The relation between language and cognition in children aged 3 to 9 : The acquisition of grammatical gender in French

The French language has a grammatical gender system in which all nouns are assigned either a masculine or a feminine gender. Nouns provide two types of gender cues that can potentially guide gender attribution: morphophonological cues carried by endings and semantic cues (natural gender). The first goal of this study was to describe the acquisition of the probabilistic system based on phonological oppositions on word endings by French-speaking children. The second goal was to explore the extent to which this system affects categorization. In the study, 3- to 9-year-olds assigned gender categorization to invented nouns whose endings were typically masculine, typically feminine, or neutral. Two response conditions were used. In the determiner condition, children indicated the gender class by orally providing the determiner un or une marked for gender. In the picture condition, responses were given by pointing to the picture of a Martian-like female or male person that would be best called by each spoken pseudoword. Results indicated that as young as 3 years, children associated the determiner corresponding to the ending bias at greater than chance levels. Ending-consistent performance increased from 3 to 9 years of age. Moreover, from 4 years of age onward, sensitivity to endings aVected categorization. Starting at that age, pictures were selected according to endings at greater than chance levels. This eVect also increased with age. The discussion deals with the mechanisms of language acquisition and the relation between language and cognition

From nanotechnology to nanomedicine: applications to cancer research

Scientific advances have significantly improved the practice of medicine by providing objective and quantitative means for exploring the human body and disease states. These innovative technologies have already profoundly improved disease detection, imaging, treatment and patient follow-up. Today's analytical limits are at the nanoscale level (one-billionth of a meter) enabling a detailed exploration at the level of DNA, RNA, proteins and metabolites which are in fact nano-objects. This translational review aims at integrating some recent advances from micro- and nano-technologies with high potential for improving daily oncology practice

Exposure to androstenes influences processing of emotional words

There is evidence that human-produced androstenes affect attitudinal, emotional, and physiological states in a context-dependent manner, suggesting that they could be involved in modulating social interactions. For instance, androstadienone appears to increase attention specifically to emotional information. Most of the previous work focused on one or two androstenes. Here, we tested whether androstenes affect linguistic processing, using three different androstene compounds. Participants (90 women and 77 men) performed a lexical decision task after being exposed to an androstene or to a control treatment (all compounds were applied on the philtrum). We tested effects on three categories of target words, varying in emotional valence: positive, competitive, and neutral words (e.g., hope, war, and century, respectively). Results show that response times were modulated by androstene treatment and by emotional valence of words. Androstenone, but not androstadienone and androstenol, significantly slowed down the reaction time to words with competitive valence. Moreover, men exposed to androstenol showed a significantly reduced error rate, although men tended to make more errors than women in general. This suggests that these androstenes modulate the processing of emotional words, namely some particular lexical emotional content may become more salient under the effect of androstenes

C-terminal amino acids are essential for human heat shock protein 70 dimerization

The human inducible heat shock protein 70 (hHsp70), which is involved in several major pathologies, including neurodegenerative disorders and cancer, is a key molecular chaperone and contributes to the proper protein folding and maintenance of a large number of protein structures. Despite its role in disease, the current structural knowledge of hHsp70 is almost exclusively based on its Escherichia coli homolog, DnaK, even though these two proteins only share ~50 % amino acid identity. For the first time, we describe a complete heterologous production and purification strategy that allowed us to obtain a large amount of soluble, full-length, and non-tagged hHsp70. The protein displayed both an ATPase and a refolding activity when combined to the human Hsp40. Multi-angle light scattering and bio-layer interferometry analyses demonstrated the ability of hHsp70 to homodimerize. The role of the C-terminal part of hHsp70 was identified and confirmed by a study of a truncated version of hHsp70 that could neither dimerize nor present refolding activity

Working memory, Reading and Mathematical Skills in children with developmental coordination disorder

The aim of the present study was investigate the relationship between working memory and reading and mathematical skills in 55 children diagnosed with developmental coordination disorder (DCD). The findings indicate a pervasive memory deficit in all memory measures. In particular, deficits observed in visuospatial short-term and working memory tasks were significantly worse than in the verbal short-term memory ones. On the basis of these deficits, the sample was divided into high and low visuospatial memory ability groups. The low visuospatial memory group performed significantly worse on the attainment measures compared to the high visuospatial memory group, even when the contribution of IQ was taken into account. When the sample was divided into high and low verbal working memory ability groups, verbal working memory skills made a unique contribution to attainment only when verbal IQ was taken into account, but not when performance IQ was statistically controlled. It is possible that the processing demands of the working memory tasks together with the active motor component reflected in the visuospatial memory tasks and performance IQ subtest both play a crucial role in learning in children with DCD

Assessing reading comprehension with narrative and expository texts: dimensionality and relationship with fluency, vocabulary and memory

Reading comprehension assessment should rely on valid instruments that enable adequate conclusions to be taken regarding students’ reading comprehension performance. In this article, two studies were conducted to collect validity evidence for the vertically scaled forms of two Tests of Reading Comprehension for Portuguese elementary school students in the second to fourth grades, one with narrative texts (TRC-n) and another with expository ones (TRC-e). Two samples of 950 and 990 students participated in Study 1, the study of the dimensionality of the TRC-n and TRC-e forms, respectively. Confirmatory factor analyses provided evidence of an acceptable fit for the one-factor solution for all test forms. Study 2 included 218 students to collect criterion-related validity. The scores obtained in each of the test forms were significantly correlated with the ones obtained in other reading comprehension measures and with the results obtained in oral reading fluency, vocabulary and working memory tests. Evidence suggests that the test forms are valid measures of reading comprehension.CIEC – Research Centre on Child Studies, IE, UMinho (FCT R&D unit 317), Portugal. Grant FCOMP-01-0124-FEDER-010733 from Fundação para a Ciência e Tecnologia (FCT) and the European Regional Development Fund (FEDER) through the European program COMPETE (Operational Program for Competitiveness Factors) under the National Strategic Reference Framework (QREN). It was also supported by FCT grant SFRH/BD/94763/2013.info:eu-repo/semantics/publishedVersio

Targeted Delivery of Chemotherapy Agents Using a Liver Cancer-Specific Aptamer

Using antibody/aptamer-drug conjugates can be a promising method for decreasing toxicity, while increasing the efficiency of chemotherapy.In this study, the antitumor agent Doxorubicin (Dox) was incorporated into the modified DNA aptamer TLS11a-GC, which specifically targets LH86, a human hepatocellular carcinoma cell line. Cell viability tests demonstrated that the TLS11a-GC-Dox conjugates exhibited both potency and target specificity. Importantly, intercalating Dox into the modified aptamer inhibited nonspecific uptake of membrane-permeable Dox to the non-target cell line. Since the conjugates are selective for cells that express higher amounts of target proteins, both criteria noted above are met, making TLS11a-GC-Dox conjugates potential candidates for targeted delivery to liver cancer cells.Considering the large number of available aptamers that have specific targets for a wide variety of cancer cells, this novel aptamer-drug intercalation method will have promising implications for chemotherapeutics in general

A Simple but Highly Effective Approach to Evaluate the Prognostic Performance of Gene Expression Signatures

BACKGROUND: Highly parallel analysis of gene expression has recently been used to identify gene sets or 'signatures' to improve patient diagnosis and risk stratification. Once a signature is generated, traditional statistical testing is used to evaluate its prognostic performance. However, due to the dimensionality of microarrays, this can lead to false interpretation of these signatures. PRINCIPAL FINDINGS: A method was developed to test batches of a user-specified number of randomly chosen signatures in patient microarray datasets. The percentage of random generated signatures yielding prognostic value was assessed using ROC analysis by calculating the area under the curve (AUC) in six public available cancer patient microarray datasets. We found that a signature consisting of randomly selected genes has an average 10% chance of reaching significance when assessed in a single dataset, but can range from 1% to ∼40% depending on the dataset in question. Increasing the number of validation datasets markedly reduces this number. CONCLUSIONS: We have shown that the use of an arbitrary cut-off value for evaluation of signature significance is not suitable for this type of research, but should be defined for each dataset separately. Our method can be used to establish and evaluate signature performance of any derived gene signature in a dataset by comparing its performance to thousands of randomly generated signatures. It will be of most interest for cases where few data are available and testing in multiple datasets is limited

N-glycosylation of mouse TRAIL-R and human TRAIL-R1 enhances TRAIL-induced death.

APO2L/TRAIL (TNF-related apoptosis-inducing ligand) induces death of tumor cells through two agonist receptors, TRAIL-R1 and TRAIL-R2. We demonstrate here that N-linked glycosylation (N-glyc) plays also an important regulatory role for TRAIL-R1-mediated and mouse TRAIL receptor (mTRAIL-R)-mediated apoptosis, but not for TRAIL-R2, which is devoid of N-glycans. Cells expressing N-glyc-defective mutants of TRAIL-R1 and mouse TRAIL-R were less sensitive to TRAIL than their wild-type counterparts. Defective apoptotic signaling by N-glyc-deficient TRAIL receptors was associated with lower TRAIL receptor aggregation and reduced DISC formation, but not with reduced TRAIL-binding affinity. Our results also indicate that TRAIL receptor N-glyc impacts immune evasion strategies. The cytomegalovirus (CMV) UL141 protein, which restricts cell-surface expression of human TRAIL death receptors, binds with significant higher affinity TRAIL-R1 lacking N-glyc, suggesting that this sugar modification may have evolved as a counterstrategy to prevent receptor inhibition by UL141. Altogether our findings demonstrate that N-glyc of TRAIL-R1 promotes TRAIL signaling and restricts virus-mediated inhibition