Condition dependence in biosynthesized chemical defenses of an aposematic and mimetic Heliconius butterfly

Aposematic animals advertise their toxicity or unpalatability with bright warning coloration. However, acquiring and maintaining chemical defenses can be energetically costly, and consequent associations with other important traits could shape chemical defense evolution. Here, we have tested whether chemical defenses are involved in energetic trade-offs with other traits, or whether the levels of chemical defenses are condition dependent, by studying associations between biosynthesized cyanogenic toxicity and a suite of key life-history and fitness traits in a Heliconius butterfly under a controlled laboratory setting. Heliconius butterflies are well known for the diversity of their warning color patterns and widespread mimicry and can both sequester the cyanogenic glucosides of their Passiflora host plants and biosynthesize these toxins de novo. We find energetically costly life-history traits to be either unassociated or to show a general positive association with biosynthesized cyanogenic toxicity. More toxic individuals developed faster and had higher mass as adults and a tendency for increased lifespan and fecundity. These results thus indicate that toxicity level of adult butterflies may be dependent on individual condition, influenced by genetic background or earlier conditions, with maternal effects as one strong candidate mechanism. Additionally, toxicity was higher in older individuals, consistent with previous studies indicating accumulation of toxins with age. As toxicity level at death was independent of lifespan, cyanogenic glucoside compounds may have been recycled to release resources relevant for longevity in these long-living butterflies. Understanding the origins and maintenance of variation in defenses is necessary in building a more complete picture of factors shaping the evolution of aposematic and mimetic systems.Peer reviewe

Developmental stage-dependent response and preference for host plant quality in an insect herbivore

Larval-derived nutritional reserves are essential in shaping insects' adult fitness. Early larval instars of many Lepidopteran species are often sessile, and the conditions experienced by these larvae are often highly dependent on the mother's oviposition choice. Later larval stages are more mobile and therefore can choose their food whenever alternatives are available. We tested how feeding on a drought-exposed host plant impacts life history in an insect herbivore, and whether the observed responses depended on developmental stage. We used drought to alter host plant quality of the ribwort plantain, Plantago lanceolata, and assessed whether host plant preference of postdiapause larvae and adult females increased their own or their offspring's performance, respectively, in the Glanville fritillary butterfly, Melitaea cinxia. Larval response to drought-exposed host plants varied with developmental stage: early larval stages (prediapause) had decreased survival and body mass on drought-exposed plants, while later larval stages (postdiapause) developed faster, weighed more and had a higher growth rate on the drought-exposed plants. Postdiapause larvae also showed a preference for drought-exposed host plants, i.e. those that increased their performance, but only when fed on well-watered host plants. Adult females, on the other hand, showed an oviposition preference for well-watered plants, hence matching the performance of their prediapause but not their postdiapause offspring. Our results highlight how variation in environmental conditions generates stage-specific responses in insects. Individuals fine-tune their own or their offspring's diet by behavioural adjustments when variation in host plant quality is available.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

Lääkkeiden ja ravintovalmisteiden käyttö harvinaisten sairauksien hoidossa : Kysely harvinaissairaita hoitaville lääkäreille

Euroopan unionin määritelmän mukaan harvinaissairauksiksi katsotaan sairaudet, joita sairastaa enintään viisi ihmistä 10 000 ihmistä kohti. Suomessa sosiaali- ja terveysministeriö asetti vuonna 2012 työryhmän, joka laati ehdotuksen harvinaisten sairauksien kansalliseksi ohjelmaksi vuosiksi 2014–2017. Yksi toimenpide-ehdotuksista on harvinaislääkkeiden saatavuuden parantaminen. Kela otti vastuulleen selvittää harvinaissairauksien hoidossa käytettäviä lääkehoitoja ja niiden korvattavuutta. Tämän tutkimuksen tarkoitus on kuvata, millaisia lääke- ja ravintovalmistehoitoja harvinaissairauksien hoidossa Suomessa käytetään ja kuinka usein lääkkeet kuuluvat avohoidossa käytettäessä lääkekorvausjärjestelmään. Tutkimusaineisto koottiin sähköisellä kyselyllä, joka lähetettiin harvinaissairauksia hoitaville lääkäreille henkilökohtaisessa sähköpostiviestissä maaliskuussa 2014. Kyselyyn vastasi 129 lääkäriä, eli 33 % niistä, joille kysely lähetettiin. Lääkärit mainitsivat kyselyssä 145 lääkeainetta ja 55 ravintovalmistetta, joita käytetään harvinaissairauksien hoidossa. Lääkärien mainitsemista lääkkeistä 86 % ja kolmannes ravintovalmisteista oli korvattavia. Varsinaisista harvinaislääkkeistä yhtä lukuun ottamatta kaikki olivat korvattavia. Vaikka valtaosa harvinaissairauksien hoidossa käytettävistä lääkkeistä on korvattavia, osalla potilaista kustannukset voivat kuitenkin kasvaa suuriksi, jos sairauden hoidossa tarvitaan useita valmisteita, jotka eivät ole korvattavia. Nykyinen lääkekorvausjärjestelmä ei riittävästi huomioi harvinaissairauksien lääkehoitoja, koska järjestelmä perustuu lääkeyritysten tekemiin hakemuksiin ja korvattavuuden edellytyksenä on, että valmisteen käyttöaihe sisältää harvinaissairauden

Multisite musculoskeletal pain predicts medically certified disability retirement among Finns

BackgroundMusculoskeletal pain at several sites (multisite pain) is more common than single-site pain. Little is known on its effects on disability pension (DP) retirement. MethodsA nationally representative sample comprised 4071 Finns in the workforce aged 30 to 63. Data (questionnaire, interview, clinical examination) were gathered in 2000-2001 and linked with national DP registers for 2000-2011. Pain during the preceding month in 18 locations was combined into four sites (neck, upper limbs, low back, lower limbs). Hazard ratios (HR) of DP were estimated by Cox regression. ResultsThe HR of any DP (n=477) was 1.6 (95% confidence interval 1.2-2.1) for one, 2.5 (1.9-3.3) for two, 3.1 (2.3-4.3) for three and 5.6 (4.0-7.8) for four pain sites, when adjusted for age and gender. When additionally adjusted for clinically assessed chronic diseases, the HRs varied from 1.4 (1.0-1.8) to 3.5 (2.5-4.9), respectively. When further adjusted for physical and psychosocial workload, education, body mass index, smoking, exercise and sleep disorders, the HRs were 1.3 (0.9-1.7), 1.6 (1.2-2.2), 1.8 (1.3-2.5) and 2.5 (1.8-3.6). The number of pain sites was especially strong in predicting DPs due to musculoskeletal diseases (HRs in the full model; 3.1 to 4.3), but it also predicted DPs due to other somatic diseases (respective HRs 1.3 to 2.3); pain in all four sites was also predictive of DPs due to mental disorders (full model HR 2.2). ConclusionsThe number of pain sites independently predicted DP retirement. Employees with multisite pain may need specific support to maintain their work ability.Peer reviewe

Electron-capture branch of 100Tc and tests of nuclear wave functions for double-beta decays

We present a measurement of the electron-capture branch of $^{100}$Tc. Our value, $B(\text{EC}) = (2.6 \pm 0.4) \times 10^{-5}$, implies that the $^{100}$Mo neutrino absorption cross section to the ground state of $^{100}$Tc is roughly one third larger than previously thought. Compared to previous measurements, our value of $B(\text{EC})$ prevents a smaller disagreement with QRPA calculations relevant to double-$\beta$ decay matrix elements