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1.
Mol Cell Proteomics ; 11(4): M111.011544, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22199229

RESUMO

A significant challenge in biology is to functionally annotate novel and uncharacterized proteins. Several approaches are available for deducing the function of proteins in silico based upon sequence homology and physical or genetic interaction, yet this approach is limited to proteins with well-characterized domains, paralogs and/or orthologs in other species, as well as on the availability of suitable large-scale data sets. Here, we present a quantitative proteomics approach extending the protein network of core histones H2A, H2B, H3, and H4 in Saccharomyces cerevisiae, among which a novel associated protein, the previously uncharacterized Ydl156w, was identified. In order to predict the role of Ydl156w, we designed and applied integrative bioinformatics, quantitative proteomics and biochemistry approaches aiming to infer its function. Reciprocal analysis of Ydl156w protein interactions demonstrated a strong association with all four histones and also to proteins strongly associated with histones including Rim1, Rfa2 and 3, Yku70, and Yku80. Through a subsequent combination of the focused quantitative proteomics experiments with available large-scale genetic interaction data and Gene Ontology functional associations, we provided sufficient evidence to associate Ydl156w with multiple processes including chromatin remodeling, transcription and DNA repair/replication. To gain deeper insights into the role of Ydl156w in histone biology we investigated the effect of the genetic deletion of ydl156w on H4 associated proteins, which lead to a dramatic decrease in the association of H4 with RNA polymerase III proteins. The implication of a role for Ydl156w in RNA Polymerase III mediated transcription was consequently verified by RNA-Seq experiments. Finally, using these approaches we generated a refined network of Ydl156w-associated proteins.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Histonas/metabolismo , Proteômica/métodos , RNA Polimerase III/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Ligação a DNA/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Transcrição Gênica
2.
Am Ann Deaf ; 161(4): 424-443, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27818399

RESUMO

In a synthesis of the research, the authors present findings from communication and literacy studies conducted with children and youth with deafblindness, ages 0-22 years, and published in peer-reviewed journals, 1990-2015. Findings are organized within the structure of the four aspects of communication: form, function, content, context. The studies implemented child-guided and systematic instructional approaches. Studies on form addressed tangible representations, gestures, pictures, and technologies to increase expressive communication rates, and included research focusing on specific functions. Most of the research on context addressed the coaching of adult communication partners to improve responsiveness. Research on communication by children who are deafblind has focused almost exclusively on improving expressive communication. Therefore, there is a need for research on receptive communication and comprehension. In the area of literacy, studies are needed on emergent literacy and reading and writing interventions for children who are deafblind.


Assuntos
Comunicação , Surdocegueira/complicações , Surdocegueira/psicologia , Intervenção Educacional Precoce , Alfabetização , Adolescente , Criança , Pré-Escolar , Humanos
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