G Protein Subunit Dissociation and Translocation Regulate Cellular Response to Receptor Stimulation

We examined the role of G proteins in modulating the response of living cells to receptor activation. The response of an effector, phospholipase C-β to M3 muscarinic receptor activation was measured using sensors that detect the generation of inositol triphosphate or diacylglycerol. The recently discovered translocation of Gβγ from plasma membrane to endomembranes on receptor activation attenuated this response. A FRET based G protein sensor suggested that in contrast to translocating Gβγ, non-translocating Gβγ subunits do not dissociate from the αq subunit on receptor activation leading to prolonged retention of the heterotrimer state and an accentuated response. M3 receptors with tethered αq induced differential responses to receptor activation in cells with or without an endogenous translocation capable γ subunit. G protein heterotrimer dissociation and βγ translocation are thus unanticipated modulators of the intensity of a cell's response to an extracellular signal

Measurement of gauge blocks by interferometry

The key comparison EURAMET.L-K1.2011 on gauge blocks was carried out in the framework of a EURAMET project starting in 2012 and ending in 2015. It involved the participation of 24 National Metrology Institutes from Europe and Egypt, respectively. 38 gauge blocks of steel and ceramic with nominal central lengths between 0.5 mm and 500 mm were circulated. The comparison was conducted in two loops with two sets of artifacts. A statistical technique for linking the reference values was applied. As a consequence the reference value of one loop is influenced by the measurements of the other loop although they did not even see the artifacts of the others. This influence comes solely from three "linking laboratories" which measure both sets of artifacts. In total there were 44 results were not fully consistent with the reference values. This represents 10% of the full set of 420 results which is a considerable high number. At least 12 of them are clearly outliers where the participants have been informed by the pilot as soon as possible. The comparison results help to support the calibration and measurement capabilities (CMCs) of the laboratories involved in the CIPM MRA

Subcellular optogenetic inhibition of G proteins generates signaling gradients and cell migration

Cells sense gradients of extracellular cues and generate polarized responses such as cell migration and neurite initiation. There is static information on the intracellular signaling molecules involved in these responses, but how they dynamically orchestrate polarized cell behaviors is not well understood. A limitation has been the lack of methods to exert spatial and temporal control over specific signaling molecules inside a living cell. Here we introduce optogenetic tools that act downstream of native G protein–coupled receptor (GPCRs) and provide direct control over the activity of endogenous heterotrimeric G protein subunits. Light-triggered recruitment of a truncated regulator of G protein signaling (RGS) protein or a Gβγ-sequestering domain to a selected region on the plasma membrane results in localized inhibition of G protein signaling. In immune cells exposed to spatially uniform chemoattractants, these optogenetic tools allow us to create reversible gradients of signaling activity. Migratory responses generated by this approach show that a gradient of active G protein αi and βγ subunits is sufficient to generate directed cell migration. They also provide the most direct evidence so for a global inhibition pathway triggered by Gi signaling in directional sensing and adaptation. These optogenetic tools can be applied to interrogate the mechanistic basis of other GPCR-modulated cellular functions

Corticotropin Releasing Factor-Induced CREB Activation in Striatal Neurons Occurs via a Novel Gβγ Signaling Pathway

The peptide corticotropin-releasing factor (CRF) was initially identified as a critical component of the stress response. CRF exerts its cellular effects by binding to one of two cognate G-protein coupled receptors (GPCRs), CRF receptor 1 (CRFR1) or 2 (CRFR2). While these GPCRs were originally characterized as being coupled to Gαs, leading to downstream activation of adenylyl cyclase (AC) and subsequent increases in cAMP, it has since become clear that CRFRs couple to and activate numerous other downstream signaling cascades. In addition, CRF signaling influences the activity of many diverse brain regions, affecting a variety of behaviors. One of these regions is the striatum, including the nucleus accumbens (NAc). CRF exerts profound effects on striatal-dependent behaviors such as drug addiction, pair-bonding, and natural reward. Recent data indicate that at least some of these behaviors regulated by CRF are mediated through CRF activation of the transcription factor CREB. Thus, we aimed to elucidate the signaling pathway by which CRF activates CREB in striatal neurons. Here we describe a novel neuronal signaling pathway whereby CRF leads to a rapid Gβγ- and MEK-dependent increase in CREB phosphorylation. These data are the first descriptions of CRF leading to activation of a Gβγ-dependent signaling pathway in neurons, as well as the first description of Gβγ activation leading to downstream CREB phosphorylation in any cellular system. Additionally, these data provide additional insight into the mechanisms by which CRF can regulate neuronal function

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

Chernobyl radioactivity on the Black Sea coast of Turkey

After the Chernobyl reactor accident, Eastern Black Sea coast was one of the heavily contaminated regions of Turkey. Clouds loaded with radioactive isotopes arrived the region on May 1986 and emptied their contents with the heavy rains that are frequently seen in the region. In order to asses the current level of contamination, several different samples, moss, lichen, litter, surface soil and soil cores were collected on August 1994. Samples were brought to the laboratory and their moisture, pH and organic matter contents were determined. Gamma-ray spectra of the samples were collected with a HpGe detector. Cs-137 was the major isotope observed. Activity of most litter samples were below 1000 Bq/kg, while most of the moss samples had activities below 5000 Bq/kg, there were a few with higher Cs-137 activities. Surface soil samples generally had activities less than 2000 Bq/kg and depth profiles of cesium activities in the soil cores showed regional variations

Autocrine motility factor receptor expression implies an unfavourable prognosis in resected stage I pulmonary adenocarcinomas

18th Annual Meeting of the European-Association-for-Cardiothoracic-Surgery/12th Annual Meeting of the European-Society-of-Thoracic-Surgeons -- SEP 12-15, 2004 -- Leipzig, GERMANYWOS: 000231906000010PubMed: 16184720Background : Pulmonary adenocarcinomas constitute a different histological subtype among the histological subtypes of non small cell lung carcinomas by showing comparably unfavourable rates of prognosis and different immunobiological features. Autonomous motility of tumour cells plays an important role in the regulation of local invasion and distant metastasis of tumour lesions which have great impact on overall survival. AMF (Autocrine motility factor) is a tumour secreted cytokine that stimulates motility during invasion and metastasis via its receptor, AMFR. We conducted an immunohistochemical study to investigate AMFR expression in pulmonary adenocarcinomas and its effect on survival. Material and methods: We assessed AMFR expression using a monoclonal antibody (3F3A) in a total of 32 surgical specimens with stage I pulmonary adenocarcinomas that underwent curative resection. We analyzed AMFR expression as a possible prognostic factor on survival and its correlations with clinicopathological features. Results: A total of 19 (59.3%) specimens showed AMFR expression. The 3-year survival rates of AMFR positive and AMFR negative patients were 47.3% and 84.6%, respectively, which was a significant difference (P = 0.0197). The univariate predictors of surgical outcome were AMFR expression (P = 0.032) and perineural invasion (P = 0.038). However, multivariate analysis revealed AMFR expression (P = 0.045) as the only independent prognostic factor. Conclusions : AMFR expression predicts an unfavourable surgical outcome in patients with stage I pulmonary adenocarcinomas.European Assoc Cardiothorac Surg, European Soc Thorac Sur

On the non-linear dynamics of torus-shaped and cylindrical shell structures

In this study, the non-linear dynamic analysis of torus-shaped and cylindrical shell-like structures has been studied. The applied material is assumed as the functionally graded material (FGM). The structures are considered to be used for important machines such as wind turbines. The effects of some environmental factors on the analysis like temperature and humidity have been considered. The strain field has been calculated in general form and in continue the dynamic governing equations of torus structure have been derived based on the first-order shear deformation theory. The rotation around two independent axes in the torus coordinate system is considered and time-dependent equations are solved using SAPM semi-analytical method. The stresses and deformations generated in the torus and cylindrical shaped structures are plotted. The rotation of structures has been attended due to some transportation purposes. The effect of internal pressures as well as rotational speed at torus and cylindrical structures has been investigated in several numerical diagrams. The results are presented in the form of graphs that consider the rotational effects, loading, thermal and humid (hygro-thermal) environments, and size of the structures. This research can provide scientific perspectives to researchers who will examine the dynamic analysis of torus and cylindrical shaped structures

polyaniline-pumice composites

In this study, electrical conductivity, photoconductivity, absorbance and thermal properties of polyaniline (PANI) and polyaniline-pumice composites were investigated. Temperature dependent conductivity and photoconductivity measurements were carried out in the temperature range of 80-400K. The measurements revealed that the dominant conduction mechanisms in polyaniline and 15% pumice doped composite were hopping conduction. The low activation energies calculated for 36% pumice doped composite indicated that this sample has highly defective and degenerate structure due to the high pumice content. Polyaniline and pumice doped composites showed semiconductor behavior with the exponential variation of inverse temperature dependence of electrical conductivity. Photoconductivities of the PANI and PANI-pumice composites under various illumination intensities were studied and it was found for all samples that the conductivity increased with increasing temperature and light intensity, but decreased with increasing pumice content in the structure. Absorbance spectrum has been determined in the wavelength range of 300-700 nm and it was found that the band gap values decreased as the pumice content was increased. Thermogravimetric analysis have shown for all samples that the mass loss has started above around 300 K due to the loss of moisture from the structures. As a result of this work, it was found that polyaniline and polyaniline-pumice composites had low resistivity and high band gaps and could be used as a window layer semiconductor in heterojunction solar cell applications. (C) 2011 Elsevier B.V. All rights reserved