The placenta protects the fetal circulation from anxiety-driven elevations in maternal serum levels of brain-derived neurotrophic factor.

Brain-derived neurotrophic factor (BDNF) plays crucial roles in brain function. Numerous studies report alterations in BDNF levels in human serum in various neurological conditions, including mood disorders such as depression. However, little is known about BDNF levels in the blood during pregnancy. We asked whether maternal depression and/or anxiety during pregnancy were associated with altered serum BDNF levels in mothers (n = 251) and their new-born infants (n = 212). As prenatal exposure to maternal mood disorders significantly increases the risk of neurological conditions in later life, we also examined the possibility of placental BDNF transfer by developing a new mouse model. We found no association between maternal symptoms of depression and either maternal or infant cord blood serum BDNF. However, maternal symptoms of anxiety correlated with significantly raised maternal serum BDNF exclusively in mothers of boys (r = 0.281; P = 0.005; n = 99). Serum BDNF was significantly lower in male infants than female infants but neither correlated with maternal anxiety symptoms. Consistent with this observation, we found no evidence for BDNF transfer across the placenta. We conclude that the placenta protects the developing fetus from maternal changes in serum BDNF that could otherwise have adverse consequences for fetal development

Cord serum brain-derived neurotrophic factor levels at birth associate with temperament outcomes at one year

Altered serum levels of brain-derived neurotrophic factor (BDNF) are consistently linked with neurological disorders. BDNF is also increasingly implicated in the pathogenesis of neurodevelopmental disorders, particularly those found more frequently in males. At birth, male infants naturally have significantly lower serum BDNF levels (∼10–20% lower than females), which may render them more vulnerable to neurodevelopmental disorders. We previously characterized serum BDNF levels in mothers and their newborn infants as part of the Grown in Wales Study. Here, we analyzed whether cord serum BDNF levels at birth correlate with sex-specific outcomes at one year. The Bayley Scale of Infant Development, Third Edition (BSID-III) and Laboratory Temperament Assessment Battery (Lab-TAB) tasks were used to assess infant behavior and neurodevelopment at 12–14 months (mean ± SD: 13.3 ± 1.6 months; 46% male; n = 56). We found no relationship between serum BDNF levels at birth and BSID-III neurodevelopmental outcomes (cognitive or language), nor with infant behaviors in the Lab-TAB unpredictable mechanical toy or maternal separation tasks. In the sustained attention task, there was a significant positive relationship between serum BDNF and infant negative affect (B = 0.06, p = 0.018) and, for boys only, between serum BDNF and intensity of facial interest (B = 0.03, p = 0.005). However, only the latter remained after correction for multiple testing. This sex-specific association between cord serum BDNF and a parameter of attention at 12–14 months provides some support for the hypothesis that reduced serum BDNF levels at birth are linked to an increased risk for neurodevelopmental disorders

Epithelial-mesenchymal transition, IP3 receptors and ER-PM junctions: translocation of Ca2+ signalling complexes and regulation of migration

Disconnection of a cell from its epithelial neighbours and the formation of a mesenchymal phenotype are associated with profound changes in the distribution of cellular components and the formation of new cellular polarity. We observed a dramatic redistribution of inositol trisphosphate receptors (IP3Rs) and stromal interaction molecule 1 (STIM1)-competent endoplasmic reticulum–plasma membrane junctions (ER–PM junctions) when pancreatic ductal adenocarcinoma (PDAC) cells disconnect from their neighbours and undergo individual migration. In cellular monolayers IP3Rs are juxtaposed with tight junctions. When individual cells migrate away from their neighbours IP3Rs preferentially accumulate at the leading edge where they surround focal adhesions. Uncaging of inositol trisphosphate (IP3) resulted in prominent accumulation of paxillin in focal adhesions, highlighting important functional implications of the observed novel structural relationships. ER–PM junctions and STIM1 proteins also migrate to the leading edge and position closely behind the IP3Rs, creating a stratified distribution of Ca2+ signalling complexes in this region. Importantly, migration of PDAC cells was strongly suppressed by selective inhibition of IP3Rs and store-operated Ca2+ entry (SOCE), indicating that these mechanisms are functionally required for migration

A quantitative evaluation of thin slice sampling for parent-infant interactions

Behavioural coding is time-intensive and laborious. Thin slice sampling provides an alternative approach, aiming to alleviate the coding burden. However, little is understood about whether different behaviours coded over thin slices are comparable to those same behaviours over entire interactions. To provide quantitative evidence for the value of thin slice sampling for a variety of behaviours. We used data from three populations of parent-infant interactions: mother-infant dyads from the Grown in Wales (GiW) cohort (n = 31), mother-infant dyads from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (n = 14), and father-infant dyads from the ALSPAC cohort (n = 11). Mean infant ages were 13.8, 6.8, and 7.1 months, respectively. Interactions were coded using a comprehensive coding scheme comprised of 11–14 behavioural groups, with each group comprised of 3–13 mutually exclusive behaviours. We calculated frequencies of verbal and non-verbal behaviours, transition matrices (probability of transitioning between behaviours, e.g., from looking at the infant to looking at a distraction) and stationary distributions (long-term proportion of time spent within behavioural states) for 15 thin slices of full, 5-min interactions. Measures drawn from the full sessions were compared to those from 1-, 2-, 3- and 4-min slices. We identified many instances where thin slice sampling (i.e., < 5 min) was an appropriate coding method, although we observed significant variation across different behaviours. We thereby used this information to provide detailed guidance to researchers regarding how long to code for each behaviour depending on their objectives

Fatty acid ethyl ester synthase inhibition ameliorates ethanol-induced Ca2+-dependent mitochondrial dysfunction and acute pancreatitis

Objective: Non-oxidative metabolism of ethanol (NOME) produces fatty acid ethyl esters (FAEEs) via carboxylester lipase (CEL) and other enzyme action implicated in mitochondrial injury and acute pancreatitis (AP). This study investigated the relative importance of oxidative and non-oxidative pathways in mitochondrial dysfunction, pancreatic damage and development of alcoholic AP, and whether deleterious effects of NOME are preventable. Design: Intracellular calcium ([Ca2+]C), NAD(P)H, mitochondrial membrane potential and activation of apoptotic and necrotic cell death pathways were examined in isolated pancreatic acinar cells in response to ethanol and/or palmitoleic acid (POA) in the presence or absence of 4-methylpyrazole (4-MP) to inhibit oxidative metabolism. A novel in vivo model of alcoholic AP induced by intraperitoneal administration of ethanol and POA was developed to assess the effects of manipulating alcohol metabolism. Results: Inhibition of OME with 4-MP converted predominantly transient [Ca2+]C rises induced by low ethanol/POA combination to sustained elevations, with concurrent mitochondrial depolarisation, fall of NAD(P)H and cellular necrosis in vitro. All effects were prevented by 3-benzyl-6-chloro-2-pyrone (3-BCP), a CEL inhibitor. 3-BCP also significantly inhibited rises of pancreatic FAEE in vivo and ameliorated acute pancreatic damage and inflammation induced by administration of ethanol and POA to mice. Conclusions: A combination of low ethanol and fatty acid that did not exert deleterious effects per se became toxic when oxidative metabolism was inhibited. The in vitro and in vivo damage was markedly inhibited by blockade of CEL, indicating the potential for development of specific therapy for treatment of alcoholic AP via inhibition of FAEE generation

Foreign Banks are Branching out: Changing Geographies of Hungarian Banking, 1987–1999

Walking through the streets of Budapest in spring 1999 could have given you the following impression: the supermarkets (Spar), the milk products sold there (Danone, Müller), and the property markets (OBI) come from different Western European countries such as the Netherlands, France and Germany. Almost all fast food restaurants (McDonalds, Pizza Hut, KFC) and many hotels (Hilton, Mariott) have their origins in the US; shoes and clothes offered in downtown are designed in Italy or France (Benetton, Marco Polo); medicine is predominantly produced in Switzerland (Novartis, Roche) and the banks as well as the car dealerships have their roots everywhere in the so-called Western world - usually including Japan and other Asian countries with major (car) companies - but not in Hungary itself...