The acquisition of pronouns by French children: A parallel study of production and comprehension

This study examines syntactic and morphological aspects of the production and comprehension of pronouns by 99 typically developing French-speaking children aged 3 years, 5 months to 6 years, 5 months. A fine structural analysis of subject, object, and reflexive clitics suggests that whereas the object clitic chain crosses the subject chain, the reflexive clitic chain is nested within it. We argue that this structural difference introduces differences in processing complexity, chain crossing being more complex than nesting. In support of this analysis, both production and comprehension experiments show that children have more difficulty with object than with reflexive clitics (with more omissions in production and more erroneous judgments in sentences involving Principle B in comprehension). Concerning the morphological aspect, French subject and object pronouns agree in gender with their referent. We report serious difficulties with pronoun gender both in production and comprehension in children around the age of 4 (with nearly 30% errors in production and chance level judgments in comprehension), which tend to disappear by age 6. The distribution of errors further suggests that the masculine gender is processed as the default value. These findings provide further insights into the relationship between comprehension and production in the acquisition process.

Local acquisition of methicillin-resistance in predominant Staphylococcus aureus clones of western Switzerland.

Objectives: Recent population genetic studies suggest that the Staphylococcal Chromosome Cassettes mec (SCCmec) was acquired at a global scale much more frequently than previously thought. We hypothesized that such acquisitions can also be observed at a local level. In the present study, we aimed at investigating the diversity of SCCmec in a local MRSA population, where the dissemination of four MRSA clones has been observed (JCM 2007, 45: 3729). Methods: All the MRSA isolates (one per patient) recovered in the Vaud canton of Switzerland from January 2005 to December 2008 were analyzed in this study. We used the Double Locus Sequence Typing (DLST) method, based on clfB and spa loci, and the e-BURST algorithm to group the types with one allele in common (i.e. clone). To increase the discriminatory power of the DLST method, a third polymorphic marker (clfA) was further analyzed on a sub-sample of isolates. The SCCmec type of each isolate was determined with the first two PCRs of the Kondo scheme. Results: DLST analysis indicated that 1884/2036 isolates (92.5%) belong to the four predominant clones. A majority of isolates in each clone harboured an identical SCCmec type: 61/64 (95%) isolates to DLST clone 1−1 SCCmec IV, 1282/1323 (97%) to clone 2−2 SCCmec II, 237/288 (82%) to clone 3−3 SCCmec IV, and 192/209 (92%) to clone 4−4 SCCmec I. Unexpectedly, different SCCmec types were present in a single predominant DLST clone: SCCmec V plus one unusual type in 3 isolates of clone 1−1; SCCmec I, IV, V, VI plus two unusual types in 41 isolates of clone 2−2; SCCmec I, II, VI plus three unusual types in 51 isolates of clone 3−3; and SCCmec II, IV, V plus one unusual type in 17 isolates of clone 4−4. Interestingly, adding a third locus generally did not change the classification of incongruent SCCmec types, suggesting that these SCCmec elements have been acquired locally during the dissemination of the clones. Conclusion: Although the SCCmec diversity within clones was relatively low at a local level, a significant proportion of isolates with different SCCmec have been identified in the four major clones. This suggests that the local acquisition of SCCmec elements is not a rare event and illustrates the great capacity of S. aureus to quickly adapt to its environment by acquiring new genetic elements.

Pleiotropy in the melanocortin system: expression levels of this system are associated with melanogenesis and pigmentation in the tawny owl (Strix aluco).

The adaptive function of melanin-based coloration is a long-standing debate. A recent genetic model suggested that pleiotropy could account for covariations between pigmentation, behaviour, morphology, physiology and life history traits. We explored whether the expression levels of genes belonging to the melanocortin system (MC1R, POMC, PC1/3, PC2 and the antagonist ASIP), which have many pleiotropic effects, are associated with melanogenesis (through variation in the expression of the genes MITF, SLC7A11, TYR, TYRP1) and in turn melanin-based coloration. We considered the tawny owl (Strix aluco) because individuals vary continuously from light to dark reddish, and thus, colour variation is likely to stem from differences in the levels of gene expression. We measured gene expression in feather bases collected in nestlings at the time of melanin production. As expected, the melanocortin system was associated with the expression of melanogenic genes and pigmentation. Offspring of darker reddish fathers expressed PC1/3 to lower levels but tended to express PC2 to higher levels. The convertase enzyme PC1/3 cleaves the POMC prohormone to obtain ACTH, while the convertase enzyme PC2 cleaves ACTH to produce α-melanin-stimulating hormone (α-MSH). ACTH regulates glucocorticoids, hormones that modulate stress responses, while α-MSH induces eumelanogenesis. We therefore conclude that the melanocortin system, through the convertase enzymes PC1/3 and PC2, may account for part of the interindividual variation in melanin-based coloration in nestling tawny owls. Pleiotropy may thus account for the covariation between phenotypic traits involved in social interactions (here pigmentation) and life history, morphology, behaviour and physiology.

Human-to-bovine jump of Staphylococcus aureus CC8 is associated with the loss of a β-hemolysin converting prophage and the acquisition of a new staphylococcal cassette chromosome.

Staphylococcus aureus can colonize and infect both humans and animals, but isolates from both hosts tend to belong to different lineages. Our recent finding of bovine-adapted S. aureus showing close genetic relationship to the human S. aureus clonal complex 8 (CC8) allowed us to examine the genetic basis of host adaptation in this particular CC. Using total chromosome microarrays, we compared the genetic makeup of 14 CC8 isolates obtained from cows suffering subclinical mastitis, with nine CC8 isolates from colonized or infected human patients, and nine S. aureus isolates belonging to typical bovine CCs. CC8 isolates were found to segregate in a unique group, different from the typical bovine CCs. Within this CC8 group, human and bovine isolates further segregated into three subgroups, among which two contained a mix of human and bovine isolates, and one contained only bovine isolates. This distribution into specific clusters and subclusters reflected major differences in the S. aureus content of mobile genetic elements (MGEs). Indeed, while the mixed human-bovine clusters carried commonly human-associated β-hemolysin converting prophages, the bovine-only isolates were devoid of such prophages but harbored an additional new non-mec staphylococcal cassette chromosome (SCC) unique to bovine CC8 isolates. This composite cassette carried a gene coding for a new LPXTG-surface protein sharing homologies with a protein found in the environmental bacterium Geobacillus thermoglucosidans. Thus, in contrast to human CC8 isolates, the bovine-only CC8 group was associated with the combined loss of β-hemolysin converting prophages and gain of a new SCC probably acquired in the animal environment. Remaining questions are whether the new LPXTG-protein plays a role in bovine colonization or infection, and whether the new SCC could further acquire antibiotic-resistance genes and carry them back to human.

Clonal acquisition of the Ly49A NK cell receptor is dependent on the trans-acting factor TCF-1.

Families of clonally expressed major histocompatibility complex (MHC) class I-specific receptors provide specificity to and regulate the function of natural killer (NK) cells. One of these receptors, mouse Ly49A, is expressed by 20% of NK cells and inhibits the killing of H-2D(d) but not D(b)-expressing target cells. Here, we show that the trans-acting factor TCF-1 binds to two sites in the Ly49A promoter and regulates its activity. Moreover, we find that TCF-1 determines the size of the Ly49A NK cell subset in vivo in a dosage-dependent manner. We propose that clonal Ly49A acquisition during NK cell development is regulated by TCF-1.

Building the niche through time: using 13,000 years of data to predict the effects of climate change on three tree species in Europe

Aim Species distribution models (SDMs) based on current species ranges underestimate the potential distribution when projected in time and/or space. A multi-temporal model calibration approach has been suggested as an alternative, and we evaluate this using 13,000 years of data. Location Europe. Methods We used fossil-based records of presence for Picea abies, Abies alba and Fagus sylvatica and six climatic variables for the period 13,000 to 1000yr bp. To measure the contribution of each 1000-year time step to the total niche of each species (the niche measured by pooling all the data), we employed a principal components analysis (PCA) calibrated with data over the entire range of possible climates. Then we projected both the total niche and the partial niches from single time frames into the PCA space, and tested if the partial niches were more similar to the total niche than random. Using an ensemble forecasting approach, we calibrated SDMs for each time frame and for the pooled database. We projected each model to current climate and evaluated the results against current pollen data. We also projected all models into the future. Results Niche similarity between the partial and the total-SDMs was almost always statistically significant and increased through time. SDMs calibrated from single time frames gave different results when projected to current climate, providing evidence of a change in the species realized niches through time. Moreover, they predicted limited climate suitability when compared with the total-SDMs. The same results were obtained when projected to future climates. Main conclusions The realized climatic niche of species differed for current and future climates when SDMs were calibrated considering different past climates. Building the niche as an ensemble through time represents a way forward to a better understanding of a species' range and its ecology in a changing climate.

Aliskiren monotherapy does not cause paradoxical blood pressure rises: meta-analysis of data from 8 clinical trials.

Angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and diuretics all cause reactive rises in plasma renin concentration, but particularly high levels have been reported with aliskiren. This prompted speculation that blockade of plasma renin activity with aliskiren could be overwhelmed, leading to paradoxical increases in blood pressure. This meta-analysis of data from 4877 patients from 8 randomized, double-blind, placebo- and/or active-controlled trials examined this hypothesis. The analysis focused on the incidence of paradoxical blood pressure increases above predefined thresholds, after > or =4 weeks of treatment with 300 mg of aliskiren, angiotensin receptor blockers (300 mg of irbesartan, 100 mg of losartan, or 320 mg of valsartan), 10 mg of ramipril, 25 mg of hydrochlorothiazide, or placebo. There were no significant differences in the frequency of increases in systolic (>10 mm Hg; P=0.30) or diastolic (>5 mm Hg; P=0.65) pressure among those treated with aliskiren (3.9% and 3.1%, respectively), angiotensin receptor blockers (4.0% and 3.7%), ramipril (5.7% and 2.6%), or hydrochlorothiazide (4.4% and 2.7%). Increases in blood pressure were considerably more frequent in the placebo group (12.6% and 11.4%; P<0.001). None of the 536 patients with plasma renin activity data who received 300 mg of aliskiren exhibited an increase in systolic pressure >10 mm Hg that was associated with an increase in plasma renin activity >0.1 ng/mL per hour. In conclusion, the incidence of blood pressure increases with aliskiren was similar to that during treatment with other antihypertensive drugs. Blood pressure rises on aliskiren treatment were not associated with increases in plasma renin activity. This meta-analysis found no evidence that aliskiren uniquely causes paradoxical rises in blood pressure.

Effect of white-matter lesions on the risk of periprocedural stroke after carotid artery stenting versus endarterectomy in the International Carotid Stenting Study (ICSS): a prespecified analysis of data from a randomised trial.

BACKGROUND: Findings from randomised trials have shown a higher early risk of stroke after carotid artery stenting than after carotid endarterectomy. We assessed whether white-matter lesions affect the perioperative risk of stroke in patients treated with carotid artery stenting versus carotid endarterectomy. METHODS: Patients with symptomatic carotid artery stenosis included in the International Carotid Stenting Study (ICSS) were randomly allocated to receive carotid artery stenting or carotid endarterectomy. Copies of baseline brain imaging were analysed by two investigators, who were masked to treatment, for the severity of white-matter lesions using the age-related white-matter changes (ARWMC) score. Randomisation was done with a computer-generated sequence (1:1). Patients were divided into two groups using the median ARWMC. We analysed the risk of stroke within 30 days of revascularisation using a per-protocol analysis. ICSS is registered with controlled-trials.com, number ISRCTN 25337470. FINDINGS: 1036 patients (536 randomly allocated to carotid artery stenting, 500 to carotid endarterectomy) had baseline imaging available. Median ARWMC score was 7, and patients were dichotomised into those with a score of 7 or more and those with a score of less than 7. In patients treated with carotid artery stenting, those with an ARWMC score of 7 or more had an increased risk of stroke compared with those with a score of less than 7 (HR for any stroke 2·76, 95% CI 1·17-6·51; p=0·021; HR for non-disabling stroke 3·00, 1·10-8·36; p=0·031), but we did not see a similar association in patients treated with carotid endarterectomy (HR for any stroke 1·18, 0·40-3·55; p=0·76; HR for disabling or fatal stroke 1·41, 0·38-5·26; p=0·607). Carotid artery stenting was associated with a higher risk of stroke compared with carotid endarterectomy in patients with an ARWMC score of 7 or more (HR for any stroke 2·98, 1·29-6·93; p=0·011; HR for non-disabling stroke 6·34, 1·45-27·71; p=0·014), but there was no risk difference in patients with an ARWMC score of less than 7. INTERPRETATION: The presence of white-matter lesions on brain imaging should be taken into account when selecting patients for carotid revascularisation. Carotid artery stenting should be avoided in patients with more extensive white-matter lesions, but might be an acceptable alternative to carotid endarterectomy in patients with less extensive lesions. FUNDING: Medical Research Council, the Stroke Association, Sanofi-Synthélabo, the European Union Research Framework Programme 5.