Activation and targeting of extracellular signal-regulated kinases by beta-arrestin scaffolds.

Using both confocal immunofluorescence microscopy and biochemical approaches, we have examined the role of beta-arrestins in the activation and targeting of extracellular signal-regulated kinase 2 (ERK2) following stimulation of angiotensin II type 1a receptors (AT1aR). In HEK-293 cells expressing hemagglutinin-tagged AT1aR, angiotensin stimulation triggered beta-arrestin-2 binding to the receptor and internalization of AT1aR-beta-arrestin complexes. Using red fluorescent protein-tagged ERK2 to track the subcellular distribution of ERK2, we found that angiotensin treatment caused the redistribution of activated ERK2 into endosomal vesicles that also contained AT1aR-beta-arrestin complexes. This targeting of ERK2 reflects the formation of multiprotein complexes containing AT1aR, beta-arrestin-2, and the component kinases of the ERK cascade, cRaf-1, MEK1, and ERK2. Myc-tagged cRaf-1, MEK1, and green fluorescent protein-tagged ERK2 coprecipitated with Flag-tagged beta-arrestin-2 from transfected COS-7 cells. Coprecipitation of cRaf-1 with beta-arrestin-2 was independent of MEK1 and ERK2, whereas the coprecipitation of MEK1 and ERK2 with beta-arrestin-2 was significantly enhanced in the presence of overexpressed cRaf-1, suggesting that binding of cRaf-1 to beta-arrestin facilitates the assembly of a cRaf-1, MEK1, ERK2 complex. The phosphorylation of ERK2 in beta-arrestin complexes was markedly enhanced by coexpression of cRaf-1, and this effect is blocked by expression of a catalytically inactive dominant inhibitory mutant of MEK1. Stimulation with angiotensin increased the binding of both cRaf-1 and ERK2 to beta-arrestin-2, and the association of beta-arrestin-2, cRaf-1, and ERK2 with AT1aR. These data suggest that beta-arrestins function both as scaffolds to enhance cRaf-1 and MEK-dependent activation of ERK2, and as targeting proteins that direct activated ERK to specific subcellular locations

Means and covariance functions for geostatistical compositional data: an axiomatic approach

This work focuses on the characterization of the central tendency of a sample of compositional data. It provides new results about theoretical properties of means and covariance functions for compositional data, with an axiomatic perspective. Original results that shed new light on the geostatistical modeling of compositional data are presented. As a first result, it is shown that the weighted arithmetic mean is the only central tendency characteristic satisfying a small set of axioms, namely continuity, reflexivity and marginal stability. Moreover, this set of axioms also implies that the weights must be identical for all parts of the composition. This result has deep consequences on the spatial multivariate covariance modeling of compositional data. In a geostatistical setting, it is shown as a second result that the proportional model of covariance functions (i.e., the product of a covariance matrix and a single correlation function) is the only model that provides identical kriging weights for all components of the compositional data. As a consequence of these two results, the proportional model of covariance function is the only covariance model compatible with reflexivity and marginal stability

Remarks on the method of comparison equations (generalized WKB method) and the generalized Ermakov-Pinney equation

The connection between the method of comparison equations (generalized WKB method) and the Ermakov-Pinney equation is established. A perturbative scheme of solution of the generalized Ermakov-Pinney equation is developed and is applied to the construction of perturbative series for second-order differential equations with and without turning points.Comment: The collective of the authors is enlarged and the calculations in Sec. 3 are correcte

Reference to the index of the correspondence of Walter Stone and Edmund Morris Miller, 1948 - 1964.

Edmund Morris Miller (1881-1964) scholar, Professor of Philosophy and Psychology and Librarian at the University of Tasmania, had extensive correspondence with Walter Stone, publisher and book collector of Sydney and publisher of Biblionews , between 1948 and 1964 about book collecting and Australian literature. Letters include references to J.K. Morris (d. 1958) ,Henry Kendall and Rev. Thornton Reed's thesis on Kendall, Fred. Bloomfield, Roderick Quinn, C.J. Brennan, W.E. Fitzhenry (editor of The Bulletin ), M. Gilmour and to The Tasmanian, Launceston's first newspaper (9). Morris Miller sometimes enclosed copies of his letters to others, including J.K. Morris (1951), and there are also letters from W.E. Fitzhenry of The Bulletin sent by Morris. Miller to Stone for his files

Congenital rubella syndrome in Iran

BACKGROUND: Congenital rubella syndrome (CRS) can be prevented with appropriate vaccination programs. The prevalence rates of rubella and CRS in Iran are unknown; therefore, the risk of exposure in pregnant women is not clear. The prevalence of CRS in the pre-vaccine period can be estimated by evaluating the proportion of children in the population with sensorineural hearing loss attributable to rubella. METHODS: This was a case-control study to estimate prevalence of CRS in Tehran (Iran) by evaluating the proportion of children with sensorineural hearing loss attributable to rubella. The study used rubella antibody titer as an indicator, and compared the prevalence of rubella antibody between children with and without sensorineural hearing loss. Using these findings, the proportion of cases of sensorineural hearing loss attributable to rubella was estimated. RESULTS: A total of 225 children aged 1 to 4 years were entered into the study (113 cases and 112 controls). There was a significant difference between cases and controls with regard to rubella antibody seropositivity (19.5% vs. 8.9%, respectively, odds ratio = 2.47, 95% CI = 1.04–5.97). The proportion of sensorineural hearing loss cases attributable to rubella was found to be 12%, corresponding to a CRS prevalence of 0.2/1000. CONCLUSION: The prevalence of CRS was approximately 0.2/1000 before rubella vaccination in Iran, Moreover; the results suggest that implementation of appropriate rubella vaccination programs could potentially prevent about 12% of cases of sensorineural hearing loss in Iranian children. This data could potentially be used as baseline data, which in conjunction with an appropriate method, to establish a surveillance system for rubella vaccination in Iran. An appropriate surveillance system is needed, because the introduction of a rubella vaccine without epidemiological data and an adequate monitoring program could result in the shifting of rubella cases to higher ages, and increasing the incidence of CRS

Chlamydial infection among patients attending STD and genitourinary clinics in Taiwan

<p>Abstract</p> <p>Background</p> <p>The main objective of this study is to examine the epidemiology of <it>Chlamydia trachomatis </it>(CT) infection amongst patients (473 men, 180 women) seen two hospitals in Taiwan.</p> <p>Methods</p> <p>Between July 2004 and June 2005, a total of 653 patients provided first-void urine samples for examination of CT using PCR assay.</p> <p>Results</p> <p>The overall prevalence of CT infection was 18.4% (95% confidence interval [CI] 17.3–19.5). Prevalence for men and women were 16.7 % (95% CI 15.3–18.0%) and 22.8% (95% CI 17.5–28.1%), respectively. Age group-specific prevalence was 25.7% (95% CI 22.5–28.9%) in < 20 year olds, 23.5% (95% CI 20.3–26.7%) in 20–24 year olds, 22.3% (95% CI 18.9–25.7%) in 25–30 year olds, and 11.5% (95% CI 10.3–12.7%) in > 30 year olds. Independent risk factors for chlamydial infection included younger age (aged ≤ 30 years) (adjusted odds ratio [AOR] = 2.44; 95% CI 1.52–3.84; <it>p </it>< 0.001), inconsistent condom use (AOR = 2.01; 95% CI 1.32–3.06; <it>p </it>< 0.001), being symptomatic (dysuria, urethral discharge) at the time of testing (AOR = 1.84; 95% CI 1.21–2.80; <it>p </it>< 0.001), and having <it>N. gonorrhoeae </it>infection (AOR = 3.82; 95% CI 2.20–6.58; <it>p </it>< 0.001).</p> <p>Conclusion</p> <p>Genital chlamydial infection is an important sexually transmitted disease in Taiwan. Young Taiwanese persons attending a STD clinic should be screened for CT infection and counselled on condom use.</p

Draft genome sequence of uncultured upland soil cluster gammaproteobacteria gives molecular insights into high-affinity methanotrophy

Aerated soils form the second largest sink for atmospheric CH₄. A nearcomplete genome of uncultured upland soil cluster Gammaproteobacteria that oxidize CH₄ at 2.5 ppmv was obtained from incubated Antarctic mineral cryosols. This first genome of high-affinity methanotrophs can help resolve the mysteries about their phylogenetic affiliation and metabolic potential

Individual freedom versus collective responsibility: too many rights make a wrong?

Individuals might reasonably expect the freedom to make their own decisions regarding their health. However, what happens when an individual's wishes conflict with what is in that individual's best interests? How far should an individual's rights be restricted for his or her own benefit? Similarly, what limitations should be placed on an individual's behaviour when that person's wishes go against what is good for the population in general? Here we discuss the issues that can arise when the rights of individuals conflict with individual and population benefits in relation to infectious diseases

Epstein-Barr Virus Associated Modulation of Wnt Pathway Is Not Dependent on Latent Membrane Protein-1

Previous studies have indicated that Epstein-Barr virus (EBV) can modulate the Wnt pathway in virus-infected cells and this effect is mediated by EBV-encoded oncogene latent membrane protein 1 (LMP1). Here we have reassessed the role of LMP1 in regulating the expression of various mediators of the canonical Wnt cascade. Contradicting the previous finding, we found that the levels of E-cadherin, β-catenin, Glycogen Synthase Kinase 3ß (GSK3β), axin and α-catenin were not affected by the expression of LMP1 sequences from normal B cells or nasopharyngeal carcinoma. Moreover, we also show that LMP1 expression had no detectable effect on the E-cadherin and β-catenin interaction and did not induce transcriptional activation of β-catenin. Taken together these studies demonstrate that EBV-mediated activation of Wnt pathway is not dependent on the expression of LMP1