ABSTRACT
AIMS: The aim of this study was to investigate a miRNA expression profile in type 1 diabetes mellitus (T1DM) patients with DKD (cases) or without this complication (controls). METHODS: Expression of 48 miRNAs was screened in plasma of 58 T1DM patients (23 controls, 18 with moderate DKD, and 17 with severe DKD) using TaqMan Low Density Array cards (Thermo Fisher Scientific). Then, five of the dysregulated miRNAs were selected for validation in an independent sample of 10 T1DM controls and 19 patients with DKD (10 with moderate DKD and 9 with severe DKD), using RT-qPCR. Bioinformatic analyses were performed to explore the putative target genes and biological pathways regulated by the validated miRNAs. RESULTS: Among the 48 miRNAs investigated in the screening analysis, 9 miRNAs were differentially expressed between DKD cases and T1DM controls. Among them, the five most dysregulated miRNAs were chosen for validation in an independent sample. In the validation sample, miR-21-3p and miR-378-3p were confirmed to be upregulated in patients with severe DKD, while miR-16-5p and miR-29a-3p were downregulated in this group compared to T1DM controls and patients with moderate DKD. MiR-503-3p expression was not validated. Bioinformatic analyses indicate that the four validated miRNAs regulate genes from PI3K/Akt, fluid shear stress and atherosclerosis, AGE-RAGE, TGF-ß1, and relaxin signaling pathways. CONCLUSIONS: Our study found four miRNAs differentially expressed in patients with severe DKD, providing significant information about the biological pathways in which they are involved.
Subject(s)
Diabetes Mellitus, Type 1/blood , Diabetic Nephropathies/blood , MicroRNAs/blood , Adolescent , Adult , Case-Control Studies , Computational Biology/methods , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/genetics , Diabetic Nephropathies/diagnosis , Diabetic Nephropathies/genetics , Female , Gene Expression Profiling/methods , Humans , Male , MicroRNAs/genetics , Microarray Analysis , Real-Time Polymerase Chain Reaction , Signal Transduction/genetics , Young AdultABSTRACT
Choices based on exclusion have been investigated in different species because of its emergent nature, leading to evidence of rudimentary symbolic behavior in non-verbal organisms. Simple discrimination procedures provide a simple method to investigate exclusion performance, in which each trial consists of the simultaneous presentation of two stimuli, one with a positive function (S+) and one with a negative function (S-). In exclusion probe trials, an undefined stimulus (UnS) is presented with a familiar S-, and choices based on exclusion may lead to choosing the UnS, excluding the previously known S-. Novelty control trials (S+/UnS) are also conducted to assess the possible preference for the UnS. In this case, if performance is not controlled by novelty, then the subjects must choose the S+ and not the UnS. The present study investigated exclusion performance in visual simple simultaneous discrimination tasks in eight dogs. The results indicated that seven of eight dogs showed evidence of exclusion performance (p < .05). These findings corroborate the literature that shows that dogs are capable of responding by exclusion, suggesting that potentially symbolic behavior may rely on basic behavioral learning and conditioning principles.(AU)
Subject(s)
Animals , Dogs , Reinforcement, Psychology , Discrimination LearningABSTRACT
Choices based on exclusion have been investigated in different species because of its emergent nature, leading to evidence of rudimentary symbolic behavior in non-verbal organisms. Simple discrimination procedures provide a simple method to investigate exclusion performance, in which each trial consists of the simultaneous presentation of two stimuli, one with a positive function (S+) and one with a negative function (S-). In exclusion probe trials, an undefined stimulus (UnS) is presented with a familiar S-, and choices based on exclusion may lead to choosing the UnS, excluding the previously known S-. Novelty control trials (S+/UnS) are also conducted to assess the possible preference for the UnS. In this case, if performance is not controlled by novelty, then the subjects must choose the S+ and not the UnS. The present study investigated exclusion performance in visual simple simultaneous discrimination tasks in eight dogs. The results indicated that seven of eight dogs showed evidence of exclusion performance (p < .05). These findings corroborate the literature that shows that dogs are capable of responding by exclusion, suggesting that potentially symbolic behavior may rely on basic behavioral learning and conditioning principles...
Subject(s)
Animals , Dogs , Discrimination Learning , Reinforcement, PsychologyABSTRACT
O responder por exclusão, que se supõe ser um dos mecanismos pelos quais crianças aprendem a relacionar palavras novas a objetos ou eventos, tem sido amplamente replicado em situação de laboratório. O presente estudo, conduzido com seis crianças, teve por objetivo investigar o responder por exclusão em um contexto de brincadeira, com estímulos manipuláveis, e verificar se este contexto favorece a aprendizagem da relação nome - objeto, após uma única tentativa de exclusão. Em cada tentativa o experimentador falava o nome de um brinquedo conhecido e a tarefa da criança era pegá-lo e jogá-lo dentro de uma caixa grande, disposta à frente da criança. Em meio a essas tentativas, eram introduzidas três sondas de exclusão (o nome falado era novo e havia um brinquedo novo exposto no ambiente); três outras sondas verificavam se a relação entre o nome e o brinquedo havia sido aprendida. Todas as crianças responderam por exclusão, mas somente uma mostrou aprendizagem após uma única tentativa.
Laboratory studies have repeatedly replicated the phenomenon of exclusion responding, which has been assumed as one of the mechanisms by which children learn to relate novel words to objects or events. The present study, conducted with six children, aimed to investigate exclusion responding in a play setting, with stimuli that could be manipulated, and to verify whether the play setting would favor learning of the relationships between names and objects after a single exclusion trial. In several trials the experimenter spoke the name of a familiar toy and the child's task was to pick this toy up and throw it into a box, placed in front of the child. Three exclusion probes were interspersed among these trials (the spoken name was novel and there was a novel toy available); three other probes verified whether the relationships between the novel name and the toy had been learned. All children responded by exclusion but only one of them demonstrated learning the relationships in a single trial.
Subject(s)
Humans , Male , Female , Child, Preschool , Choice Behavior , Learning , Play and PlaythingsABSTRACT
O responder por 'exclusão', que se supõe ser um dos mecanismos pelos quais crianças aprendem a relacionar palavras novas a objetos ou eventos, tem sido amplamente replicado em situação de laboratório. O presente estudo, conduzido com seis crianças, teve por objetivo investigar o responder por exclusão em um contexto de brincadeira, com estímulos manipuláveis, e verificar se este contexto favorece a aprendizagem da relação nome - objeto, após uma única tentativa de exclusão. Em cada tentativa o experimentador falava o nome de um brinquedo conhecido e a tarefa da criança era pegá-lo e jogá-lo dentro de uma caixa grande, disposta à frente da criança. Em meio a essas tentativas, eram introduzidas três sondas de exclusão (o nome falado era novo e havia um brinquedo novo exposto no ambiente); três outras sondas verificavam se a relação entre o nome e o brinquedo havia sido aprendida. Todas as crianças responderam por exclusão, mas somente uma mostrou aprendizagem após uma única tentativa.(AU)
Laboratory studies have repeatedly replicated the phenomenon of exclusion responding, which has been assumed as one of the mechanisms by which children learn to relate novel words to objects or events. The present study, conducted with six children, aimed to investigate exclusion responding in a play setting, with stimuli that could be manipulated, and to verify whether the play setting would favor learning of the relationships between names and objects after a single exclusion trial. In several trials the experimenter spoke the name of a familiar toy and the child's task was to pick this toy up and throw it into a box, placed in front of the child. Three exclusion probes were interspersed among these trials (the spoken name was novel and there was a novel toy available); three other probes verified whether the relationships between the novel name and the toy had been learned. All children responded by exclusion but only one of them demonstrated learning the relationships in a single trial.(AU)