Morpho-Syntactic Abilities of Unbalanced Bilingual Children: A Closer Look at the Weaker Language

Previous studies evaluating morpho-syntactic abilities in the Weaker Language of unbalanced bilingual children are scarce; and they bring inconclusive evidence on the nature of the Weaker Language development. The current study looked into morpho-syntactic profiles of bilingual Russian–Hebrew speaking children in the Weaker Language [the Weaker Heritage Language (HL-Russian) and the Weaker Societal Language (SL-Hebrew)] as compared to balanced bilinguals, unbalanced bilinguals in the Dominant Language and bilinguals with Specific Language Impairment (SLI). Four groups of bilingual children aged 5;5–6;5 participated: unbalanced bilinguals with the Weaker HL-Russian and the Dominant SL-Hebrew (HL-weak: n = 39), unbalanced bilinguals with the Weaker SL-Hebrew and the Dominant HL-Russian (SL-weak: n = 19); balanced bilinguals (BB: n = 38), and bilinguals with SLI (biSLI: n = 23). Children’s morpho-syntactic abilities in both languages were investigated using LITMUS (Language Impairment Testing in Multilingual Settings) Sentence Repetition Tasks (based on Marinis and Armon-Lotem, 2015). Quantitative analysis of morpho-syntactic abilities showed that unbalanced bilinguals scored lower in the Weaker Language as compared to balanced bilinguals and unbalanced bilinguals in the Dominant Language, yet, higher than bilinguals with SLI. Error patterns were similar across bilingual groups with TLD and could be traced to cross-linguistic influence. By contrast, error profiles of unbalanced bilinguals in the Weaker Language and bilinguals with SLI bore fundamental differences. Whereas unbalanced bilinguals in the Weaker Language opted for complex structures, relying on the available resources from the Dominant Language; bilinguals with SLI simplified complex syntactic structures. To conclude, the study shows that the Weaker Language of unbalanced bilinguals with TLD develop qualitatively similarly to the languages of balanced bilinguals and the Dominant Language in unbalanced bilinguals, albeit delayed or influenced by the Dominant Language to a larger extent. Conversely, the study brings evidence that linguistic profiles of unbalanced bilinguals with TLD in the Weaker Language and bilinguals with SLI differ, pointing at a deviant pattern of acquisition in children with SLI

Independent and Combined Effects of Socioeconomic Status (SES) and Bilingualism on Children’s Vocabulary and Verbal Short-Term Memory

The current study explores the influence of socioeconomic status (SES) and bilingualism on the linguistic skills and verbal short-term memory of preschool children. In previous studies comparing children of low and mid-high SES, the terms “a child with low-SES” and “a child speaking a minority language” are often interchangeable, not enabling differentiated evaluation of these two variables. The present study controls for this confluence by testing children born and residing in the same country and attending the same kindergartens, with all bilingual children speaking the same heritage language (HL-Russian). A total of 120 children (88 bilingual children: 44 with low SES; and 32 monolingual children: 16 with low SES) with typical language development, aged 5; 7–6; 7, were tested in the societal language (SL-Hebrew) on expressive vocabulary and three repetition tasks [forward digit span (FWD), nonword repetition (NWR), and sentence repetition (SRep)], which tap into verbal short-term memory. The results indicated that SES and bilingualism impact different child abilities. Bilingualism is associated with decreased vocabulary size and lower performance on verbal short-term memory tasks with higher linguistic load in the SL-Hebrew. The negative effect of bilingualism on verbal short-term memory disappears once vocabulary is accounted for. SES influences not only linguistic performance, but also verbal short-term memory with lowest linguistic load. The negative effect of SES cannot be solely attributed to lower vocabulary scores, suggesting that an unprivileged background has a negative impact on children’s cognitive development beyond a linguistic disadvantage. The results have important clinical implications and call for more research exploring the varied impact of language and life experience on children’s linguistic and cognitive skills

Interlinking showy traits: co-engineering of scent and colour biosynthesis in flowers

The phenylpropanoid pathway gives rise to metabolites that determine floral colour and fragrance. These metabolites are one of the main means used by plants to attract pollinators, thereby ensuring plant survival. A lack of knowledge about factors regulating scent production has prevented the successful enhancement of volatile phenylpropanoid production in flowers. In this study, the Production of Anthocyanin Pigment1 ( Pap1 ) Myb transcription factor from Arabidopsis thaliana , known to regulate the production of non-volatile phenylpropanoids, including anthocyanins, was stably introduced into Petunia hybrida . In addition to an increase in pigmentation, Pap1 -transgenic petunia flowers demonstrated an increase of up to tenfold in the production of volatile phenylpropanoid/benzenoid compounds. The dramatic increase in volatile production corresponded to the native nocturnal rhythms of volatile production in petunia. The application of phenylalanine to Pap1 -transgenic flowers led to an increase in the otherwise negligible levels of volatiles emitted during the day to nocturnal levels. On the basis of gene expression profiling and the levels of pathway intermediates, it is proposed that both increased metabolic flux and transcriptional activation of scent and colour genes underlie the enhancement of petunia flower colour and scent production by Pap1 . The co-ordinated regulation of metabolic steps within or between pathways involved in vital plant functions, as shown here for two showy traits determining plant–pollinator interactions, provides a clear advantage for plant survival. The use of a regulatory factor that activates scent production creates a new biotechnological strategy for the metabolic architecture of fragrance, leading to the creation of novel genetic variability for breeding purposes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75040/1/j.1467-7652.2008.00329.x.pd

Language in autism: domains, profiles and co-occurring conditions

This article reviews the current knowledge state on pragmatic and structural language abilities in autism and their potential relation to extralinguistic abilities and autistic traits. The focus is on questions regarding autism language profles with varying degrees of (selective) impairment and with respect to potential comorbidity of autism and language impairment: Is language impairment in autism the co-occurrence of two distinct conditions (comorbidity), a consequence of autism itself (no comorbidity), or one possible combination from a series of neurodevelopmental properties (dimensional approach)? As for language profles in autism, three main groups are identifed, namely, (i) verbal autistic individuals without structural language impairment, (ii) verbal autistic individuals with structural language impairment, and (iii) minimally verbal autistic individuals. However, this tripartite distinction hides enormous linguistic heterogeneity. Regarding the nature of language impairment in autism, there is currently no model of how language difculties may interact with autism characteristics and with various extralinguistic cognitive abilities. Building such a model requires carefully designed explorations that address specifc aspects of language and extralinguistic cognition. This should lead to a fundamental increase in our understanding of language impairment in autism, thereby paving the way for a substantial contribution to the question of how to best characterize neurodevelopmental disorders

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

The Epigenetic Evolution of Glioma Is Determined by the IDH1 Mutation Status and Treatment Regimen

Tumor adaptation or selection is thought to underlie therapy resistance in glioma. To investigate longitudinal epigenetic evolution of gliomas in response to therapeutic pressure, we performed an epigenomic analysis of 132 matched initial and recurrent tumors from patients with IDH-wildtype (IDHwt) and IDH-mutant (IDHmut) glioma. IDHwt gliomas showed a stable epigenome over time with relatively low levels of global methylation. The epigenome of IDHmut gliomas showed initial high levels of genome-wide DNA methylation that was progressively reduced to levels similar to those of IDHwt tumors. Integration of epigenomics, gene expression, and functional genomics identified HOXD13 as a master regulator of IDHmut astrocytoma evolution. Furthermore, relapse of IDHmut tumors was accompanied by histologic progression that was associated with survival, as validated in an independent cohort. Finally, the initial cell composition of the tumor microenvironment varied between IDHwt and IDHmut tumors and changed differentially following treatment, suggesting increased neoangiogenesis and T-cell infiltration upon treatment of IDHmut gliomas. This study provides one of the largest cohorts of paired longitudinal glioma samples with epigenomic, transcriptomic, and genomic profiling and suggests that treatment of IDHmut glioma is associated with epigenomic evolution toward an IDHwt-like phenotype.</p