Prelude to malignancy: A gene expression signature in normal mammary gland from breast cancer patients suggests pre-tumorous alterations and is associated with adverse outcomes.

Despite advances in early detection and treatment strategies, breast cancer recurrence and mortality remain a significant health issue. Recent insights suggest the prognostic potential of microscopically healthy mammary gland, in the vicinity of the breast lesion. Nonetheless, a comprehensive understanding of the gene expression profiles in these tissues and their relationship to patient outcomes remain missing. Furthermore, the increasing trend towards breast-conserving surgery may inadvertently lead to the retention of existing cancer-predisposing mutations within the normal mammary gland. This study assessed the transcriptomic profiles of 242 samples from 83 breast cancer patients with unfavorable outcomes, including paired uninvolved mammary gland samples collected at varying distances from primary lesions. As a reference, control samples from 53 mammoplasty individuals without cancer history were studied. A custom panel of 634 genes linked to breast cancer progression and metastasis was employed for expression profiling, followed by whole-transcriptome verification experiments and statistical analyses to discern molecular signatures and their clinical relevance. A distinct gene expression signature was identified in uninvolved mammary gland samples, featuring key cellular components encoding keratins, CDH1, CDH3, EPCAM cell adhesion proteins, matrix metallopeptidases, oncogenes, tumor suppressors, along with crucial genes (FOXA1, RAB25, NRG1, SPDEF, TRIM29, and GABRP) having dual roles in cancer. Enrichment analyses revealed disruptions in epithelial integrity, cell adhesion, and estrogen signaling. This signature, named KAOS for Keratin-Adhesion-Oncogenes-Suppressors, was significantly associated with reduced tumor size but increased mortality rates. Integrating molecular assessment of non-malignant mammary tissue into disease management could enhance survival prediction and facilitate personalized patient care.

Interference Resolution in Nonfluent Variant Primary Progressive Aphasia: Evidence From a Picture-Word Interference Task.

BACKGROUND: Picture-word interference tasks have been used to investigate (a) the time course of lexical access in individuals with primary progressive aphasia (PPA) and (b) how these individuals resolve competition during lexical selection. OBJECTIVE: To investigate the time course of Greek-speaking individuals with PPA to produce grammatical gender-marked determiner phrases by examining their picture-naming latencies in the context of distractor words. METHOD: Eight individuals with nonfluent variant PPA (nfv-PPA; M age = 62.8 years) and eight cognitively intact controls (M age = 61.1 years) participated in our study. In a picture-word interference task, the study participants named depicted objects by producing determiner + noun sequences. Interference was generated by manipulating the grammatical gender of the depicted objects and distractor words. Two stimulus onset asynchronies were used: +200 ms and +400 ms. RESULTS: The individuals with nfv-PPA exhibited longer picture-naming latencies than the controls (P = 0.003). The controls exhibited interference from incongruent distractors at both asynchronies (P < 0.001); the individuals with PPA exhibited interference from incongruent distractors only at the +400-ms interval (P = 0.002). The gender-congruency effect was stronger for the individuals with PPA than for the controls at the +400-ms interval (P = 0.05); the opposite pattern was observed at the +200-ms interval (P = 0.024). CONCLUSION: Gender interference resolution was abnormal in the individuals with nfv-PPA. The results point to deficits in lexicosyntactic networks that compromised the time course of picture-naming production.

The Impact of Primary Progressive Aphasia on Picture Naming and General Language Ability.

BACKGROUND: Primary progressive aphasia (PPA) is a clinical syndrome that is characterized by progressive deterioration of language while other cognitive domains remain relatively intact. The extent to which print exposure and cortical volume atrophy jointly influence picture naming and general language ability in individuals with PPA remains underexplored. OBJECTIVE: To investigate the language performance of individuals with the nonfluent variant of primary progressive aphasia (nfvPPA) and to explore the impact of print exposure and cortical volume atrophy on their language ability. METHOD: We compared 14 Greek individuals with nfvPPA and similar age, education, disease duration, and cognitive ability with age-, gender- and education-matched Greek controls on picture naming and on language tasks of the Boston Diagnostic Aphasia Examination-Short Form, including oral word reading, word and sentence repetition, complex ideational material, and reading comprehension. The effects of print exposure and left-hemisphere cortical volume on the individuals' language performance were estimated through stepwise regression models. RESULTS: The language performance of the individuals with nfvPPA was affected by print exposure and cortical volume atrophy. Picture naming and word reading were affected by print exposure. The highest contributions of cortical volume atrophy were found for the repetition, complex ideational material, and reading comprehension tasks. CONCLUSION: Print exposure and cortical volume atrophy may help explain variability in the language performance of nfvPPA individuals with similar age, education, disease duration, and cognitive ability.

Intellectual development in young children with autism spectrum disorders: A longitudinal study.

Intelligence profiles in autism have been characterized by great variability. The questions of how autistic children's intelligence changes over time, and what factors influence these changes deserve study as part of efforts to document child autism profiles, but also because the relationship between intellectual functioning and children's background characteristics is poorly understood, particularly in a longitudinal context. A total of 39 autistic children and 39 age-matched neurotypical children (5-9 years old) completed two IQ assessments at preschool age and up to 4 years later. Repeated-measures analyses assessed longitudinal changes in the children's verbal (VIQ), performance (PIQ), and full-scale IQ (FSIQ) at group level. We further sought to identify clusters with distinct profiles in each group by adopting an unsupervised K-means clustering approach, and detect possible between-subgroup differences in terms of children's socioeconomic status and autism severity. The largest cluster in the autistic group was composed of children whose PIQ significantly dropped at follow-up, while the second largest cluster improved in all quotients; the smallest cluster, wherein children had more highly educated mothers than the rest of the clusters, was characterized by large improvement in VIQ. For the neurotypical children, there was a two-cluster division; the majority of them improved in the three quotients, while very few dropped in PIQ at follow-up. The relation between socioeconomic status and IQ changes was significant for both groups. The findings demonstrate both the complexity of intelligence changes in autism and the need to view this complexity through the lens of the children's socioeconomic diversity.

Figurative language processing in autism spectrum disorders: A review.

Impairments in the broader domain of pragmatics are considered to be a defining feature of Autism Spectrum Disorders (ASD). A challenging aspect of pragmatic competence is the ability to process nonliteral language. Interestingly, previous studies in figurative language comprehension in ASD have demonstrated conflicting results regarding participants' performance. The main scientific debate focuses on the underlying skills which facilitate processing of nonliteral speech in ASD. Namely, Theory of Mind (ToM), language abilities and Executive functions (EFs) are regarded as factors affecting autistic individuals' performance. This review addresses figurative language comprehension in ASD in light of the above three interpretive accounts. We reviewed data from recent studies in this field concluding that autistic children indeed encounter systematic difficulties in the processing of non-literal language. Moreover, only ToM and verbal skills were found to correlate the most with figurative language comprehension in ASD. Notably, we found that differences related to research methodology and tasks' properties may have led to discrepancies between studies' results. Finally, we argue that future studies should encompass in their experimental design figurative comprehension tasks with minimal linguistic demands and also measures of ToM, verbal ability and EFs in order to shed more light in the independent contribution of those skills to the processing of nonliteral language in ASD.

Autism Detection in Children: Integrating Machine Learning and Natural Language Processing in Narrative Analysis.

Despite the consensus that early identification leads to better outcomes for individuals with autism spectrum disorder (ASD), recent research reveals that the average age of diagnosis in the Greek population is approximately six years. However, this age of diagnosis is delayed by an additional two years for families from lower-income or minority backgrounds. These disparities result in adverse impacts on intervention outcomes, which are further burdened by the often time-consuming and labor-intensive language assessments for children with ASD. There is a crucial need for tools that increase access to early assessment and diagnosis that will be rigorous and objective. The current study leverages the capabilities of artificial intelligence to develop a reliable and practical model for distinguishing children with ASD from typically-developing peers based on their narrative and vocabulary skills. We applied natural language processing-based extraction techniques to automatically acquire language features (narrative and vocabulary skills) from storytelling in 68 children with ASD and 52 typically-developing children, and then trained machine learning models on the children's combined narrative and expressive vocabulary data to generate behavioral targets that effectively differentiate ASD from typically-developing children. According to the findings, the model could distinguish ASD from typically-developing children, achieving an accuracy of 96%. Specifically, out of the models used, hist gradient boosting and XGBoost showed slightly superior performance compared to the decision trees and gradient boosting models, particularly regarding accuracy and F1 score. These results bode well for the deployment of machine learning technology for children with ASD, especially those with limited access to early identification services.

Reading comprehension differences between children with Autism Spectrum Disorder and low cognitive abilities and children with Autism Spectrum Disorder and intact cognitive skills: the roles of decoding, fluency and morphosyntax.

Introduction: Reading comprehension is one of the most important skills learned in school and it has an important contribution to the academic success of children with Autism Spectrum Disorder (ASD). Though previous studies have investigated reading comprehension difficulties in ASD and highlighted factors that contribute to these difficulties, this evidence has mainly stemmed from children with ASD and intact cognitive skills. Also, much emphasis has been placed on the relation between reading comprehension and word recognition skills, while the role of other skills, including fluency and morphosyntax, remains underexplored. This study addresses these gaps by investigating reading comprehension in two groups of school-aged children with ASD, one with intact and one with low cognitive abilities, also exploring the roles of word decoding, fluency and morphosyntax in each group's reading comprehension performance. Methods: The study recruited 16 children with ASD and low cognitive abilities, and 22 age-matched children with ASD and intact cognitive skills. The children were assessed on four reading subdomains, namely, decoding, fluency, morphosyntax, and reading comprehension. Results: The children with ASD and low cognitive abilities scored significantly lower than their peers with intact cognitive abilities in all reading subdomains, except for decoding, verb production and compound word formation. Regression analyses showed that reading comprehension in the group with ASD and intact cognitive abilities was independently driven by their decoding and fluency skills, and to a lesser extent, by morphosyntax. On the other hand, the children with ASD and low cognitive abilities mainly drew on their decoding, and to a lesser extent, their morphosyntactic skills to perform in reading comprehension. Discussion: The results suggest that reading comprehension was more strongly affected in the children with ASD and low cognitive abilities as compared to those with intact cognitive skills. About half of the children with ASD and intact cognitive skills also exhibited mild-to-moderate reading comprehension difficulties, further implying that ASD may influence reading comprehension regardless of cognitive functioning. Finally, strengths in decoding seemed to predominantly drive cognitively-impaired children's reading performance, while the group with ASD and intact cognitive skills mainly recruited fluency and metalinguistic lexical skills to cope with reading comprehension demands, further suggesting that metalinguistic awareness may be a viable way to enhance reading comprehension in ASD.

Prognostic Factors Influencing Survival in Ovarian Cancer Patients: A 10-Year Retrospective Study.

OBJECTIVE: To analyze the factors associated with overall survival (OS) and progression-free survival (PFS) in patients with ovarian cancer in Cyprus. METHODS: We retrospectively analyzed data from patients with histologically confirmed epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC). RESULTS: A total of 106 women diagnosed with ovarian cancer were included, with a median age at diagnosis of 58 years. The Kaplan-Meier survival analysis showed a median OS of 41 months (95% C.I = 36.9, 45.1), and the FIGO stage (p < 0.001), type of surgery (p < 0.001) and performance status (p < 0.001) were identified as statistically significant prognostic factors for OS. PFS analysis revealed the FIGO stage (p = 0.006) and the performance status (p < 0.001) as significant prognostic factors. Additionally, a Cox regression analysis for median OS was performed for patients with high-grade serous carcinoma, identifying the performance status, FIGO stage, and type of surgery as prognostic factors in univariate analysis. However, in the subsequent multivariate analysis, the performance status and the FIGO stage were confirmed to be the only statistically significant prognostic factors for OS (p < 0.05). CONCLUSIONS: This study confirms that the FIGO stage, performance status, and surgery type were considered as prognostic factors for OS in ovarian cancer.

Animacy Processing in Autism: Event-Related Potentials Reflect Social Functioning Skills.

Though previous studies with autistic individuals have provided behavioral evidence of animacy perception difficulties, the spatio-temporal dynamics of animacy processing in autism remain underexplored. This study investigated how animacy is neurally encoded in autistic adults, and whether potential deficits in animacy processing have cascading deleterious effects on their social functioning skills. We employed a picture naming paradigm that recorded accuracy and response latencies to animate and inanimate pictures in young autistic adults and age- and IQ-matched healthy individuals, while also employing high-density EEG analysis to map the spatio-temporal dynamics of animacy processing. Participants' social skills were also assessed through a social comprehension task. The autistic adults exhibited lower accuracy than controls on the animate pictures of the task and also exhibited altered brain responses, including larger and smaller N100 amplitudes than controls on inanimate and animate stimuli, respectively. At late stages of processing, there were shorter slow negative wave latencies for the autistic group as compared to controls for the animate trials only. The autistic individuals' altered brain responses negatively correlated with their social difficulties. The results suggest deficits in brain responses to animacy in the autistic group, which were related to the individuals' social functioning skills.

Re-Examining Labels in Neurocognitive Research: Evidence from Bilingualism and Autism as Spectrum-Trait Cases.

Despite the fact that the urge to investigate bilingualism and neurodevelopmental disorders as continuous indices rather than categorical ones has been well-voiced among researchers with respect to research methodological approaches, in the recent literature, when it comes to examining language, cognitive skills and neurodivergent characteristics, it is still the case that the most prevalent view is the categorisation of adults or children into groups. In other words, there is a categorisation of individuals, e.g., monolingual vs. bilingual children or children with typical and atypical/non-typical/non-neurotypical development. We believe that this labelling is responsible for the conflicting results that we often come across in studies. The aim of this review is to bring to the surface the importance of individual differences through the study of relevant articles conducted in bilingual children and children with autism, who are ideal for this study. We concur with researchers who already do so, and we further suggest moving away from labels and instead shift towards the view that not everything is either white or black. We provide suggestions as to how this shift could be implemented in research, while mostly aiming at starting a discourse rather than offering a definite path.

Cognitive flexibility in autism: Evidence from young autistic children.

We examined the cognitive flexibility performance of young autistic children and a group of neurotypical peers. Thirty-six autistic children (72-83 months) and 200 age-matched typically-developing children were assessed on the Children's Color Trails Test (CCTT), a semantic and a phonemic verbal fluency task. The results showed that the autistic children performed worse than their neurotypical peers in the switching component of the CCTT. In the fluency tests, the autistic group generated overall fewer word items than their neurotypical peers, however, their poorer performance was driven by specific linguistic stimuli in the fluency tasks. The findings suggest that cognitive flexibility for the autistic children was affected in the nonverbal CCTT only, while poor performance in semantic and phonemic fluency seemed to be inherent to the language properties of the verbal fluency tasks.

Bilingualism effects in pronoun comprehension: Evidence from children with autism.

The prevalence of autism worldwide has risen steadily in the last two decades, while bilingualism is also becoming increasingly prevalent in today's rapidly globalizing world. The current study aimed to investigate bilingualism effects in the pronoun resolution skills of children with autism in comparison to age-matched monolingual children with autism, as well as monolingual and bilingual children of typical development (Ν = 20 participants per group). Results showed that autistic children had general difficulty anchoring ambiguous pronouns to entities that were linguistically expressed in discourse, yet, the bilingual children with autism were more sensitive to the topicality of the entities in syntactic subject position and more prone to identify them as suitable referents of ambiguous null pronouns as compared to their monolingual peers. The findings suggest that bilingualism is not detrimental to autistic children's pronoun resolution skills. The current study aimed at determining how bilingualism influences ambiguous pronoun comprehension in children with autism as compared to bilingual and monolingual children of typical development. The findings show that bilingualism was not detrimental to the autistic children's pronoun resolution skills, further suggesting that having acquired more than one language does not exacerbate autistic children's deficits in the comprehension of pronouns.

Aberrant Expression and Prognostic Potential of IL-37 in Human Lung Adenocarcinoma.

Interleukin-37 (IL-37) is a relatively new IL-1 family cytokine that, due to its immunoregulatory properties, has lately gained increasing attention in basic and translational biomedical research. Emerging evidence supports the implication of this protein in any human disorder in which immune homeostasis is compromised, including cancer. The aim of this study was to explore the prognostic and/or diagnostic potential of IL-37 and its receptor SIGIRR (single immunoglobulin IL-1-related receptor) in human tumors. We utilized a series of bioinformatics tools and -omics datasets to unravel possible associations of IL-37 and SIGIRR expression levels and genetic aberrations with tumor development, histopathological parameters, distribution of tumor-infiltrating immune cells, and survival rates of patients. Our data revealed that amongst the 17 human malignancies investigated, IL-37 exhibits higher expression levels in tumors of lung adenocarcinoma (LUAD). Moreover, the expression profiles of IL-37 and SIGIRR are associated with LUAD development and tumor stage, whereas their high mRNA levels are favorable prognostic factors for the overall survival of patients. What is more, IL-37 correlates positively with a LUAD-associated transcriptomic signature, and its nucleotide changes and expression levels are linked with distinct infiltration patterns of certain cell subsets known to control LUAD anti-tumor immune responses. Our data indicate the potential value of IL-37 and its receptor SIGIRR to serve as biomarkers and/or immune-checkpoint therapeutic targets for LUAD patients. Further, the data highlight the urgent need for further exploration of this cytokine and the underlying pathogenetic mechanisms to fully elucidate its implication in LUAD development and progression.

High prevalence of somatic PIK3CA and TP53 pathogenic variants in the normal mammary gland tissue of sporadic breast cancer patients revealed by duplex sequencing.

The mammary gland undergoes hormonally stimulated cycles of proliferation, lactation, and involution. We hypothesized that these factors increase the mutational burden in glandular tissue and may explain high cancer incidence rate in the general population, and recurrent disease. Hence, we investigated the DNA sequence variants in the normal mammary gland, tumor, and peripheral blood from 52 reportedly sporadic breast cancer patients. Targeted resequencing of 542 cancer-associated genes revealed subclonal somatic pathogenic variants of: PIK3CA, TP53, AKT1, MAP3K1, CDH1, RB1, NCOR1, MED12, CBFB, TBX3, and TSHR in the normal mammary gland at considerable allelic frequencies (9 × 10-2- 5.2 × 10-1), indicating clonal expansion. Further evaluation of the frequently damaged PIK3CA and TP53 genes by ultra-sensitive duplex sequencing demonstrated a diversified picture of multiple low-level subclonal (in 10-2-10-4 alleles) hotspot pathogenic variants. Our results raise a question about the oncogenic potential in non-tumorous mammary gland tissue of breast-conserving surgery patients.

Comprehensive cancer-oriented biobanking resource of human samples for studies of post-zygotic genetic variation involved in cancer predisposition.

The progress in translational cancer research relies on access to well-characterized samples from a representative number of patients and controls. The rationale behind our biobanking are explorations of post-zygotic pathogenic gene variants, especially in non-tumoral tissue, which might predispose to cancers. The targeted diagnoses are carcinomas of the breast (via mastectomy or breast conserving surgery), colon and rectum, prostate, and urinary bladder (via cystectomy or transurethral resection), exocrine pancreatic carcinoma as well as metastases of colorectal cancer to the liver. The choice was based on the high incidence of these cancers and/or frequent fatal outcome. We also collect age-matched normal controls. Our still ongoing collection originates from five clinical centers and after nearly 2-year cooperation reached 1711 patients and controls, yielding a total of 23226 independent samples, with an average of 74 donors and 1010 samples collected per month. The predominant diagnosis is breast carcinoma, with 933 donors, followed by colorectal carcinoma (383 donors), prostate carcinoma (221 donors), bladder carcinoma (81 donors), exocrine pancreatic carcinoma (15 donors) and metachronous colorectal cancer metastases to liver (14 donors). Forty percent of the total sample count originates from macroscopically healthy cancer-neighboring tissue, while contribution from tumors is 12%, which adds to the uniqueness of our collection for cancer predisposition studies. Moreover, we developed two program packages, enabling registration of patients, clinical data and samples at the participating hospitals as well as the central system of sample/data management at coordinating center. The approach used by us may serve as a model for dispersed biobanking from multiple satellite hospitals. Our biobanking resource ought to stimulate research into genetic mechanisms underlying the development of common cancers. It will allow all available "-omics" approaches on DNA-, RNA-, protein- and tissue levels to be applied. The collected samples can be made available to other research groups.

Rapid Assessment of Resection Margins During Breast Conserving Surgery Using Intraoperative Flow Cytometry.

BACKGROUND: Positive margins are the most important factor for recurrence of the disease after breast-conserving surgery. Several methods have been developed throughout the years to evaluate the margin status during surgery in an attempt to assist the surgeon in excising the whole tumor at once, a goal that has not yet been accomplished. PATIENTS AND METHODS: In our study, we compared intraoperative flow cytometry (iFC) with cytology and pathology in order to evaluate 606 samples of margins and tumors corresponding to 99 patients with invasive ductal carcinoma of no special type and invasive lobular carcinoma obtained from breast-conserving surgeries. RESULTS: Using the pathology as the gold standard, flow cytometry had 93.3% sensitivity, 92.4% specificity, and 92.5% accuracy. Cytology had 82.3% sensitivity, 94.6% specificity, and 94.2% accuracy. CONCLUSIONS: Our data support the suggestion that iFC is a novel, reliable technique that allows rapid evaluation of the excision margins of lumpectomies, thus improving the precision of breast-conserving surgery. Among the advantages of iFC are that it does not rely on the expertise of a pathologist or cytologist, it is low cost, and it has no additional psychological effect on patients, because no re-operation is needed.

Theory of Mind Deficits and Neurophysiological Operations in Autism Spectrum Disorders: A Review.

Theory of Mind (ToM) is a multifaceted skill set which encompasses a variety of cognitive and neurobiological aspects. ToM deficits have long been regarded as one of the most disabling features in individuals with Autism Spectrum Disorder. One of the theories that attempts to account for these impairments is that of "broken mirror neurons". The aim of this review is to present the most recent available studies with respect to the connection between the function of mirror neurons in individuals with ASD and ToM-reflecting sensorimotor, social and attentional stimuli. The majority of these studies approach the theory of broken mirror neurons critically. Only studies from the last 15 years have been taken into consideration. Findings from electroencephalography (EEG) studies so far indicate that further research is necessary to shed more light on the mechanisms underlying the connection(s) between ToM and neurophysiological operations.

Cognitive Mechanisms of Monolingual and Bilingual Children in Monoliterate Educational Settings: Evidence From Sentence Repetition.

Sentence repetition (SR) tasks have been extensively employed to assess bilingual children's linguistic and cognitive resources. The present study examined whether monoliterate bilingual children differ from their monolingual (and monoliterate) peers in SR accuracy and cognitive tasks, and investigated links between vocabulary, updating, verbal and visuospatial working memory and SR performance in the same children. Participants were two groups of 35 children, 8-12 years of age: one group consisted of Albanian-Greek monoliterate bilingual children and the other of Greek monolingual children attending a monolingual-Greek educational setting. The findings demonstrate that the two groups performed similarly in the grammaticality scores of the SR. However, monolinguals outperformed the monoliterate bilinguals in SR accuracy, as well as in the visuospatial working memory and updating tasks. The findings did not indicate any bilingual advantage in cognitive performance. The results also demonstrate that updating and visuospatial working memory significantly predicted monolingual children's SR accuracy scores, whereas Greek vocabulary predicted the performance of our monoliterate bilingual children in the same task. We attribute this outcome to the fact that monoliterate bilingual children do not rely on their fluid cognitive resources to perform the task, but instead rely on language proficiency (indicated by expressive vocabulary) while performing the SR.

The impact of bilingualism on the narrative ability and the executive functions of children with autism spectrum disorders.

While there is ample evidence that monolingual children with Autism Spectrum Disorders (ASD) face difficulties with narrative story-telling and executive functions (EF), there is considerable uncertainty about how bilingualism impacts these skills in autism. The current study explores the effect of bilingualism on the narrative and EF skills of forty 7-to-12-year-old bilingual and monolingual children with ASD, as well as forty age-matched bilingual and monolingual children of typical development (TD). Narrative production data were elicited using the Edmonton Narrative Norms Instrument (ENNI; Schneider et al., 2005), which was developed to measure narrative production at a microstructural and macrostructural level. The same children were administered two EF tasks, namely, a global-local visual attention task and a 2-back working memory task. In story-telling, bilingual children with ASD achieved higher scores than monolingual children with ASD on story structure complexity and use of adverbial clauses, and they tended to use significantly fewer ambiguous referential forms than their monolingual peers with ASD. In the global-local task, bilingual children with ASD were faster and more accurate in global trials than monolingual children with ASD, who tended to be more susceptible to interference from locally presented information than the other experimental groups. Higher accuracy and faster response times were also observed for bilingual children with ASD in the 2-back task. Further correlation analyses between the story-telling and EF tasks revealed that bilingual children with ASD drew on a broader range of EF in narrative production than their monolingual peers. The overall findings reveal that bilingual children with ASD outperformed their monolingual peers with ASD in both the microstructure and macrostructure of their narrative production, as well as in their visual attention and working memory skills.

Intein-mediated site-specific conjugation of Quantum Dots to proteins in vivo.

We describe an intein based method to site-specifically conjugate Quantum Dots (QDs) to target proteins in vivo. This approach allows the covalent conjugation of any nanostructure and/or nanodevice to any protein and thus the targeting of such material to any intracellular compartment or signalling complex within the cells of the developing embryo. We genetically fused a pleckstrin-homology (PH) domain with the N-terminus half of a split intein (IN). The C-terminus half (IC) of the intein was conjugated to QDs in vitro. IC-QD's and RNA encoding PH-IN were microinjected into Xenopus embryos. In vivo intein-splicing resulted in fully functional QD-PH conjugates that could be monitored in real time within live embryos. Use of Near Infra Red (NIR)-emitting QDs allowed monitoring of QD-conjugates within the embryo at depths where EGFP is undetectable demonstrating the advantages of QD's for this type of experiment. In conclusion, we have developed a novel in vivo methodology for the site-specific conjugation of QD's and other artificial structures to target proteins in different intracellular compartments and signaling complexes.