Mitochondrial dynamics during mouse oocyte maturation

Mitochondria provide the primary source of ATP for the oocyte and pre-implantation embryo and undergo a number of redistributions during oocyte maturation which may be related to developmental competence. The experiments presented in this thesis aim to examine the changes in distribution and function of mitochondria during the transition from the germinal vesicle stage to the mature metaphase II arrested egg. Mitochondrial distribution was monitored throughout oocyte maturation and accumulation of mitochondria around the first meiotic spindle was observed. This was dependent on the activities of microtubules and their associated motor proteins dynein and kinesin. Migration of the spindle to the oocyte cortex was accompanied by mitochondria but at polar body extrusion a dramatic reorganisation of mitochondria away from the cortical domain occurred, suggesting that a mechanism exists for retention of these important organelles in the oocyte during this asymmetric cell division. The role of the mitochondrial adapter proteins Trak and Miro in establishing redistribution of mitochondria was also addressed. Finally, a novel recombinant FRET probe for measuring ATP was validated for use in oocytes. Use of this probe revealed alterations to both ATP levels and ATP consumption at different stages of oocyte maturation. Furthermore, whilst the first meiotic spindle was found to be dependent on mitochondrial activity to retain its structure and function, attempts to identify subcellular heterogeneity in ATP supply and demand related to the distribution of mitochondria around the spindle did not reveal any differences. However, the presence of cumulus cells surrounding the oocyte as part of a cumulus-oocyte complex was found to influence ATP levels in the oocyte; oocytes matured as part of a cumulus-oocyte complex had higher ATP levels than those observed in oocytes which had been denuded of cumulus cells. This was found to be dependent on the presence of gap junctional communication between the somatic and germ cell compartments, since inhibition of gap junctions abolished the higher ATP levels observed in cumulus enclosed oocytes

Circulating microRNA changes in patients with impaired glucose regulation

© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. We analysed if levels of four miRNAs would change after a lifestyle intervention involving dietary and exercises in prediabetes. MiRNAs previously shown to be associated with diabetes (Let-7a, Let-7e, miR-144 and miR-92a) were extracted from serum pre- and post-intervention. mRNA was extracted from fat-tissue for gene expression analyses. The intervention resulted in increased Let-7a and miR-92a. We found correlations between miRNAs and clinical variables (triglycerides, cholesterol, insulin, weight and BMI). We also found correlations between miRNAs and target genes, revealing a link between miR-92a and IGF system. A lifestyle intervention resulted in marked changes in miRNAs. The association of miRNAs with insulin and the IGF system (both receptors and binding proteins) may represent a mechanism of regulating IGFs metabolic actions

Effect of D2R, NMDAR and CB1R genetic variants associated with cannabis use and childhood trauma in first-episode psychosis in a Brazilian population [abstract only]

Introduction Gene-environment interactions increase psychosis risk (Gayer-Anderson et al. Soc Psychiatry Psychiatr Epidemiol 2020; 55(5):645-657). However, identifying the genetic variants involved and how they interact with environmental risk factors underlying psychosis remains challenging. Objectives To investigate whether there are gene-environment interactions in the relationships of childhood trauma, lifetime cannabis use, and single nucleotide variants (SNVs) of dopamine D2 receptor (D2R: DRD2), N-methyl-d-aspartate receptor (NMDAR: GRIN1, GRIN2A and GRIN2B) and cannabinoid receptor type 1 (CB1R: CNR1) with psychosis. Methods In a population-based case-control study nested in an incident study (STREAM, Brazil) (Del-Ben et al. Br J of Psychiatry 2019; 215(6):726-729), part of the EU-GEI consortium (Gayer-Anderson et al. Soc Psychiatry Psychiatr Epidemiol 2020; 55(5):645-657), 143 first-episode psychosis patients and 286 community-based controls of both sexes aged between 16 and 64 years were included over a period of 3 years. Twenty-three SNVs of D2R (rs1799978, rs7131056, rs6275), NMDAR (GRIN1: rs4880213, rs11146020; GRIN2A: rs1420040, rs11866328; GRIN2B: rs890, rs2098469, rs7298664), and CB1R genes (CNR1: rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898), were genotyped from peripheral blood DNA using a custom Illumina HumanCoreExome-24 BeadChip. Environmental adversities were evaluated using the Cannabis Experience Questionnaire (Di Forti et al. The Lancet Psychiatry 2009; 6(5):427–436) and the Childhood Trauma Questionnaire (Grassi-Oliveira et al. Rev Saude Publica 2006; 40(2):249-55). Associations between SNVs and environmental risk factors were performed using the nonparametric multifactor dimensionality reduction software (version 3.0.2). Results Single locus analysis showed no association among the 23 SNVs with psychosis; however, gene-environment analysis was significant for the polymorphic loci rs12720071 and rs7766029 in CNR1. The best association models were the two-factor representing by the combination of CNR1 rs12720071 with lifetime cannabis use (p<0.001), and CNR1 rs12720071 with childhood trauma (p<0.05), both suggesting an increased risk of psychosis. Additionally, when considering the interaction of both environmental factors in the same model, we found CNR1 rs7766029 to be associated with psychosis (p<0.001). Conclusions Our study supports the hypothesis of gene-environment interactions for psychosis involving the T allele carriers of CNR1 SNVs (rs12720071 and rs7766029), childhood trauma and lifetime cannabis use in psychosis

Mooring line fatigue damage evaluation for floating marine energy converters: Field measurements and prediction

publication-status: Publishedtypes: ArticleThe vision of large-scale commercial arrays of floating marine energy converters (MECs) necessitates the robust, yet cost-effective engineering of devices. Given the continuous environmental loading, fatigue has been iden- tified as one of the key engineering challenges. In particular the mooring sys- tem which warrants the station-keeping of such devices is subject to highly cyclic, non-linear load conditions, mainly induced by the incident waves. To ensure the integrity of the mooring system the lifecycle fatigue spec- trum must be predicted in order to compare the expected fatigue damage against the design limits. The fatigue design of components is commonly as- sessed through numerical modelling of representative load cases. However, for new applications such as floating marine energy converters numerical models are often scantily validated. This paper describes an approach where load measurements from large- scale field trials at the South West Mooring Testing Facility (SWMTF) are used to calculate and predict the fatigue damage. The described procedure employs a Rainflow cycle analysis in conjunction with the Palmgren-Miner rule to estimate the accumulated damage for the deployment periods and individual sea states. This approach allows an accurate fatigue assessment and prediction of mooring lines at a design stage, where field trial load measurements and wave climate information of potential installation sites are available. The mooring design can thus be optimised regarding its fatigue life and costly safety factors can be reduced. The proposed method also assists in monitoring and assessing the fatigue life during deployment periods

The 2dF Galaxy Redshift Survey: the dependence of galaxy clustering on luminosity and spectral type

We investigate the dependence of galaxy clustering on luminosity and spectral type using the 2dF Galaxy Redshift Survey (2dFGRS). Spectral types are assigned using the principal-component analysis of Madgwick et al. We divide the sample into two broad spectral classes: galaxies with strong emission lines ('late types') and more quiescent galaxies ('early types'). We measure the clustering in real space, free from any distortion of the clustering pattern owing to peculiar velocities, for a series of volume-limited samples. The projected correlation functions of both spectral types are well described by a power law for transverse separations in the range 2<(σ/h-1 Mpc)<15, with a marginally steeper slope for early types than late types. Both early and late types have approximately the same dependence of clustering strength on luminosity, with the clustering amplitude increasing by a factor of 2.5 between L* and 4L*. At all luminosities, however, the correlation function amplitude for the early types is 50 per cent higher than that of the late types. These results support the view that luminosity, and not type, is the dominant factor in determining how the clustering strength of the whole galaxy population varies with luminosity

Electroexcitation of the Δ+(1232)\Delta^{+}(1232) at low momentum transfer

We report on new p$(e,e^\prime p)\pi^\circ$ measurements at the $\Delta^{+}(1232)$ resonance at the low momentum transfer region. The mesonic cloud dynamics is predicted to be dominant and rapidly changing in this kinematic region offering a test bed for chiral effective field theory calculations. The new data explore the low $Q^2$ dependence of the resonant quadrupole amplitudes while extending the measurements of the Coulomb quadrupole amplitude to the lowest momentum transfer ever reached. The results disagree with predictions of constituent quark models and are in reasonable agreement with dynamical calculations that include pion cloud effects, chiral effective field theory and lattice calculations. The reported measurements suggest that improvement is required to the theoretical calculations and provide valuable input that will allow their refinements

Gene and environmental risk factors: interplay between CNR1 genetic variants cannabis use, childhood trauma and psychosis [abstract only]

Background: Cannabis use and childhood trauma have been proposed as environmental risk factors for psychosis and its known that gene-environment (G×E) interactions increase the risk of psychosis [1]. In particular, a recent finding suggests a link between genetic variants in the cannabinoid receptor type 1 (CNR1) gene, which encodes CB1 receptors and is expressed widely in the central and peripheral systems, and cannabis playing a role in the multifactorial pathogenesis of psychosis [2]. However, how the genetic variants interact with lifetime cannabis use and other environmental risk factors, such as childhood trauma, underlying psychosis remains challenging. Objective: To investigate whether there are associations of gene and environmental factors with psychosis, as well as G×E interactions in the relationship between lifetime cannabis use, childhood trauma, and single nucleotide variants (SNVs) of CNR1 and psychosis in a Brazilian sample. Methods: In a population-based case-control study nested in an incident study (STREAM, Brazil) [3], part of the WP2 EU-GEI consortium, 143 first-episode psychosis patients (FEPp) and 286 community-based controls of both sexes, aged between 16 and 64 years, were included over a period of three years. Thirteen SNVs of CNR1 gene (rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898), were genotyped from peripheral blood DNA using a custom Illumina HumanCoreExome-24 BeadChip genotyping arrays (GWAS Cardiff chip). Environmental adversities were evaluated using the Cannabis Experience and the Childhood Trauma Questionnaires. Data were analysed using a binary logistic regression model (Adj OR, 95% CI), including a binary outcome (community-based controls and FEPp), adjusted by sex, age, skin colour, years of education and tobacco smoking. Genotype frequencies were analysed under the dominant model (homozygous ancestral x heterozygous + homozygous variant). The significance level was set at α≤0.05. Results: Lifetime cannabis use and childhood trauma increased the risk for psychosis (OR=3.7; 2.6-6.195% CI, p<0.001; OR=3.0; 1.9-4.7 95% CI, p<0.001, respectively). We also showed that the presence of CNR1 rs12720071-T-allele moderated the association between lifetime cannabis use and psychosis (OR=6.0; 2.0-17.5 95% CI; p=0.001). Moreover, the combination of CNR1 rs12720071-T-allele carriers with childhood trauma also suggests a change in the risk of psychosis (OR=3.6; 1.4-9.0 95% CI; p=0.006). No significant associations between the environmental factors and other SNVs were found. Conclusions: We demonstrated a significant interaction between CNR1 rs12720071 SNV and two important environmental risk factors in their association with psychosis. T allele carriers of CNR1 rs12720071 had a higher risk of psychosis when lifetime cannabis use or childhood trauma were present. Our results suggest a G×E interaction involving the CNR1 gene, trauma and cannabis in psychosis. We will explore the associations between genetic and epigenetic markers of the CNR1 gene with environmental factors in larger and longer follow-up cohorts to better understand the mechanisms of endocannabinoid system dysfunction in the etiology of psychosis

Bone marrow-derived and resident liver macrophages display unique transcriptomic signatures but similar biological functions

Abstract: Background and aims: Kupffer cells (KCs), the resident tissue macrophages of the liver, play a crucial role in the clearance of pathogens and other particulate materials that reach the systemic circulation. Recent studies have identified KCs as a yolk sac-derived resident macrophage population that is replenished independently of monocytes in the steady state. Although it is now established that following local tissue injury, bone-marrow derived monocytes may infiltrate the tissue and differentiate into macrophages, the extent to which newly differentiated macrophages functionally resemble the KCs they have replaced has not been extensively studied. Methods and results: Here we show using intravital microscopy, morphometric analysis and gene expression profiling that bone marrow derived “KCs” accumulating as a result of genotoxic injury resemble, but are not identical to their yolk-sac (YS) counterparts. An ion homeostasis gene signature, including genes associated with scavenger receptor function and extracellular matrix deposition, allows discrimination between these two KC populations. Reflecting the differential expression of scavenger receptors, YS-derived KCs were more effective at accumulating Ac-LDL, whereas surprisingly they were poorer than BM-derived KCs when assessed for uptake of a range of bacterial pathogens. The two KC populations were almost indistinguishable in regard to i) response to LPS challenge, ii) phagocytosis of effete RBCs and iii) their ability to contain infection and direct granuloma formation against Leishmania donovani, a KC-tropic intracellular parasite. Conclusions: BM-derived KCs differentiate locally to resemble YS-derived KC in most but not all respects, with implications for models of infectious diseases, liver injury and bone marrow transplantation. In addition, the gene signature we describe adds to the tools available for distinguishing KC subpopulations based on their ontology

Job satisfaction dimensions in public accounting practice

This paper investigates gender differences in reported job satisfaction and career choices revealed by a postal survey of accountants from the Queensland Division of the Institute of Chartered Accountants in Australia. Of particular interest are levels of satisfaction with remuneration and promotion. Two moderating factors of career age and firm size are also considered. Consistent with prior research, female accountants reported dissatisfaction with their opportunities for promotion. However, unlike prior research there was no evidence of a gender effect in remuneration levels, and in reported satisfaction with remuneration. Nor were there differences in satisfaction across age bands, and public accounting firms of different size. The link between satisfaction levels of female accountants and their career choices of leaving their current employer, moving to parttime employment, or leaving the accounting profession was also investigated. Consistent with a large body of organisational and accounting research, low levels of job satisfaction were associated with higher turnover intentions for female accountants

Biomarkers of Multiple Sclerosis

The search for an ideal multiple sclerosis biomarker with good diagnostic value, prognostic reference and an impact on clinical outcome has yet to be realized and is still ongoing. The aim of this review is to establish an overview of the frequent biomarkers for multiple sclerosis that exist to date. The review summarizes the results obtained from electronic databases, as well as thorough manual searches. In this review the sources and methods of biomarkers extraction are described; in addition to the description of each biomarker, determination of the prognostic, diagnostic, disease monitoring and treatment response values besides clinical impact they might possess. We divided the biomarkers into three categories according to the achievement method: laboratory markers, genetic-immunogenetic markers and imaging markers. We have found two biomarkers at the time being considered the gold standard for MS diagnostics. Unfortunately, there does not exist a single solitary marker being able to present reliable diagnostic value, prognostic value, high sensitivity and specificity as well as clinical impact. We need more studies to find the best biomarker for MS.publishersversionPeer reviewe