Selfish Mutations: the Genetic Basis of the Paternal Age Effect

As the mean age of childrearing grows, the effect of parental age on genetic disease and child health becomes ever more important. A number of autosomal dominant disorders show a dramatic paternal age effect due to selfish mutations: substitutions that grant spermatogonial stem cells (SSCs) a selective advantage in the testes of the father but have a deleterious effect in offspring. I present a mathematical model to analyse the normal function of the stem cell compartment, which provides a framework for SSC renewal and accommodates differences between animal systems. In order to model the SSC mutation accumulation, a Markov chain was used to model the probabilities of mutation and positive selection with cell divisions. This model provided average numbers of mutant sperm produced with increasing paternal age. The proportions of mutant to wildtype cells with increasing paternal age was used to generate a simulated population and observed/expected curves. These were then fitted against existing disease and sequencing data. The parameter for the probability of positive selection per division of a mutant cell was estimated. Incidence of the diseases was predicted closely for most disorders and was influenced by the site-specific mutation rate caused by hypermutable CpG sites and the number of mutable alleles. The incidence of disease was explained satisfactorily only when a combination of positive selection and the site-specific mutation rate were included in the analysis. To provide experimental evidence for the hyposthesis that paternal age effect mutations present a selective advantage, I selected the mutation in the RET (REarranged during Transfection) gene that causes multiple endocrine neoplasia type 2B. SSCs were created by inducing differentiation to spermatogonia of induced pluripotent stem cells. Wildtype and mutant SSCs were generated by transfection with a plasmid containing the normal RET gene and the gene containing the disease mutation, respectively. Mutant SSCs showed increased proliferation in culture. This effect was counteracted when the mutant receptors were saturated with their ligand, GDNF (glial-derived neurotropic factor). This research demonstrated theoretical and experimental evidence for positive selection in SSCs for multiple endocrine neoplasia type 2B and other paternal age effect syndromes

UVES Spectroscopy of T Chamaeleontis: Line Variability, Mass Accretion Rate and Spectro-astrometric Analysis

Although advances in exoplanet detection techniques have seen an increase in discoveries, observing a planet in the earliest stages of formation still remains a difficult task. Here four epochs of spectra of the transitional disk object T Cha are analysed to determine whether spectro-astrometry can be used to detect a signal from its proposed protoplanet, T Cha b. The unique properties of T Cha are also further constrained. H{\alpha} and [O I]{\lambda} 6300, the most prominent lines, were analysed using spectro-astrometry. H{\alpha} being a direct accretion tracer is the target for the T Cha b detection while [O I]{\lambda} 6300 is considered to be an indirect tracer of accretion. [O I]{\lambda} 6300 is classified as a broad low velocity component (BC LVC). The mass accretion rate was derived for all epochs using new [O I]{\lambda} 6300 LVC relationships and the H{\alpha} line luminosity. It is shown that a wind is the likely origin of the [O I]{\lambda} 6300 line and that the [O I]{\lambda} 6300 line serves as a better accretion tracer than H{\alpha} in this case. From the comparison between M acc([OI]) and M acc(H{\alpha}) it is concluded that T Cha is not an intrinsically weak accretor but rather that a significant proportion of the H{\alpha} emission tracing accretion is obscured. T Cha b is not detected in the spectro-astrometric analysis yet a detection limit of 0.5 mas is derived. The analysis in this case was hampered by spectro-astrometric artefacts and by the unique properties of T Cha. While it seems that spectro-astrometry as a means of detecting exoplanets in TDs can be challenging it can be used to put an limit on the strength of the H{\alpha} emission from accreting planetary companions and thus can have an important input into the planning of high angular resolution observations

UNDERSTANDING THE ROLE OF ADVICE NETWORKS IN SOFTWARE DEVELOPMENT

The demand for software-enabled products and services continus unabated in almost all facets of life. With this increasing demand comes an intense pressure on the developers of software to be innovative in all aspects. While researchers have examined how a variety of individual, group, and organizational factors shape innovation in information systems development, the role of advice networks has received limited consideration to date. A greater understanding of advice network structures in software development is important as numerous studies from the social network tradition demonstrate that advice seeking behaviors play a key role in people´s ability to do their jobs effectively. Drawing from social network theory, we develop a number of hypotheses relating the structure of a software developer´s advice network for technological developments to personal innovativeness. To test these hypotheses, social network analysis and interview data will be gathered from a software development division of a large organization

Changing the Introductory IS Course to Improve Future Enrollments: An Irish Perspective

A significant challenge facing the IS discipline worldwide is the reversal of the low numbers of students currently enrolling in IS courses. While there is a growing body of literature which offers various insights into the IS enrollment crisis, almost all of this work is either from U.S. scholars or based on findings from U.S. universities. This paper seeks to bring a much needed international perspective to this issue. The setting for this paper is the Kemmy Business School at the University of Limerick in Ireland where enrollments on the IS program have grown from a low of 12 in 2007 to 70 in 2011, a five fold increase. Using a set of steps laid out by Firth et al. (2008) we detail how this success was achieved. Supported by focus group and survey data, we provide new ideas on how to engage business school students in the IS discipline in a way that encourages them to specialize in the discipline. This paper presents a useful and immediately applicable plan for all IS programs that are seeking to grow or strengthen their offerings

MANAGING INFORMATION OVERLOAD; EXAMINING THE ROLE OF THE HUMAN FILTER

With the increasing processing power and plummeting costs of multimedia technologies, our ability to ubiquitously access and disseminate information continues to become indefinitely easier. However, emerging research shows that we are struggling to process information as fast as it arrives. The problem of information overload is a significant one for contemporary organisations as it can adversely affect productivity, decision-making, and employee morale. To combat this problem, organisations often resort to investing in technical solutions such as business intelligence software or semantic technologies. While such technical approaches can certainly aid in making sense of information overload, less attention has been directed at understanding how social behaviours within inter-personal networks – the primary conduit of information – have evolved to deal with the surge of digital information. Using social network analysis and interview evidence from two information intensive firms, this study finds a small number of information specialists who emerge to filter useful information into and around the intra-organizational network. The article concludes with a discussion of the theoretical and practical implications of our findings

COGNITIVE CONTROL AND SOCIAL MEDIA OVERLOAD

The use of social media technologies in the workplace is proliferating at an incredible pace. However, recent research reports that our inability to cope with the slew of social media communications is creating mental health problems, hampering productivity, generating stress, and lowering morale. This paper investigates how three aspects of cognitive control (i.e. fear of missing out, internet cognitive failure, and deficient self-regulation) affect communication and information overload. We test the model by collecting data from 129 students from an US and an Irish university. Partial Least Squares (PLS) techniques were used to test the model. The findings suggest that (1) communication overload is explained by fear of missing out, Internet cognitive failure, and deficient self-regulation, whereas (2) information overload is explained by only Internet cognitive failure and deficient self-regulation

UNDERSTANDING THE INFLUENCE OF TECHNOSTRESS ON WORKERS’ JOB SATISFACTION IN GIG-ECONOMY: AN EXPLORATORY INVESTIGATION

Gig-economy is a recent concept that has been attracting growing attention. Online labour markets (OLMs) are a prominent part of gig-economy and require completion of tasks digitally through platforms such as MTurk and Upwork. The World Bank estimated the total market size of OLMs to be $4.8 billion in 2016 which is expected to increase up to$25 billion in 2020. Despite the rapid growth of OLMs, the implications of workers’ wellbeing in such markets are not well understood and highly debated. A report commissioned by EU-OSHA has identified psycho-social risks associated with the work in OLMs. The highly competitive and fast-paced nature of OLMs necessitates workers to multitask and perform intense technology-enabled work which may lead to technostress. This paper investigates workers’ job satisfaction in OLMs using technostress and job characteristic theories with the aim of providing an in-depth understanding of the experiences and perceptions of workers. Our research model has both theoretical and practical implications which will help to diagnose potential problems and improve the wellbeing of workers by formulating strategies for OLMs and workers. The paper presents the results of a pilot study in a popular OLM using structural equation modelling

Examining the Antecedents to Innovation in Electronic Networks of Practice

The way in which firms innovate ideas and bring them to market is undergoing a fundamental change. Useful knowledge is increasingly dispersed outside the firm’s boundaries and the exceptionally fast time to market for many products and services suggest that some very different organising principles for innovation are needed. These developments have led to an increased interest in the electronic network of practice concept to facilitate innovation. This paper argues that innovative behaviour in electronic networks of practice is determined by three interacting systems — individual motivations, network communication structure, and the social context of the network. The theoretical position of the interactive process theory of innovation is used to support this claim

Selective Mutation Accumulation: A Computational Model of the Paternal Age Effect

Motivation: As the mean age of parenthood grows, the effect of parental age on genetic disease and child health becomes ever more important. A number of autosomal dominant disorders show a dramatic paternal age effect due to selfish mutations: substitutions that grant spermatogonial stem cells (SSCs) a selective advantage in the testes of the father, but have a deleterious effect in offspring. In this paper we present a computational technique to model the SSC niche in order to examine the phenomenon and draw conclusions across different genes and disorders. Results: We used a Markov chain to model the probabilities of mutation and positive selection with cell divisions. The model was fitted to available data on disease incidence and also mutation assays of sperm donors. Strength of selective advantage is presented for a range of disorders including Apert\u27s syndrome and achondroplasia. Incidence of the diseases was predicted closely for most disorders and was heavily influenced by the site-specific mutation rate and the number of mutable alleles. The model also successfully predicted a stronger selective advantage for more strongly activating gain-of-function mutations within the same gene. Both positive selection and the rate of copy-error mutations are important in adequately explaining the paternal age effect. Availability and Implementation: C++/R source codes and documentation including compilation instructions are available under GNU license at https://github.com/anwala/NicheSimulation. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online