Contaminants in Commercial Preparations of ‘Purified’ Small Leucine-Rich Proteoglycans May Distort Mechanistic Studies

This paper reports the perplexing results that came about because of seriously impure commercially available reagents. Commercial reagents and chemicals are routinely ordered by scientists and are expected to have been rigorously assessed for their purity. Unfortunately, we found this assumption to be risky. Extensive work was carried out within our laboratory using commercially-sourced preparations of the small leucine-rich proteoglycans, decorin and biglycan, to investigate their influence on nerve cell growth. Unusual results compelled us to analyse the composition and purity of both preparations of these proteoglycans using both mass spectrometry and Western blotting, with and without various enzymatic deglycosylations. Commercial ‘decorin’ and ‘biglycan’ were found to contain a mixture of proteoglycans including not only both decorin and biglycan but also fibromodulin and aggrecan. The unexpected effects of ‘decorin’ and ‘biglycan’ on nerve cell growth could be explained by these impurities. Decorin and biglycan contain either chondroitin or dermatan sulphate glycosaminoglycan chains whilst fibromodulin only contains keratan sulphate and the large (>2,500 kDa), highly glycosylated aggrecan, contains both keratan and chondroitin sulphate. The different structure, molecular weights and composition of these impurities significantly affected our work and any conclusions that could be made. These findings beg the question as to whether scientists need to verify the purity of each commercially obtained reagent used in their experiments. The implications of these findings are vast, since the effects of these impurities may already have led to inaccurate conclusions and reports in the literature with concomitant loss of researchers’ funds and time

In Vitro Fertilization and Risk for Hypertensive Disorders of Pregnancy: Associations With Treatment Parameters

With an increasing proportion of pregnancies being conceived using assisted-reproductive technology, important changes to in vitro fertilization (IVF) such as the use of cryopreserved oocytes or embryos have been made. It is now established that adverse maternal and infant perinatal outcomes are associated with both assisted reproductive technologies and subfertility

Narrative skills in adolescents with a history of SLI in relation to non-verbal IQ scores

There is a debate about whether the language of children with primary language disorders and normal cognitive levels is qualitatively different from those with language impairments who have low or borderline non-verbal IQ (NVIQ). As children reach adolescence, this distinction may be even harder to ascertain, especially in naturalistic settings. Narrative may provide a useful, ecologically valid way in which to assess the language ability of adolescents with specific language impairment (SLI) who have intact or lowered NVIQ and to determine whether there is any discernable difference in every day language. Nineteen adolescents with a history of SLI completed two narrative tasks: a story telling condition and a conversational condition. Just under half the group (n = 8) had non-verbal IQs of 85. The remaining 11 had NVIQs in the normal range or above. Four areas of narrative (productivity, syntax, cohesion and performance) were assessed. There were no differences between the groups on standardized tests of language. However, the group with low NVIQ were poorer on most aspects of narrative, suggesting that cognitive level is important, even when language is the primary disorder. The groups showed similar patterns of differences between story telling and conversational narrative. It was concluded that adolescents with a history of SLI and poor cognitive levels have poorer narrative skills than those with normal range NVIQ even though these may not be detected by standardized assessment. Their difficulties present as qualitatively similar to those with normal range NVIQ and narratives appear impoverished rather than inaccurate

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

Early identification of children at risk of communication disorders: Introducing a novel battery of Dynamic Assessments for infants

Purpose Many children with communication disorders (CD) experience lengthy gaps between parental reporting of concerns and formal identification by professionals. This means that children with CD are denied access to early interventions that may help to support the development of communication skills and prevent possible negative sequelae associated with long-term outcomes. This may be due, in part, to the lack of assessment instruments available for children younger than three years of age. This study therefore reports on promising preliminary data from a novel set of valid dynamic assessment measures designed for infants. Methods We recruited 53 low-risk children and two groups of children considered to be at high risk for CD (n=17 social-high-risk and n=22 language high-risk) due to family members with language and social communication difficulties. Children were between 1 and 2 years of age and were assessed using a battery of five dynamic assessment (DA) tasks related to receptive vocabulary, motor imitation, response to joint attention, turn taking and social requesting. A set of standardised measures was also used. Results The DA tasks showed high levels of inter-rater reliability and relationships with age across a cross-sectional sample of children from the low-risk group. Three tasks showed moderate to strong correlations with standardised measures taken at the same age, with particularly strong correlations between the DA of receptive vocabulary and other receptive language measures. The DA of receptive vocabulary was also the only task to discriminate between the three risk groups, with the social-high-risk group scoring lower. Conclusions These results provide preliminary information about early DA tasks, forming the basis for further research into their utility. DA tasks might eventually facilitate the development of new methods for detecting CD in very young children, allowing earlier intervention and support

In vitro fertilization and risk for hypertensive disorders of pregnancy: associations with treatment parameters

With an increasing proportion of pregnancies being conceived using assisted-reproductive technology, important changes to in vitro fertilization (IVF) such as the use of cryopreserved oocytes or embryos have been made. It is now established that adverse maternal and infant perinatal outcomes are associated with both assisted reproductive technologies and subfertility

A prosodically controlled word and nonword repetition task for 2- to 4- year-olds: Evidence from typically developing children

An association has been found between nonword repetition and language skills in school-aged children with both typical and atypical language development (Dollaghan & Campbell, 1998; Ellis Weismer et al., 2000; Gathercole & Baddeley, 1990; Montgomery, 2002). This raises the possibility that younger children’s repetition performance may be predictive of later language deficits. In order to investigate this possibility, it is important to establish that elicited repetition with very young children is both feasible and informative. To this end, a repetition task was designed and carried out with 66 children aged 2-4. The task consisted of 18 words and 18 matched nonwords that were systematically manipulated for length and prosodic structure. In addition, an assessment of receptive vocabulary was administered. The repetition task elicited high levels of response. Total scores as well as word and nonword scores were sensitive to age. Lexical status and item length affected performance regardless of age: words were repeated more accurately than nonwords, and one-syllable items were repeated more accurately than two-syllable items, which were in turn repeated more accurately than three-syllable items. The effect of prosodic structure was also significant. Whole syllable errors were almost exclusive to unstressed syllables, with those preceding stress being most vulnerable. Performance on the repetition task was significantly correlated with performance on the receptive vocabulary test. Since this repetition task was effective in eliciting responses from most of the 2 to 4-year-old participants, tapped developmental change in their repetition skills, and revealed patterns in their performance, it has the potential to identify deficits in very early repetition skills that may be indicative of wider language difficulties

Exposure to rosiglitazone, a PPAR-gamma agonist, in late gestation reduces the abundance of factors regulating cardiac metabolism and cardiomyocyte size in the sheep fetus

It is unknown whether cardiomyocyte hypertrophy and the transition to fatty acid oxidation as the main source of energy after birth is dependent on the maturation of the cardiomyocytes' metabolic system, or on the limitation of substrate availability before birth. This study aimed to investigate whether intrafetal administration of a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, rosiglitazone, during late gestation can stimulate the expression of factors regulating cardiac growth and metabolism in preparation for birth, and the consequences of cardiac contractility in the fetal sheep at ∼140 days gestation. The mRNA expression and protein abundance of key factors regulating growth and metabolism were quantified using quantitative RT-PCR and Western blot analysis, respectively. Cardiac contractility was determined by measuring the Ca(2+) sensitivity and maximum Ca(2+)-activated force of skinned cardiomyocyte bundles. Rosiglitazone-treated fetuses had a lower cardiac abundance of insulin-signaling molecules, including insulin receptor-β, insulin receptor substrate-1 (IRS-1), phospho-IRS-1 (Tyr-895), phosphatidylinositol 3-kinase (PI3K) regulatory subunit p85, PI3K catalytic subunit p110α, phospho-3-phosphoinositide-dependent protein kinase 1 (Ser-241), protein kinase B (Akt-1), phospho-Akt (Ser-273), PKCζ, phospho-PKCζ(Thr-410), Akt substrate 160 kDa (AS160), phospho-AS160 (Thr-642), and glucose transporter type-4. Additionally, cardiac abundance of regulators of fatty acid β-oxidation, including adiponectin receptor 1, AMPKα, phospho-AMPKα (Thr-172), phospho-acetyl CoA carboxylase (Ser-79), carnitine palmitoyltransferase-1, and PGC-1α was lower in the rosiglitazone-treated group. Rosiglitazone administration also resulted in a decrease in cardiomyocyte size. Rosiglitazone administration in the late-gestation sheep fetus resulted in a decreased abundance of factors regulating cardiac glucose uptake, fatty acid β-oxidation, and cardiomyocyte size. These findings suggest that activation of PPAR-γ using rosiglitazone does not promote the maturation of cardiomyocytes; rather, it may decrease cardiac metabolism and compromise cardiac health later in life.Shervi Lie, Melisa Hui, I. Caroline McMillen, Beverly S. Muhlhausler, Giuseppe S. Posterino, Stacey L. Dunn, Kimberley C. Wang, Kimberley J. Botting, Janna L. Morriso

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