Role of Jak2/Stat5/Cis pathway components in zebrafish development

By utilizing the zebrafish as a research model, the function of specific cell signalling pathway components in development was investigated. This revealed new roles for the so-called Jak2/Stat5/Cis pathway in blood and sensory organ development, and a conserved prolactin pathway despite divergent functions between species.

Mechanism of allosteric regulation of transglutaminase 2 by GTP

Allosteric regulation is a fundamental mechanism of biological control. Here, we investigated the allosteric mechanism by which GTP inhibits cross-linking activity of transglutaminase 2 (TG2), a multifunctional protein, with postulated roles in receptor signaling, extracellular matrix assembly, and apoptosis. Our findings indicate that at least two components are involved in functionally coupling the allosteric site and active center of TG2, namely (i) GTP binding to mask a conformationally destabilizing switch residue, Arg-579, and to facilitate interdomain interactions that promote adoption of a compact, catalytically inactive conformation and (ii) stabilization of the inactive conformation by an uncommon H bond between a cysteine (Cys-277, an active center residue) and a tyrosine (Tyr-516, a residue located on a loop of the p-barrel 1 domain that harborst he GTP-bindings ite). Although not essential for GTP-mediated inhibition of cross-linking, this H bond enhances the rate of formation of the inactive conformer.

Pop3p is essential for the activity of the RNase MRP and RNase P ribonucleoproteins in vivo

RNase MRP is a ribonucleoprotein (RNP) particle which is involved in the processing of pre-rRNA at site A3 in internal transcribed spacer 1. Although RNase MRP has been analysed functionally, the structure and composition of the particle are not well characterized. A genetic screen for mutants which are synthetically lethal (sl) with a temperature-sensitive (ts) mutation in the RNA component of RNase MRP (rrp2-1) identified an essential gene, POP3, which encodes a basic protein of 22.6 kDa predicted molecular weight. Overexpression of Pop3p fully suppresses the ts growth phenotype of the rrp2-1 allele at 34°C and gives partial suppression at 37°C. Depletion of Pop3p in vivo results in a phenotype characteristic of the loss of RNase MRP activity; A3 cleavage is inhibited, leading to under-accumulation of the short form of the 5.8S rRNA (5.8SS) and formation of an aberrant 5.8S rRNA precursor which is 5'-extended to site A2. Pop3p depletion also inhibits pre-tRNA processing; tRNA primary transcripts accumulate, as well as spliced but 5'- and 3'-unprocessed pre-tRNAs. The Pop3p depletion phenotype resembles those previously described for mutations in components of RNase MRP and RNase P (rrp2-1, rpr1-1 and pop1-1). Immunoprecipitation of epitope-tagged Pop3p co-precipitates the RNA components of both RNase MRP and RNase P. Pop3p is, therefore, a common component of both RNPs and is required for their enzymatic functions in vivo. The ubiquitous RNase P RNP, which has a single protein component in Bacteria and Archaea, requires at least two protein subunits for its function in eukaryotic cells.

Integrated fluid-thermal-structural numerical analysis for the quenching of metallic components

The quenching of a metal component with a channel section in a water tank is numerically simulated. Computational fluid dynamics (CFD) is used to model the multiphase flow and the heat transfer in film boiling, nucleate boiling and convective cooling processes to calculate the difference in heat transfer rate around the component and then combining with the thermal simulation and structure analysis of the component to study the effect of heat transfer rate on the distortion of the U-channel component. A model is also established to calculate the residual stress produced by quenching. The coupling fluid-thermal-structural simulation provides an insight into the deformation of the component and can be used to perform parameter analysis to reduce the distortion of the component. © 2011 Shanghai Jiaotong University and Springer-Verlag Berlin Heidelberg.

Measuring core inflation in Bangladesh : an unobserved components approach

This paper attempts to construct a core inflation measure for Bangladesh using an Unobserved Components modelling approach. One advantage of the Unobserved Components approach is that this method satisfies some essential statistical criteria for a core inflation measure, which are not guaranteed to be met in other traditional exclusionbased methods. The estimated core inflation series performs well in tracking headline inflation and picking the major turning points in actual inflation. It is also found that there is a negative covariance between the shocks to the core inflation and cyclical inflation, indicating that there may be positive correlation between demand and supply shocks in Bangladesh.

Edge evaluation using necessary components

We classify all the different kinds of errors that can occur in edge detection and then develop measures for quantifying these errors. It is shown that these sets of measures are complete and independent and form necessary components of an edge-evaluation scheme. The principle that an edge-evaluation measure should have certain qualitative properties is used to develop a method for combining these error components into a single combined measure.

Determining motion components using the point distribution model

The Point Distribution Model (PDM) has proven effective in modelling variations in shape in sets of images, including those in which motion is involved such as body and hand tracking. This paper proposes an extension to the PDM through a re-parameterisation of the model which uses factors such as the angular velocity and distance travelled for sets of points on a moving shape. This then enables non-linear quantities such as acceleration and the average velocity of the body to be expressed in a linear model by the PDM. Results are shown for objects with known acceleration and deceleration components, these being a simulated pendulum modelled using simple harmonic motion and video sequences of a real pendulum in motion.

Insights into the biodiversity and social benchmarking components of the Northern Australian fire management and carbon abatement programmes

Much of northern Australia’s tropical savannas are subject to annual intense and extensive late dry season wildfires, much of this occurring on Aboriginal land. Based on the successful West Arnhem Land Fire Abatement (WALFA) model, which has resulted in significantly reduced greenhouse gas emissions, fire abatement programmes are planned for other significant regions of northern Australia. This study offers an introduction to the ideas behind a proposed environmental and social benchmarking project that aims to evaluate the potential benefits of expanding the fire abatement program in northern Australia, under the leadership of NAILSMA and its partners. Gaining a better understanding of the biodiversity, social and cultural outcomes of these fire abatement activities is an important component of demonstrating multiple benefits of these programmes. We emphasize the role of both biodiversity and cultural mapping to establish benchmarks and baseline states, with the involvement of Indigenous communities being a key element to optimize social and biodiversity benefits. Consultation with Traditional Owners and ranger groups to establish an agreed set of targets, indicators and sampling protocols and methodologies are critical component of this process. Examples of preliminary work to date are provided.

Evolution of JAK-STAT pathway components : mechanisms and role in immune system development

Background
Lying downstream of a myriad of cytokine receptors, the Janus kinase (JAK) – Signal transducer and activator of transcription (STAT) pathway is pivotal for the development and function of the immune system, with additional important roles in other biological systems. To gain further insight into immune system evolution, we have performed a comprehensive bioinformatic analysis of the JAK-STAT pathway components, including the key negative regulators of this pathway, the SH2-domain containing tyrosine phosphatase (SHP), Protein inhibitors against Stats (PIAS), and Suppressor of cytokine signaling (SOCS) proteins across a diverse range of organisms.

Results
Our analysis has demonstrated significant expansion of JAK-STAT pathway components co-incident with the emergence of adaptive immunity, with whole genome duplication being the principal mechanism for generating this additional diversity. In contrast, expansion of upstream cytokine receptors appears to be a pivotal driver for the differential diversification of specific pathway components.

Conclusion
Diversification of JAK-STAT pathway components during early vertebrate development occurred concurrently with a major expansion of upstream cytokine receptors and two rounds of whole genome duplications. This produced an intricate cell-cell communication system that has made a significant contribution to the evolution of the immune system, particularly the emergence of adaptive immunity.