The expansion of GPCR transactivation-dependent signalling to include serine/threonine kinase receptors represents a new cell signalling frontier

G protein-coupled receptor (GPCR) signalling is mediated through transactivation-independent signalling pathways or the transactivation of protein tyrosine kinase receptors and the recently reported activation of the serine/threonine kinase receptors, most notably the transforming growth factor-β receptor family. Since the original observation of GPCR transactivation of protein tyrosine kinase receptors, there has been considerable work on the mechanism of transactivation and several pathways are prominent. These pathways include the “triple membrane bypass” pathway and the generation of reactive oxygen species. The recent recognition of GPCR transactivation of serine/threonine kinase receptors enormously broadens the GPCR signalling paradigm. It may be predicted that the transactivation of serine/threonine kinase receptors would have mechanistic similarities with transactivation of tyrosine kinase pathways; however, initial studies suggest that these two transactivation pathways are mechanistically distinct. Important questions are the relative importance of tyrosine and serine/threonine transactivation pathways, the contribution of transactivation to overall GPCR signalling, mechanisms of transactivation and the range of cell types in which this phenomenon occurs. The ultimate significance of transactivation-dependent signalling remains to be defined but it appears to be prominent and if so will represent a new cell signalling frontier.     

Rolling of Al-SiC_p Composites

Aluminum based metal matrix composites are offering o utstanding properties in a number of automotive and aircraft components and body structures. The major advantages of these composite materials are their high st rength to weight ratio, high stiffness, high hardness, wear resistance, low coef ficient of thermal expansion, superior dimensional stability and versatility to designer. In addition to these their isotropic properties, good forming characte ristics, easy availability of cheaper reinforcements...     

Excretion of acid hydrolases during molting inPhilosamia ricini

Summary The level of the acid hydrolases -glucuronidase (EC 3.2.3.11), acid phosphatase (EC 3.1.3.2) and acid protease (EC 3.4.4) was studied during larval growth and molting inP. ricini. The level of activity of these enzymes remained low during larval growth; however, the level increased sharply at the time of molting and declined sharply thereafter in the newly ecdysed insect. Interestingly, the diminished activity of these enzymes was almost quantitatively recovered in the cast-off cuticle. The excretion of acid hydrolases through the cast-off cuticle has hitherto not been reported in insects during molting.     

Effect of molasses binder on the physical and mechanical properties

Molasses was used as an alternative binder to the bentonite binder. The change in moisture absorption by pellets prepared with different iron ores and different molasses contents were investigated. Iron ore properties exerted the major effect on pellet behavior and final pellet quality. The absorbed moisture content of pellets prepared without binder, bentonite-added pellets, and molasses-added pellets were in the range of 7.72%–9.95%, 9.62%–10.84%, and 6.14%-6.69%, respectively. The wet pellet compressive strength of molasses-added pellets(43–230 N/pellet) was superior to that of bentonite-added pellets(9.47–11.92 N/pellet). The compressive strength of dried molasses-modified pellets increased to 222–394 N/pellet, which is currently the highest value achieved for dried pellets.     

A genome-wide association study for celiac disease identifies risk variants in the region harboring IL2 and IL21

We tested 310,605 SNPs for association in 778 individuals with celiac disease and 1,422 controls. Outside the HLA region, the most significant finding (rs13119723; P = 2.0 x 10(-7)) was in the KIAA1109-TENR-IL2-IL21 linkage disequilibrium block. We independently confirmed association in two further collections (strongest association at rs6822844, 24 kb 5' of IL21; meta-analysis P = 1.3 x 10(-14), odds ratio = 0.63), suggesting that genetic variation in this region predisposes to celiac disease.     

Formalising and Detecting Community Structures in Real World Complex Networks

Community structure is an integral characteristic of real world networks whichever processes or areas they emerge from. This paper addresses the problem of community structure detection theoretically as well as computationally. The authors introduce a number of concepts such as the neighbourhood and strength of a subgraph, p-community, local maximal p-community, hubs, and outliers that play elemental role in formalising the concept of community structure in complex networks. A few preliminary results have been derived that lead to the development of an algorithm for community structure detection in undirected unweighted networks. The algorithm is based on a local seed expansion strategy that uses the concept of interaction coefficient. The authors have analysed the algorithm on a number of parameters such as accuracy, stability, and quality on synthetic and real world networks from different areas.     

Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus

Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the α-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-α primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.     

The PDZ2 domain of zonula occludens-1 and -2 is a phosphoinositide binding domain

Zonula occludens proteins (ZO) are postsynaptic density protein-95 discs large-zonula occludens (PDZ) domain-containing proteins that play a fundamental role in the assembly of tight junctions and establishment of cell polarity. Here, we show that the second PDZ domain of ZO-1 and ZO-2 binds phosphoinositides (PtdInsP) and we identified critical residues involved in the interaction. Furthermore, peptide and PtdInsP binding of ZO PDZ2 domains are mutually exclusive. Although lipid binding does not seem to be required for plasma membrane localisation of ZO-1, phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P ₂) binding to the PDZ2 domain of ZO-2 regulates ZO-2 recruitment to nuclear speckles. Knockdown of ZO-2 expression disrupts speckle morphology, indicating that ZO-2 might play an active role in formation and stabilisation of these subnuclear structures. This study shows for the first time that ZO isoforms bind PtdInsPs and offers an alternative regulatory mechanism for the formation and stabilisation of protein complexes in the nucleus.     

Optimal sampling frequency for volatility forecast models for the Indian stock markets

This paper evaluates the performance of conditional variance models using high‐frequency data of the National Stock Index (S&P CNX NIFTY) and attempts to determine the optimal sampling frequency for the best daily volatility forecast. A linear combination of the realized volatilities calculated at two different frequencies is used as benchmark to evaluate the volatility forecasting ability of the conditional variance models (GARCH (1, 1)) at different sampling frequencies. From the analysis, it is found that sampling at 30 minutes gives the best forecast for daily volatility. The forecasting ability of these models is deteriorated, however, by the non‐normal property of mean adjusted returns, which is an assumption in conditional variance models. Nevertheless, the optimum frequency remained the same even in the case of different models (EGARCH and PARCH) and different error distribution (generalized error distribution, GED) where the error is reduced to a certain extent by incorporating the asymmetric effect on volatility. Our analysis also suggests that GARCH models with GED innovations or EGRACH and PARCH models would give better estimates of volatility with lower forecast error estimates. Copyright © 2008 John Wiley & Sons, Ltd.