Identification of the Imprinted KLF14 Transcription Factor Undergoing Human-Specific Accelerated Evolution

Imprinted genes are expressed in a parent-of-origin manner and are located in clusters throughout the genome. Aberrations in the expression of imprinted genes on human Chromosome 7 have been suggested to play a role in the etiologies of Russell-Silver Syndrome and autism. We describe the imprinting of KLF14, an intronless member of the Krüppel-like family of transcription factors located at Chromosome 7q32. We show that it has monoallelic maternal expression in all embryonic and extra-embryonic tissues studied, in both human and mouse. We examine epigenetic modifications in the KLF14 CpG island in both species and find this region to be hypomethylated. In addition, we perform chromatin immunoprecipitation and find that the murine Klf14 CpG island lacks allele-specific histone modifications. Despite the absence of these defining features, our analysis of Klf14 in offspring from DNA methyltransferase 3a conditional knockout mice reveals that the gene's expression is dependent upon a maternally methylated region. Due to the intronless nature of Klf14 and its homology to Klf16, we suggest that the gene is an ancient retrotransposed copy of Klf16. By sequence analysis of numerous species, we place the timing of this event after the divergence of Marsupialia, yet prior to the divergence of the Xenarthra superclade. We identify a large number of sequence variants in KLF14 and, using several measures of diversity, we determine that there is greater variability in the human lineage with a significantly increased number of nonsynonymous changes, suggesting human-specific accelerated evolution. Thus, KLF14 may be the first example of an imprinted transcript undergoing accelerated evolution in the human lineage

Divergence of Mammalian Higher Order Chromatin Structure Is Associated with Developmental Loci

Several recent studies have examined different aspects of mammalian higher order chromatin structure - replication timing, lamina association and Hi-C inter-locus interactions - and have suggested that most of these features of genome organisation are conserved over evolution. However, the extent of evolutionary divergence in higher order structure has not been rigorously measured across the mammalian genome, and until now little has been known about the characteristics of any divergent loci present. Here, we generate a dataset combining multiple measurements of chromatin structure and organisation over many embryonic cell types for both human and mouse that, for the first time, allows a comprehensive assessment of the extent of structural divergence between mammalian genomes. Comparison of orthologous regions confirms that all measurable facets of higher order structure are conserved between human and mouse, across the vast majority of the detectably orthologous genome. This broad similarity is observed in spite of many loci possessing cell type specific structures. However, we also identify hundreds of regions (from 100 Kb to 2.7 Mb in size) showing consistent evidence of divergence between these species, constituting at least 10% of the orthologous mammalian genome and encompassing many hundreds of human and mouse genes. These regions show unusual shifts in human GC content, are unevenly distributed across both genomes, and are enriched in human subtelomeric regions. Divergent regions are also relatively enriched for genes showing divergent expression patterns between human and mouse ES cells, implying these regions cause divergent regulation. Particular divergent loci are strikingly enriched in genes implicated in vertebrate development, suggesting important roles for structural divergence in the evolution of mammalian developmental programmes. These data suggest that, though relatively rare in the mammalian genome, divergence in higher order chromatin structure has played important roles during evolution

Cobots implementation in manufacturing systems: literature review and open questions

In companies, Industry 4.0 technologies offer several advantages in terms of flexibility, data availability and fast reaction to changes. Some of these systems can couple the benefits of human flexibility with assistive technology as collaborative robots (Cobots). Although the recent literature has already discussed how Cobots could bring many benefits to the manufacturing system, their use still requires significant knowledge about system features, design methods for semi-automatic manufacturing lines/cells, micro and macro layout configuration, the impact of Cobots on humans, and more. Without adequate knowledge of the impact of Cobots on the different parts of the manufacturing system, the use of Cobots could find several barriers and practical limits in the short future. In this paper, we try to investigate the Cobots’ impact on manufacturing systems and their interaction with humans. To achieve this goal, we conduct a structured literature review. In particular, we classify selected papers by considering the methodology used and some performance factors. Finally, we propose some open questions and a future research agenda

Assembly Line Balancing with Inexperienced and Trainer Workers

In this paper, we present a simple assembly line balancing problem for two different sets of workers: trainer workers who are more experienced and likely older, and inexperienced workers who are usually younger and require more time to perform some tasks. Therefore, the main characteristic of this problem is that trainer workers are involved in helping and supporting inexperienced ones in executing some tasks which are more complicated to be carried out. Moreover, task times vary according to the stations where they can be performed due to different sets of equipment we can find in each of them. The problem is modelled as a linear program and solved optimally by applying it to a real-case application. The developed model can be successfully applied in order to help companies to manage a high level of turnover

Assembly line balancing and worker assignment considering workers' expertise and perceived physical effort

In manual assembly systems, workers' differences in terms of skills, level of expertise and perceived physical effort largely affect the assembly line balancing and system performance. Traditional long-term strategic decisions may not respond to workforce changes and needs, resulting in frequent requests for line rebalancing. In this study, we propose a methodological framework and an easy-to-use Assembly Line Worker Assignment and Rebalancing Problem with different options: workers' assignment considering their performance variability, integration of worker dependent physical exertion constraints and possibility to use trainers to assist inexperienced workers. A bi-objective linear programming model is proposed aiming to minimise the cycle time and the number of reassigned tasks to respect the initial design while integrating new workers with different characteristics. The $\varepsilon$ epsilon-constraint approach is used to build Pareto frontiers for this bi-objective problem. This approach is applied to three real cases. The obtained results show that the developed model can be successfully used in manufacturing companies to help the production managers to deal with workforce turnover and skills heterogeneity

RNA-based gene duplication: mechanistic and evolutionary insights.

Gene copies that stem from the mRNAs of parental source genes have long been viewed as evolutionary dead-ends with little biological relevance. Here we review a range of recent studies that have unveiled a significant number of functional retroposed gene copies in both mammalian and some non-mammalian genomes. These studies have not only revealed previously unknown mechanisms for the emergence of new genes and their functions but have also provided fascinating general insights into molecular and evolutionary processes that have shaped genomes. For example, analyses of chromosomal gene movement patterns via RNA-based gene duplication have shed fresh light on the evolutionary origin and biology of our sex chromosomes