Misfolded but not Malicious: Prion Proteins in Budding Yeast

Prion proteins, although frequently associated with neurodegenerative diseases, are not universally harmful to cells. Instead, prions may serve as a beneficial epigenetic mechanism, allowing cells to alter their phenotype to adapt to adverse environmental conditions. Prions form when a protein adopts alternate and stable folding conformation. The Garcia Lab aims to identify beneficial prions using the budding yeast, Saccharomyces cerevisiae. We are particularly interested in prion conformations of RNA modifying enzymes (RMEs), because these proteins can affect the expression of many genes simultaneously. After screening hundreds of yeast strains, the Garcia Lab identified six strains of yeast – associated with potentially alternate conformations of the RMEs Abd1, Cet1, Ppm2, Pus4, Pus6 and Trm5 – that exhibited resistance to harmful chemicals. Extensive tests are needed to confirm that their resistance to stress is caused by a prion-based conformation of the RNA modifying enzymes. Here, experiments describing the meiotic inheritance, protein dependance, and cytoplasmic inheritance of these resistance phenotypes are presented. The initial results are key to attributing the previously identified growth states to a prion conformation of each of the six RNA modifying enzymes. The Garcia lab will continue to investigate these putative prions in future experiments to determine the mechanism for resistance. This research represents an important contribution to our understanding of prions as a protein-based epigenetic mechanism and their effects on key cell processes

The role of collaboration in the cognitive development of young children: a systematic review.

BACKGROUND: Collaboration is a key facilitator of cognitive development in early childhood; this review evaluates which factors mediate the impact of collaborative interactions on cognitive development in children aged 4-7 years. METHODS: A systematic search strategy identified relevant studies (n = 21), which assessed the role of ability on the relationship between collaboration and cognitive development. Other factors that interact with ability were also assessed: gender, sociability/friendship, discussion, age, feedback and structure. RESULTS: Immediate benefits of collaboration on cognitive development are highlighted for same-age peers. Collaborative interactions are beneficial for tasks measuring visual perception, problem-solving and rule-based thinking, but not for word-reading and spatial perspective-taking. Collaboration is particularly beneficial for lower-ability children when there is an ability asymmetry. High-ability children either regressed or did not benefit when paired with lower-ability participants. CONCLUSIONS: Overall, the studies included within this review indicate that brief one-off interactions can have a significant, positive effect on short-term cognitive development in children of infant school age. The longer-term advantages of collaboration are still unclear. Implications for practice and future research are discussed

Psychopharmacological and Other Treatments in Preschool Children with Attention-Deficit/Hyperactivity Disorder: Current Evidence and Practice

Objective: This article reviews rational approaches to treating attention-deficit/hyperactivity disorder (ADHD) in preschool children, including pharmacological and nonpharmacological treatments. Implications for clinical practice are discussed. Data Sources: We searched MEDLINE, PsychINFO, Cumulative Index to Nursing & Allied Health, Educational Resources Information Center, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects for relevant literature published in English from 1967 to 2007 on preschool ADHD. We also reviewed the references cited in identified reports. Study Selection: Studies were reviewed if the sample included at least some children younger than 6 years of age or attending kindergarten, the study participants had a diagnosis of ADHD or equivalent symptoms, received intervention aimed at ADHD symptoms, and included a relevant outcome measure. Data Extraction: Studies were reviewed for type of intervention and outcome relevant to ADHD and were rated for the level of evidence for adequacy of the data to inform clinical practice. Conclusions: The current level of evidence for adequacy of empirical data to inform clinical practice for shortterm treatment of ADHD in preschool children is Level A for methylphenidate and Level B for parent behavior training, child training, and additive-free elimination diet

Association between theory of mind and mental state talk in preschoolers and later social competence and behaviour

This study had 2 primary aims: (a) to investigate the concurrent links between preschool‐aged children's theory of mind (ToM) and mental state talk at 55 months and (b) to examine the longitudinal associations between preschool‐aged children's social understanding, as indicated by their ToM, and mental references, and their later social competence and behaviour at 69 months. Participants included 73 children and their mothers. ToM was assessed using a battery that consisted of 6 standardized tasks, and social competence and behaviour were assessed via teacher ratings. We observed an association between children's ToM and their mental state talk, specifically regarding cognition references during interactions with their mothers. Moreover, both children's ToM and mental references were longitudinally related to social competence and behaviour but only in girls. Our results support that ToM, which was assessed using false belief tasks, and the child's tendencies to refer to mental states during everyday interactions are 2 important related markers of children's social understanding and that both are linked to children's social competence and behaviour. The importance of considering gender‐specific effects when investigating children's social cognition is also highlighted

Die unbewältigte Vergangenheit: the Third Generation and the Holocaust in Recent Literature and Film

Processing the Holocaust and its disruption to society has emerged as a significant preoccupation, both privately and publicly, since the war ended almost seventy years ago. By taking up the topic, contemporary artists, often called the third generation, die Enkel or die Dritten in German, argue that grappling with the past is a process that cannot yet be laid to rest. The cultural production of some of these artists is the focus of this study. Some, like German literary scholar Ernestine Schlant, have argued that past efforts to process history have been lacking. Her review of West German, post-war literature, The Language of Silence, is surveyed for the purpose of understanding how previous generations tackled the topic and how success in confronting the issues could be measured. Four artists represent their views on the burden of history in works produced in the first decade of the new century. In Schweigen die Täter, reden die Enkel, Claudia Brunner describes her efforts to recognize and deal with the feelings of Phantomschmerzen as a result of being a descendent of a Nazi perpetrator. Himmelskörper, by Tanja Dückers, portrays a new mother trying to discover the secrets her grandmother harbors; Uwe von Seltmann wrestles with the legacy of unpunished crimes in Karlebachs Vermächtnis; and, denial takes center stage as Jens Schanze documents his family\u27s attempts to end the silence about a Nazi grandfather in the film Winterkinder. Lest it be thought contemporary artists saw no importance in the legacy of the Holocaust or were not inclined to tackle political issues, this study contends that modern artists are not only capable of confronting the past, but that they find the confrontation still necessary. Given their temporal distance to the era, they have an advantage over previous generations to approach the issues with more objectivity and composure. They do this work in service to others who seek to understand the pain and guilt they feel; to those who sense secrets in their family\u27s history that remain buried and harmful; to those who were wronged; to those who suffer from long-suppressed conflict; and, to those who care deeply, also from afar, that German society successfully digest, but not forget, the history

The role of therapist communication style in parent-child interaction therapy.

Research has found a relationship between treatment success and parental compliance with treatment programs. The current study explored how therapist characteristics impact on parental compliance with a behavioral parent-training program (Parent-Child Interaction Therapy). Also, differences in maternal satisfaction with the treatment program and therapist were explored. The participants were 45 mothers with children between the ages of 24 months and 83 months. Each mother was taught effective parenting strategies using one of three therapist communication styles: (a) positive therapist, (b) neutral therapist, and (c) negative therapist. Although all groups demonstrated an increase in their skill level from pretreatment to posttreatment, mothers in the negative therapist group used the target positive skills at a significantly higher rate at posttreatment than the other groups. No differences were found on maternal satisfaction. Results are discussed with regard to the importance of considering therapist variables when providing parent training

Hunting for Prions: Propagating Putative Prion States in Budding Yeast

Prions have been closely associated with fatal neurodegenerative diseases. Recent evidence, however, suggests that prions also represent an additional class of epigenetic mechanism that is biologically beneficial. From an evolutionary standpoint, the ability to change phenotypes without requiring changes to the genome, as prions do, would be hugely beneficial in fluctuating environments. Through overexpressing proteins and introducing environmental stressors, two techniques known to increase de novo prion formation, we performed a large-scale screen of many RNA-modifying enzymes in budding yeast to test if they harbor beneficial prionogenic behavior. From this screen, six induced prion-like states were found to be mitotically stable and infectious. We show that many of these putative prions are dominant and are dependent on chaperone proteins, which is consistent with a prion-based epigenetic mechanism. Prion-based inheritance is expanding on the central dogma of biology, contributing to the belief that prions work as an epigenetic mechanism for passing on heritable traits