ABSTRACT
Introducción: Las dificultades del aprendizaje son las alteraciones de mayor presencia en las aulas escolares y sus indicadores pueden diagnosticarse y prevenirse desde edades tempranas. El objetivo de esta investigación fue validar el Test para la detección temprana de las dificultades en el aprendizaje de la lectura y escritura. Métodos: El enfoque de la investigación fue cuantitativo, descriptivo y de corte transversal. Se utilizó la validez de constructo acorde con la propuesta original del test y de fiabilidad a través del Alpha de Cronbach en una muestra de 501 niños ecuatorianos de cuatro años. Resultados: La validación del instrumento evidencia una moderada correlación entre las sub-tareas y alta correlación entre las sub-tareas y el puntaje total. La fiabilidad es buena, α= 0.71, muy próxima a la de la población española α= 0.73. Por lo que, la prueba puede ser utilizada en el contexto ecuatoriano en su versión original, adecuando en las instrucciones dos palabras a la realidad lingüística del país y para la calificación los puntos de corte de dificultad. Conclusión: Considerando su valor y fácil aplicación se recomienda el uso de la prueba de lectura en contextos educativos y de salud.
Introduction: Learning difficulties are the alterations with the most significant presence in school classrooms, and their indicators can be diagnosed and prevented early. This research aimed to validate the test for the early detection of difficulties in learning to read and write. Methods: The research approach was quantitative, descriptive, and cross-sectional. Construct validity was used according to the original proposal of the test and reliability through Cronbach's alpha in a sample of 501 four-year-old Ecuadorian children. Results: The validation of the instrument shows a moderate correlation between the subtasks and a high correlation between the subtasks and the total score. The reliability is good, α = 0.71, very close to that of the Spanish population α = 0.73. Therefore, the test can be used in the Ecuadorian context in its original version, adapting two words in the instructions to the linguistic reality of the country and for the qualification of the cutoff points of difficulty. Conclusion: With the easy application of the "test of reading" in 4-year-old children, the authors recommended its application for the identification of dyslexia and phonological processing deficits in school children in Ecuador. The reading test's validity allows its application at a regional level.
Subject(s)
Humans , Child, Preschool , Articulation Disorders , Reading , Comprehension , Open Reading Frames , Reading Frames , DyslexiaABSTRACT
Cell cycle dysfunction can cause severe diseases, including neurodegenerative disease and cancer. Mutations in cyclin-dependent kinase inhibitors controlling the G1 phase of the cell cycle are prevalent in various cancers. Mice lacking the tumor suppressors p16(Ink4a) (Cdkn2a, cyclin-dependent kinase inhibitor 2a), p19(Arf) (an alternative reading frame product of Cdkn2a,), and p27(Kip1) (Cdkn1b, cyclin-dependent kinase inhibitor 1b) result in malignant progression of epithelial cancers, sarcomas, and melanomas, respectively. Here, we generated knockout mouse models for each of these three cyclin-dependent kinase inhibitors using engineered nucleases. The p16(Ink4a) and p19(Arf) knockout mice were generated via transcription activator-like effector nucleases (TALENs), and p27(Kip1) knockout mice via clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR/Cas9). These gene editing technologies were targeted to the first exon of each gene, to induce frameshifts producing premature termination codons. Unlike preexisting embryonic stem cell-based knockout mice, our mouse models are free from selectable markers or other external gene insertions, permitting more precise study of cell cycle-related diseases without confounding influences of foreign DNA.
Subject(s)
Animals , Mice , Cell Cycle , Codon, Nonsense , Cyclin-Dependent Kinase Inhibitor p16 , DNA , Exons , G1 Phase , Genome , Melanoma , Mice, Knockout , Mutagenesis, Insertional , Neurodegenerative Diseases , Phosphotransferases , Reading Frames , SarcomaABSTRACT
While cancer immunotherapy has gained much deserved attention in recent years, many areas regarding the optimization of such modalities remain unexplored, including the development of novel approaches and the strategic combination of therapies that target multiple aspects of the cancer-immunity cycle. Our own work involves the use of gene transfer technology to promote cell death and immune stimulation. Such immunogenic cell death, mediated by the combined transfer of the alternate reading frame (p14ARF in humans and p19Arf in mice) and the interferon-β cDNA in our case, was shown to promote an antitumor immune response in mouse models of melanoma and lung carcinoma. With these encouraging results, we are now setting out on the road toward translational and preclinical development of our novel immunotherapeutic approach. Here, we outline the perspectives and challenges that we face, including the use of human tumor and immune cells to verify the response seen in mouse models and the incorporation of clinically relevant models, such as patient-derived xenografts and spontaneous tumors in animals. In addition, we seek to combine our immunotherapeutic approach with other treatments, such as chemotherapy or checkpoint blockade, with the goal of reducing dosage and increasing efficacy. The success of any translational research requires the cooperation of a multidisciplinary team of professionals involved in laboratory and clinical research, a relationship that is fostered at the Cancer Institute of Sao Paulo.
Subject(s)
Humans , Genetic Therapy/methods , Reading Frames/genetics , Interferon-beta/therapeutic use , Gene Transfer Techniques , Immunotherapy/methods , Neoplasms/therapy , Cell Death/genetics , Cyclin-Dependent Kinase Inhibitor p16/genetics , Tumor Suppressor Protein p14ARF/genetics , Neoplasms/immunologyABSTRACT
BACKGROUND AND PURPOSE: Studies of cases of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) confirmed by multiplex ligation-dependent probe amplification (MLPA) have determined the clinical characteristics, genotype, and relations between the reading frame and phenotype for different countries. This is the first such study from India. METHODS: A retrospective genotype-phenotype analysis of 317 MLPA-confirmed patients with DMD or BMD who visited the neuromuscular clinic of a quaternary referral center in southern India. RESULTS: The 317 patients comprised 279 cases of DMD (88%), 32 of BMD (10.1%), and 6 of intermediate phenotype (1.9%). Deletions accounted for 91.8% of cases, with duplications causing the remaining 8.2%. There were 254 cases of DMD (91%) with deletions and 25 (9%) due to duplications, and 31 cases (96.8%) of BMD with deletions and 1 (3.2%) due to duplication. All six cases of intermediate type were due to deletions. The most-common mutation was a single-exon deletion. Deletions of six or fewer exons constituted 68.8% of cases. The deletion of exon 50 was the most common. The reading-frame rule held in 90% of DMD and 94% of BMD cases. A tendency toward a lower IQ and earlier wheelchair dependence was observed with distal exon deletions, though a significant correlation was not found. CONCLUSIONS: The reading-frame rule held in 90% to 94% of children, which is consistent with reports from other parts of the world. However, testing by MLPA is a limitation, and advanced sequencing methods including analysis of the structure of mutant dystrophin is needed for more-accurate assessments of the genotype-phenotype correlation.
Subject(s)
Child , Humans , Cohort Studies , Dystrophin , Exons , Genetic Association Studies , Genotype , India , Multiplex Polymerase Chain Reaction , Muscular Dystrophy, Duchenne , Phenotype , Reading Frames , Referral and Consultation , Retrospective Studies , WheelchairsABSTRACT
BACKGROUND: Muscular dystrophy is an X-linked recessive disorder caused by mutations in the DMD gene. Muscular dystrophy is classified into 2 types; Duchenne muscular dystrophy (DMD), which has severe clinical symptoms, and Becker muscular dystrophy (BMD), which has much milder clinical symptoms. Phenotypic progression to either DMD or BMD can be predicted by analyzing mutations in DMD by using the reading frame rule. METHODS: Of 88 patients with mutations in DMD, which were detected using Multiplex Ligation-dependent Probe Amplification DMD test kit (MRC-Holland, The Netherlands), medical records of 5 patients with non-contiguous duplications were reviewed. These rare non-contiguous duplications in DMD were compared with those reported previously. RESULTS: We identified 3 novel non-contiguous duplications in DMD that included exons 2-7 and 45-51, exons 5-37 and 50-59, and exons 52-53 and 56-61. The 5 patients with these non-contiguous duplications showed the phenotypic features of DMD. Especially, duplication of exons 52-53 and 56-61 was observed in a family, i.e., 2 DMD-affected brothers and their carrier mother. CONCLUSIONS: Prediction of phenotypes associated with complex non-contiguous duplications by using the reading frame rule is difficult because the duplications affect the expression of DMD together. Because most patients with non-contiguous duplications showed the phenotypic features of DMD, the reading frame rule should be interpreted cautiously. This study provides important insights on the non-contiguous duplications in DMD for understanding genotype-phenotype correlations and for developing dystrophin for therapeutic purposes.
Subject(s)
Humans , Dystrophin , Exons , Genetic Association Studies , Medical Records , Mothers , Multiplex Polymerase Chain Reaction , Muscular Dystrophies , Muscular Dystrophy, Duchenne , Phenotype , Reading Frames , SiblingsABSTRACT
T-cell receptor gamma alternate reading frame protein (TARP) is expressed by human prostate epithelial, prostate cancer, and mammary cancer cells, but is not found in normal mammary tissue. To date, this protein has only been described in humans. Additionally, no animal model has been established to investigate the potential merits of TARP as tumor marker or a target for adoptive tumor immunotherapy. In this study conducted to characterize feline T-cell receptor gamma sequences, constructs very similar to human TARP transcripts were obtained by RACE from the spleen and prostate gland of cats. Transcription of TARP in normal, hyperplastic, and neoplastic feline mammary tissues was evaluated by conventional RT-PCR. In felines similarly to the situation reported in humans, a C-region encoding two open reading frames is spliced to a J-region gene. In contrast to humans, the feline J-region gene was found to be a pseudogene containing a deletion within its recombination signal sequence. Our findings demonstrated that the feline TARP ortholog is transcribed in the prostate gland and mammary tumors but not normal mammary tissues as is the case with human TARP.
Subject(s)
Animals , Cats , Humans , Racial Groups , Immunotherapy , Models, Animal , Open Reading Frames , Prostate , Prostatic Neoplasms , Protein Sorting Signals , Pseudogenes , Reading Frames , Receptors, Antigen, T-Cell , Recombination, Genetic , SpleenABSTRACT
La investigación explora las relaciones entre las características de las interacciones establecidas para propiciar la interpretación de un texto narrativo y las inferencias que los niños hacen sobre él. Ésta se enmarca en la psicología educativa, cognitiva y cultural. 4 grupos de preescolar participaron en el estudio con un total de 48 niños. El diseño fue descriptivo exploratorio. Se hizo un análisis cualitativo - análisis del discurso - y uno cuantitativo - análisis de redes sociales - para procesar los datos. Se encontró que los niños cuya maestra propiciaba más interacciones alrededor del texto buscando una comprensión como transacción texto -lector, lograron mayor elaboración inferencial y los niños cuyas docentes propusieron interacciones en las que planteaban discusiones sobre información explícita en el texto, realizaron pocas inferencias y de menor complejidad.
This research explores the relationship between the characteristics of interactions established to favor the narrative text interpretation and the inferences that children make on it. This is marked in the educative, cognitive and cultural psychologist. In this research participated four groups of kinder garden with a total of forty eight children. This was a descriptive and explorative design. Was realized a discursive analysis and a social nets analysis to process information. It was find that children which teacher favor more interactions and better interactions raised a textual analyses got a high inferencial elaboration, and children which teachers proposed low interaction raised discussions about explicit information in the text, realized a few inferences and with a low level of elaboration.
Subject(s)
Child Development , Child, Preschool , Reading Frames , Comprehension , Interpersonal Relations , Schools, Nursery , Faculty , Social Construction of Gender , Social Network AnalysisABSTRACT
Fast-sequencing throughput methods have increased the number of completely sequenced bacterial genomes to about 400 by December 2006, with the number increasing rapidly. These include several strains. In silico methods of comparative genomics are of use in categorizing and phylogenetically sorting these bacteria. Various word-based tools have been used for quantifying the similarities and differences between entire genomes. The simple di-nucleotide frequency comparison, codon specificity and k-mer repeat detection are among some of the well-known methods. In this paper, we show that the Mutual Information function, which is a measure of correlations and a concept from Information Theory, is very effective in determining the similarities and differences among genome sequences of various strains of bacteria such as the plant pathogen Xylella fastidiosa, marine Cyanobacteria Prochlorococcus marinus or animal and human pathogens such as species of Ehrlichia and Legionella. The short-range three-base periodicity, small sequence repeats and long-range correlations taken together constitute a genome signature that can be used as a technique for identifying new bacterial strains with the help of strains already catalogued in the database. There have been several applications of using the Mutual Information function as a measure of correlations in genomics but this is the first whole genome analysis done to detect strain similarities and differences.
Subject(s)
Base Composition , Base Sequence , Chromosomes, Bacterial/chemistry , Computational Biology/methods , DNA, Bacterial/analysis , Databases, Genetic , Enterobacteriaceae/chemistry , Genome, Bacterial , Genomics/methods , Gram-Negative Aerobic Rods and Cocci/chemistry , Gram-Negative Bacteria/chemistry , Gram-Positive Cocci/chemistry , Gram-Positive Endospore-Forming Rods/chemistry , Random Allocation , Reading Frames/genetics , Sequence Homology, Nucleic AcidABSTRACT
<p><b>UNLABELLED</b>From large-scale sequence of human fetal liver cDNA library, we have obtained a full-length cDNA from an EST after further sequencing. It has been demonstrated by the alignment comparison with data base available that it is a novel member of Ubc family and got the number from GeneBank: UBF-F1 AF 294842.</p><p><b>AIM AND METHODS</b>To demonstrate its authenticity, UBF was amplified from the total RNA of human fetal liver and HL-60 cell line using RT-PCR, and the PCR products were further sequenced and compared with the original UBF sequence. To evaluate the expression level and subcellular location of UBF in human multiple tissues, in situ hybridization was carried out on the frozen section of human fetal multiple tissues and HL-60 cell line with DIG-labeled UBF cDNA probes.</p><p><b>RESULTS</b>The experimental results of RT-PCR and sequencing showed that the sequence of RT-PCR products were the same as the original UBF. The experimental results of in situ hybridization showed that UBF was expressed widely by human multiple fetal tissues and the expression level were very high in HL-60 cells.</p><p><b>CONCLUSION</b>It is suggested that the special structure of UBF is authentic, and the expression profiling research of UBF shows that UBF is expressed widely by human multiple fetal tissues and the expression level is very high in HL-60 cells, implying that UBF plays the important function in the developing tissues and leukemia cells. It is also suggested that UBF may be functionally related with the nucleic-involving cellular activities based on the results of sub-cellular localizations.</p>
Subject(s)
Humans , Amino Acid Sequence , Cloning, Molecular , Gene Expression Profiling , HL-60 Cells , Molecular Sequence Data , Pol1 Transcription Initiation Complex Proteins , Genetics , Reading Frames , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Ubiquitin-Conjugating Enzymes , Classification , UbiquitinationABSTRACT
<p><b>OBJECTIVE</b>To clone, identify and phylogenetically characterize a clade B-Thai HIV isolate representing the most prevalent virus in Henan province.</p><p><b>METHODS</b>Peripheral blood mononuclear cells (PBMCs) from an HIV-1 infected patient in Henan Province were separated, and co-cultivated with phytohemagglutinin-stimulated healthy donor PBMCs. Proviral DNA was extracted from productively infected PBMCs. The full-length HIV-1 genome was amplified by using the LA Tag long template PCR system. Primers were positioned in conserved regions within the HIV-1 long terminal repeats. Purified PCR products were T-A ligated into a pWSK29-T vector(CNHN 24 clone). Three recombinant clones containing virtually full-length HIV-1 genome were identified by PCR. The full-length genome was sequenced by using the primer-walking approach. Nucleotide sequence similarities were calculated by the local-homology algorithm. Phylogenetic trees of gag, pol and env reading frames were constructed using the Phylip software.</p><p><b>RESULTS</b>HIV-1 C3V4 sequences indicate that the epidemic in this area was B-Thai subtype. V3 loop multiple amino acid sequence alignments showed amino acid alterations at nine positions. The 9,010 bp genomic sequence derived from isolate CNHN 24 contained all known structural and regulatory genes of an HIV-1 genome. No major deletions, insertions, or rearrangements were found. The highest homologies of the gag, pol, vpr, and vif reading frames to the corresponding clade B-Thai RL 42 sequences were 95.42%-97.08%. Phylogenetic trees showed the closest relationship of CNHN 24 and RL 42.</p><p><b>CONCLUSION</b>The cloning and characterization of a virtually full-length HIV-1 B-Thai subtype in central China was completed in our laboratory. The data should be helpful to future studies on the genetic diversity of HIV-1.</p>
Subject(s)
Female , Humans , Amino Acid Sequence , Base Sequence , Blood Donors , China , Cloning, Molecular , DNA, Viral , Genetics , Genome, Viral , HIV Infections , Virology , HIV-1 , Classification , Genetics , Leukocytes, Mononuclear , Virology , Phylogeny , Reading Frames , Sequence Analysis, DNA , Sequence HomologyABSTRACT
El Instituto de Maternidad Natalio Aramayo, centro de referencia en obstetricia de la ciudad de La Paz, ha implantado un sistema de informaciòn computarizado desde 1990. Esta comunicaciòn comparte con el lector el proceso de implantaciòn de este sistema: Este proceso surge como consecuencia de la identificaciòn previa de los problemas institucionales, entre cuyas alternativas de soluciòn se encontraba el sistema de infromaciòn, cuya implantaciòn persiguio: 1) Optimo llenado de la historia perinatal bàsica simplificada. 2) Establecer un flujo/ruta del documento. 3) Archivo de la historia clìnica. 4) Procesamiento oportuno de la informaciòn. La evaluaciòn del proceso verifica y discute el cumplimiento de los objetivos, proporciona informaciòn sobre los problemas encontrados y sus soluciones. Brinda ademàs un informe del estado actual del sistema de informaciòn, asi como los resultados de una evaluaciòn efectuada por alumnos del internado rotatorio. Finalmente se concluye que el sistema implantado proporciona informaciòn sobre la poblaciòn atendida la patologìa prevalente y otras, que facilitan la toma de decisiones y permite la evaluaciòn de las actividades. Constituye un instrumento valioso que sumando a otros, podria lograr la transformaciòn de la instituciòn en la que fue implantado.