Limacina helicina is the dominant pelagic gastropod mollusc species in temperate and polar ecosystems, where it contributes significantly to food webs and vertical flux. Currently, considerable uncertainty exists in the interpretation of L. helicina’s life cycle, hindering our understanding of its potential responses to environmental change. Here, we present size-frequency data on L. helicina collected from three consecutive years (2008–2010) in a North Pacific temperate fjord. Two methods of length-frequency analysis were used to infer the growth of L. helicina, i.e. linking successive means extracted from finite-mixture distributions, and using the ELEFAN software to fit seasonally oscillating versions of the von Bertalanffy growth equation to the available length-frequency data. Against a background of continuous low level spawning between spring and autumn, both approaches identified two sets of major cohorts, i.e. (i) spring cohorts (G1) spawned in March/April by (ii) overwintering cohorts (G). G overwintered with minimal to low growth, before undergoing rapid growth the following spring and completing the cycle by spawning the G1 generation and disappearing from the population by May/June. Our findings are discussed in the context of L. helicina response to climate change.
Metformin, an oral antihyperglycemic, is increasingly being prescribed to pregnant women with gestational diabetes. Metformin is a hydrophilic cation and relies on organic cation transporters to move across cell membranes. We previously demonstrated that human and mouse placentas predominantly express organic cation transporter 3 (OCT3), but the impact of this transporter on maternal and fetal disposition of metformin is unknown. Using immunofluorescence colocalization studies in term human placenta, we showed that OCT3 is localized to the basal (fetal-facing) membrane of syncytiotrophoblast cells with no expression on the apical (maternal-facing) membrane. OCT3 positive staining was also observed in fetal capillaries. To determine the in vivo role of OCT3 in maternal and fetal disposition of metformin, we determined metformin maternal pharmacokinetics and overall fetal exposure in wild-type and -null pregnant mice. After oral dosing of [C]metformin at gestational day 19, the systemic drug exposure (AUC) in maternal plasma was slightly reduced by ∼16% in the pregnant mice. In contrast, overall fetal AUC was reduced by 47% in the pregnant mice. Consistent with our previous findings in nonpregnant mice, metformin tissue distribution was respectively reduced by 70% and 52% in the salivary glands and heart in pregnant mice. Our in vivo data in mice clearly demonstrated a significant role of Oct3 in facilitating metformin fetal distribution and exposure during pregnancy. Modulation of placental OCT3 expression or activity by gestational age, genetic polymorphism, or pharmacological inhibitors may alter fetal exposure to metformin or other drugs transported by OCT3.
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