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1.
Infancy ; 29(3): 302-326, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38217508

RESUMO

The valid assessment of vocabulary development in dual-language-learning infants is critical to developmental science. We developed the Dual Language Learners English-Spanish (DLL-ES) Inventories to measure vocabularies of U.S. English-Spanish DLLs. The inventories provide translation equivalents for all Spanish and English items on Communicative Development Inventory (CDI) short forms; extended inventories based on CDI long forms; and Spanish language-variety options. Item-Response Theory analyses applied to Wordbank and Web-CDI data (n = 2603, 12-18 months; n = 6722, 16-36 months; half female; 1% Asian, 3% Black, 2% Hispanic, 30% White, 64% unknown) showed near-perfect associations between DLL-ES and CDI long-form scores. Interviews with 10 Hispanic mothers of 18- to 24-month-olds (2 White, 1 Black, 7 multi-racial; 6 female) provide a proof of concept for the value of the DLL-ES for assessing the vocabularies of DLLs.


Assuntos
Citrus sinensis , Malus , Multilinguismo , Criança , Lactente , Humanos , Feminino , Vocabulário , Linguagem Infantil , Testes de Linguagem , Idioma
2.
Int J Mol Sci ; 25(4)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38396969

RESUMO

Calcific aortic valve disease (CAVD) is characterized by the fibrosis and mineralization of the aortic valve, which leads to aortic stenosis and heart failure. At the cellular level, this is due to the osteoblastic-like differentiation of valve interstitial cells (VICs), resulting in the calcification of the tissue. Unfortunately, human VICs are not readily available to study CAVD pathogenesis and the implicated mechanisms in vitro; however, adipose-derived stromal/stem cells (ASCs), carrying the patient's specific genomic features, have emerged as a promising cell source to model cardiovascular diseases due to their multipotent nature, availability, and patient-specific characteristics. In this study, we describe a comprehensive transcriptomic analysis of tissue-engineered, scaffold-free, ASC-embedded mineralized tissue sheets using bulk RNA sequencing. Bioinformatic and gene set enrichment analyses revealed the up-regulation of genes associated with the organization of the extracellular matrix (ECM), suggesting that the ECM could play a vital role in the enhanced mineralization observed in these tissue-engineered ASC-embedded sheets. Upon comparison with publicly available gene expression datasets from CAVD patients, striking similarities emerged regarding cardiovascular diseases and ECM functions, suggesting a potential link between ECM gene expression and CAVDs pathogenesis. A matrisome-related sub-analysis revealed the ECM microenvironment promotes the transcriptional activation of the master gene runt-related transcription factor 2 (RUNX2), which is essential in CAVD development. Tissue-engineered ASC-embedded sheets with enhanced mineralization could be a valuable tool for research and a promising avenue for the identification of more effective aortic valve replacement therapies.


Assuntos
Valvopatia Aórtica , Estenose da Valva Aórtica , Valva Aórtica/patologia , Calcinose , Humanos , Estenose da Valva Aórtica/metabolismo , Calcinose/metabolismo , Valvopatia Aórtica/metabolismo , Células-Tronco/metabolismo , Células Cultivadas
3.
J Neurochem ; 167(4): 556-570, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37837197

RESUMO

Neovascularization is a critical process in tumor progression and malignant transformation associated with neurofibromatosis type 1 (NF1). Indeed, fibroblasts are known to play a key role in the tumoral microenvironment modification by producing an abundant collagenous matrix, but their contribution in paracrine communication pathways is poorly understood. Here, we hypothesized that NF1 heterozygosis in human dermal fibroblasts could promote angiogenesis through exosomes secretion. The purposes of this study are to identify the NF1 fibroblast-derived exosome protein contents and to determine their proangiogenic activity. Angiogenic proteome measurement confirmed the overexpression of VEGF and other proteins involved in vascularization. Tube formation of microvascular endothelial cells was also enhanced in presence of exosomes derived from NF1 skin fibroblasts. NF1 tissue-engineered skin (NF1-TES) generation showed a significantly denser microvessels networks compared to healthy controls. The reduction of exosomes production with an inhibitor treatment demonstrated a drastic decrease in blood vessel formation within the dermis. Our results suggest that NF1 haploinsufficiency alters the dermal fibroblast function and creates a pro-angiogenic signal via exosomes, which increases the capillary formation. This study highlights the potential of targeting exosome secretion and angiogenesis for therapeutic interventions in NF1.


Assuntos
Exossomos , Neurofibromatose 1 , Humanos , Células Endoteliais/metabolismo , Neurofibromatose 1/metabolismo , Neovascularização Patológica , Fibroblastos , Pele , Exossomos/metabolismo , Microambiente Tumoral
4.
Public Health Nutr ; 26(1): 106-121, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35272726

RESUMO

OBJECTIVE: To document perfluoroalkyl acids (PFAA) and bisphenol-A (BPA) exposure in four First Nation communities in northern Quebec compared with the Canadian Health Measures Survey (CHMS Cycle 5 2016-2017) and examine the associations between dietary consumption and chemical exposure. DESIGN: We used cross-sectional data from the JES-YEH! project conducted in collaboration with four First Nation communities in 2015. A FFQ collected information on diet, and PFAA and BPA were measured in biological samples. We used generalised linear models to test the associations between food intake and chemical biomarkers. SETTING: Northern Quebec. PARTICIPANTS: Youth aged 3-19 years (n 198). RESULTS: Mean perfluorononanoic acid (PFNA) levels were significantly higher in JES-YEH! than CHMS, and BPA levels were higher among those aged 12-19 years compared with CHMS. Dairy products were associated with PFNA among Anishinabe and Innu participants (geometric mean ratio 95 % CI: 1·53 (95 % CI 1·03, 2·29) and 1·52 (95 % CI 1·05, 2·20), respectively). PFNA was also associated with ultra-processed foods (1·57 (95 % CI 1·07, 2·31)) among Anishinabe, and with wild fish and berries (1·44 (95 % CI 1·07, 1·94); 1·75 (95 % CI 1·30, 2·36)) among Innu. BPA was associated with cheese (1·72 (95 % CI 1·19, 2·50)) and milk (1·53 (95 % CI 1·02, 2·29)) among Anishinabe, and with desserts (1·71 (95 % CI 1·07, 2·74)), processed meats (1·55 (95 % CI 1·00, 2·38)), wild fish (1·64 (95 % CI 1·07, 2·49)) and wild berries (2·06 (95 % CI 1·37, 3·10)) among Innu. CONCLUSIONS: These results highlight the importance of better documenting food-processing and packaging methods, particularly for dairy products, and their contribution to endocrine disruptors exposures as well as to promote minimally processed and unpackaged foods to provide healthier food environments for youth in Indigenous communities and beyond.


Assuntos
Dieta , Fluorocarbonos , Animais , Canadá , Quebeque , Estudos Transversais
5.
Stroke ; 53(4): 1263-1275, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34991336

RESUMO

BACKGROUND: Variants in the ring finger protein 213 (RNF213) gene are known to be associated with increased predisposition to cerebrovascular diseases development. Genomic studies have identified RNF213 as a major risk factor of Moyamoya disease in East Asian descendants. However, little is known about the RNF213 (ring finger protein 213) biological functions or its associated pathogenic mechanisms underlying Moyamoya disease. METHODS: To investigate RNF213 loss-of-function effect in endothelial cell, stable RNF213-deficient human cerebral endothelial cells were generated using the CRISPR-Cas9 genome editing technology. RESULTS: In vitro assays, using RNF213 knockout brain endothelial cells, showed clear morphological changes and increased blood-brain barrier permeability. Downregulation and delocalization of essential interendothelial junction proteins involved in the blood-brain barrier maintenance, such as PECAM-1 (platelet endothelial cell adhesion molecule-1), was also observed. Brain endothelial RNF213-deficient cells also showed an abnormal potential to transmigration of leukocytes and secreted high amounts of proinflammatory cytokines. CONCLUSIONS: Taken together, these results indicate that RNF213 could be a key regulator of cerebral endothelium integrity, whose disruption could be an early pathological mechanism leading to Moyamoya disease. This study also further reinforces the importance of blood-brain barrier integrity in the development of Moyamoya disease and other RNF213-associated diseases.


Assuntos
Adenosina Trifosfatases , Doença de Moyamoya , Ubiquitina-Proteína Ligases , Adenosina Trifosfatases/genética , Células Endoteliais/metabolismo , Endotélio , Predisposição Genética para Doença , Humanos , Doença de Moyamoya/patologia , Fatores de Transcrição , Ubiquitina-Proteína Ligases/genética
6.
Chem Senses ; 472022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35522081

RESUMO

Olfactory and gustatory dysfunctions (OD, GD) are prevalent symptoms following COVID-19 and persist in 6%-44% of individuals post-infection. As only few reports have described their prognosis after 6 months, our main objective was to assess the prevalence of OD and GD 11-month post-COVID-19. We also aimed to determine intraclass correlation coefficients (ICC) of chemosensory self-ratings for the follow-up of chemosensory sensitivity. We designed an observational study and distributed an online questionnaire assessing chemosensory function to healthcare workers with a RT-PCR-confirmed SARS-CoV-2 infection 5- and 11-month post-COVID-19. Specifically, we assessed olfaction, gustation, and trigeminal sensitivity (10-point visual analog scale) and function (4-point Likert scale). We further measured clinically relevant OD using the Chemosensory Perception Test, a psychophysical test designed to provide a reliable remote olfactory evaluation. We included a total of 366 participants (mean [SD] age of 44.8 (11.7) years old). They completed the last online questionnaire 10.6 months (0.7) after the onset of COVID-19 symptoms. Of all participants, 307 (83.9%) and 301 (82.2%) individuals retrospectively reported lower olfactory or gustatory sensitivity during the acute phase of COVID-19. At the time of evaluation, 184 (50.3%) and 163 (44.5%) indicated reduced chemosensory sensitivity, 32.2% reported impairment of olfactory function while 24.9% exhibited clinically relevant OD. Olfactory sensitivity had a high test-retest reliability (ICC: 0.818; 95% CI: 0.760-0.860). This study suggests that chemosensory dysfunctions persist in a third of COVID-19 patients 11 months after COVID-19. OD appears to be a common symptom of post-COVID-19 important to consider when treating patients.


Assuntos
COVID-19 , Transtornos do Olfato , Adulto , COVID-19/epidemiologia , Seguimentos , Pessoal de Saúde , Humanos , Pessoa de Meia-Idade , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/etiologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , SARS-CoV-2 , Distúrbios do Paladar/diagnóstico , Distúrbios do Paladar/epidemiologia , Distúrbios do Paladar/etiologia
7.
Biotechnol Bioeng ; 119(7): 1938-1948, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35289393

RESUMO

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease affecting upper and lower motor neurons (MNs). To investigate whether Schwann cells could be involved in the disease pathogenesis, we developed a tissue-engineered three-dimensional (3D) in vitro model that combined MNs cocultured with astrocytes and microglia seeded on top of a collagen sponge populated with epineurium fibroblasts to enable 3D axonal migration. C2C12 myoblasts were seeded underneath the sponge in the presence or absence of Schwann cells. To reproduce an ALS cellular microenvironment, MNs, astrocytes, and microglia were extracted from SOD1G93A mice recapitulating many aspects of the human disease. This 3D ALS in vitro model was compared with a 3D control made of cells isolated from SOD1WT mice. We showed that normal Schwann cells strongly enhanced MN axonal migration in the 3D control model but had no effect in the ALS model. However, ALS-derived Schwann cells isolated from SOD1G93A mice failed to significantly improve axonal migration in both models. These results suggest that a cell therapy using healthy Schwann cells may not be effective in promoting axonal regeneration in ALS. In addition, this 3D ALS model could be used to study the impact of other cell types on ALS by various combinations of normal and diseased cells.


Assuntos
Esclerose Lateral Amiotrófica , Doenças Neurodegenerativas , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Animais , Modelos Animais de Doenças , Camundongos , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Células de Schwann/metabolismo , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo
8.
Int J Mol Sci ; 23(20)2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36293057

RESUMO

Corneal wound healing involves communication between the different cell types that constitute the three cellular layers of the cornea (epithelium, stroma and endothelium), a process ensured in part by a category of extracellular vesicles called exosomes. In the present study, we isolated exosomes released by primary cultured human corneal epithelial cells (hCECs), corneal fibroblasts (hCFs) and corneal endothelial cells (hCEnCs) and determined whether they have wound healing characteristics of their own and to which point they modify the genetic and proteomic pattern of these cell types. Exosomes released by all three cell types significantly accelerated wound closure of scratch-wounded hCECs in vitro compared to controls (without exosomes). Profiling of activated kinases revealed that exosomes from human corneal cells caused the activation of signal transduction mediators that belong to the HSP27, STAT, ß-catenin, GSK-3ß and p38 pathways. Most of all, data from gene profiling analyses indicated that exosomes, irrespective of their cellular origin, alter a restricted subset of genes that are completely different between each targeted cell type (hCECs, hCFS, hCEnCs). Analysis of the genes specifically differentially regulated for a given cell-type in the microarray data using the Ingenuity Pathway Analysis (IPA) software revealed that the mean gene expression profile of hCECs cultured in the presence of exosomes would likely promote cell proliferation and migration whereas it would reduce differentiation when compared to control cells. Collectively, our findings represent a conceptual advance in understanding the mechanisms of corneal wound repair that may ultimately open new avenues for the development of novel therapeutic approaches to improve closure of corneal wounds.


Assuntos
Lesões da Córnea , Exossomos , Humanos , Exossomos/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Células Endoteliais/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Proteômica , Cicatrização/fisiologia , Córnea/metabolismo , Lesões da Córnea/metabolismo , Células Epiteliais/metabolismo , Movimento Celular
9.
Chem Senses ; 462021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34423831

RESUMO

Several studies have revealed either self-reported chemosensory alterations in large groups or objective quantified chemosensory impairments in smaller populations of patients diagnosed with COVID-19. However, due to the great variability in published results regarding COVID-19-induced chemosensory impairments and their follow-up, prognosis for chemosensory functions in patients with such complaints remains unclear. Our objective is to describe the various chemosensory alterations associated with COVID-19 and their prevalence and evolution after infection. A cross-sectional study of 704 healthcare workers with a RT-PCR-confirmed SARS-CoV-2 infection between 2020 February 28 and 2020 June 14 was conducted 3-7 months after onset of symptoms. Data were collected with an online questionnaire. Outcomes included differences in reported chemosensory self-assessment of olfactory, gustatory, and trigeminal functions across time points and Chemosensory Perception Test scores from an easy-to-use at-home self-administered chemosensory test. Among the 704 participants, 593 (84.2%) were women, the mean (SD) age was 42 (12) years, and the questionnaire was answered on average 4.8 (0.8) months after COVID-19. During COVID-19, a decrease in olfactory, gustatory, and trigeminal sensitivities was reported by 81.3%, 81.5%, and 48.0%, respectively. Three to 7 months later, reduced sensitivity was still reported by 52.0%, 41.9%, and 23.3%, respectively. Chemosensory Perception Test scores indicate that 19.5% of participants had objective olfactory impairment. These data suggest a significant proportion of COVID-19 cases have persistent chemosensory impairments at 3-7 months after their infection, but the majority of those who had completely lost their olfactory, gustatory, and trigeminal sensitivities have improved.


Assuntos
COVID-19/complicações , Transtornos do Olfato/etiologia , Distúrbios do Paladar/etiologia , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , COVID-19/etiologia , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/epidemiologia , Prevalência , Autorrelato , Inquéritos e Questionários , Distúrbios do Paladar/epidemiologia , Fatores de Tempo
10.
Analyst ; 145(10): 3678-3685, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32307493

RESUMO

One of the great challenges in identifying effective therapy in many neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), is the lack of reliable biomarkers. In this study, we applied infrared imaging microspectroscopy, a valuable technique to investigate biomolecule fingerprints and secondary structure of proteins within biological tissue. We hypothesized that, since skin and CNS have the same embryonic origin, spectral differences associated with ALS-specific pathological events will be readily detectable through skin testing using this technique. Cells from healthy individuals and ALS patients were isolated from skin biopsies in order to generate tissue-engineered in vitro skin (TES). Infrared spectra of the generated TES were recorded using a focal-plane-array Fourier transform infrared (FPA-FTIR) spectrometer, and hierarchical cluster analysis of the spectral data was performed in order to establish clear differences between the tested TES specimens. Interestingly, our analyses showed that it was readily possible to discriminate ALS- and control-TES solely based on differences in associated FTIR spectra, mainly located between 1149 and 1473 cm-1, attributed to disruption of phospholipid cell membranes, extracellular matrix remodeling or cholesterol accumulation. Spectral differences within the TES samples may therefore be associated with disease state, paving the way for the identification of biomarkers in ALS.


Assuntos
Esclerose Lateral Amiotrófica/diagnóstico , Esclerose Lateral Amiotrófica/metabolismo , Pele/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Estudos de Casos e Controles , Humanos
11.
Hum Mol Genet ; 25(21): 4771-4786, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28175304

RESUMO

Recent genetic studies yielded conflicting results regarding a role for the variant chromogranin B (CHGB)P413L allele as a disease modifier in ALS. Moreover, potential deleterious effects of the CHGBP413L variant in ALS pathology have not been investigated. Here we report that in transfected cultured cells, the variant CHGBL413 protein exhibited aberrant properties including mislocalization, failure to interact with mutant superoxide dismutase 1 (SOD1) and defective secretion. The CHGBL413 transgene in SOD1G37R mice precipitated disease onset and pathological changes related to misfolded SOD1 specifically in female mice. However, the CHGBL413 variant also slowed down disease progression in SOD1G37R mice, which is in line with a very slow disease progression that we report for a Swedish woman with ALS who is carrier of two mutant SOD1D90A alleles and two variant CHGBP413L and CHGBR458Q alleles. In contrast, overexpression of the common CHGBP413 allele in SOD1G37R mice did not affect disease onset but significantly accelerated disease progression and pathological changes. As in transgenic mice, the CHGBP413L allele conferred an earlier ALS disease onset in women of Japanese and French Canadian origins with less effect in men. Evidence is presented that the sex-dependent effects of CHGBL413 allelic variant in ALS may arise from enhanced neuronal expression of CHGB in females because of a sex-determining region Y element in the gene promoter. Thus, our results suggest that CHGB variants may act as modifiers of onset and progression in some ALS populations and especially in females because of higher expression levels compared to males.


Assuntos
Esclerose Lateral Amiotrófica/genética , Cromogranina B/genética , Cromogranina B/metabolismo , Alelos , Animais , Técnicas de Cultura de Células , Modelos Animais de Doenças , Progressão da Doença , Feminino , Frequência do Gene/genética , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Neurônios Motores/metabolismo , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Fatores Sexuais , Medula Espinal/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo
13.
J Child Lang ; 45(3): 807-825, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29143696

RESUMO

Social feedback is a driving force for speech development. A recent study provided a key finding to explain how contingent responses influence developmental change: infant speech-related vocalizations are contingent on responses to prior speech-related vocalizations (Warlaumont et al., 2014). However, the study did not distinguish between different speech-related vocalizations, vowel-like (V) and consonant-vowel (CV) vocalizations, which is important because CV vocalizations are a precursor to words. The present study explored parents' responses to infants' vocalizations and infants' subsequent vocal production at a point when vocalizations become more like adult speech. The relative proportion of CVs following contingent responses to CV did not differ between 10- and 12-months-olds; however, there was only a significant contingent relationship between responses to CV and subsequent CV production in 12-month-olds. Results suggest a developmental transition and a social feedback loop for the production of more developmentally advanced sounds when infants are learning their first words.


Assuntos
Retroalimentação , Desenvolvimento da Linguagem , Relações Pais-Filho , Fonética , Meio Social , Percepção da Fala , Feminino , Humanos , Lactente , Masculino , Psicolinguística
14.
CMAJ ; 189(21): E739-E746, 2017 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-28554947

RESUMO

BACKGROUND: Infant mortality is higher in Indigenous than non-Indigenous populations, but comparable data on infant morbidity are lacking in Canada. We evaluated disparities in infant morbidities experienced by Indigenous populations in Canada. METHODS: We used linked population-based birth and health administrative data from Quebec, Canada, to compare hospitalization rates, an indicator of severe morbidity, in First Nations, Inuit and non-Indigenous singleton infants (< 1 year) born between 1996 and 2010. RESULTS: Our cohort included 19 770 First Nations, 3930 Inuit and 225 380 non-Indigenous infants. Compared with non-Indigenous infants, all-cause hospitalization rates were higher in First Nations infants (unadjusted risk ratio [RR] 2.05, 95% confidence interval [CI] 1.99-2.11; fully adjusted RR 1.43, 95% CI 1.37-1.50) and in Inuit infants (unadjusted RR 1.96, 95% CI 1.87-2.05; fully adjusted RR 1.37, 95% CI 1.24-1.52). Higher risks of hospitalization (accounting for multiple comparisons) were observed for First Nations infants in 12 of 16 disease categories and for Inuit infants in 7 of 16 disease categories. Maternal characteristics (age, education, marital status, parity, rural residence and Northern residence) partly explained the risk elevations, but maternal chronic illnesses and gestational complications had negligible influence overall. Acute bronchiolitis (risk difference v. non-Indigenous infants, First Nations 37.0 per 1000, Inuit 39.6 per 1000) and pneumonia (risk difference v. non-Indigenous infants, First Nations 41.2 per 1000, Inuit 61.3 per 1000) were the 2 leading causes of excess hospitalizations in Indigenous infants. INTERPRETATION: First Nations and Inuit infants had substantially elevated burdens of hospitalizations as a result of diseases of multiple systems. The findings identify substantial unmet needs in disease prevention and medical care for Indigenous infants.


Assuntos
Bronquiolite/etnologia , Disparidades em Assistência à Saúde/etnologia , Hospitalização/estatística & dados numéricos , Mortalidade Infantil/etnologia , Pneumonia/etnologia , Adulto , Feminino , Humanos , Indígenas Norte-Americanos , Lactente , Recém-Nascido , Masculino , Razão de Chances , Gravidez , Complicações na Gravidez/etnologia , Resultado da Gravidez/etnologia , Quebeque/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
15.
Infancy ; 22(3): 344-361, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-33158357

RESUMO

Previous research has demonstrated that social interactions underlie the development of object-directed imitation. For example, infants differentially learn object action sequences from a live social partner compared to a social partner over a video monitor; however, what is not well understood is what aspects of social interactions influence social learning. Previous studies have found variable influences of different types of caregiver responsiveness on attention, language, and cognitive development. Therefore, the purpose of this study was to examine how the responsive style of a social partner influenced the learning of object-directed action sequences. Infants interacted with either a sensitive or redirective experimenter before the learning trial. Results revealed infants changed their patterns of engagement; infants interacting with a sensitive experimenter had longer periods of attentional engagement than infants interacting with a redirective experimenter. Furthermore, during the learning trial, the amount of sensitivity during interaction with the social partner predicted learning scores. These findings suggest that infants' attention is influenced by social partners' interactive style during ongoing interaction, which subsequently affects how infants learn from these social partners.

16.
Nat Genet ; 39(1): 80-5, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17159980

RESUMO

The past decade has seen great advances in unraveling the biological basis of hereditary ataxias. Molecular studies of spinocerebellar ataxias (SCA) have extended our understanding of dominant ataxias. Causative genes have been identified for a few autosomal recessive ataxias: Friedreich's ataxia, ataxia with vitamin E deficiency, ataxia telangiectasia, recessive spastic ataxia of Charlevoix-Saguenay and ataxia with oculomotor apraxia type 1 (refs. 6,7) and type 2 (ref. 8). Nonetheless, genes remain unidentified for most recessive ataxias. Additionally, pure cerebellar ataxias, which represent up to 20% of all ataxias, remain poorly studied with only two causative dominant genes being described: CACNA1A (ref. 9) and SPTBN2 (ref. 10). Here, we report a newly discovered form of recessive ataxia in a French-Canadian cohort and show that SYNE1 mutations are causative in all of our kindreds, making SYNE1 the first identified gene responsible for a recessively inherited pure cerebellar ataxia.


Assuntos
Ataxia Cerebelar/genética , Genes Recessivos , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Adulto , Idoso , Sequência de Aminoácidos , Animais , Sequência de Bases , Cerebelo/metabolismo , Mapeamento Cromossômico , Proteínas do Citoesqueleto , Análise Mutacional de DNA , Feminino , Testes Genéticos , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , Proteínas do Tecido Nervoso/metabolismo , Proteínas Nucleares/metabolismo , Quebeque
17.
Hum Mol Genet ; 22(12): 2350-60, 2013 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-23446633

RESUMO

The mutations P56S and T46I in the gene encoding vesicle-associated membrane protein-associated protein B/C (VAPB) cause ALS8, a familial form of amyotrophic lateral sclerosis (ALS). Overexpression of mutant forms of VAPB leads to cytosolic aggregates, suggesting a gain of function of the mutant protein. However, recent work suggested that the loss of VAPB function could be the major mechanism leading to ALS8. Here, we used multiple genetic and experimental approaches to study whether VAPB loss of function might be sufficient to trigger motor neuron degeneration. In order to identify additional ALS-associated VAPB mutations, we screened the entire VAPB gene in a cohort of ALS patients and detected two mutations (A145V and S160Δ). To directly address the contribution of VAPB loss of function in ALS, we generated zebrafish and mouse models with either a decreased or a complete loss of Vapb expression. Vapb knockdown in zebrafish led to swimming deficits. Mice knocked-out for Vapb showed mild motor deficits after 18 months of age yet had innervated neuromuscular junctions (NMJs). Importantly, overexpression of VAPB mutations were unable to rescue the motor deficit caused by Vapb knockdown in zebrafish and failed to cause a toxic gain-of-function defect on their own. Thus, Vapb loss of function weakens the motor system of vertebrate animal models but is on its own unable to lead to a complete ALS phenotype. Our findings are consistent with the notion that VAPB mutations constitute a risk factor for motor neuron disease through a loss of VAPB function.


Assuntos
Esclerose Lateral Amiotrófica/metabolismo , Proteínas de Membrana/metabolismo , Mutação de Sentido Incorreto , Proteínas de Transporte Vesicular/metabolismo , Sequência de Aminoácidos , Esclerose Lateral Amiotrófica/genética , Animais , Sequência de Bases , Estudos de Coortes , Feminino , Humanos , Masculino , Proteínas de Membrana/química , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Dados de Sequência Molecular , Alinhamento de Sequência , Proteínas de Transporte Vesicular/química , Proteínas de Transporte Vesicular/genética , Peixe-Zebra
18.
Am J Bot ; 102(8): 1342-55, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26290557

RESUMO

UNLABELLED: • Premises of the study: Understanding the influence of recent glacial and postglacial periods on species' distributions is key for predicting the effects of future environmental changes. We investigated the influence of two physiographic landscapes on population structure and postglacial colonization of two white pine species of contrasting habitats: P. monticola, which occurs in the highly mountainous region of western North America, and P. strobus, which occurs in a much less mountainous area in eastern North America.• METHODS: To characterize the patterns of genetic diversity and population structure across the ranges of both species, 158 and 153 single nucleotide polymorphism (SNP) markers derived from expressed genes were genotyped on range-wide samples of 61 P. monticola and 133 P. strobus populations, respectively.• KEY RESULTS: In P. monticola, a steep latitudinal decrease in genetic diversity likely resulted from postglacial colonization involving rare long-distance dispersal (LDD) events. In contrast, no geographic patterns of diversity were detected in P. strobus, suggesting recolonization via a gradually advancing front or frequent LDD events. For each species, structure analyses identified two distinct southern and northern genetic groups that likely originated from two different glacial lineages. At a finer scale, and for the two species, smaller subgroups were detected that could be remnants of cryptic refugia.• CONCLUSION: During postglacial colonization, the western and eastern North American landscapes had different impacts on genetic signatures in P. monticola compared with P. strobus. We discuss the importance of our findings for conservation programs and predictions of species' response to climate change.


Assuntos
Variação Genética , Pinus/fisiologia , Dispersão Vegetal , Canadá , Mudança Climática , Pinus/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Polimorfismo de Nucleotídeo Único , Estados Unidos
19.
J Child Lang ; 42(3): 538-61, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-24923871

RESUMO

Existing studies have observed a robust relationship between infants' pointing gestures and language outcomes. By contrast, infants' overall vocal production is not related to language outcomes. One possible explanation for the association between pointing and language is that pointing gestures, as compared to vocalizations, may elicit more verbal responses from social partners that are facilitative for language learning. To test this, we observed forty-seven infants aged 1;0 during free play with their mothers and fathers separately to compare parents' verbal responses to infants' pointing gestures and object-directed vocalizations. Results showed that, compared to object-directed vocalizations, infants' pointing elicited more verbal responses from parents, particularly object labels. Moreover, mothers were more likely than fathers to provide labels. These results may help explain why pointing is associated with indices of language acquisition, but the production of vocalizations is not.


Assuntos
Gestos , Comportamento do Lactente , Relações Pais-Filho , Comportamento Verbal , Feminino , Humanos , Lactente , Desenvolvimento da Linguagem , Masculino
20.
Mol Diagn Ther ; 28(2): 201-214, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38267771

RESUMO

Anal squamous cell carcinoma (ASCC) is a rare gastrointestinal malignancy associated with high-risk human papillomavirus (HPV) and is currently one of the fastest-growing causes of cancer incidence and mortality in developed countries. Although next-generation sequencing technologies (NGS) have revolutionized cancer and immuno-genomic research in various tumor types, a limited amount of clinical research has been developed to investigate the expression and the functional characterization of genomic data in ASCC. Herein, we comprehensively assess recent advancements in "omics" research, including a systematic analysis of genome-based studies, aiming to identify the most relevant ASCC cancer driver gene expressions and their associated signaling pathways. We also highlight the most significant biomarkers associated with anal cancer progression, gene expression of potential diagnostic biomarkers, expression of therapeutic drug targets, and emerging treatment opportunities. This review stresses the urgent need for developing target-specific therapies in ASCC. By illuminating the molecular characteristics and drug-target expression in ASCC, this study aims to provide insights for the development of precision medicine in anal cancer.


Assuntos
Neoplasias do Ânus , Carcinoma de Células Escamosas , Humanos , Biomarcadores , Neoplasias do Ânus/diagnóstico , Neoplasias do Ânus/genética , Neoplasias do Ânus/epidemiologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Genômica , Recidiva Local de Neoplasia/patologia
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