentic and lotic habitats in Indiana and Ohio. Akaike information criterion (AIC) model selection identified the most parsimonious linear regression model to predict swimming performance of Spotfin Shiner and Bluntnose Minnow independently. Overall, larger Spotfin Shiners were superior swimmers compared with smaller individuals. In both species, individuals having more streamlined heads and elongated caudal regions were better swimmers. Additionally, Spotfin Shiners that were collected from lotic environments were generally better swimmers than individuals from lentic environments. Models did not recover sex-specific effects in either species—or meaningful total length, or habitat effects, in Bluntnose Minnows. Overall, this study provides evidence of a complex series of swimming performance covariates when assessing or understanding performance. This has implications for aquatic population, assemblage, and community ecology as well as management and conservation efforts

School Administrators’ Perceptions of Critical Teacher Skills

Forty school administrators in the Lower Hudson Valley of New York State were surveyed about the characteristics of preservice and novice teachers believed most critical. These administrators represented a broad and socio-demographically diverse cross-section of rural, suburban and urban school districts. The administrators collectively rated establishing rapport with students and behavior management as the most critical skills for preservice and new teachers to possess. Examining roles separately, assistant principals valued rapport with students and creating effective lessons as most important, whereas principals rated effectively communicating with parents and guardians, and reflecting on teaching performance as being most important. The most frequently cited reason for not hiring or reappointing a candidate was lack of engagement with students. An ability to collaborate with colleagues as well as competence in working with students with disabilities and ELLS represent skills administrators also valued in teacher candidates. Furthermore, administrators identified authentic classroom experiences prior to student teaching as invaluable preparation for the classroom and a “difference-maker” in the quality and effectiveness of preservice teacher candidates. Finally, administrators noted areas of current and future job demand; need and growth areas for teachers were reported to be STEM and STEAM, Special Education, Bilingual/Language Education, and Dual Certification

The only known egg of the Night Parrot? A molecular and morphometric assessment of an alleged egg from the Tanami Desert

The Night Parrot Pezoporus occidentalis is a much sought-after, recently ‘rediscovered’, endangered nocturnal parrot, endemic to arid Central Australia. Very little is known of its ecology, and its eggs have never been formally described. The literature on the eggs of the Night Parrot is collated here, and the provenance of an alleged Night Parrot egg found in the Tanami Desert, Northern Territory, in 1983 was assessed using DNA analysis and physical characteristics. Anecdotal reports from the late 19th–early 20th Century indicate that the Night Parrot lays a clutch of two to six roundish, white eggs. We suggest that its eggs are probably similar to and slightly larger than those of its congener, the Ground Parrot P. wallicus. The alleged Night Parrot egg was definitively identified by mitochondrial DNA analysis to be from the Brown Quail Synoicus ypsilophorus. This represents the first evidence of breeding by this species in the Tanami Desert, and lays to rest a long-standing misconception regarding the parrot

Advancing Nucleosynthesis in Self-consistent, Multidimensional Models of Core-Collapse Supernovae

We investigate core-collapse supernova (CCSN) nucleosynthesis in polar axisymmetric simulations using the multidimensional radiation hydrodynamics code CHIMERA. Computational costs have traditionally constrained the evolution of the nuclear composition in CCSN models to, at best, a 14-species $\alpha$-network. Such a simplified network limits the ability to accurately evolve detailed composition, neutronization and the nuclear energy generation rate. Lagrangian tracer particles are commonly used to extend the nuclear network evolution by incorporating more realistic networks in post-processing nucleosynthesis calculations. Limitations such as poor spatial resolution of the tracer particles, estimation of the expansion timescales, and determination of the "mass-cut" at the end of the simulation impose uncertainties inherent to this approach. We present a detailed analysis of the impact of these uncertainties on post-processing nucleosynthesis calculations and implications for future models.Comment: Proceedings of the 13th Symposium on Nuclei in the Cosmos. 7-11 July 2014. Debrecen, Hungar