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1.
Clin Linguist Phon ; 37(4-6): 363-384, 2023 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-36121007

RESUMEN

In speech sound intervention, consonant clusters promote generalisation (i.e. improvement in untreated sounds and words), ostensibly due to their relative complexity compared to other phonological targets. However, our understanding of clusters as intervention targets is largely restricted to those in word-initial position (e.g. [fl-], flip). The present study extends available work to consider the effects of word-final consonant cluster targets (e.g. [-ks]). Phonologically complex word-final clusters may be morphologically simple (e.g. mix) or morphologically complex (e.g. packs, inflected with third-person singular) - yet this cross-domain complexity remains an understudied phenomenon. Presently, two case studies provide an initial investigation of word-final cluster intervention targets for children with phonologically based speech sound disorders. Intervention targets for both Anna (3;7 [years;months]) and David (4;1) featured the phonologically complex word-final cluster [-ks], with Anna's target being morphologically simple and David's being morphologically complex. Intervention was provided in 45-minute, individual sessions three times per week for a maximum of 18 sessions. Both children demonstrated high target accuracy by intervention's end. Following intervention, both children demonstrated progress in intelligibility and ability to produce word-final consonant clusters; David further demonstrated generalisation across multiple measures. Results are interpreted with consideration of individual differences and existing research on complexity in phonological intervention. Overall, present findings motivate continued research, as manipulation of word-final complexity allows for emphasis on a context that is relevant for children with speech sound disorders, for peers with difficulties in morphology (including word-final grammatical morphemes) and for the substantial proportion of children demonstrating weaknesses in both domains.


Asunto(s)
Fonética , Trastorno Fonológico , Niño , Humanos , Habla , Trastorno Fonológico/terapia , Medición de la Producción del Habla , Logopedia/métodos
2.
Int J Biling Educ Biling ; 25(3): 922-941, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35399223

RESUMEN

The current work investigates whether language dominance predicts transfer of skills across cognitive-linguistic levels from the native language (Spanish) to the second language (English) in bilingual preschoolers. Sensitivity to cognates (elephant/elefante in English/Spanish) and metalinguistic awareness (MLA) have both been shown to transfer from the dominant to the nondominant language. Examining these types of transfer together using a continuous measure of language dominance may allow us to better understand the effect of the home language in children learning a majority language in preschool. Forty-six preschool-aged, Spanish-English bilinguals completed English receptive vocabulary and metalinguistic tasks indexing cognate effects and MLA. Language dominance was found to predict crosslinguistic (cognate) facilitation from Spanish to English. In addition, MLA skills also transferred from Spanish to English for children with lower English proficiency, and no transfer of MLA was evident for children with higher English proficiency. Altogether, findings suggest that transfer from a dominant first language to a nondominant second language happens at linguistic and cognitive-linguistic levels in preschoolers, although possibly influenced by second language proficiency. The current study has implications for supporting the home language for holistic cognitive-linguistic development.

3.
Biophys J ; 106(11): 2364-74, 2014 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-24896115

RESUMEN

Transmural heterogeneities in Na/K pump current (IP), transient outward K(+)-current (Ito), and Ca(2+)-current (ICaL) play an important role in regulating electrical and contractile activities in the ventricular myocardium. Prior studies indicated angiotensin II (A2) may determine the transmural gradient in Ito, but the effects of A2 on IP and ICaL were unknown. In this study, myocytes were isolated from five muscle layers between epicardium and endocardium. We found a monotonic gradient in both Ip and Ito, with the lowest currents in ENDO. When AT1Rs were inhibited, EPI currents were unaffected, but ENDO currents increased, suggesting endogenous extracellular A2 inhibits both currents in ENDO. IP- and Ito-inhibition by A2 yielded essentially the same K0.5 values, so they may both be regulated by the same mechanism. A2/AT1R-mediated inhibition of IP or Ito or stimulation of ICaL persisted for hours in isolated myocytes, suggesting continuous autocrine secretion of A2 into a restricted diffusion compartment, like the T-system. Detubulation brought EPI IP to its low ENDO value and eliminated A2 sensitivity, so the T-system lumen may indeed be the restricted diffusion compartment. These studies showed that 33-50% of IP, 57-65% of Ito, and a significant fraction of ICaL reside in T-tubule membranes where they are transmurally regulated by autocrine secretion of A2 into the T-system lumen and activation of AT1Rs. Increased AT1R activation regulates each of these currents in a direction expected to increase contractility. Endogenous A2 activation of AT1Rs increases monotonically from EPI to ENDO in a manner similar to reported increases in passive tension when the ventricular chamber fills with blood. We therefore hypothesize load is the signal that regulates A2-activation of AT1Rs, which create a contractile gradient that matches the gradient in load.


Asunto(s)
Angiotensina II/metabolismo , Ventrículos Cardíacos/metabolismo , Contracción Miocárdica , Miocitos Cardíacos/metabolismo , Potasio/metabolismo , Función Ventricular , Potenciales de Acción , Animales , Perros , Endocardio/citología , Endocardio/metabolismo , Endocardio/fisiología , Ventrículos Cardíacos/citología , Transporte Iónico , Miocitos Cardíacos/citología , Miocitos Cardíacos/fisiología , Pericardio/citología , Pericardio/metabolismo , Pericardio/fisiología , Canales de Potasio/metabolismo , Sarcolema/metabolismo
4.
Virus Res ; 341: 199322, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38228190

RESUMEN

The emergence of highly infectious pathogens with their potential for triggering global pandemics necessitate the development of effective treatment strategies, including broad-spectrum antiviral therapies to safeguard human health. This study investigates the antiviral activity of emetine, dehydroemetine (DHE), and congeneric compounds against SARS-CoV-2 and HCoV-OC43, and evaluates their impact on the host cell. Concurrently, we assess the potential cardiotoxicity of these ipecac alkaloids. Significantly, our data reveal that emetine and the (-)-R,S isomer of 2,3-dehydroemetine (designated in this paper as DHE4) reduce viral growth at nanomolar concentrations (i.e., IC50 ∼ 50-100 nM), paralleling those required for inhibition of protein synthesis, while calcium channel blocking activity occurs at elevated concentrations (i.e., IC50 ∼ 40-60 µM). Our findings suggest that the antiviral mechanisms primarily involve disruption of host cell protein synthesis and is demonstrably stereoisomer specific. The prospect of a therapeutic window in which emetine or DHE4 inhibit viral propagation without cardiotoxicity renders these alkaloids viable candidates in strategies worthy of clinical investigation.


Asunto(s)
Alcaloides , Emetina , Emetina/análogos & derivados , Humanos , Emetina/farmacología , Ipeca/farmacología , Cardiotoxicidad , Antivirales/toxicidad
5.
Stud Health Technol Inform ; 305: 365-368, 2023 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-37387041

RESUMEN

Despite the fact that many researchers and teachers reported that distance education can be equated with traditional face-to-face form education, the question of analyzing the quality of knowledge gained in distance education is open. This study was conducted on the basis of the Department of Medical Cybernetics and Informatics named after S.A. Gasparyan of Russian National Research Medical University. N.I. Pirogov for the period from September 1, 2021 to March 14, 2023 and included results of answers of two variance of test on the same topic. The responses of students who missed the lectures were not included in the processing. For 556 students with distance education, the lesson was held remotely using https://meet.google.com and for 846 students the lesson was performed in face-to-face form education. Students' answers to test tasks were collected using the Google form https://docs.google.com/forms/…The data base statistical assessment and statistical description were made in Microsoft Excel 2010 and IBM SPSS Statistics programs version 23. In this study, it was shown that the results of the learned material assessment for distance education and traditional face-to-face form education are statistically significantly different (p<0.001). The topic studied in face-to-face format was assimilated by 0.85 points better (the difference was five percent of the correct answers received).


Asunto(s)
Educación a Distancia , Estudiantes , Humanos , Universidades , Escolaridad , Aprendizaje
6.
J Commun Disord ; 101: 106281, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36434924

RESUMEN

PURPOSE: Percent grammatical utterances (PGU) provides clinicians and researchers with meaningful information on young children's grammatical abilities (Eisenberg & Guo, 2016). However, work is still needed to place PGU within the context of conventional language sample measures and understand how PGU reflects grammatical development in bilingual populations. The current study focuses on Spanish-English bilingual preschoolers to examine: 1) change in Spanish and English PGU over one year of preschool English instruction, 2) associations between PGU and other language sample measures within each language and across time, and 3) the types and frequency of error patterns in each language. METHOD: Play-based language samples were elicited in English and Spanish from bilingual children (n = 19) at the beginning and end of an instructional preschool year in English. PGU was derived from each sample along with other language sample measures (e.g., mean length of utterance). We examined change in PGU from Time 1 to Time 2, and correlations between Time 1 PGU and Time 2 PGU for each language. Specific grammatical errors were described in terms of their frequency in each language and stability across time. RESULTS: Average English PGU increased from Time 1 to Time 2, and correlated with other language sample measures. Conversely, average Spanish PGU did not increase from Time 1 to Time 2, nor did PGU correlate with any other Spanish measure. Error patterns in each language reflected grammatical differences across English and Spanish. CONCLUSIONS: Our results revealed distinct developmental patterns in bilingual children's first and second languages. Associations between time points and measures in English contrasted with disassociations in Spanish. Error patterns revealed more detailed information as to how bilingual children begin to acquire grammatical structures in each of their languages. We provide a case example to illustrate how grammaticality and error patterns can be used to characterize children's language abilities. We conclude with clinical implications of grammaticality in Spanish-English bilingual children.


Asunto(s)
Multilingüismo , Niño , Preescolar , Humanos , Lenguaje Infantil , Hispánicos o Latinos , Lenguaje , Pruebas del Lenguaje
7.
Int J Speech Lang Pathol ; 22(1): 106-116, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31046472

RESUMEN

Purpose: The purpose of this tutorial is to inform assessment, treatment and research approaches that are uniquely tailored to bilingual children with and without developmental language disorder (DLD), a communication disorder characterised by weaknesses in language production and comprehension.Method: A review is presented on what is known about joint language activation in adult and child bilinguals. This supports a discussion of the bilingual profile, which includes cross-language interactions and associations with broader cognitive functions. This is followed by consideration on how these bilingual phenomena may manifest in the context of relatively weak language skills, as is the case with DLD.Result: In addition to exploring the bilingual profile, guidelines are provided for incorporating cognates - a type of translation equivalent with distinct overlap in form and meaning that enhances cross-linguistic interactions - in language assessment, therapy and research.Conclusion: The field of speech-language pathology would benefit from more tools specifically designed for bilingual children. Already, there is interest in clinical applications of cognates, as they may support transfer and generalisation across languages. Future research is needed to better explore this potential in child bilinguals, particularly those with DLD. Such work would help establish a developmental bilingual language processing model with clinical relevance.


Asunto(s)
Trastornos del Desarrollo del Lenguaje , Multilingüismo , Patología del Habla y Lenguaje , Adulto , Niño , Femenino , Humanos , Masculino
8.
Am J Speech Lang Pathol ; 29(3): 1212-1225, 2020 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-32750283

RESUMEN

Purpose Defining parameters for typical development in bilingual children's first and second languages can serve as the basis for accurate language assessment. This is the first study to characterize Vietnamese and English grammatical development in a sample of bilingual children. Method Participants were 89 Vietnamese-English bilingual children, aged 3-8 years. Children completed story retell tasks in Vietnamese and English. Stories were transcribed and analyzed for grammaticality, error patterns, subordination index, and types of subordinating clauses. Of key interest were associations with age and identifying developmental patterns that were shared across languages or unique to a given language. Results Age correlated with more measures in English than in Vietnamese, suggesting that older children had higher grammaticality and greater syntactic complexity in English than younger children. Children also produced greater syntactic complexity with age in Vietnamese, but not higher grammaticality. There were a set of error patterns shared across languages (e.g., object omission) and patterns specific to each language (e.g., classifier errors in Vietnamese, tense errors in English). While children produced nominal, adverbial, and relative clauses in Vietnamese and English, the proportion of each clause type differed by language. Conclusions Results from this typically developing sample provide a reference point to improve clinical practice. Characterizing developmental patterns in sentence structure in Vietnamese and English lays the groundwork for investigations of language disorders in this bilingual population.


Asunto(s)
Multilingüismo , Adolescente , Pueblo Asiatico , Niño , Lenguaje Infantil , Humanos , Lenguaje , Pruebas del Lenguaje
9.
J Cell Physiol ; 219(1): 23-30, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19023868

RESUMEN

Mesenchymal stem cells (MSCs) participate in the wound healing process in mammalians. Adhesion of MSCs to endothelium is a key step in the homing of MSCs circulating in the bloodstream to the sites of injury and inflammation. Because endothelial cells (ECs) may become apoptotic under certain pro-inflammatory conditions, we investigated the effects of pro-inflammatory, TNF-alpha and IL-1 beta, and pro-apoptotic agents, actinomycin D, cycloheximide, okadaic acid, wortmannin, and staurosporine, on human MSCs (hMSCs) adhesion to ECs. Treatment of ECs with pro-apoptotic agents markedly increased adhesion of hMSCs to ECs. This adhesion correlated with reduction of mitochondrial membrane potential, inhibition of NADH dehydrogenases, and release of von Willebrand factor (vWF) by ECs. Treatment of ECs with exogenous vWF also stimulated hMSC adhesion. These data provide evidence that apoptosis of ECs may regulate homing of hMSCs to the sites of tissue injury. These results are consistent with the hypothesis that activation of apoptotic signaling pathways in ECs releases vWF which regulates hMSC adhesion to ECs.


Asunto(s)
Apoptosis/fisiología , Adhesión Celular/fisiología , Células Endoteliales/fisiología , Células Madre Mesenquimatosas/fisiología , Androstadienos/farmacología , Animales , Antígenos de Superficie/metabolismo , Células Cultivadas , Cicloheximida/farmacología , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Humanos , Interleucina-1beta/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Potencial de la Membrana Mitocondrial/fisiología , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , NADH Deshidrogenasa/metabolismo , Ácido Ocadaico/farmacología , Inhibidores de la Síntesis de la Proteína/farmacología , Transducción de Señal/fisiología , Estaurosporina/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Wortmanina , Factor de von Willebrand/metabolismo
10.
J Monolingual Biling Speech ; 1(1): 118-142, 2019 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-33778490

RESUMEN

Best practice for bilingual speakers involves considering performance in each language the client uses. To support this practice for young clients, a comprehensive understanding of how bilingual children develop skills in each language is needed. To that end, the present work investigates relative use of English tense and agreement (T/A) morphemes - a skill frequently considered as part of a complete language assessment - in Spanish-English developing bilingual preschoolers with varying levels of language ability. Results indicate that developing bilingual children with both typical and weak language skills demonstrate greater use of copula and auxiliary BE relative to third person singular, past tense and auxiliary DO. Findings thus reveal a relative ranking of T/A morphemes in developing bilingual children that differs from that of English monolingual children, who demonstrate relatively later emergence and productivity of auxiliary BE. In turn, findings demonstrate the importance of utilizing appropriate comparisons in clinical practice.

11.
Circulation ; 116(7): 706-13, 2007 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-17646577

RESUMEN

BACKGROUND: Biological pacemaking has been performed with viral vectors, human embryonic stem cells, and adult human mesenchymal stem cells (hMSCs) as delivery systems. Only with human embryonic stem cells are data available regarding stability for >2 to 3 weeks, and here, immunosuppression has been used to facilitate survival of xenografts. The purpose of the present study was to determine whether hMSCs provide stable impulse initiation over 6 weeks without the use of immunosuppression, the "dose" of hMSCs that ensures function over this period, and the catecholamine responsiveness of hMSC-packaged pacemakers. METHODS AND RESULTS: A full-length mHCN2 cDNA subcloned in a pIRES2-EGFP vector was electroporated into hMSCs. Transfection efficiency was estimated by GFP expression. I(HCN2) was measured with patch clamp, and cells were administered into the left ventricular anterior wall of adult dogs in complete heart block and with backup electronic pacemakers. Studies encompassed 6 weeks. I(HCN2) for all cells was 32.1+/-1.3 pA/pF (mean+/-SE) at -150 mV. Pacemaker function in intact dogs required 10 to 12 days to fully stabilize and persisted consistently through day 42 in dogs receiving > or =700,000 hMSCs (approximately 40% of which carried current). Rhythms were catecholamine responsive. Tissues from animals killed at 42 days manifested neither apoptosis nor humoral or cellular rejection. CONCLUSIONS: hMSCs provide a means for administering catecholamine-responsive biological pacemakers that function stably for 6 weeks and manifest no cellular or humoral rejection at that time. Cell doses >700,000 are sufficient for pacemaking when administered to left ventricular myocardium.


Asunto(s)
Corazón/fisiología , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/fisiología , Adulto , Animales , Células Cultivadas , Perros , Conductividad Eléctrica , Electrocardiografía , Epinefrina/farmacología , Bloqueo Cardíaco/fisiopatología , Humanos , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización , Canales Iónicos/genética , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Ratones , Técnicas de Placa-Clamp , Canales de Potasio , Transfección , Trasplante Heterólogo
12.
Lang Speech Hear Serv Sch ; 49(2): 260-276, 2018 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-29621805

RESUMEN

Purpose: This work explores the clinical relevance of three measures of morpheme use for preschool-age Spanish-English bilingual children with varying language skills. The 3 measures reflect accuracy, diversity (the tense marker total), and productivity (the tense and agreement productivity score [TAP score]) of the English tense and agreement system. Method: Measures were generated from language samples collected at the beginning and end of the participants' preschool year. Participants included 74 typically developing Spanish-English bilinguals and 19 peers with low language skills. The morpheme measures were evaluated with regard to their relationships with other language sample measures, their ability to reflect group differences, and their potential for capturing morphological development at group and individual levels. Results: Across both groups, the tense marker total and TAP scores were associated with other language measures and demonstrated both group differences and growth over time. The accuracy measure met few of these benchmarks. Conclusion: The tense marker total and TAP score, which were designed to capture emerging morphological abilities, contribute valuable information to a comprehensive language assessment of young bilinguals developing English. Case examples are provided to illustrate the clinical significance of including these measures in assessment.


Asunto(s)
Desarrollo del Lenguaje , Pruebas del Lenguaje/normas , Multilingüismo , Lenguaje Infantil , Preescolar , Femenino , Hispánicos o Latinos/psicología , Humanos , Trastornos del Desarrollo del Lenguaje/diagnóstico , Lingüística , Masculino
13.
Circulation ; 114(10): 992-9, 2006 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-16923750

RESUMEN

BACKGROUND: Biological pacemakers (BPM) implanted in canine left bundle branch function competitively with electronic pacemakers (EPM). We hypothesized that BPM engineered with the use of mE324A mutant murine HCN2 (mHCN2) genes would improve function over mHCN2 and that BPM/EPM tandems confer advantage over either approach alone. METHODS AND RESULTS: In cultured neonatal rat myocytes, activation midpoint was -46.9 mV in mE324A versus -66.1 mV in mHCN2 (P < 0.05). mE324A manifested a positive shift of voltage dependence of gating kinetics of activation and deactivation compared with mHCN2 (P < 0.05) in myocytes as well as Xenopus oocytes. In intact dogs in complete atrioventricular block, saline (control), mHCN2, or mE324A virus was injected into left bundle branch, and EPM were implanted (VVI 45 bpm). Twenty-four-hour ECGs were monitored for 14 days. With EPM discontinued, there was no difference in duration of overdrive suppression among groups. However, basal heart rates in controls were less than those in mHCN2, which did not differ from those in E324A (45 versus 57 versus 53 bpm; P < 0.05). When spontaneous rate fell below 45 bpm, EPM intervened at that rate, triggering 83% of beats in control, contrasting (P < 0.05) with 26% (mHCN2) and 36% (mE324A). On day 14, epinephrine (1 microg/kg per minute IV) induced a 50% heart rate increase in all mE324A, one third of mHCN2, and one fifth of control (P < 0.05 mE324A versus control or mHCN2). CONCLUSIONS: mE324A induces faster, more positive pacemaker current activation than mHCN2 and stable, catecholamine-sensitive rhythms in situ that compete with EPM comparably but more catecholamine responsively than mHCN2. BPM/EPM tandems function reliably, reduce the number of EPM beats, and confer sympathetic responsiveness to the tandem.


Asunto(s)
Canales Iónicos/fisiología , Marcapaso Artificial , Función Ventricular , Animales , Animales Recién Nacidos , Línea Celular , Modelos Animales de Enfermedad , Perros , Bloqueo Cardíaco/fisiopatología , Bloqueo Cardíaco/terapia , Humanos , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización , Canales Iónicos/genética , Ratones , Técnicas de Placa-Clamp , Canales de Potasio , Ratas , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/terapia
14.
FEBS J ; 274(17): 4375-84, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17725712

RESUMEN

The voltage-gated potassium channel Kv4.3 was coexpressed with its beta-subunit Kv channel-interacting protein 2 and the angiotensin type 1 receptor in HEK-293 cells. Proteomic analysis of proteins coimmunoprecipitated with Kv4.3 revealed that Kv4.3 is associated with Rap guanine nucleotide exchange factors MR-GEF and EPAC-1. Previously, we demonstrated that Kv4.3 interacts with the angiotensin type 1 receptor in HE293 cells and cardiac myocytes. On the basis of this, we investigated the angiotensin type 1 receptor signaling to small G-proteins Ras and Rap-1 in the presence and absence of the Kv4.3-Kv channel-interacting protein 2 macromolecular complex. Ras activation was not significantly affected by coexpression of Kv4.3 and Kv channel-interacting protein 2. Ras exhibited a rapid activation-inactivation pattern with maximum activity at 2.5 min after addition of angiotensin II. In contrast, activation of Rap-1 was affected dramatically by coexpression of Kv4.3 and Kv channel-interacting protein 2 with the angiotensin type 1 receptor. In the absence of Kv4.3 and Kv channel-interacting protein 2, stimulation of the angiotensin type 1 receptor resulted in steady activation of Rap-1 that reached a plateau 25 min after addition of angiotensin II. In the presence of Kv4.3 and Kv channel-interacting protein 2, Rap-1 reaches a maximum activity 2.5 min after addition of angiotensin II and then deactivates rapidly, demonstrating a pattern of activation similar to that of Ras. Our findings show that Kv4.3 regulates angiotensin type 1 receptor signaling to the small G-protein Rap-1.


Asunto(s)
Activación del Canal Iónico , Receptor de Angiotensina Tipo 1/metabolismo , Canales de Potasio Shal/metabolismo , Línea Celular , Factores de Intercambio de Guanina Nucleótido , Humanos , Proteoma , Transducción de Señal
15.
J Electrocardiol ; 40(6 Suppl): S199-201, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17993323

RESUMEN

Heart failure survival after diagnosis has barely changed for more than half a century. Recently, investigation has focused on differentiation of stem cells in vitro and their delivery for use in vivo as replacement cardiac contractile elements. Here we report preliminary results using mesenchymal stem cells partially differentiated to a cardiac lineage in vitro. When delivered to the canine heart on an extracellular matrix patch to replace a full-thickness ventricular defect in vivo, they improve regional mechanical function. The delivered cells were also tracked, and some became myocytes with mature sarcomeres.


Asunto(s)
Trasplante de Células Madre Mesenquimatosas/métodos , Infarto del Miocardio/patología , Infarto del Miocardio/cirugía , Animales , Perros , Proyectos Piloto , Resultado del Tratamiento
16.
J Speech Lang Hear Res ; 60(8): 2199-2216, 2017 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-28750415

RESUMEN

Purpose: The emergence of tense-morpheme marking during language acquisition is highly variable, which confounds the use of tense marking as a diagnostic indicator of language impairment in linguistically diverse populations. In this study, we seek to better understand tense-marking patterns in young bilingual children by comparing phonological influences on marking of 2 word-final tense morphemes. Method: In spontaneous connected speech samples from 10 Spanish-English dual language learners aged 56-66 months (M = 61.7, SD = 3.4), we examined marking rates of past tense -ed and third person singular -s morphemes in different environments, using multiple measures of phonological context. Results: Both morphemes were found to exhibit notably contrastive marking patterns in some contexts. Each was most sensitive to a different combination of phonological influences in the verb stem and the following word. Conclusions: These findings extend existing evidence from monolingual speakers for the influence of word-final phonological context on morpheme production to a bilingual population. Further, novel findings not yet attested in previous research support an expanded consideration of phonological context in clinical decision making and future research related to word-final morphology.


Asunto(s)
Multilingüismo , Fonética , Proteínas Bacterianas , Preescolar , Humanos , Pruebas del Lenguaje , Aprendizaje , Liasas
17.
Circ Arrhythm Electrophysiol ; 10(5): e004508, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28500172

RESUMEN

BACKGROUND: Although multiple approaches have been used to create biological pacemakers in animal models, induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have not been investigated for this purpose. We now report pacemaker function of iPSC-CMs in a canine model. METHODS AND RESULTS: Embryoid bodies were derived from human keratinocytes, their action potential characteristics determined, and their gene expression profiles and markers of differentiation identified. Atrioventricular blocked dogs were immunosuppressed, instrumented with VVI pacemakers, and injected subepicardially into the anterobasal left ventricle with 40 to 75 rhythmically contracting embryoid bodies (totaling 1.3-2×106 cells). ECG and 24-hour Holter monitoring were performed biweekly. After 4 to 13 weeks, epinephrine (1 µg kg-1 min-1) was infused, and the heart removed for histological or electrophysiological study. iPSC-CMs largely lost the markers of pluripotency, became positive for cardiac-specific markers. and manifested If-dependent automaticity. Epicardial pacing of the injection site identified matching beats arising from that site by week 1 after implantation. By week 4, 20% of beats were electronically paced, 60% to 80% of beats were matching, and mean and maximal biological pacemaker rates were 45 and 75 beats per minute. Maximum night and day rates of matching beats were 53±6.9 and 69±10.4 beats per minute, respectively, at 4 weeks. Epinephrine increased rate of matching beats from 35±4.3 to 65±4.0 beats per minute. Incubation of embryoid bodies with the vital dye, Dil, revealed the persistence of injected cells at the site of administration. CONCLUSIONS: iPSC-CMs can integrate into host myocardium and create a biological pacemaker. Although this is a promising development, rate and rhythm of the iPSC-CMs pacemakers remain to be optimized.


Asunto(s)
Bloqueo Atrioventricular/cirugía , Relojes Biológicos , Diferenciación Celular , Frecuencia Cardíaca , Células Madre Pluripotentes Inducidas/trasplante , Miocitos Cardíacos/trasplante , Trasplante de Células Madre , Potenciales de Acción , Animales , Bloqueo Atrioventricular/metabolismo , Bloqueo Atrioventricular/fisiopatología , Estimulación Cardíaca Artificial , Línea Celular , Modelos Animales de Enfermedad , Perros , Electrocardiografía , Técnicas Electrofisiológicas Cardíacas , Perfilación de la Expresión Génica/métodos , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Factor 4 Similar a Kruppel , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Miocitos Cardíacos/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Proteínas Proto-Oncogénicas c-myc/genética , Proteínas Proto-Oncogénicas c-myc/metabolismo , Recuperación de la Función , Factores de Transcripción SOXB1/genética , Factores de Transcripción SOXB1/metabolismo , Factores de Tiempo , Transcriptoma , Transfección
18.
Circ Res ; 94(7): 952-9, 2004 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-14988226

RESUMEN

We tested the ability of human mesenchymal stem cells (hMSCs) to deliver a biological pacemaker to the heart. hMSCs transfected with a cardiac pacemaker gene, mHCN2, by electroporation expressed high levels of Cs+-sensitive current (31.1+/-3.8 pA/pF at -150 mV) activating in the diastolic potential range with reversal potential of -37.5+/-1.0 mV, confirming the expressed current as I(f)-like. The expressed current responded to isoproterenol with an 11-mV positive shift in activation. Acetylcholine had no direct effect, but in the presence of isoproterenol, shifted activation 15 mV negative. Transfected hMSCs influenced beating rate in vitro when plated onto a localized region of a coverslip and overlaid with neonatal rat ventricular myocytes. The coculture beating rate was 93+/-16 bpm when hMSCs were transfected with control plasmid (expressing only EGFP) and 161+/-4 bpm when hMSCs were expressing both EGFP+mHCN2 (P<0.05). We next injected 10(6) hMSCs transfected with either control plasmid or mHCN2 gene construct subepicardially in the canine left ventricular wall in situ. During sinus arrest, all control (EGFP) hearts had spontaneous rhythms (45+/-1 bpm, 2 of right-sided origin and 2 of left). In the EGFP+mHCN2 group, 5 of 6 animals developed spontaneous rhythms of left-sided origin (rate=61+/-5 bpm; P<0.05). Moreover, immunostaining of the injected regions demonstrated the presence of hMSCs forming gap junctions with adjacent myocytes. These findings demonstrate that genetically modified hMSCs can express functional HCN2 channels in vitro and in vivo, mimicking overexpression of HCN2 genes in cardiac myocytes, and represent a novel delivery system for pacemaker genes into the heart or other electrical syncytia.


Asunto(s)
Terapia Genética , Canales Iónicos/fisiología , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Proteínas Musculares/fisiología , Miocitos Cardíacos/fisiología , Acetilcolina/farmacología , Agonistas Adrenérgicos beta/farmacología , Animales , Células Cultivadas/efectos de los fármacos , Células Cultivadas/fisiología , Células Cultivadas/trasplante , Cesio/farmacología , Colinérgicos/farmacología , Técnicas de Cocultivo , Perros , Electroporación , Uniones Comunicantes/fisiología , Uniones Comunicantes/ultraestructura , Frecuencia Cardíaca , Ventrículos Cardíacos/citología , Humanos , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización , Transporte Iónico/efectos de los fármacos , Isoproterenol/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Ratones , Miocitos Cardíacos/efectos de los fármacos , Técnicas de Placa-Clamp , Canales de Potasio , Ratas , Proteínas Recombinantes de Fusión/fisiología , Transfección
19.
Int J Billing ; 20(6): 714-731, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33664630

RESUMEN

OBJECTIVES: The purpose of this study was to determine whether four different cognate identification methods resulted in notably different classifications of cognate status for Peabody Picture Vocabulary Test-Third Edition (PPVT-III) test items and to investigate whether differences across criteria would impact findings of cognate effects in adult and preschool-aged Spanish-English bilingual speakers. METHODOLOGY: We compared four cognate identification methods: an objective criterion based on phonological overlap; two subjective criteria based on a translation elicitation task; and a hybrid criterion integrating objective and subjective standards. We then used each criterion to investigate cognate effects on the PPVT-III in 26 adult and 73 child Spanish-English bilinguals. DATA AND ANALYSIS: The test items identified as cognates by each criterion were compared (Experiment 1). Then, cognate advantage magnitudes, cognate accuracy rates, non-cognate accuracy rates, and number of individuals demonstrating the cognate advantage were investigated in both adult (Experiment 2) and child bilinguals (Experiment 3). CONCLUSIONS: Objective and subjective cognate identification methods were found to select notably different subsets of test items as cognates. Further, the methods led to differences in cognate effects, as well as in cognate and non-cognate accuracy rates, for both child and adult bilinguals. ORIGINALITY: Although the cognate advantage has been widely studied in adult bilinguals, research on the cognate advantage in child bilinguals is limited and methods of identifying cognates are inconsistent across studies. The present study provides information about cognate effects in a young population and is the first comparison of objective and subjective approaches to cognate identification. IMPLICATIONS: This study extends previous work on cognate word processing in both child and adult bilinguals. Further, results offer an evaluation of methodologies that are critical for investigating the cognate advantage. This both facilitates interpretation of previous findings and can be used to guide methodological decisions in future research.

20.
PLoS One ; 8(9): e73929, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24069252

RESUMEN

Mesenchymal stem cells natively circulating or delivered into the blood stream home to sites of injury. The mechanism of mesenchymal stem cell homing to sites of injury is poorly understood. We have shown that the development of apoptosis in endothelial cells stimulates endothelial cell adhesiveness for mesenchymal stem cells. Adhesion of mesenchymal stem cells to apoptotic endothelial cells depends on the activation of endothelial caspases and p38 MAPK. Activation of p38 MAPK in endothelial cells has a primary effect while the activation of caspases potentiates the mesenchymal stem cell adhesion. Overall, our study of the mesenchymal stem cell interaction with endothelial cells indicates that mesenchymal stem cells recognize and specifically adhere to distressed/apoptotic endothelial cells.


Asunto(s)
Caspasas/metabolismo , Células Endoteliales/metabolismo , Células Madre Mesenquimatosas/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Inhibidores de Caspasas/farmacología , Adhesión Celular/efectos de los fármacos , Células Cultivadas , Activación Enzimática/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Lipooxigenasa/metabolismo , Potencial de la Membrana Mitocondrial , Mitocondrias/metabolismo , Fosfolipasas A2/metabolismo , Fosforilación
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