Early restriction of placental growth results in placental structural and gene expression changes in late gestation independent of fetal hypoxemia

Placental restriction and insufficiency are associated with altered patterns of placental growth, morphology, substrate transport capacity, growth factor expression, and glucocorticoid exposure. We have used a pregnant sheep model in which the intrauterine environment has been perturbed by uterine carunclectomy (Cx). This procedure results in early restriction of placental growth and either the development of chronic fetal hypoxemia (PaO₂≤17 mmHg) in late gestation or in compensatory placental growth and the maintenance of fetal normoxemia (PaO2>17 mmHg). Based on fetal PaO₂, Cx, and Control ewes were assigned to either a normoxemic fetal group (Nx) or a hypoxemic fetal group (Hx) in late gestation, resulting in 4 groups. Cx resulted in a decrease in the volumes of fetal and maternal connective tissues in the placenta and increased placental mRNA expression of IGF2, vascular endothelial growth factor (VEGF), VEGFR-2, ANGPT2, and TIE2 There were reduced volumes of trophoblast, maternal epithelium, and maternal connective tissues in the placenta and a decrease in placental GLUT1 and 11βHSD2 mRNA expression in the Hx compared to Nx groups. Our data show that early restriction of placental growth has effects on morphological and functional characteristics of the placenta in late gestation, independent of whether the fetus becomes hypoxemic. Similarly, there is a distinct set of placental changes that are only present in fetuses that were hypoxemic in late gestation, independent of whether Cx occurred. Thus, we provide further understanding of the different placental cellular and molecular mechanisms that are present in early placental restriction and in the emergence of later placental insufficiency.Song Zhang, Paige Barker, Kimberley J. Botting, Claire T. Roberts, Christine M. McMillan, Isabella Caroline McMillen, Janna L. Morriso

Associated reading skills in children with a history of Specific Language Impairment (SLI)

A large cohort of 200 eleven-year-old children with Specific Language Impairment (SLI) were assessed on basic reading accuracy and on reading comprehension as well as language tasks. Reading skills were examined descriptively and in relation to early language and literacy factors. Using stepwise regression analyses in which age and nonverbal IQ were controlled for, it was found that a single word reading measure taken at 7 years was unsurprisingly a strong predictor of the two different types of reading ability. However, even with this measure included, a receptive syntax task (TROG) entered when reading accuracy score was the DV. Furthermore, a test of expressive syntax/narrative and a receptive syntax task completed at 7 years entered into the model for word reading accuracy. When early reading accuracy was excluded from the analyses, early phonological skills also entered as a predictor of both reading accuracy and comprehension at 11 years. The group of children with a history of SLI were then divided into those with no literacy difficulties at 11 and those with some persisting literacy impairment. Using stepwise logistic regression, and again controlling for IQ and age, 7 years receptive syntax score (but not tests of phonology, expressive vocabulary or expressive syntax/narrative) entered as a positive predictor of membership of the ‘no literacy problems’ group regardless of whether early reading accuracy was controlled for in step one. The findings are discussed in relation to the overlap of SLI and dyslexia and the long term sequelae of language impairment

High potential for weathering and climate effects of non-vascular vegetation in the Late Ordovician

It has been hypothesized that predecessors of today’s bryophytes significantly increased global chemical weathering in the Late Ordovician, thus reducing atmospheric CO2 concentration and contributing to climate cooling and an interval of glaciations. Studies that try to quantify the enhancement of weathering by non-vascular vegetation, however, are usually limited to small areas and low numbers of species, which hampers extrapolating to the global scale and to past climatic conditions. Here we present a spatially explicit modelling approach to simulate global weathering by non-vascular vegetation in the Late Ordovician. We estimate a potential global weathering flux of 2.8 (km3 rock) yr−1, defined here as volume of primary minerals affected by chemical transformation. This is around three times larger than today’s global chemical weathering flux. Moreover, we find that simulated weathering is highly sensitive to atmospheric CO2 concentration. This implies a strong negative feedback between weathering by non-vascular vegetation and Ordovician climate

Placental adaptations in growth restriction

The placenta is the primary interface between the fetus and mother and plays an important role in maintaining fetal development and growth by facilitating the transfer of substrates and participating in modulating the maternal immune response to prevent immunological rejection of the conceptus. The major substrates required for fetal growth include oxygen, glucose, amino acids and fatty acids, and their transport processes depend on morphological characteristics of the placenta, such as placental size, morphology, blood flow and vascularity. Other factors including insulin-like growth factors, apoptosis, autophagy and glucocorticoid exposure also affect placental growth and substrate transport capacity. Intrauterine growth restriction (IUGR) is often a consequence of insufficiency, and is associated with a high incidence of perinatal morbidity and mortality, as well as increased risk of cardiovascular and metabolic diseases in later life. Several different experimental methods have been used to induce placental insufficiency and IUGR in animal models and a range of factors that regulate placental growth and substrate transport capacity have been demonstrated. While no model system completely recapitulates human IUGR, these animal models allow us to carefully dissect cellular and molecular mechanisms to improve our understanding and facilitate development of therapeutic interventions.Song Zhang, Timothy R.H. Regnault, Paige L. Barker, Kimberley J. Botting, Isabella C. McMillen, Christine M. McMillan, Claire T. Roberts and Janna L. Morriso

Human metabolism and elimination of the anthocyanin, cyanidin-3-glucoside: a 13C-tracer study

BACKGROUND: Evidence suggests that the consumption of anthocyanin-rich foods beneficially affects cardiovascular health; however, the absorption, distribution, metabolism, and elimination (ADME) of anthocyanin-rich foods are relatively unknown. OBJECTIVE: We investigated the ADME of a (13)C5-labeled anthocyanin in humans. DESIGN: Eight male participants consumed 500 mg isotopically labeled cyanidin-3-glucoside (6,8,10,3',5'-(13)C5-C3G). Biological samples were collected over 48 h, and (13)C and (13)C-labeled metabolite concentrations were measured by using isotope-ratio mass spectrometry and liquid chromatography-tandem mass spectrometry. RESULTS: The mean +/- SE percentage of (13)C recovered in urine, breath, and feces was 43.9 +/- 25.9% (range: 15.1-99.3% across participants). The relative bioavailability was 12.38 +/- 1.38% (5.37 +/- 0.67% excreted in urine and 6.91 +/- 1.59% in breath). Maximum rates of (13)C elimination were achieved 30 min after ingestion (32.53 +/- 14.24 mug(13)C/h), whereas (13)C-labeled metabolites peaked (maximum serum concentration: 5.97 +/- 2.14 mumol/L) at 10.25 +/- 4.14 h. The half-life for (13)C-labeled metabolites ranged between 12.44 +/- 4.22 and 51.62 +/- 22.55 h. (13)C elimination was greatest between 0 and 1 h for urine (90.30 +/- 15.28 mug/h), at 6 h for breath (132.87 +/- 32.23 mug/h), and between 6 and 24 h for feces (557.28 +/- 247.88 mug/h), whereas the highest concentrations of (13)C-labeled metabolites were identified in urine (10.77 +/- 4.52 mumol/L) and fecal samples (43.16 +/- 18.00 mumol/L) collected between 6 and 24 h. Metabolites were identified as degradation products, phenolic, hippuric, phenylacetic, and phenylpropenoic acids. CONCLUSION: Anthocyanins are more bioavailable than previously perceived, and their metabolites are present in the circulation fo

Depression and Anxiety Change from Adolescence to Adulthood in Individuals with and without Language Impairment

This prospective longitudinal study aims to determine patterns and predictors of change in depression and anxiety from adolescence to adulthood in individuals with language impairment (LI). Individuals with LI originally recruited at age 7 years and a comparison group of age-matched peers (AMPs) were followed from adolescence (16 years) to adulthood (24 years). We determine patterns of change in depression and anxiety using the Child Manifest Anxiety Scale-Revised (CMAS-R) and Short Moods and Feelings Questionnaire (SMFQ). In addition to examining associations with gender, verbal and nonverbal skills, we use a time-varying variable to investigate relationships between depression and anxiety symptoms and transitions in educational/employment circumstances. The results show that anxiety was higher in participants with LI than age matched peers and remained so from adolescence to adulthood. Individuals with LI had higher levels of depression symptoms than did AMPs at 16 years. Levels in those with LI decreased post-compulsory schooling but rose again by 24 years of age. Those who left compulsory school provision (regardless of school type) for more choice-driven college but who were not in full-time employment or study by 24 years of age were more likely to show this depression pathway. Verbal and nonverbal skills were not predictive of this pattern of depression over time. The typical female vulnerability for depression and anxiety was observed for AMPs but not for individuals with LI. These findings have implications for service provision, career/employment advice and support for individuals with a history of LI during different transitions from adolescence to adulthood

Defining language impairments in a subgroup of children with autism spectrum disorder

Autism spectrum disorder (ASD) is diagnosed on the basis of core impairments in pragmatic language skills, which are found across all ages and subtypes. In contrast, there is significant heterogeneity in language phenotypes, ranging from nonverbal to superior linguistic abilities, as defined on standardized tests of vocabulary and grammatical knowledge. The majority of children are verbal but impaired in language, relative to age-matched peers. One hypothesis is that this subgroup has ASD and co-morbid specific language impairment (SLI). An experiment was conducted comparing children with ASD to children with SLI and typically developing controls on aspects of language processing that have been shown to be impaired in children with SLI: repetition of nonsense words. Patterns of performance among the children with ASD and language impairment were similar to those with SLI, and contrasted with the children with ASD and no language impairment and typical controls, providing further evidence for the hypothesis that a subgroup of children with ASD has co-morbid SLI. The findings are discussed in the context of brain imaging studies that have explored the neural bases of language impairment in ASD and SLI, and overlap in the genes associated with elevated risk for these disorders.M01 RR00533 - NCRR NIH HHS; R01 DC10290 - NIDCD NIH HHS; U19 DC03610 - NIDCD NIH HH

Social, emotional, and behavioral functioning of secondary school students with low academic and language performance: perspectives from students, teachers, and parents

Adolescence is a time of transition when young people with language difficulties are at increased risk of experiencing social, emotional, and behavioral difficulties (SEBD). Most studies of social, emotional, and behavioral functioning (SEBF) in individuals with language difficulties focus on children with a clinical diagnosis of language impairment. This study explores SEBF in a nonclinical group of 12-year-old students with low educational and language performance from their own perspectives and those of their parents and teachers

Monsters: interdisciplinary explorations in monstrosity

There is a continued fascination with all things monster. This is partly due to the popular reception of Mary Shelley’s Monster, termed a “new species” by its overreaching but admiringly determined maker Victor Frankenstein in the eponymous novel first published in 1818. The enduring impact of Shelley’s novel, which spans a plethora of subjects and genres in imagery and themes, raises questions of origin and identity, death, birth and family relationships as well as the contradictory qualities of the monster. Monsters serve as metaphors for anxieties of aberration and innovation. Stephen Asma (2009) notes that monsters represent evil or moral transgression and each epoch, to speak with Michel Foucault, evidences a “particular type of monster” (2003, 66). Academic debates tend to explore how social and cultural threats come to be embodied in the figure of a monster and their actions literalize our deepest fears. Monsters in contemporary culture, however, have become are more humane than ever before. Monsters are strong, resilient, creative and sly creatures. Through their playful and invigorating energy they can be seen to disrupt and unsettle. They still cater to the appetite for horror, but they also encourage us to feel empathy. The encounter with a monster can enable us to stop, wonder and change our attitudes towards technology and our body and each other. This commentary article considers the use of the concepts of ‘monsters’ or ‘monstrosity’ in literature, contemporary research, culture and teaching contexts at the intersection of the Humanities and the Social Sciences

Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

Over 30 years ago Professor David Barker first proposed the theory that events in early life could explain an individual\u27s risk of non-communicable disease in later life: the developmental origins of health and disease (DOHaD) hypothesis. During the 1990s the validity of the DOHaD hypothesis was extensively tested in a number of human populations and the mechanisms underpinning it characterised in a range of experimental animal models. Over the past decade, researchers have sought to use this mechanistic understanding of DOHaD to develop therapeutic interventions during pregnancy and early life to improve adult health. A variety of animal models have been used to develop and evaluate interventions, each with strengths and limitations. It is becoming apparent that effective translational research requires that the animal paradigm selected mirrors the tempo of human fetal growth and development as closely as possible so that the effect of a perinatal insult and/or therapeutic intervention can be fully assessed. The guinea pig is one such animal model that over the past two decades has demonstrated itself to be a very useful platform for these important reproductive studies. This review highlights similarities in the in utero development between humans and guinea pigs, the strengths and limitations of the guinea pig as an experimental model of DOHaD and the guinea pig\u27s potential to enhance clinical therapeutic innovation to improve human health. (Figure presented.)