The Bipartite Structure of the tRNA m\u3csup\u3e1\u3c/sup\u3eA58 Methyltransferase from \u3cem\u3eS. cerevisiae\u3c/em\u3e is Conserved in Humans

Among all types of RNA, tRNA is unique given that it possesses the largest assortment and abundance of modified nucleosides. The methylation at N1 of adenosine 58 is a conserved modification, occurring in bacterial, archaeal, and eukaryotic tRNAs. In the yeast Saccharomyces cerevisiae, the tRNA 1-methyladenosine 58 (m1A58) methyltransferase (Mtase) is a two-subunit enzyme encoded by the essential genes TRM6 (GCD10) and TRM61 (GCD14). While the significance of many tRNA modifications is poorly understood, methylation of A58 is known to be critical for maintaining the stability of initiator tRNAMet in yeast. Furthermore, all retroviruses utilize m1A58-containing tRNAs to prime reverse transcription, and it has been shown that the presence of m1A58 in human tRNA3 Lys is needed for accurate termination of plus-strand strong-stop DNA synthesis during HIV-1 replication. In this study we have identified the human homologs of the yeast m1A Mtase through amino acid sequence identity and complementation of trm6 and trm61 mutant phenotypes. When coexpressed in yeast, human Trm6p and Trm61p restored the formation of m1A in tRNA, modifying both yeast initiator tRNAMet and human tRNA3 Lys. Stable hTrm6p/hTrm61p complexes purified from yeast maintained tRNA m1A Mtase activity in vitro. The human m1A Mtase complex also exhibited substrate specificity—modifying wild-type yeast tRNAi Met but not an A58U mutant. Therefore, the human tRNA m1A Mtase shares both functional and structural homology with the yeast tRNA m1A Mtase, possessing similar enzymatic activity as well as a conserved binary composition

Conserved Amino Acids in Each Subunit of the Heteroligomeric tRNA m\u3csup\u3e1\u3c/sup\u3eA58 Mtase from \u3cem\u3eSaccharomyces cerevisiae\u3c/em\u3e Contribute to tRNA Binding

In Saccharomyces cerevisiae, a two-subunit methyltransferase (Mtase) encoded by the essential genes TRM6 and TRM61 is responsible for the formation of 1-methyladenosine, a modified nucleoside found at position 58 in tRNA that is critical for the stability of . The crystal structure of the homotetrameric m1A58 tRNA Mtase from Mycobacterium tuberculosis, TrmI, has been solved and was used as a template to build a model of the yeast m1A58 tRNA Mtase heterotetramer. We altered amino acids in TRM6 and TRM61 that were predicted to be important for the stability of the heteroligomer based on this model. Yeast strains expressing trm6 and trm61 mutants exhibited growth phenotypes indicative of reduced m1A formation. In addition, recombinant mutant enzymes had reduced in vitro Mtase activity. We demonstrate that the mutations introduced do not prevent heteroligomer formation and do not disrupt binding of the cofactor S-adenosyl-l-methionine. Instead, amino acid substitutions in either Trm6p or Trm61p destroy the ability of the yeast m1A58 tRNA Mtase to bind , indicating that each subunit contributes to tRNA binding and suggesting a structural alteration of the substrate-binding pocket occurs when these mutations are present

Public School Choice and Desegregation in Arkansas

Public school choice is an umbrella term for policies that allow students to enroll in a public school other than their residentially-assigned school. Public school choice, also called openenrollment, is typically divided into two categories: intra-district choice, transfers to schools in the same district, and inter-district choice, transfers to schools in other districts

Immunometabolism in Caenorhabditis elegans

Here, we discuss 5 concepts that have emerged in studies of metabolic and immune interactions in C. elegans. The major emerging theme is that the immune response and the ability to survive pathogen infection is heavily influenced by pathogen-induced changes in host metabolism

Dynamic Patterns of Transcript Abundance of Transposable Element Families in Maize.

Transposable Elements (TEs) are mobile elements that contribute the majority of DNA sequences in the maize genome. Due to their repetitive nature, genomic studies of TEs are complicated by the difficulty of properly attributing multi-mapped short reads to specific genomic loci. Here, we utilize a method to attribute RNA-seq reads to TE families rather than particular loci in order to characterize transcript abundance for TE families in the maize genome. We applied this method to assess per-family expression of transposable elements in >800 published RNA-seq libraries representing a range of maize development, genotypes, and hybrids. While a relatively small proportion of TE families are transcribed, expression is highly dynamic with most families exhibiting tissue-specific expression. A large number of TE families were specifically detected in pollen and endosperm, consistent with reproductive dynamics that maintain silencing of TEs in the germ line. We find that B73 transcript abundance is a poor predictor of TE expression in other genotypes and that transcript levels can differ even for shared TEs. Finally, by assessing recombinant inbred line and hybrid transcriptomes, complex patterns of TE transcript abundance across genotypes emerged. Taken together, this study reveals a dynamic contribution of TEs to maize transcriptomes

Individual differences in susceptibility to false memories: The effect of memory specificity

Previous research has highlighted the wide individual variability in susceptibility to the false memories produced by the Deese/Roediger-McDermott (DRM) procedure [Deese, J. (1959). On the prediction of occurrence of particular verbal intrusions in immediate recall. Journal of Experimental Psychology, 58, 17–22; Roediger, H. L., III, & McDermott, K. B. (1995). Creating false memories: Remembering words not presented in lists. Journal of Experimental Psychology: Learning, Memory, & Cognition, 21, 803–814]. The current study investigated whether susceptibility to false memories is influenced by individual differences in the specificity of autobiographical memory retrieval. Memory specificity was measured using the Sentence Completion for Events from the Past Test (SCEPT) [Raes, F., Hermans, D., Williams, J. M. G., & Eelen, P. (2007). A sentence completion procedure as an alternative to the Autobiographical Memory Test for assessing overgeneral memory in non-clinical populations. Memory, 15, 495-507]. Memory specificity did not correlate with correct recognition, but a specific retrieval style was positively correlated with levels of false recognition. It is proposed that the contextual details that frequently accompany false memories of nonstudied lures are more accessible in individuals with specific retrieval styles

Entrepreneurship and mutuality: social capital in processes and practices.

Social capital, which offers the broader theoretical construct to which networks and networking relate, is now recognized as an important influence in entrepreneurship. Broadly understood as resources embedded in networks and accessed through social connections, research has mainly focused on measuring structural, relational and cognitive dimensions of the concept. While useful, these measurements tell us little about how social capital, as a relational artefact and connecting mechanism, actually works in practice. As a social phenomenon which exists between individuals and contextualized through social networks and groups, we draw upon established social theory to offer an enhanced practical understanding of social capital - what it does and how it operates. Drawing on the work of Pierre Bourdieu and Robert Putnam, we contribute to understanding entrepreneurship as a socially situated and influenced practice. From this perspective, our unit of analysis is the context within which entrepreneurs are embedded. We explored the situated narratives and practices of a group of 15 entrepreneurs from 'Inisgrianan', a small town in the northwest of Ireland. We adopted a qualitative approach, utilizing an interpretive naturalistic philosophy. Findings show how social capital can enable, and how the mutuality of shared interests allows, encourages and engages entrepreneurs in sharing entrepreneurial expertise

Molecular Mechanisms of Nonalcoholic Fatty Liver Disease: Potential Role for 12-Lipoxygenase

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of pathologies associated with fat accumulation in the liver. NAFLD is the most common cause of liver disease in the United States, affecting up to a third of the general population. It is commonly associated with features of metabolic syndrome, particularly insulin resistance. NAFLD shares the basic pathogenic mechanisms with obesity and insulin resistance, such as mitochondrial, oxidative and endoplasmic reticulum stress. Lipoxygenases catalyze the conversion of poly-unsaturated fatty acids in the plasma membrane—mainly arachidonic acid and linoleic acid—to produce oxidized pro-inflammatory lipid intermediates. 12-Lipoxygenase (12-LOX) has been studied extensively in setting of inflammation and insulin resistance. As insulin resistance is closely associated with development of NAFLD, the role of 12-LOX in pathogenesis of NAFLD has received increasing attention in recent years. In this review we discuss the role of 12-LOX in NAFLD pathogenesis and its potential role in emerging new therapeutics

Perceived impact of formulating, implementing and enacting national mental health policies recommendations in practice:An exploratory qualitative study within child and adolescent mental health services in Scotland

OBJECTIVE: To understand the process of formulating, implementing and enacting national recommendations into practice, by exploring the interactions between government policymakers and national and local organisations supporting and delivering policy implementation within a Child and Adolescent Mental Health Service (CAMHS) context in Scotland. METHODS: Data collection involved 16 semi-structured individual and four focus group interviews with a purposeful sample of policymakers, national health and social care stakeholders and local outpatient and inpatient CAMHS teams representing three NHS health boards in Scotland. RESULTS: Study participants highlighted the challenges of navigating through evolving and often conflicting policy agendas, seen to not acknowledging the current evidence base or experiential learning from services and prior evaluations. Accounts of transformation fatigue often emerged from increased expectations for staff to adopt new approaches to accommodate constantly changing recommendations. Participants also reported a lack of integration and implementation support from national health and social care organisations, leading to duplication of effort and gaps in provision or waste. Policy recommendations were perceived as sometimes vague, lacking clarity about how to deliver service transformation using a whole-system approach. The collective narratives reflected increased tension between the need for local autonomy to innovate and the limitations created vertically by the relative inflexibility of policy recommendations, and horizontally by the proliferation of national organisations delivering the same transformation aims using different approaches in a resource-constrained environment. CONCLUSION: The findings contribute to the wider literature by offering an exploration of importance of evaluation and evidence uptake in policy formulation; the roles and remits in supporting the implementation of policy recommendations; and how the dynamics of central control and local autonomy might impact on the local enactment of policy recommendations