Pseudogene rescue: an adaptive mechanism of codon reassignment

Alterations to the genetic code – codon reassignments – have occurred many times in life’s history, despite the fact that genomes are coadapted to their genetic codes and therefore alterations are likely to be maladaptive. A potential mechanism for adaptive codon reassignment, which could trigger either a temporary period of codon ambiguity or a permanent genetic code change, is the reactivation of a pseudogene by a nonsense suppressor mutant transfer RNA. I examine the population genetics of each stage of this process and find that pseudogene rescue is plausible and also readily explains some features of extant variability in genetic codes.

Optimising memory usage in n-tuple neural networks

The use of n-tuple or weightless neural networks as pattern recognition devices is well known (Aleksander and Stonham, 1979). They have some significant advantages over the more common and biologically plausible networks, such as multi-layer perceptrons; for example, n-tuple networks have been used for a variety of tasks, the most popular being real-time pattern recognition, and they can be implemented easily in hardware as they use standard random access memories. In operation, a series of images of an object are shown to the network, each being processed suitably and effectively stored in a memory called a discriminator. Then, when another image is shown to the system, it is processed in a similar manner and the system reports whether it recognises the image; is the image sufficiently similar to one already taught? If the system is to be able to recognise and discriminate between m-objects, then it must contain m-discriminators. This can require a great deal of memory. This paper describes various ways in which memory requirements can be reduced, including a novel method for multiple discriminator n-tuple networks used for pattern recognition. By using this method, the memory normally required to handle m-objects can be used to recognise and discriminate between 2^m — 2 objects.

Stops making sense: translational trade-offs and stop codon reassignment

Background Efficient gene expression involves a trade-off between (i) premature termination of protein synthesis; and (ii) readthrough, where the ribosome fails to dissociate at the terminal stop. Sense codons that are similar in sequence to stop codons are more susceptible to nonsense mutation, and are also likely to be more susceptible to transcriptional or translational errors causing premature termination. We therefore expect this trade-off to be influenced by the number of stop codons in the genetic code. Although genetic codes are highly constrained, stop codon number appears to be their most volatile feature. Results In the human genome, codons readily mutable to stops are underrepresented in coding sequences. We construct a simple mathematical model based on the relative likelihoods of premature termination and readthrough. When readthrough occurs, the resultant protein has a tail of amino acid residues incorrectly added to the C-terminus. Our results depend strongly on the number of stop codons in the genetic code. When the code has more stop codons, premature termination is relatively more likely, particularly for longer genes. When the code has fewer stop codons, the length of the tail added by readthrough will, on average, be longer, and thus more deleterious. Comparative analysis of taxa with a range of stop codon numbers suggests that genomes whose code includes more stop codons have shorter coding sequences. Conclusions We suggest that the differing trade-offs presented by alternative genetic codes may result in differences in genome structure. More speculatively, multiple stop codons may mitigate readthrough, counteracting the disadvantage of a higher rate of nonsense mutation. This could help explain the puzzling overrepresentation of stop codons in the canonical genetic code and most variants.

Extending feature usage: a study of the post-adoption of electronic medical records

Technology Acceptance Model (TAM) posits that Perceived Ease of Use (PEOU) and Perceived Usefulness (PU) influence the ‘intention to use’. The Post-Acceptance Model (PAM) posits that continued use is influenced by prior experience. In order to study the factors that influence how professionals use complex systems, we create a tentative research model that builds on PAM and TAM. Specifically we include PEOU and the construct ‘Professional Association Guidance’. We postulate that feature usage is enhanced when professional associations influence PU by highlighting additional benefits. We explore the theory in the context of post-adoption use of Electronic Medical Records (EMRs) by primary care physicians in Ontario. The methodology can be extended to other professional environments and we suggest directions for future research.

Measuring student perception and actual usage of online learning management system

Online learning management systems are in use to facilitate the face to face learning process in many universities. There are many variables that shape and influence a student’s perception of an online learning management system. This study investigates whether there is a relationship between the perception of a student regarding the learning management system and their actual usage of such system. It is believed to help better understand the student usage of online learning management system. An online questionnaire was published on a course management system for a selected subject and the student participation was voluntary. Results indicate that no significant relationship between the perception students had about the learning management system and the actual use of the system. Interestingly, a significant relationship was found between having internet access away from university and the student perception about the system. Students who had internet access away from university had better perception about the learning management system even though there was no significant difference in the level of online learning management system usage between the groups.

Acceptable use policy and employee computer usage: case of Sri Lankan software development industry

Organizations introduce acceptable use policies to deter employee computer misuse. Despite the controlling, monitoring and other forms of interventions employed, some employees misuse the organizational computers to carry out their personal work such as sending emails, surfing internet, chatting, playing games etc. These activities not only waste productive time of employees but also bring a risk to the organization. A questionnaire was administrated to a random sample of employees selected from large and medium scale software development organizations, which measured the work computer misuse levels and the factors that influence such behavior. The presence of guidelines provided no evidence of significant effect on the level of employee computer misuse. Not having access to Internet /email away from work and organizational settings were identified to be the most significant influences of work computer misuse.

Codon and mRNA sequence optimization of microdystrophin transgenes improves expression and physiological outcome in dystrophic mdx mice following AAV2/8 gene transfer

Duchenne muscular dystrophy is a fatal muscle-wasting disorder. Lack of dystrophin compromises the integrity of the sarcolemma and results in myofibers that are highly prone to contraction-induced injury. Recombinant adenoassociated virus (rAAV)-mediated dystrophin gene transfer strategies to muscle for the treatment of Duchenne muscular dystrophy (DMD) have been limited by the small cloning capacity of rAAV vectors and high titers necessary to achieve efficient systemic gene transfer. In this study, we assess the impact of codon optimization on microdystrophin (ΔAB/R3-R18/ΔCT) expression and function in the mdx mouse and compare the function of two different configurations of codon-optimized microdystrophin genes (ΔAB/R3-R18/ΔCT and ΔR4-R23/ΔCT) under the control of a muscle-restrictive promoter (Spc5-12). Codon optimization of microdystrophin significantly increases levels of microdystrophin mRNA and protein after intramuscular and systemic administration of plasmid DNA or rAAV2/8. Physiological assessment demonstrates that codon optimization of ΔAB/R3-R18/ΔCT results in significant improvement in specific force, but does not improve resistance to eccentric contractions compared with noncodon-optimized ΔAB/ R3-R18/ΔCT. However, codon-optimized microdystrophin ΔR4-R23/ΔCT completely restored specific force generation and provided substantial protection from contraction-induced injury. These results demonstrate that codon optimization of microdystrophin under the control of a muscle-specific promoter can significantly improve expression levels such that reduced titers of rAAV vectors will be required for efficient systemic administration.

Precise analysis of array usage in scientific programs

The automatic transformation of sequential programs for efficient execution on parallel computers involves a number of analyses and restructurings of the input. Some of these analyses are based on computing array sections, a compact description of a range of array elements. Array sections describe the set of array elements that are either read or written by program statements. These sections can be compactly represented using shape descriptors such as regular sections, simple sections, or generalized convex regions. However, binary operations such as Union performed on these representations do not satisfy a straightforward closure property, e.g., if the operands to Union are convex, the result may be nonconvex. Approximations are resorted to in order to satisfy this closure property. These approximations introduce imprecision in the analyses and, furthermore, the imprecisions resulting from successive operations have a cumulative effect. Delayed merging is a technique suggested and used in some of the existing analyses to minimize the effects of approximation. However, this technique does not guarantee an exact solution in a general setting. This article presents a generalized technique to precisely compute Union which can overcome these imprecisions.

Factors affecting dairy farmers' attitudes towards antimicrobial medicine usage in cattle in England and Wales

There has been growing concern about bacterial resistance to antimicrobials in the farmed livestock sector. Attention has turned to sub-optimal use of antimicrobials as a driver of resistance. Recent reviews have identified a lack of data on the pattern of antimicrobial use as an impediment to the design of measures to tackle this growing problem. This paper reports on a study that explored use of antibiotics by dairy farmers and factors influencing their decision-making around this usage. We found that respondents had either recently reduced their use of antibiotics, or planned to do so. Advice from their veterinarian was instrumental in this. Over 70% thought reducing antibiotic usage would be a good thing to do. The most influential source of information used was their own veterinarian. Some 50% were unaware of the available guidelines on use in cattle production. However, 97% thought it important to keep treatment records. The Theory of Planned Behaviour was used to identify dairy farmers’ drivers and barriers to reduce use of antibiotics. Intention to reduce usage was weakly correlated with current and past practice of antibiotic use, whilst the strongest driver was respondents’ belief that their social and advisory network would approve of them doing this. The higher the proportion of income from milk production and the greater the chance of remaining in milk production, the significantly higher the likelihood of farmers exhibiting positive intention to reduce antibiotic usage. Such farmers may be more commercially minded than others and thus more cost-conscious or, perhaps, more aware of possible future restrictions. Strong correlation was found between farmers’ perception of their social referents’ beliefs and farmers’ intent to reduce antibiotic use. Policy makers should target these social referents, especially veterinarians, with information on the benefits from, and the means to, achieving reductions in antibiotic usage. Information on sub-optimal use of antibiotics as a driver of resistance in dairy herds and in humans along with advice on best farm practice to minimise risk of disease and ensure animal welfare, complemented with data on potential cost savings from reduced antibiotic use would help improve poor practice.