Maternal exposure to increased synthetic glucocorticoids (GC) during pregnancy is known to disturb fetal development and increase the risk of long-term disease. Maternal exposure to elevated levels of natural GC is likely to be common yet is relatively understudied. The placenta plays an important role in regulating fetal exposure to maternal GC but is itself vulnerable to maternal insults. This study uses a mouse model of maternal corticosterone (Cort) exposure to investigate its effects on the developing placenta. Mice were treated with Cort (33 μg/kg·h) for 60 h starting at embryonic d 12.5 (E12.5) before collection of placentas at E14.5 and E17.5. Although Cort exposure did not affect fetal size, placentas of male fetuses were larger at E17.5 in association with changes in placental Igf2. This increase in size was associated with an increase in placental thickness and an increase in placental junctional zone volume. Placentas from female fetuses were of normal size and had no changes in growth factor mRNA levels. The expression of the protective enzyme 11β-hydroxysteroid dehydrogenase type 2 was increased at E14.5 but was decreased in males at E17.5. In contrast, the expression of Nr3c1 (which encodes the GC receptor) was increased during the Cort exposure and remained elevated at E17.5 in the placentas of male fetuses. Our study has shown that maternal Cort exposure infers a sex-specific alteration to normal placental growth and growth factor expression, thus further adding to our understanding of the mechanisms of male dominance of programmed disease.

Suppressor of cytokine signaling 3 (SOCS3), as a key regulator of cytokine signaling, has the potential to modulate numerous cellular processes. Its involvement in inflammatory disease is well established, and there is increasing evidence for a role in breast cancer as a regulator of signal transducers and activators of transcription (STATs). Here we show that over‐expression of SOCS3 markedly supresses STAT3 expression, and abrogates STAT5 phosphorylation, resulting in decreased cell proliferation in T47D breast cancer cells, and decreased proliferation and anchorage‐independent growth in MCF7 cells. Using T47D cells, we elucidated the signaling pathways and transcription factors involved in SOCS3 expression in response to prolactin, a key mammotropic hormone. Quantitative real time PCR was used to examine SOCS3 mRNA expression, IP/WB was used to examine STAT phosphorylation, luciferase reporter assays, chromatin immunoprecipitation (ChIP) and gel shift assays allowed evaluation of cis‐elements and trans‐factors regulating SOCS3 expression. We demonstrate that prolactin‐induced SOCS3 expression is STAT‐dependant, predominantly involving STAT5, although STAT1 is also associated with the promoter. In addition, prolactin‐induced SOCS3 promoter activation requires PKA‐stimulated Sp1 binding to the GC‐rich region of the promoter. Finally, we show that PRL‐induced SOCS3 expression can be potentiated by co‐treatment with PGE₂. This study demonstrates that SOCS3 acts as an anti‐proliferative agent in breast cancer cells, and highlights the complexity of SOCS3 regulation and crosstalk.

To succeed at post-secondary education, it’s essential that students develop an understanding of their own knowledge and learning processes. This metacognition of learning, or ‘meta-learning’, helps students to become more effective learners, as they become more aware of their self-regulatory processes and recognise the effectiveness of their study strategies. To increase biomedical science students’ self-awareness, we have designed and implemented meta-learning assessment tasks across our biomedical science courses. Most students reported that meta-learning tasks had a positive impact on their learning, as they prompted self-regulatory processes of forethought and self-reflection. We found that students were equally likely to change or not change their study strategies across subsequent semesters. Those students that did not change were generally high achievers, believing their study approaches were most effective, but their performance did not improve across semesters. In contrast, students who adapted, mostly by modifying how they appraised and rearranged records or improved planning and time management, performed less well overall but significantly improved their performance across semesters. Meta-learning tasks may prompt students to become more self-reflective and independent learners by affecting their approach to learning, enabling them to reflect on their study strategies, adapt and improve performance, and may enable the development of lifelong learning skills.

Alcohol consumption throughout pregnancy can cause metabolic dysregulation, including glucose intolerance in progeny. This study determined if periconceptional (PC) alcohol (12% v/v in a liquid diet) (PC:EtOH) consumed exclusively around conception results in similar outcomes in Sprague‐Dawley rats. Control (C) rats were given a liquid diet containing no alcohol but matched to ensure equal caloric intake. PC maternal alcohol intake (from 4 days before conception until day 4 of gestation), resulted in offspring with elevated fasting plasma glucose (~10–25%, P < 0.05), impaired glucose tolerance ( P < 0.05), and decreased insulin sensitivity ( P < 0.01) at 6 months of age. This was associated with increased hepatic gluconeogenesis and sex‐specific alterations in peripheral protein kinase B (AKT) signaling. These changes were accompanied by increased mRNA expression of DNA methyltransferases (DNMTs) 1, 3a, and 3b (1.5‐ to 1.9‐fold, P < 0.05) in fetal liver in late gestation, suggesting PC:EtOH may cause epigenetic changes that predispose offspring to metabolic dysfunction. Exposure to a postnatal (PN) high‐fat and cholesterol diet (HFD) from 3 months of age caused hyperinsulinemia (~2‐fold increase, P < 0.001) and exacerbated the metabolic dysfunction in male offspring exposed to PC:EtOH but had no additive effects in females. Given many women may drink alcohol while planning a pregnancy, it is crucial to increase public awareness regarding the effects of alcohol consumption around conception on offspring health.—Gårdebjer, E. M., Anderson, S. T., Pantaleon, M., Wlodek, M. E., Moritz, K. M. Maternal alcohol intake around the time of conception causes glucose intolerance and insulin insensitivity in rat offspring, which is exacerbated by a postnatal high‐fat diet. FASEB J . 29, 2690–2701 (2015). www.fasebj.org

Generalized obesity, regional adiposity, hyperinsulinemia and hypertriglyceridemia are all potential indicators of equine metabolic syndrome (EMS). This study aimed to assess the relationship between morphometric measurements of body condition and metabolic hormone concentrations in ponies, with and without a neck crest or generalised obesity. Twenty-six ponies were assigned a body condition score (BCS) and cresty neck score (CNS). Height, girth, and neck measurements were taken. An oral glucose test (OGT; 0.75g dextrose/kg BW) was performed and blood samples collected prior to and 2 hours post dosing. Basal blood samples were analysed for blood glucose, serum insulin, triglyceride and leptin, and plasma HMW adiponectin concentrations. Post-prandial samples were analysed for serum insulin concentration. The ponies were grouped as having a) a normal to fleshy body status (BCS ≤7 and CNS ≤2; n = 10); b) having a high CNS, but without generalised obesity (BCS ≤7 and CNS ≥3; n = 11), or c) being obese (BCS ≥8 and CNS ≥1; n = 5). Responses to the OGT indicated that both normal and insulin-dysregulated ponies were included in the cohort. Post-prandial serum insulin was positively associated with CNS (P<0.035) and ponies with a CNS ≥ 3 had 5 times greater odds of being insulin-dysregulated. The high CNS group had a greater insulin response to the OGT than those in the normal/fleshy group (P = 0.006), whereas obese ponies did not differ from the other two groups. Basal HMW adiponectin was negatively correlated with post-prandial insulin concentrations (r = -0.5, P = 0.009), as well as being decreased in the group with a high CNS, compared to the obese group (P = 0.05). Cresty neck score was more predictive of insulin dysregulation than BCS, and this may be relevant to the diagnosis of EMS. Adiponectin may also be a measure of insulin dysregulation that is independent of body condition.

Objectives: To elucidate the ability of pharmacy students to self-regulate their learning, and determine the impact of their self-regulatory behaviors on student learning outcomes.Methods: This study utilized a mixed methods approach using ‘meta-learning’ assessment tasks to identify the learning strategies used and relied on by second year pharmacy students (n=139), and to determine the relationships between the quality of strategies and academic achievement.Results: The results demonstrate that although students have used a wide range of strategies, they rely on a small number. When prompted to use more advanced strategies, the quality of strategies reported were significantly related to academic achievement, with significant relationships between achievement and goal setting, self-efficacy, self-satisfaction, self-evaluation and adaptive reactions.Conclusion: These findings suggest that high achieving students use higher quality forethought and self-reflective strategies than poor achieving students. P...