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The pre-mRNA retention and splicing complex controls tRNA maturation by promoting TAN1 expression

The conserved pre-mRNA retention and splicing (RES) complex, which in yeast consists of Bud13p, Snu17p and Pml1p, is thought to promote nuclear retention of unspliced pre-mRNAs and enhance splicing of a subset of transcripts. Here, we find that the absence of Bud13p or Snu17p causes greatly reduced levels of the modified nucleoside N(4)-acetylcytidine (ac(4)C) in tRNA and that a lack of Pml1p redu

Eukaryotic wobble uridine modifications promote a functionally redundant decoding system

The translational decoding properties of tRNAs are modulated by naturally occurring modifications of their nucleosides. Uridines located at the wobble position (nucleoside 34 [U(34)]) in eukaryotic cytoplasmic tRNAs often harbor a 5-methoxycarbonylmethyl (mcm(5)) or a 5-carbamoylmethyl (ncm(5)) side chain and sometimes an additional 2-thio (s(2)) or 2'-O-methyl group. Although a variety of models

Association of yeast Upf1p with direct substrates of the NMD pathway

Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that detects and degrades transcripts containing premature translation termination codons. Gene expression profiling experiments have shown that inactivation of the NMD pathway leads to the accumulation of both aberrant, nonsense-containing mRNAs, and many apparently wild-type transcripts. Such increases in transcript steady-state leve

Elevated levels of two tRNA species bypass the requirement for elongator complex in transcription and exocytosis

The Saccharomyces cerevisiae Elongator complex consisting of the six Elp1-Elp6 proteins has been proposed to participate in three distinct cellular processes: transcriptional elongation, polarized exocytosis, and formation of modified wobble uridines in tRNA. Therefore it was important to clarify whether Elongator has three distinct functions or whether it regulates one key process that leads to m

The Kluyveromyces lactis gamma-toxin targets tRNA anticodons

Kluyveromyces lactis killer strains secrete a heterotrimeric toxin (zymocin), which causes an irreversible growth arrest of sensitive yeast cells. Despite many efforts, the target(s) of the cytotoxic gamma-subunit of zymocin has remained elusive. Here we show that three tRNA species tRNA(Glu)(mcm(5)s(2)UUC), tRNA(Lys)(mcm(5)s(2)UUU), and tRNA(Gln)(mcm(5)s(2)UUG) are the targets of gamma-toxin. The

An early step in wobble uridine tRNA modification requires the Elongator complex

Elongator has been reported to be a histone acetyltransferase complex involved in elongation of RNA polymerase II transcription. In Saccharomyces cerevisiae, mutations in any of the six Elongator protein subunit (ELP1-ELP6) genes or the three killer toxin insensitivity (KTI11-KTI13) genes cause similar pleiotropic phenotypes. By analyzing modified nucleosides in individual tRNA species, we show th

The Saccharomyces cerevisiae TAN1 gene is required for N4-acetylcytidine formation in tRNA

The biogenesis of transfer RNA is a process that requires many different factors. In this study, we describe a genetic screen aimed to identify gene products participating in this process. By screening for mutations lethal in combination with a sup61-T47:2C allele, coding for a mutant form of, the nonessential TAN1 gene was identified. We show that the TAN1 gene product is required for formation o

Dual function of the tRNA(m(5)U54)methyltransferase in tRNA maturation

A 5-methyluridine (m(5)U) residue at position 54 is a conserved feature of bacterial and eukaryotic tRNAs. The methylation of U54 is catalyzed by the tRNA(m5U54)methyltransferase, which in Saccharomyces cerevisiae is encoded by the nonessential TRM2 gene. In this study, we identified four different strains with mutant forms of tRNA(Ser)CGA. The absence of the TRM2 gene in these strains decreased t

Identification of the TRM2 gene encoding the tRNA(m5U54)methyltransferase of Saccharomyces cerevisiae

The presence of 5-methyluridine (m5U) at position 54 is a ubiquitous feature of most bacterial and eukaryotic elongator tRNAs. In this study, we have identified and characterized the TRM2 gene that encodes the tRNA(m5U54)methyltransferase, responsible for the formation of this modified nucleoside in Saccharomyces cerevisiae. Transfer RNA isolated from TRM2-disrupted yeast strains does not contain

The Future of Fighter Pilot Training? Live Virtual Constructive in Large Force Exercises : Perceived and Expected Training Value

Objective: This study investigates whether and how perceived training value varies among fighter pilots participating in a large force exercise (LFE), and whether they expect Live Virtual Constructive (LVC) training to enhance training value of future LFEs. Background: LVC technology is maturing but its expected training value is under-investigated, especially regarding future LVC in LFEs. Method:

Exploring unmanned systems with virtual prototypes in augmented reality video

The potential of unmanned systems is vast, but pre-procurement evaluation is challenging. This study explores potential uses of and interaction with unmanned ground vehicles (UGVs) for dismounted infantry. A remote user study with Swedish Armed Forces personnel is described. Many factors influencing future use and interaction were found. Moreover, this study shows the potential of the innovative m

A live mindset in Live Virtual Constructive simulations : a spin-up for future LVC air combat training

Combining Live, Virtual, and Constructive (LVC) aircraft in the same training scenario holds promise for developing and enhancing fighter pilot training. The simulator study reported here builds on joint pilot-researcher co-design work of beyond visual range LVC training (LVC-T) scenarios to provide training value to pilots in both Live and Virtual aircraft. One fourship of pilots simulated Live e

A method to identify investigative blind spots (MIBS) : Addressing blunt-end factors of ultra-safe organizations’ investigation-work-as-done

Ultra-safe organizations, such as Air Navigation Service Providers (ANSPs), have extensive safety management organizations and generally excellent safety records with very few serious incidents and accidents. This development has been supported by increasingly advanced and effective methods. However, recent research has uncovered how the application of even advanced incident investigation methods

Air Transport System Agility : The Agile Response Capability (ARC) Methodology for Crisis Preparedness

Aviation is a highly inter-connected system. This means that a problem in one area may cause effects in other countries or parts of the Air Transport System (ATS). Examples range from local air traffic disruptions to the 2010 volcanic ash crisis. Agility, like resilience, refers to the ability to cope with dynamics and complexity in a flexible manner, by adjusting and adapting performance and the

LVC Allocator : Aligning training value with scenario design for envisioned LVC training of fast-jet pilots

Live virtual constructive (LVC) flight simulations mix pilots flying actual aircraft, pilots flying in simulators, and computer-generated forces, in joint scenarios. Training resources invested in LVC scenarios must give a high return, and therefore pilots in both live aircraft and simulators need to experience training value for the extensive resources invested in both, an aspect not emphasized i

Exploring resilience at interconnected system levels in air traffic management

This chapter raises issues and ideas for exploring resilience, stemming from various research disciplines, projected on the domain of air traffic management and aviation at interconnected system levels. Attempts are made to connect micro, meso, and macro levels in the aviation sector identifying corresponding research challenges. Examples of this ongoing research are given on how theory has alread

Using requirements engineering in the development of resilience guidelines for critical infrastructure

The purpose of this paper is to show how requirements engineering techniques can be used to structure the development of non-technical aspects of socio-technical systems, such as guidelines. An adapted requirements engineering approach was chosen to elicit requirements for resilience guidelines within an EU Horizon 2020 multi-national project aimed at developing resilience guidelines for crisis ma

Workarounds and trade-offs in information security-An exploratory study

Purpose-The purpose of this paper is to investigate relationships between workarounds (solutions to handling trade-offs between competing or misaligned goals and gaps in policies and procedures), perceived trade-offs, information security (IS) policy compliance, IS expertise/knowledge and IS demands. Design/methodology/approach-The research purpose is addressed using survey data from a nationwide

Sensemaking following surprise in the cockpit—a re-framing problem

Re-framing is the process by which a person “fills the gap” between what is expected and what has been observed, that is, to try and make sense of what is going on following a surprise. It is an active and adaptive process guided by expectations, which are based on knowledge and experience. In this article, surprise situations in cockpit operations are examined by investigating the re-framing proc

Towards understanding work-as-done in air traffic management safety assessment and design

This paper describes the approach taken and the results to develop guidance, to include Resilience Engineering principles in methodology for safety assessment of functional changes, in Air Traffic Management (ATM). It summarizes the process of deriving resilience principles for ATM, originating from Resilience Engineering concepts and transposed into ATM operations. These principles are the founda