Automated stilbene UV fluorescence measurement

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Automatisoitu stilbeenien UV-fluoresenssin mittaus

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A mixture of U.S. Food and Drug Administration-approved monoaminergic drugs protects the retina from light damage in diverse models of night blindness

Purpose: The purpose of this study was to test the extent of light damage in different models of night blindness and apply these paradigms in testing the therapeutic efficacy of combination therapy by drugs acting on the Gi, Gs, and Gq protein-coupled receptors. Methods: Acute bright light exposure was used to test susceptibility to light damage in mice lacking the following crucial phototransduction proteins: rod transducin (GNAT1), cone transducin (GNAT2), visual arrestin 1 (ARR1), and rhodopsin kinase 1 (GRK1). Mice were intraperitoneally injected with either vehicle or drug combination consisting of metoprolol (β1-receptor antagonist), bromocriptine (dopamine family-2 receptor agonist) and tamsulosin (α1-receptor antagonist) before bright light exposure. Light damage was primarily assessed with optical coherence tomography and inspection of cone population in retinal whole mounts. Retinal inflammation was assessed in a subset of experiments using autofluorescence imaging by scanning laser ophthalmoscopy and by postmortem inspection of microglia and astrocyte activity. Results: The Gnat1-/- mice showed slightly increased susceptibility to rod light damage, whereas the Gnat2-/- mice were very resistant. The Arr1-/- and Grk1-/- mice were sensitive for both rod and cone light damage and showed robust retinal inflammation 7 days after bright light exposure. Pretreatment with metoprolol + bromocriptine + tamsulosin rescued the retina in all genetic backgrounds, starting at doses of 0.2 mg/kg metoprolol, 0.02 mg/kg bromocriptine, and 0.01 mg/kg tamsulosin in the Gnat1-/- mice. The therapeutic drug doses increased in parallel with light-damage severity. Conclusions: Our results suggest that congenital stationary night blindness and Oguchi disease patients can be at an elevated risk of the toxic effects of bright light. Furthermore, systems pharmacology drug regimens that stimulate Gi signaling and attenuate Gs and Gq signaling present a promising disease-modifying therapy for photoreceptor degenerative diseases

ARGUMENTOINTIA PAINOTTAVA LUONNONTIETEEN KOULUOPETUS – KATSAUS TAVOITTEISIIN

Tässä artikkelissa tarkastellaan argumentointia painottavan luonnontieteen kouluopetuksen tavoitteita kansainvälisen tutkimuskirjallisuuden pohjalta. Tarkasteluun valittiin 14 luonnontieteen kouluopetuksen kansainvälistä tutkimusartikkelia, joissa esiintyvät kuvaukset argumentoinnin tavoitteista luokiteltiin niissä esiintyvien teemojen perusteella. Tavoitekuvauksista erottui kolme pääteemaa: koulussa opetettavien luonnontieteiden autenttisuuden lisääminen, oppilaiden ajattelu- ja vuorovaikutustaitojen kehittymisen tukeminen sekä sisältötiedon osaamisen ja luonnontieteellisen sivistyksen syventäminen. Autenttisen kuvan välittäminen luonnontieteistä oppilaille näyttäytyi edellytyksenä muiden oppimistavoitteiden saavuttamiselle. Tavoitteiden tunnistaminen edesauttaa argumentoinnin painottamista suomalaisessa luonnontieteen opetuksessa.Tässä artikkelissa tarkastellaan argumentointia painottavan luonnontieteen kouluopetuksen tavoitteita kansainvälisen tutkimuskirjallisuuden pohjalta. Tarkasteluun valittiin 14 luonnontieteen kouluopetuksen kansainvälistä tutkimusartikkelia, joissa esiintyvät kuvaukset argumentoinnin tavoitteista luokiteltiin niissä esiintyvien teemojen perusteella. Tavoitekuvauksista erottui kolme pääteemaa: koulussa opetettavien luonnontieteiden autenttisuuden lisääminen, oppilaiden ajattelu- ja vuorovaikutustaitojen kehittymisen tukeminen sekä sisältötiedon osaamisen ja luonnontieteellisen sivistyksen syventäminen. Autenttisen kuvan välittäminen luonnontieteistä oppilaille näyttäytyi edellytyksenä muiden oppimistavoitteiden saavuttamiselle. Tavoitteiden tunnistaminen edesauttaa argumentoinnin painottamista suomalaisessa luonnontieteen opetuksessa

Genome-Wide Linkage Analysis of Human Auditory Cortical Activation Suggests Distinct Loci on Chromosomes 2, 3, and 8

Neural processes are explored through macroscopic neuroimaging and microscopic molecular measures, but the two levels remain primarily detached. The identification of direct links between the levels would facilitate use of imaging signals as probes of genetic function and, vice versa, access to molecular correlates of imaging measures. Neuroimaging patterns have been mapped for a few isolated genes, chosen based on their connection with a clinical disorder. Here we propose an approach that allows an unrestricted discovery of the genetic basis of a neuroimaging phenotype in the normal human brain. The essential components are a subject population that is composed of relatives and selection of a neuroimaging phenotype that is reproducible within an individual and similar between relatives but markedly variable across a population. Our present combined magnetoencephalography and genome-wide linkage study in 212 healthy siblings demonstrates that auditory cortical activation strength is highly heritable and, specifically in the right hemisphere, regulated oligogenically with linkages to chromosomes 2q37, 3p12, and 8q24. The identified regions delimit as candidate genes TRAPPC9, operating in neuronal differentiation, and ROBO1, regulating projections of thalamocortical axons. Identification of normal genetic variation underlying neurophysiological phenotypes offers a non-invasive platform for an in-depth, concerted capitalization of molecular and neuroimaging levels in exploring neural function.Peer reviewe

Second-generation antipsychotic use during pregnancy and risk of congenital malformations

Purpose To study if second-generation antipsychotic (S-GA) use during the first trimester of pregnancy is associated with an increased risk of major congenital malformations (MCM). Methods A population-based birth cohort study using national register data extracted from the Drugs and Pregnancy database in Finland, years 1996-2017. The sampling frame included 1,273,987 pregnant women. We included singleton pregnancies ending in live or stillbirth or termination of pregnancy due to severe malformation. Pregnancies with exposure to known teratogens were excluded. Women were categorized into three groups: exposed to S-GAs (n = 3478), exposed to first-generation antipsychotics (F-GAs) (n = 1030), and unexposed (no purchases of S-GAs or F-GAs during pregnancy, n = 22,540). We excluded genetic conditions and compared the prevalence of MCMs in S-GA users to the two comparison groups using multiple logistic regression models. Results Use of S-GAs during early pregnancy was not associated with an increased risk of overall MCMs compared to unexposed (adjusted odds ratio, OR 0.92; 95% CI 0.72-1.19) or to F-GA users (OR 0.82; 95% CI 0.56-1.20). Of individual S-GAs, olanzapine use was associated with an increased risk of overall MCMs (OR 2.12; 95% CI 1.19-3.76), and specifically, an increased risk of musculoskeletal malformations (OR 3.71; 95% CI 1.35-10.1) when compared to unexposed, while comparisons to F-GA users did not show significant results. Conclusions Olanzapine use is associated with an increased risk of major congenital malformations and specifically, musculoskeletal malformations. Use during pregnancy should be restricted to situations where no safer alternatives exist.Peer reviewe