Multilingual experience modulates resting-state functional connectivity and executive functioning in cognitive aging

Bi-/multilingualism has been found to act favourably on the cognitive aging (CA) trajectory due to the increased executive functioning demands that dual-language use exerts on the brain leading to contributions to neurocognitive reserve and resilience. There is a gap in the literature on how individual differences in the degree of multilingualism influence this trajectory. Furthermore, other lifestyle factors such as diet and exercise, have also been shown to influence CA, yet language experiences and lifestyle factors have rarely been examined together. This thesis aims to fill this gap by examining the unique influence of multilingual language engagement on intrinsic brain activity at-rest and working memory performance. A comprehensive language and lifestyle profile was calculated from native Norwegian multilingual speakers with English as one of their additional languages (n=90, mage=49,3, (SD=18.06), range 19-82. Resting-state Electroencephalography (rs-EEG) and working memory were assessed and regressed against a continuous measure of multilingualism (MLD) while controlling for other lifestyle-experiences. Results indicate a near-significant trend hinting that degree of multilingualism offsets the downwards aging trajectory of EEG coherence in alpha and gamma coherence across several electrode regions. A significant positive interaction between age and MLD was found for WM performance. An exploratory post-hoc analysis revealed a null relationship between functional connectivity and working memory. Results suggest that a higher degree of multilingualism leads to increased resilience against CA

MicroRNA 486-3P as a stability marker in acute coronary syndrome

Easily accessible biomarkers are needed to diagnose cardiovascular disease precisely—particularly, to distinguish between disease subtypes that are encountered in clinical practice. Per the hypothesis that plasma miRNA is valuable for this purpose, we performed complete transcriptional profiling of an miRNA discovery-set in 14 samples: three patients with ST-elevated acute myocardial infarction (STEMI) at baseline and after three months of follow-up, four with stable ischaemic heart disease (stable-IHD) and four healthy age-matched volunteers. Our aim was to determine whether we could distinguish patients with unstable plaques from stable patients following a STEMI event. After analysing miRNA profiles, we conducted a validation study comparing three-month STEMI (n=40) with stable-IHD (n=35), which confirmed that miR-486-3P differentiates patients with three-month STEMI from those with stable-IHD (P=0.019)

Relationship between CAD Risk Genotype in the Chromosome 9p21 Locus and Gene Expression. Identification of Eight New ANRIL Splice Variants

BACKGROUND: Several genome-wide association studies have recently linked a group of single nucleotide polymorphisms in the 9p21 region with cardiovascular disease. The molecular mechanisms of this link are not fully understood. We investigated five different expression microarray datasets in order to determine if the genotype had effect on expression of any gene transcript in aorta, mammary artery, carotid plaque and lymphoblastoid cells. METHODOLOGY/PRINCIPAL FINDINGS: After multiple testing correction, no genes were found to have relation to the rs2891168 risk genotype, either on a genome-wide scale or on a regional (8 MB) scale. The neighbouring ANRIL gene was found to have eight novel transcript variants not previously known from literature and these varied by tissue type. We therefore performed a detailed probe-level analysis and found small stretches of significant relation to genotype but no consistent associations. In all investigated tissues we found an inverse correlation between ANRIL and the MTAP gene and a positive correlation between ANRIL and CDKN2A and CDKN2B. CONCLUSIONS/SIGNIFICANCE: Investigation of relation of the risk genotype to gene expression is complicated by the transcript complexity of the locus. With our investigation of a range of relevant tissue we wish to underscore the need for careful attention to the complexity of the alternative splicing issues in the region and its implications to the design of future gene expression studies

Nidelva - Kunnskapsoppsummering av fiskebiologiske forhold

NVE skal i den kommende planperioden, vurdere nødvendige miljøtiltak for å nå de fastsatte miljømål for Nidelva. For å sikre et godt beslutningsgrunnlag for dette arbeidet, ønsket NVE at Agder Energi laget en samlet rapport med de mest sentrale undersøkelser og gjennomførte tiltak på lakseførende strekning i Nidelva (Tabell 1). Målet med denne sammenstilling er å avdekke flaskehalser for lakseproduksjonen og å komme med konkrete tiltak for å øke lakseproduksjonen. Hovedfokus skal være på strekningen fra inntak av Rygene kraftverk til utløpet av kraftverkstunnelen ved Helle som er 7 km fra selve elvemunningen. Arendalsvassdraget med et nedbørfelt på 4015 km2, er det største vassdraget på Sørlandet med en årlig middelvannføring på 115 m3/s. Nidelva var tidligere blant Sørlandets beste lakseelver med en registrert fangst på 12,5 tonn laks i toppåret 1883. Den opprinnelige laksebestanden ble utryddet som følge av forsuring på 1970-tallet. Innsjøkalking av flere store innsjøer i nedbørfeltet siden 1996 og kalking med doserer fra 2005 har ført til en bedring i vannkjemi og en re-etablering av en ny laksestamme basert på innvandring av laks fra andre elver og utlegging av lakserogn fra Storelva, Tvedestrand. Vassdraget er sterkt regulert med om lag 50 større og mindre magasiner i nedbørfeltet. Det er et pålegg om minstevannføring fra utløpet av innsjøen Nelaug. Dette gir en vannføring på minimum 40 m3/s på store deler av den lakseførende strekningen. Den opprinnelige lakseførende strekningen hadde sitt endepunkt nedenfor Bøylefoss. På denne strekningen finnes det i dag to elvekraftverk, Eivindstad og Rygene kraftverk. Ved begge kraftverksdammene er det installert fiskepassasjer slik at den 28 km lange strekningen er tilgjengelig for laks og sjøaure. Evenstad kraftverk ligger ca. 15 km oppstrøms Rygene kraftverk og utnytter et fall på 17 meter som i sin helhet utgjøres av dammen. Det er ikke fastsatt krav om minstevannføring i manøvreringsreglementet for Evenstad kraftverk. Det ble bygget fisketrapp i dammen i 2009. Av reguleringsinngrep er det Rygene kraftstasjon som i størst grad påvirker laksebestanden i vassdraget. Rygenefossen har nok alltid vært vanskelig å forsere for gytelaksen i Nidelva, og energien fra fossen er utnyttet til sagbruk, møller og tresliperi allerede fra 1600-tallet. Slik aktivitet har antagelig også periodevis hindret oppgang av laks. I forbindelse med byggingen av Rygene kraftstasjon, ble det støpt en kulpetrapp gjennom dammen i 1904, men man antar at denne fungerte dårlig. Den siste ombygging ved Rygenefossen, omfattet ny og høyere dam med kraftstasjon inne i fjellet og tunellutløp ved Helle slik vi kjenner det i dag. Denne sto ferdig i 1978. Det ble i tillegg bygget ny laksetrapp og sluse gjennom dammen i 1991. Inntaksdammen demmer opp en elvestrekning på ca. 1 km. En 2 km lang utløpstunell fører vannet tilbake til hovedelva ved Helle. Det er installert en omløpstunnel som kan benyttes ved kraftverksstans. Det har imidlertid vist seg at denne fører til betydelig gassovermetting i den nedenforliggende elvestrekningen. På den om lag 2,5 km lange elvestrekningen mellom Rygene og Helle, er det pålagt minstevannføring på 5 m3/s om sommeren og 1 m3/s om vinteren. Tre terskeldammer ble konstruert i forbindelse med ombygging av Rygene kraftverk i 1978 noe som førte til at store deler av denne strekningen var preget av nær stillestående basseng med lave vannhastigheter. Betydelig redusert vintervannføring samt terskelbygging har ført til at denne strekningen produserte mindre ungfisk enn før reguleringen. I 2007 ble to av tersklene fjernet for å bedre leveforholdene for anadrom laksefisk på denne strekningen.Nidelva - Kunnskapsoppsummering av fiskebiologiske forholdpublishedVersio

Endogenous control genes in complex vascular tissue samples

<p>Abstract</p> <p>Background</p> <p>Gene expression microarrays and real-time PCR are common methods used to measure mRNA levels. Each method has a fundamentally different approach of normalization between samples. Relative quantification of gene expression using real-time PCR is often done using the 2^(-ΔΔCt) method, in which the normalization is performed using one or more endogenous control genes. The choice of endogenous control gene is often arbitrary or bound by tradition. We here present an analysis of the differences in expression results obtained with microarray and real-time PCR, dependent on different choices of endogenous control genes.</p> <p>Results</p> <p>In complex tissue, microarray data and real-time PCR data show the best correlation when endogenous control genes are omitted and the normalization is done relative to total RNA mass, as measured before reverse transcription.</p> <p>Conclusion</p> <p>We have found that for real-time PCR in heterogeneous tissue samples, it may be a better choice to normalize real-time PCR Ct values to the carefully measured mass of total RNA than to use endogenous control genes. We base this conclusion on the fact that total RNA mass normalization of real-time PCR data shows better correlation to microarray data. Because microarray data use a different normalization approach based on a larger part of the transcriptome, we conclude that omitting endogenous control genes will give measurements more in accordance with actual concentrations.</p

GeneRegionScan: a Bioconductor package for probe-level analysis of specific, small regions of the genome

Summary: Whole-genome microarrays allow us to interrogate the entire transcriptome of a cell. Affymetrix microarrays are constructed using several probes that match to different regions of a gene and a summarization step reduces this complexity into a single value, representing the expression level of the gene or the expression level of an exon in the case of exon arrays. However, this simplification eliminates information that might be useful when focusing on specific genes of interest. To address these limitations, we present a software package for the R platform that allows detailed analysis of expression at the probe level. The package matches the probe sequences against a target gene sequence (either mRNA or DNA) and shows the expression levels of each probe along the gene. It also features functions to fit a linear regression based on several genetic models that enables study of the relationship between gene expression and genotype

Dissecting the shared genetic basis of migraine and mental disorders using novel statistical tools

Migraine is three times more prevalent in people with bipolar disorder or depression. The relationship between schizophrenia and migraine is less certain although glutamatergic and serotonergic neurotransmission are implicated in both. A shared genetic basis to migraine and mental disorders has been suggested but previous studies have reported weak or non-significant genetic correlations and five shared risk loci. Using the largest samples to date and novel statistical tools, we aimed to determine the extent to which migraine’s polygenic architecture overlaps with bipolar disorder, depression and schizophrenia beyond genetic correlation, and to identify shared genetic loci. Summary statistics from genome-wide association studies were acquired from large-scale consortia for migraine (n cases = 59 674; n controls = 316 078), bipolar disorder (n cases = 20 352; n controls = 31 358), depression (n cases = 170 756; n controls = 328 443) and schizophrenia (n cases = 40 675, n controls = 64 643). We applied the bivariate causal mixture model to estimate the number of disorder-influencing variants shared between migraine and each mental disorder, and the conditional/conjunctional false discovery rate method to identify shared loci. Loci were functionally characterized to provide biological insights. Univariate MiXeR analysis revealed that migraine was substantially less polygenic (2.8 K disorder-influencing variants) compared to mental disorders (8100–12 300 disorder-influencing variants). Bivariate analysis estimated that 800 (SD = 300), 2100 (SD = 100) and 2300 (SD = 300) variants were shared between bipolar disorder, depression and schizophrenia, respectively. There was also extensive overlap with intelligence (1800, SD = 300) and educational attainment (2100, SD = 300) but not height (1000, SD = 100). We next identified 14 loci jointly associated with migraine and depression and 36 loci jointly associated with migraine and schizophrenia, with evidence of consistent genetic effects in independent samples. No loci were associated with migraine and bipolar disorder. Functional annotation mapped 37 and 298 genes to migraine and each of depression and schizophrenia, respectively, including several novel putative migraine genes such as L3MBTL2, CACNB2 and SLC9B1. Gene-set analysis identified several putative gene sets enriched with mapped genes including transmembrane transport in migraine and schizophrenia. Most migraine-influencing variants were predicted to influence depression and schizophrenia, although a minority of mental disorder-influencing variants were shared with migraine due to the difference in polygenicity. Similar overlap with other brain-related phenotypes suggests this represents a pool of ‘pleiotropic’ variants that influence vulnerability to diverse brain-related disorders and traits. We also identified specific loci shared between migraine and each of depression and schizophrenia, implicating shared molecular mechanisms and highlighting candidate migraine genes for experimental validation