16 research outputs found
Modelling single nucleotide effects in phosphoglucose isomerase on dispersal in the Glanville fritillary butterfly: coupling of ecological and evolutionary dynamics
Dispersal comprises a complex life-history syndrome that influences the demographic dynamics of especially those species that live in fragmented landscapes, the structure of which may in turn be expected to impose selection on dispersal. We have constructed an individual-based evolutionary sexual model of dispersal for species occurring as metapopulations in habitat patch networks. The model assumes correlated random walk dispersal with edge-mediated behaviour (habitat selection) and spatially correlated stochastic local dynamics. The model is parametrized with extensive data for the Glanville fritillary butterfly. Based on empirical results for a single nucleotide polymorphism (SNP) in the phosphoglucose isomerase (Pgi) gene, we assume that dispersal rate in the landscape matrix, fecundity and survival are affected by a locus with two alleles, A and C, individuals with the C allele being more mobile. The model was successfully tested with two independent empirical datasets on spatial variation in Pgi allele frequency. First, at the level of local populations, the frequency of the C allele is the highest in newly established isolated populations and the lowest in old isolated populations. Second, at the level of sub-networks with dissimilar numbers and connectivities of patches, the frequency of C increases with decreasing network size and hence with decreasing average metapopulation size. The frequency of C is the highest in landscapes where local extinction risk is high and where there are abundant opportunities to establish new populations. Our results indicate that the strength of the coupling of the ecological and evolutionary dynamics depends on the spatial scale and is asymmetric, demographic dynamics having a greater immediate impact on genetic dynamics than vice versa
Long-term analysis of clear-sky new particle formation events and nonevents in Hyytiälä
New particle formation (NPF) events have been observed all around the world and are known to be a major source of atmospheric aerosol particles. Here we combine 20 years of observations in a boreal forest at the SMEAR II station (Station for Measuring Ecosystem-Atmosphere Relations) in Hyytiala, Finland, by building on previously accumulated knowledge and by focusing on clear-sky (non-cloudy) conditions. We first investigated the effect of cloudiness on NPF and then compared the NPF event and nonevent days during clear-sky conditions. In this comparison we considered, for example, the effects of calculated particle formation rates, condensation sink, trace gas concentrations and various meteorological quantities in discriminating NPF events from nonevents. The formation rate of 1.5 nm particles was calculated by using proxies for gaseous sulfuric acid and oxidized products of low volatile organic compounds, together with an empirical nucleation rate coefficient. As expected, our results indicate an increase in the frequency of NPF events under clear-sky conditions in comparison to cloudy ones. Also, focusing on clear-sky conditions enabled us to find a clear separation of many variables related to NPF. For instance, oxidized organic vapors showed a higher concentration during the clear-sky NPF event days, whereas the condensation sink (CS) and some trace gases had higher concentrations during the nonevent days. The calculated formation rate of 3 nm particles showed a notable difference between the NPF event and nonevent days during clear-sky conditions, especially in winter and spring. For springtime, we are able to find a threshold equation for the combined values of ambient temperature and CS, (CS (s(-1)) > -3.091 x 10(-5) x T (in Kelvin) + 0.0120), above which practically no clear-sky NPF event could be observed. Finally, we present a probability distribution for the frequency of NPF events at a specific CS and temperature.Peer reviewe
Urokinase plasminogen activator mediates changes in human astrocytes modeling fragile X syndrome
Astrocyte function intertwines with the extracellular matrix, whose glial cell-derived components shape neuronal plasticity. Astrocyte abnormalities are found in the brain of the mouse model for fragile X syndrome (FXS), the most common cause of inherited intellectual disability, and a monogenic cause of autism spectrum disorder. We generated human induced pluripotent stem cell-derived FXS and control astrocytes and we found that several pathways associated with urokinase plasminogen activator (uPA) that modulates degradation of extracellular matrix were activated in FXS astrocytes compared with controls. Expression of uPA was increased in FXS astrocytes and levels of uPA were also increased in conditioned medium collected from FXS astrocyte cultures. Levels of uPA correlated inversely with intracellular Ca2+ responses to activation of L-type voltage-gated calcium channels in human astrocytes. Increased uPA augmented neuronal phosphorylation of TrkB, indicating effects of uPA on neuronal plasticity. FXS-specific changes of gene expression during neuronal differentiation preceding astrogenesis likely contributed to altered properties of FXS astrocytes. Our results identified uPA as an important regulator of astrocyte function and demonstrated that increased uPA in human FXS astrocytes modulated astrocytic responses and neuronal plasticity.Peer reviewe
Monoterpenes’ oxidation capacity and rate over a boreal forest : temporal variation and connection to growth of newly formed particles
Peer reviewe
Anti-COX-2 autoantibody is a novel biomarker of immune aplastic anemia
In immune aplastic anemia (IAA), severe pancytopenia results from the immune-mediated destruction of hematopoietic stem cells. Several autoantibodies have been reported, but no clinically applicable autoantibody tests are available for IAA. We screened autoantibodies using a microarray containing >9000 proteins and validated the findings in a large international cohort of IAA patients (n = 405) and controls (n = 815). We identified a novel autoantibody that binds to the C-terminal end of cyclooxygenase 2 (COX-2, aCOX-2 Ab). In total, 37% of all adult IAA patients tested positive for aCOX-2 Ab, while only 1.7% of the controls were aCOX-2 Ab positive. Sporadic non-IAA aCOX-2 Ab positive cases were observed among patients with related bone marrow failure diseases, multiple sclerosis, and type I diabetes, whereas no aCOX-2 Ab seropositivity was detected in the healthy controls, in patients with non-autoinflammatory diseases or rheumatoid arthritis. In IAA, anti-COX-2 Ab positivity correlated with age and the HLA-DRB1*15:01 genotype. 83% of the >40 years old IAA patients with HLA-DRB1*15:01 were anti-COX-2 Ab positive, indicating an excellent sensitivity in this group. aCOX-2 Ab positive IAA patients also presented lower platelet counts. Our results suggest that aCOX-2 Ab defines a distinct subgroup of IAA and may serve as a valuable disease biomarker.Peer reviewe
Reduced anthropogenic aerosol radiative forcing caused by biogenic new particle formation
The magnitude of aerosol radiative forcing caused by anthropogenic emissions depends on the baseline state of the atmosphere under pristine preindustrial conditions. Measurements show that particle formation in atmospheric conditions can occur solely from biogenic vapors. Here, we evaluate the potential effect of this source of particles on preindustrial cloud condensation nuclei (CCN) concentrations and aerosol-cloud radiative forcing over the industrial period. Model simulations show that the pure biogenic particle formation mechanism has a much larger relative effect on CCN concentrations in the preindustrial atmosphere than in the present atmosphere because of the lower aerosol concentrations. Consequently, preindustrial cloud albedo is increased more than under present day conditions, and therefore the cooling forcing of anthropogenic aerosols is reduced. The mechanism increases CCN concentrations by 20-100% over a large fraction of the preindustrial lower atmosphere, and the magnitude of annual global mean radiative forcing caused by changes of cloud albedo since 1750 is reduced by 0.22 W m-2 (27%) to -0.60 W m-2. Model uncertainties, relatively slow formation rates, and limited available ambient measurements make it difficult to establish the significance of a mechanism that has its dominant effect under preindustrial conditions. Our simulations predict more particle formation in the Amazon than is observed. However, the first observation of pure organic nucleation has now been reported for the free troposphere. Given the potentially significant effect on anthropogenic forcing, effort should be made to better understand such naturally driven aerosol processes
Assessment of methods to measure direction-of-arrival spectrum in radio channel
Radiokanavan tarkka tunteminen on hyvin tärkeää moderneissa radioverkoissa Perinteisesti monitie-etenemisestä johtuvien viiveiden tunteminen on riittänyt, mutta adaptiivisten (älykkäiden) antennien käytön lisääntymisen myötä myös aaltojen tulokulmien tunteminen on tullut välttämättömäksi.
Viime vuosien aikana on kehitetty monia menetelmiä näiden mittaamiseksi.
Eräs mahdollisuus aaltojen tulokulmien mittaamiseksi on kääntää suuntaavaa antennia pystyakselinsa ympäri ja soveltaa sopivaa signaalinkäsittelymenetelmää tulokseen.
Mittaustulos on konvoluutio antennikuvion ja kenttäjakauman välillä.
Ideaalisessa tapauksessa kenttä saadaan siis ratkaistua suoraan dekonvoluution avulla, mutta virhetekijöiden vuoksi joudutaan käytännössä käyttämään erityisiä suodatusmenetelmiä.
Regularisointi on eräs tällainen menetelmä ja sitä onkin käytetty tässä työssä mittadatan käsittelyyn.
Toinen menetelmä, keilanmuodostus (beamforming), on käsitelty regularisoinnin ohessa vertailukohteen saamiseksi.
Saavutetussa resoluutiossa havaittiin merkittävä (noin 40%) parannus verrattuna käsittelemättömään mittadataan.
Simuloinneilla varmistettiin esitetyn teorian toimivuus.
Tulokset antavat syyn todeta, että suuntaava antenni ja regularisointi on, pienellä varauksella, toimiva yhdistelmä aallon tulosuuntien määrittämiseksi
Molekyyliallergologiset tutkimusmenetelmät suomalaisten lasten lehmänmaitoaltistustulosten ennustajina
Tiedekunta: Lääketieteellinen tiedekunta
Koulutusohjelma: Lääketieteen koulutusohjelma
Opintosuunta: Lääketieteen lisensiaatti
Tekijä: Otso Nieminen
Työn nimi: Molecular allergy diagnostics in predicting oral cow’s milk challenge outcome in
Finnish children
Työn laji: Vertaisarvioitu artikkeli
Kuukausi ja vuosi: Tammikuu 2023
Sivumäärä: Seitsemän
Avainsanat: Cow’s milk allergy, milk, IgE, molecular allergy diagnostics, oral food
challenge
Säilytyspaikka: TUHAT ja IngentaConnect
Muita tietoja: -
Tiivistelmä:
Tutkimuksen tausta
Maitoallergian diagnosoimiseen tarvitaan ruoka-ainealtistuksia, joiden toteuttaminen vaatii
paljon resursseja. Altistustarpeen vähentämiseksi tässä työssä määritettiin altistustulosta
ennustavat viitearvot maidon ja sen pääallergeenien spesifiselle IgE:lle.
Tutkimuksessa käytetyt menetelmät
Yhteensä 135 maitoallergiseksi epäiltyä lasta altistettiin avoimesti kuumentamattomalla
lehmänmaidolla (mediaani-ikä 1,8 vuotta). Altistustuloksia verrattiin mitattuihin maidon ja
sen allergeenien kaseiinin, alfa-laktalbumiinin, beta-laktoglobuliinin ja naudan
seerumialbumiinin spesifeihin IgE-vasta-ainetasoihin.
Tulokset
Viisi altistusta jätettiin tutkimuksesta pois puhtaasti subjektiivisten oireiden vuoksi. Jäljelle
jäävistä 130 altistuksesta 98 (75 %) oli positiivisia. Yhdenkään allergeenispesifisen IgE:n
erottelykyky ei ollut maidolle spesifistä IgE:tä parempi. 1–2-vuotiaiden lasten
erottelukykykäyrässä maidolle spesifisen IgE:n taso 6,30 kU/l ennusti positiivista
altistustulosta 94 %:n tarkkuudella ja 33 %:n herkkyydellä. 3–14-vuotiaiden lasten osalta taso
13,9 kU/l ennusti positiivista altistustulosta 93 %:n tarkkuudella ja 25 %:n herkkyydellä.
Keskivaikean tai vaikean reaktion saaneilla lapsilla oli korkeammat spesifisen IgE:n tasot
maidolle, alfa-laktalbumiinille ja naudan seerumialbumiinille verrattuna lievän reaktion
saaneisiin lapsiin.
Pohdinta tutkimustulosten merkityksestä
Molekyyliallergologiset tutkimusmenetelmät eivät osoittautuneet perinteistä maidolle
spesifisen IgE:n määrittämistä paremmaksi keinoksi ennustaa avoimen maitoaltistuksen
tulosta. Tutkimuksen ansiosta suomalaisille lapsille on luotu kliiniseen käyttöön soveltuvat
raja-arvot, joiden ylittyessä lapsi voidaan jättää altistamatta, mikäli myös kliiniset esitiedot
tukevat tätä päätöstä. Lisäksi tutkimus vahvisti käsitystä, ettei altistuksessa mahdollisesti
ilmenevän allergisen reaktion vakavuutta voi luotettavasti ennustaa spesifisen IgE:n avulla
Molecular allergy diagnostics in predicting oral cow's milk outcome in Finnish children
Background: Oral food challenges (OFC) are required to diagnose food allergies but are resource-intensive. Objective: To reduce the need for OFCs, we sought to determine serum specific immunoglobulin E (sIgE) cutoff levels for cow's milk and its major allergens predicting oral milk challenge outcomes in children with suspected cow's milk allergy.Methods: A total of 135 Finnish children (median age, 1.8 years [range, 1.0-14.1 years]) with suspected cow's milk allergy underwent open OFC with unheated cow's milk. The sIgE levels to milk (f2), casein (Bos d 8), alpha-lactalbumin (Bos d 4), beta-lactoglobulin (Bos d 5), and bovine serum albumin (BSA) (Bos d 6) were measured and compared with the challenge outcomes.Results: Of the 135 OFCs, 5 were excluded from the study due to purely subjective symptoms. Of the 130 remaining OFCs, 98 results (75%) were positive. In a receiver operating characteristic analysis with 1-2-year-old children, no individual allergen sIgE had a better area under the curve than milk sIgE (0.824). A milk sIgE level > 6.30 kU/L gave 94% specificity and 33% sensitivity for positive OFCs. In 3-14-year-old children, a cutoff value >13.9 kU/L predicted a positive OFC result with 93% specificity and 25% sensitivity. Children with moderate-to-severe reactions had higher sIgE levels to milk, alpha-lactalbumin, and BSA than did children with mild reactions.Conclusion: Molecular allergy diagnostics did not improve the predictive performance compared with milk sIgE. The milk sIgE value that exceeds the cutoff for 95% specificity in combination with the clinical history may help to reduce the need for OFCs. The severity of an allergic reaction cannot reliably be predicted from sIgE measurements.Peer reviewe
De novo lipogenesis is suppressed during fasting but upregulated at population decline in cyclic voles
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