The Myth of Multitasking and What It Means for Future Pharmacists.

Objective The primary purposes of this study were to determine the extent to which multitasking affects the speed and accuracy with which Doctor of Pharmacy students identify prescription errors and whether there is a relationship between students' self-perception of their multitasking ability and their actual ability.Methods One hundred twenty-one second-year pharmacy students enrolled in the required course Introduction to Dosage Forms spent one week in an experimental (multitasking) condition and one week in a control (undistracted) condition. Subjects were given 10 minutes to check 10 prescriptions and record any identified filling errors. A cellular phone was placed in each room. Subjects in the experimental (multitasking) condition answered a call from a researcher posing as a talkative customer during the prescription-checking task while subjects in the control condition were not interrupted by a cell phone call during the task. Subjects' completion times and accuracy were recorded.Results When subjects were multitasking, they took significantly longer to complete the prescription-checking task than when they were not multitasking. Furthermore, when subjects were multitasking, they scored significantly lower on the prescription-checking task than when they were not multitasking. Finally, students' self-perceptions of their multitasking abilities were not related to the speed with which they completed the prescription-checking task nor to their accuracy.Conclusion Multitasking negatively affects speed and accuracy of prescription verification in student pharmacists. Our procedure can be used as an in-class activity to demonstrate the limits of attention and to shape how future pharmacists practice.

RNA-cDNA hybrids mediate transposition via different mechanisms.

Retrotransposons can represent half of eukaryotic genomes. Retrotransposon dysregulation destabilizes genomes and has been linked to various human diseases. Emerging regulators of retromobility include RNA-DNA hybrid-containing structures known as R-loops. Accumulation of these structures at the transposons of yeast 1 (Ty1) elements has been shown to increase Ty1 retromobility through an unknown mechanism. Here, via a targeted genetic screen, we identified the rnh1Δ rad27Δ yeast mutant, which lacked both the Ty1 inhibitor Rad27 and the RNA-DNA hybrid suppressor Rnh1. The mutant exhibited elevated levels of Ty1 cDNA-associated RNA-DNA hybrids that promoted Ty1 mobility. Moreover, in this rnh1Δ rad27Δ mutant, but not in the double RNase H mutant rnh1Δ rnh201Δ, RNA-DNA hybrids preferentially existed as duplex nucleic acid structures and increased Ty1 mobility in a Rad52-dependent manner. The data indicate that in cells lacking RNA-DNA hybrid and Ty1 repressors, elevated levels of RNA-cDNA hybrids, which are associated with duplex nucleic acid structures, boost Ty1 mobility via a Rad52-dependent mechanism. In contrast, in cells lacking RNA-DNA hybrid repressors alone, elevated levels of RNA-cDNA hybrids, which are associated with triplex nucleic acid structures, boost Ty1 mobility via a Rad52-independent process. We propose that duplex and triplex RNA-DNA hybrids promote transposon mobility via Rad52-dependent or -independent mechanisms.

The effects of mood and retrieval cues on semantic memory and metacognition.

We investigated whether the previously established effect of mood on episodic memory generalizes to semantic memory and whether mood affects metacognitive judgments associated with the retrieval of semantic information. Sixty-eight participants were induced into a happy or sad mood by viewing and describing IAPS images. Following mood induction, participants saw a total of 200 general knowledge trivia items (50 open-ended and 50 multiple-choice after each of two mood inductions) and were asked to provide a metacognitive judgment about their knowledge for each item before providing a response. A sample trivia item is: Author - - To kill a mockingbird. Results indicate that mood affects the retrieval of semantic information, but only when the participant believes they possess the requested semantic information; furthermore, this effect depends upon the presence of retrieval cues. In addition, we found that mood does not affect the likelihood of different metacognitive judgments associated with the retrieval of semantic information, but that, in some cases, having retrieval cues increases accuracy of these metacognitive judgments. Our results suggest that semantic retrieval processes are minimally susceptible to the influence of affective state but does not preclude the possibility that affective state may influence encoding of semantic information.

Effects of retrieval practice and presentation modality on verbal learning: testing the limits of the testing effect.

The testing effect refers to improved memory after retrieval practice and has been researched primarily with visual stimuli. In two experiments, we investigated whether the testing effect can be replicated when the to-be-learned information is presented auditorily, or visually + auditorily. Participants learned Swahili-English word pairs in one of three presentation modalities - visual, auditory, or visual + auditory. This was manipulated between-participants in Experiment 1 and within-participants in Experiment2. All participants studied the word pairs during three study trials. Half of participants practiced recalling the English translations in response to the Swahili cue word twice before the final test whereas the other half simply studied the word pairs twice more. Results indicated an improvement in final test performance in the repeated test condition, but only in the visual presentation modality (Experiments 1 and 2) and in the visual + auditory presentation modality (Experiment 2). This suggests that the benefits of practiced retrieval may be limited to information presented in a visual modality.

Phase Separation as a Melting Pot for DNA Repeats.

Genome expression and stability are dependent on biological processes that control repetitive DNA sequences and nuclear compartmentalization. The phase separation of macromolecules has recently emerged as a major player in the control of biological pathways. Here, we summarize recent studies that collectively reveal intersections between phase separation, repetitive DNA elements, and nuclear compartments. These intersections modulate fundamental processes, including gene expression, DNA repair, and cellular lifespan, in the context of health and diseases such as cancer and neurodegeneration.

Conserved Pbp1/Ataxin-2 regulates retrotransposon activity and connects polyglutamine expansion-driven protein aggregation to lifespan-controlling rDNA repeats.

Ribosomal DNA (rDNA) repeat instability and protein aggregation are thought to be two major and independent drivers of cellular aging. Pbp1, the yeast ortholog of human ATXN2, maintains rDNA repeat stability and lifespan via suppression of RNA-DNA hybrids. ATXN2 polyglutamine expansion drives neurodegeneration causing spinocerebellar ataxia type 2 and promoting amyotrophic lateral sclerosis. Here, molecular characterization of Pbp1 revealed that its knockout or subjection to disease-modeling polyQ expansion represses Ty1 (Transposons of Yeast) retrotransposons by respectively promoting Trf4-depedendent RNA turnover and Ty1 Gag protein aggregation. This aggregation, but not its impact on retrotransposition, compromises rDNA repeat stability and shortens lifespan by hyper-activating Trf4-dependent turnover of intergenic ncRNA within the repeats. We uncover a function for the conserved Pbp1/ATXN2 proteins in the promotion of retrotransposition, create and describe powerful yeast genetic models of ATXN2-linked neurodegenerative diseases, and connect the major aging mechanisms of rDNA instability and protein aggregation.

Ataxin-2: From RNA Control to Human Health and Disease.

RNA-binding proteins play fundamental roles in the regulation of molecular processes critical to cellular and organismal homeostasis. Recent studies have identified the RNA-binding protein Ataxin-2 as a genetic determinant or risk factor for various diseases including spinocerebellar ataxia type II (SCA2) and amyotrophic lateral sclerosis (ALS), amongst others. Here, we first discuss the increasingly wide-ranging molecular functions of Ataxin-2, from the regulation of RNA stability and translation to the repression of deleterious accumulation of the RNA-DNA hybrid-harbouring R-loop structures. We also highlight the broader physiological roles of Ataxin-2 such as in the regulation of cellular metabolism and circadian rhythms. Finally, we discuss insight from clinically focused studies to shed light on the impact of molecular and physiological roles of Ataxin-2 in various human diseases. We anticipate that deciphering the fundamental functions of Ataxin-2 will uncover unique approaches to help cure or control debilitating and lethal human diseases.

Repetitive DNA loci and their modulation by the non-canonical nucleic acid structures R-loops and G-quadruplexes.

Cells have evolved intricate mechanisms to maintain genome stability despite allowing mutational changes to drive evolutionary adaptation. Repetitive DNA sequences, which represent the bulk of most genomes, are a major threat to genome stability often driving chromosome rearrangements and disease. The major source of repetitive DNA sequences and thus the most vulnerable constituents of the genome are the rDNA (rDNA) repeats, telomeres, and transposable elements. Maintaining the stability of these loci is critical to overall cellular fitness and lifespan. Therefore, cells have evolved mechanisms to regulate rDNA copy number, telomere length and transposon activity, as well as DNA repair at these loci. In addition, non-canonical structure-forming DNA motifs can also modulate the function of these repetitive DNA loci by impacting their transcription, replication, and stability. Here, we discuss key mechanisms that maintain rDNA repeats, telomeres, and transposons in yeast and human before highlighting emerging roles for non-canonical DNA structures at these repetitive loci.

Strains of Pathological Protein Aggregates in Neurodegenerative Diseases.

The presence of protein aggregates in the brain is a hallmark of neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). Considerable evidence has revealed that the pathological protein aggregates in many neurodegenerative diseases are able to self-propagate, which may enable pathology to spread from cell-to-cell within the brain. This property is reminiscent of what occurs in prion diseases such as Creutzfeldt-Jakob disease. A widely recognized feature of prion disorders is the existence of distinct strains of prions, which are thought to represent unique protein aggregate structures. A number of recent studies have pointed to the existence of strains of protein aggregates in other, more common neurodegenerative illnesses such as AD, PD, and related disorders. In this review, we outline the pathobiology of prion strains and discuss how the concept of protein aggregate strains may help to explain the heterogeneity inherent to many human neurodegenerative disorders.

Identifying the science and technology dimensions of emerging public policy issues through horizon scanning.

Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security.

Percutaneous balloon dilation of Carpentier-Edwards porcine-valved right ventricle-to-pulmonary artery conduits.

Right ventricular outflow tract (RVOT) conduit stenosis remains a significant problem for patients with right ventricle-to-pulmonary artery (RV-to-PA) conduits placed as palliation for congenital heart disease. Previous reports on balloon dilation of RVOT conduits all describe small series with varying levels of success during limited follow-up evaluation. This study reviewed all patients with RV-to-PA conduits who underwent percutaneous balloon dilation for conduit stenosis at the authors' institution from 2000 to 2011. Patients with Carpentier-Edwards (CE) model 4300 porcine-valved conduits (Edwards Lifesciences Corp., Irvine, CA) (n = 19) were compared with patients who had all other types of conduits (n = 19). Successful balloon angioplasty was defined as a 20 % decrease in the RV-to-PA gradient, a 20 % decrease in the ratio of the RV systolic-to-aortic systolic pressure, or both. Balloon dilation was successful for 57.9 % of the patients with CE conduits and for 31.6 % of patients with other types of conduits (p = 0.10, Chi square test). Logistic regression analysis showed that balloon dilation was significantly more likely to be successful with CE valves than with other types (odds ratio [OR], 6.59; 95 % confidence interval [CI], 1.22-35.49). In a continuous series of patients with stenotic RV-to-PA conduits, the CE porcine-valved conduit was more amenable to percutaneous balloon dilation than other types of RV-to-PA conduits at the midterm follow-up evaluation. This has important ramifications in terms of valve selection for patients with congenital heart disease who will require surgical reintervention for RVOT stenosis.