Effect of Metformin on miR-146a Expression

Sjögren’s Syndrome (SjS) is an autoimmune disorder that affects secretory glands in the human body, restricting their function and causing extreme dryness in areas like the mouth and eyes. miR-146a is an anti-inflammatory microRNA that targets the NFκB activation pathway. Previous studies have shown that SjS patients have increased miR-146a expression, despite having high levels of inflammation. The objective of this study was to investigate whether metformin, a diabetes drug with a wide variety of effects and potential functions, reduces levels of miR-146a expression. Metformin is known to reduce inflammation by inhibiting the activation of NFκB. THP-1 human monocytes were treated with various concentrations of metformin ranging from 12.5uM to 200uM. The cells were treated for 24 hours before total RNA was isolated, and qRT-PCR was utilized to compare miR-146a expression in metformin-treated versus untreated cells. Our results showed a dose-dependent decrease of miR-146a expression in the presence of metformin. These results are reasonable since miR-146a expression is dependent on NFκB activation, and metformin is known to inhibit the activation of NFκB. Further studies will investigate metformin’s ability to suppress inflammation in varying conditions

A Netrin-3 Like Protein is Secreted from \u3ci\u3eTetrahymena thermophila\u3c/i\u3e

Netrin proteins are a family of laminin-related secreted proteins that provide signals for axonal growth and cell migration during vertebrate development. Netrin homologs are expressed throughout the animal kingdom; however, some animals do not express a homolog of any known netrin receptors. We have previously found that the ciliated protozoan, Tetrahymena thermophila, responds to netrin-1 peptide by showing avoidance behavior. In addition, Tetrahymena secrete a protein that is immunologically similar to netrin-1 as detected by ELISA. Since netrin-3, like netrin-1, is a guidance molecule for axons and overlaps signaling pathways with netrin-1 in vertebrates, we hypothesized that netrin-3 may also act as a chemorepellent in Tetrahymena. While behavioral assays did not confirm this hypothesis, growth assays indicate that netrin-3 peptide inhibits cell division in Tetrahymena. In addition, ELISA and Western blots indicate that a netrin-3 like protein of approximately 48 kDa is secreted from Tetrahymena. Immunolocalization of this protein within the cell shows that it appears in widely distributed throughout the cell, and co-localizes with the netrin-1 like protein. Using ER tracker™, we found that some of the netrin-3-like protein co-localizes with the endoplasmic reticulum, as might be expected for a secreted protein. Further experimentation is necessary to determine the mechanism by which netrin-3 peptide inhibits growth in Tetrahymena

Observational assessment and maternal reports of motivation in children and adolescents with Down Syndrome

Despite a lack of consistent empirical evidence, there has been an ongoing assumption that intellectual disability is associated with reduced levels of motivation. The participants in this study were 33 children with Down syndrome ages 10–15 years and 33 typically developing 3–8-year-old children. Motivation was measured through observational assessments of curiosity, preference for challenge, and persistence, as well as maternal reports. There were no significant group differences on motivation tasks, but mothers of children with Down syndrome rated their children significantly lower on motivation than did parents of typically developing children. There were some intriguing group differences in the pattern of correlations among observations and parent reports. The findings challenge long-held views that individuals with intellectual disability are invariably deficient in motivation

Infants\u27 Social-Constructive Interactions with Mothers and Fathers

Four parent-infant joint-action variables were derived by combining parents\u27 vocal or object-stimulation behaviors with infants\u27 vocal or object-directed behaviors observed in the home setting. Measures of simultaneous vocalization, joint-object play, parent-vocalize/infant-object play, and infant-vocalize/parent-object stimulation were constructed to represent social-construction experiences in which shared actions between infants and parents are thought to contribute to infants\u27 cognitive development. The analyses (based on 66 infants and their parents) focused on the normative changes and stability of individual differences of these measures from 6 to 12 months and their relations with 30-month cognitive-development status. The durations of all measures increased with age. All joint-action measures showed consistency across time and the 12-month mother-infant (but not father-infant) joint-action measures were strongly related with 30-month McCarthy scores

Sequential Analysis of Mastery Behavior in 6- and 12-Month-Old Infants

We examined the pattern and direction of behaviors that reflect infants\u27 underlying mastery motivation. The sequences of mastery behavior were analyzed in a sample of 67 infants when they were 6 and 12 months old. We computed (a) the frequencies of each of six categories of mastery behavior, transitional probabilities, and z scores for each possible behavior change between the categories and (b) the transitions from a mastery behavior to an instance of positive affect. The analyses revealed significant age changes in the frequency of each category; however, the significant transitional probabilities among the six categories displayed a similar organization at both ages. The transitions from a mastery behavior to an instance of positive affect suggest that it is persistent, goal-directed behaviors that contribute to an infant\u27s feeling of efficacy

Social Mastery Motivation in Down Syndrome and Non-Delayed Infants

Indices of social mastery motivation in Down syndrome (DS) and nondelayed infants, matched on Bayley mental scores, were observed during social tasks that encouraged socially motivated behaviors and object-play tasks that did not encourage these behaviors. During the object play, the DS infants\u27 object-directed behaviors were not appreciably lower than the nondelayed infants\u27, while their social behaviors were significantly lower. During social tasks, no significant difference was found. The nondelayed infants\u27 positive affect was related to social and cognitive competence, but for the DS infants, only to social competence. The findings suggest differences in behavioral integration between the two samples

The Organization of Exploratory Behavior in Down Syndrome and Non-delayed Infants.

The exploratory behaviors of a sample of 11 infants with Down syndrome and 11 nondelayed infants, matched on Bayley mental raw scores and gender, were analyzed. Transitional probabilities and z scores were computed for each possible behavior change as well as frequencies of each behavior. The analyses revealed significant differences in how the 2 samples distribute their exploratory activities. The significant transitional probabilities among the 6 behavioral states revealed a pattern of similarities and differences. In general, both groups of infants organized their exploratory activities in a similar manner. However, there were differences that appeared to depend on the level of exploratory sophistication. The results are discussed in the context of the similarities and differences between the samples

Relation Between Mastery Behavior in Infancy and Competence in Early Childhood

The failure of developmental tests in infancy to predict later competence may be because the tests ignore important dimensions of infant functioning. Yarrow and Pedersen (1976) have suggested that one such dimension could be mastery behavior, which involves persistence and investigation. Fifty-three infants were observed at 6 and 12 months during two 24-min play sessions. The Bayley Scales of Infant Development were given at 6 and 12 months, and the McCarthy Scales of Children\u27s Abilities at 30 months. Measures of competence in infancy (successful task completion during play and the Bayley scores) were not strongly correlated with the 30-month McCarthy Scales. In contrast, infant mastery behavior during play strongly predicted McCarthy scores: The time spent investigating toys at 6 months, and persistence in solving tasks at 12 months, were behaviors significantly positively correlated with the McCarthy Scales. Thus, infant behaviors that predict later competence do not remain static, but change with age. More importantly, infants\u27 mastery behavior appears to be a more effective predictor of later development than their competence with either toys or developmental tests