Direct genetic demonstration of Gα13 coupling to the orphan G protein-coupled receptor G2A leading to RhoA-dependent actin rearrangement

G2A is an orphan G protein-coupled receptor (GPCR), expressed predominantly in T and B cells and homologous to a small group of GPCRs of unknown function expressed in lymphoid tissues. G2A is transcriptionally induced in response to diverse stimuli, and its ectopic expression suppresses transformation of B lymphoid precursors by BCR-ABL. G2A induces morphological transformation of NIH 3T3 fibroblasts. Microinjection of constructs encoding G2A into Swiss 3T3 fibroblasts induces actin reorganization into stress fibers that depends on RhoA, but not CDC42 or RAC. G2A elicits RhoA-dependent transcriptional activation of serum response factor. Direct evaluation of RhoA activity demonstrates elevated levels of RhoA-GTP in G2A-expressing cells. Microinjection of embryonic fibroblasts derived from various Galpha knockout mice establishes a requirement for Galpha 13 but not Galpha 12 or Galpha q/11 in G2A-induced actin rearrangement. In conclusion, G2A represents a family of GPCRs expressed in lymphocytes that may link diverse stimuli to cytoskeletal reorganization and transcriptional activation through a pathway involving Galpha 13 and RhoA

Capturing Plant Metabolome with Direct-Immersion in Vivo Solid Phase Microextraction of Plant Tissues

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Analytical Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/acs.analchem.5b03684 .For the first time, an in vivo sampling mode of direct immersion–solid phase microextraction (DI-SPME) was employed to capture the metabolome of living plant specimens, using apple (Malus × domestica Borkh.) as a model system. Metabolites were extracted from apple tissues and introduced by thermal desorption into a comprehensive two-dimensional gas chromatography–time-of-flight mass spectrometry instrument. The feasibility of this sampling approach, based on exploitation of microextraction principles, including negligible depletion of free analyte concentrations, solventless sampling and sample preparation, and on-site compatibility, was determined in global metabolite analysis. Rather than adopting an approach of traditional sample preparation, requiring metabolism quenching and laborious sample preparation, the objective of the study was to capture the metabolome in vivo, evaluate the feasibility of the approach to provide unbiased extraction coverage, and compare analytical precision when different SPME sampling modes are employed. The potential of in vivo DI-SPME in quantitative plant metabolomics was assessed by evaluating changes in metabolic fingerprints in response to fruit maturation. The in vivo SPME sampling approach has been demonstrated as capable of sampling living systems with high reproducibility, considering that nearly 50% of hundreds of evaluated compounds included in the determination of analytical performance met the 15% RSD FDA criterion. Esters were extracted with high repeatability (% RSD for hexyl butanoate and butyl butanoate of 16.5 and 5.9, respectively, from 9 determinations in 3 apples) and found to be upregulated in response to apple fruit maturation.Natural Sciences and Engineering Research Council of Canada (NSERC

Multiple Francisella tularensis Subspecies and Clades, Tularemia Outbreak, Utah

In July 2007, a deer fly–associated outbreak of tularemia occurred in Utah. Human infections were caused by 2 clades (A1 and A2) of Francisella tularensis subsp. tularensis. Lagomorph carcasses from the area yielded evidence of infection with A1 and A2, as well as F. tularensis subsp. holarctica. These findings indicate that multiple subspecies and clades can cause disease in a localized outbreak of tularemia

In vivo microsampling to capture the elusive exposome

Bessonneau, V., Ings, J., McMaster, M., Smith, R., Bragg, L., Servos, M., & Pawliszyn, J. (2017). In vivo microsampling to capture the elusive exposome. Scientific Reports, 7, 44038. The final and definitive publication is available through Nature publishing Group via: http://dx.doi.org/10.1038/srep44038Loss and/or degradation of small molecules during sampling, sample transportation and storage can adversely impact biological interpretation of metabolomics data. In this study, we performed in vivo sampling using solid-phase microextraction (SPME) in combination with non-targeted liquid chromatography and high-resolution tandem mass spectrometry (LC-MS/MS) to capture the fish tissue exposome using molecular networking analysis, and the results were contrasted with molecular differences obtained with ex vivo SPME sampling. Based on 494 MS/MS spectra comparisons, we demonstrated that in vivo SPME sampling provided better extraction and stabilization of highly reactive molecules, such as 1-oleoyl-sn-glycero-3-phosphocholine and 1-palmitoleoyl-glycero-3-phosphocholine, from fish tissue samples. This sampling approach, that minimizes sample handling and preparation, offers the opportunity to perform longitudinal monitoring of the exposome in biological systems and improve the reliability of exposure-measurement in exposome-wide association studies.Environment Canada, Environmental Damages Fund (Grant EC-129114) provided to Environment Canada through the Joint Oil Sands Monitoring Program

Variation in follow-up for children born very preterm in Europe

Background: Children born very preterm (&lt;32 weeks of gestation) face high risks of neurodevelopmental and health difficulties compared with children born at term. Follow-up after discharge from the neonatal intensive care unit is essential to ensure early detection and intervention, but data on policy approaches are sparse. Methods: We investigated the characteristics of follow-up policy and programmes in 11 European countries from 2011 to 2022 using healthcare informant questionnaires and the published/grey literature. We further explored how one aspect of follow-up, its recommended duration, may be reflected in the percent of parents reporting that their children are receiving follow-up services at 5 years of age in these countries using data from an area-based cohort of very preterm births in 2011/12 (N ¼ 3635). Results: Between 2011/12 and 22, the number of countries with follow-up policies or programmes increased from 6 to 11. The policies and programmes were heterogeneous in eligibility criteria, duration and content. In countries that recommended longer follow-up, parent-reported follow-up rates at 5 years of age were higher, especially among the highest risk children, born &lt;28 weeks' gestation or with birthweight &lt;1000 g: between 42.1% and 70.1%, vs. &lt;20% in most countries without recommendations. Conclusions:Large variations exist in follow-up policies and programmes for children born very preterm in Europe; differences in recommended duration translate into cross-country disparities in reported follow-up at 5 years of age.</p

Variation in follow-up for children born very preterm in Europe

Background: Children born very preterm (&lt;32 weeks of gestation) face high risks of neurodevelopmental and health difficulties compared with children born at term. Follow-up after discharge from the neonatal intensive care unit is essential to ensure early detection and intervention, but data on policy approaches are sparse. Methods: We investigated the characteristics of follow-up policy and programmes in 11 European countries from 2011 to 2022 using healthcare informant questionnaires and the published/grey literature. We further explored how one aspect of follow-up, its recommended duration, may be reflected in the percent of parents reporting that their children are receiving follow-up services at 5 years of age in these countries using data from an area-based cohort of very preterm births in 2011/12 (N ¼ 3635). Results: Between 2011/12 and 22, the number of countries with follow-up policies or programmes increased from 6 to 11. The policies and programmes were heterogeneous in eligibility criteria, duration and content. In countries that recommended longer follow-up, parent-reported follow-up rates at 5 years of age were higher, especially among the highest risk children, born &lt;28 weeks' gestation or with birthweight &lt;1000 g: between 42.1% and 70.1%, vs. &lt;20% in most countries without recommendations. Conclusions:Large variations exist in follow-up policies and programmes for children born very preterm in Europe; differences in recommended duration translate into cross-country disparities in reported follow-up at 5 years of age.</p

Lowered expression of tumor suppressor candidate MYO1C stimulates cell proliferation, suppresses cell adhesion and activates AKT

Myosin-1C (MYO1C) is a tumor suppressor candidate located in a region of recurrent losses distal to TP53. Myo1c can tightly and specifically bind to PIP2, the substrate of Phosphoinositide 3-kinase (PI3K), and to Rictor, suggesting a role for MYO1C in the PI3K pathway. This study was designed to examine MYO1C expression status in a panel of wellstratified endometrial carcinomas as well as to assess the biological significance of MYO1C as a tumor suppressor in vitro. We found a significant correlation between the tumor stage and lowered expression of MYO1C in endometrial carcinoma samples. In cell transfection experiments, we found a negative correlation between MYO1C expression and cell proliferation, and MYO1C silencing resulted in diminished cell migration and adhesion. Cells expressing excess of MYO1C had low basal level of phosphorylated protein kinase B (PKB, a.k.a. AKT) and cells with knocked down MYO1C expression showed a quicker phosphorylated AKT (pAKT) response in reaction to serum stimulation. Taken together the present study gives further evidence for tumor suppressor activity of MYO1C and suggests MYO1C mediates its tumor suppressor function through inhibition of PI3K pathway and its involvement in loss of contact inhibition.Royal Physiographic Society in Lund (Nilsson-Ehle Foundation) with grant numbers 30928, 32705 and 36388: KV. Wilhelm and Martina Lundgren Foundation: KV, AB. Assar Gabrielsson Research Foundation for Clinical Cancer Research with grant numbers FB11-15, FB12-26, FB13-05, FB14-46 and FB15-45: KV. Sahlgrenska University Hospital Foundation with grant number 8181: KV. The Knowledge Foundation with grant number HOÈ G12, 20120311: AB.http://www.plosone.orgam2016Physiolog

Advice on fishing opportunities for Barents Sea capelin in 2024 — ICES subareas 1 and 2 excluding Division 2.a west of 5°W

publishedVersio

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Microstructure evolution and thermal stability of rapidly solidified Al-Ni-Co-RE alloy

In the frame of this work, Al-5Ni-1Co-3RE (RE-Rare Earth (Mischmetal)) rapidly solidified ribbons were manufactured and analyzed. The morphology of the as-cast structure, as well as the microstructural features were analyzed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Thermal stability has been investigated by combination of four point scanning electrical resistivity measurement (ER), differential scanning calorimetry (DSC) and microhardness measurement. From the results we can conclude, that Al-5Ni-1Co-3RE rapidly solidified alloys have good thermal stability due to very slow coarsening kinetics of precipitated particles