Universality and predictability in molecular quantitative genetics

Molecular traits, such as gene expression levels or protein binding affinities, are increasingly accessible to quantitative measurement by modern high-throughput techniques. Such traits measure molecular functions and, from an evolutionary point of view, are important as targets of natural selection. We review recent developments in evolutionary theory and experiments that are expected to become building blocks of a quantitative genetics of molecular traits. We focus on universal evolutionary characteristics: these are largely independent of a trait's genetic basis, which is often at least partially unknown. We show that universal measurements can be used to infer selection on a quantitative trait, which determines its evolutionary mode of conservation or adaptation. Furthermore, universality is closely linked to predictability of trait evolution across lineages. We argue that universal trait statistics extends over a range of cellular scales and opens new avenues of quantitative evolutionary systems biology

SNP Miniplexes for Individual Identification of Random-Bred Domestic Cats.

Phenotypic and genotypic characteristics of the cat can be obtained from single nucleotide polymorphisms (SNPs) analyses of fur. This study developed miniplexes using SNPs with high discriminating power for random-bred domestic cats, focusing on individual and phenotypic identification. Seventy-eight SNPs were investigated using a multiplex PCR followed by a fluorescently labeled single base extension (SBE) technique (SNaPshot(®) ). The SNP miniplexes were evaluated for reliability, reproducibility, sensitivity, species specificity, detection limitations, and assignment accuracy. Six SNPplexes were developed containing 39 intergenic SNPs and 26 phenotypic SNPs, including a sex identification marker, ZFXY. The combined random match probability (cRMP) was 6.58 × 10(-19) across all Western cat populations and the likelihood ratio was 1.52 × 10(18) . These SNPplexes can distinguish individual cats and their phenotypic traits, which could provide insight into crime reconstructions. A SNP database of 237 cats from 13 worldwide populations is now available for forensic applications

Theories, models, simulations: a computational challenge

In this talk I would like to illustrate with examples taken from Quantum Field Theory and Biophysics how an intelligent exploitation of the unprecedented power of today's computers could led not only to the solution of pivotal problems in the theory of Strong Interactions, but also to the emergence of new lines of interdisciplinary research, while at the same time pushing the limits of modeling to the realm of living systems.Comment: 19 pages, 1 figure, conference pape

Generating narrative action schemas for suspense

A bottleneck in interactive storytelling is the authorial burden of writing narrative units, and connecting them to the interactive narrative structure. To address this problem, we present a hybrid approach that combines AI planning and evolutionary optimization in order to generated new plan operators representing possible story actions, within the framework of a planningbased interactive narrative system. We focus our work on inventing plan operators that are useful for contributing to suspenseful interactive stories, using suspense metrics that have been proposed in the literature.We devise an encoding scheme for converting a plan operator into a genetic-algorithm chromosome and vice versa, respecting constraints that are needed for an operator to be well-formed. We discuss the performance of the system, and several examples from preliminary experiments carried out to evaluate the evolved operators.This work has been supported in part by the EU FP7 ICT project SIREN (project no: 258453). We thank Arnav Jhala at UC Santa Cruz, and Antonios Liapis and Julian Togelius at IT University of Copenhagen for the discussion.peer-reviewe

Embodied Evolution in Collective Robotics: A Review

This paper provides an overview of evolutionary robotics techniques applied to on-line distributed evolution for robot collectives -- namely, embodied evolution. It provides a definition of embodied evolution as well as a thorough description of the underlying concepts and mechanisms. The paper also presents a comprehensive summary of research published in the field since its inception (1999-2017), providing various perspectives to identify the major trends. In particular, we identify a shift from considering embodied evolution as a parallel search method within small robot collectives (fewer than 10 robots) to embodied evolution as an on-line distributed learning method for designing collective behaviours in swarm-like collectives. The paper concludes with a discussion of applications and open questions, providing a milestone for past and an inspiration for future research.Comment: 23 pages, 1 figure, 1 tabl

A genetic toolkit and gene switches to limit Mycoplasma growth for biosafety applications

Mycoplasmas have exceptionally streamlined genomes and are strongly adapted to their many hosts, which provide them with essential nutrients. Owing to their relative genomic simplicity, Mycoplasmas have been used to develop chassis for biotechnological applications. However, the dearth of robust and precise toolkits for genomic manipulation and tight regulation has hindered any substantial advance. Herein we describe the construction of a robust genetic toolkit for M. pneumoniae, and its successful deployment to engineer synthetic gene switches that control and limit Mycoplasma growth, for biosafety containment applications. We found these synthetic gene circuits to be stable and robust in the long-term, in the context of a minimal cell. With this work, we lay a foundation to develop viable and robust biosafety systems to exploit a synthetic Mycoplasma chassis for live attenuated vectors for therapeutic applications

Investigative baseline reference on the status of pork pH, shear force, colour, drip and cooking loss in RYR1 mutation free, commercial 3-way crosses in Malaysia

This paper attempts to provide findings of an investigative study on the baseline status of the pork quality in Malaysia. With consumer preferences changing towards the selection of good quality meat for consumption, there is a need to establish an investigative reference for the operators in the industry to gauge the performance of their animals and pork quality. This is also important to increase the competitiveness among producers to continuously improve the pork quality available to consumers. In this study, 30 commercial three-way crossed female pigs were randomly selected from government accredited abattoirs from east and west Malaysia and longisimus dorsi were collected for the determination of pH, drip loss, cooking loss, shear force and colour. All animals were screened for the RYR1 gene and the results were then compiled with statistical analysis to obtain an investigative baseline pork quality data in Malaysia. The average pork quality obtained from this study falls within the category of Red, Soft and Exudative (RSE), with an average ultimate pH of 5.83, drip loss more than 5% and L* values at 45.94. We have proposed an investigative baseline meat quality data for Malaysian pork from the average commercial pork quality data obtained. The proposed investigative pork quality baseline data in Malaysian is comparable in terms of studies done in other established countries and/or with international standards and falls within the RSE category of acceptable quality. It provides an investigative benchmark for researchers and end-producers to judge the quality of pork in an objective manner, both for consumption and for export purpose. Moreover, continuous selection against the RYR1 gene has successfully removed the gene from the sample size above, but constant random monitoring is still advisable if farms aim to ensure the elimination of this gene from their herd

Multiplexed characterization of rationally designed promoter architectures deconstructs combinatorial logic for IPTG-inducible systems

A crucial step towards engineering biological systems is the ability to precisely tune the genetic response to environmental stimuli. In the case of Escherichia coli inducible promoters, our incomplete understanding of the relationship between sequence composition and gene expression hinders our ability to predictably control transcriptional responses. Here, we profile the expression dynamics of 8269 rationally designed, IPTG-inducible promoters that collectively explore the individual and combinatorial effects of RNA polymerase and LacI repressor binding site strengths. We then fit a statistical mechanics model to measured expression that accurately models gene expression and reveals properties of theoretically optimal inducible promoters. Furthermore, we characterize three alternative promoter architectures and show that repositioning binding sites within promoters influences the types of combinatorial effects observed between promoter elements. In total, this approach enables us to deconstruct relationships between inducible promoter elements and discover practical insights for engineering inducible promoters with desirable characteristics

Radiological evaluation of biomarkers for renal cell carcinoma

Role of MRI DWI sequences in the evaluation of early response to neo- angiogenesis inhibitors in metastatic renal cell carcinoma Purpose: Angiogenesis inhibitors have a potential role in treating metastatic renal cell carcinoma, but it is still not clear why some patients don't respond. Our objective was to look for DWI parameters able to identify patients with metastatic renal cell carcinoma who would not benefit from target therapy. RECIST1.1 was considered as Reference Standard. Methods & Materials: We prospectively enrolled 43 patients candidate to start angiogenesis inhibitors with at least one target lesion and who underwent 1,5T MRI examination with multiple bvalues DWI sequences (0,40,200,300,600): one week before (t0), 2 weeks after (t2) and 8 weeks (t8) after treatment beginning. ADC value was calculated drawing ROIs on 3 different planes. 33 patients with 38 lesions had suitable data for comparative evaluation. Results: At T8 follow-up 9 patients had partial response (PR), 20 table disease (SD), 4 progression disease (PD); average progression free survival was 272 days. PD group, as compared to DC or to PR showed significantly lower ADC values at b40 at t0 (p<0.05): we can assess that more vascularised lesions are more responsive to treatment. PD group have significantly lower ADC values then both other groups, at t0, t2 and t8, for all b-values (p<0.05). PFS and OS correlates well with ADC, in particular OS with ADC b40 at t0 (r=0,69). Coclusions: Results show that PD group has significantly lower ADC values than PR or DC everytime (t0, t2, t8) At t0 there is a better correlation between PFS or OS & ADC than PFS & dimensional criteria. ADC at t0 may help selecting patients with promising good response to angiogenesis inhibitors. Moreover at t0 and at t2 ADC has the potential to select patients who wouldn't benefit from angiogenesis inhibitors Nowadays, in the era of target therapy, it is crucial to select patients potentially responders. We have to look at cost/benefit ratio and at increasing costs of treatment options. DWI has the potential role to identify patients whose's tumor wouldn't benefit from target therapy, adding a value (ADC) to other imaging (e.g. DCE-MRI, texture imaging) and clinical parameters (e.g. miRNA) in a hypothetic multiparametric analysis.CT Texture Analysis in Clear Cell Renal Cell Carcinoma: a Radiogenomics Prospective Purpose: The aim of this study was to investigate whether quantitative parameters obtained from CT Texture Analysis (CTTA) correlate with expression of miRNA in clear cell Renal Cell Carcinoma (ccRCC). Methods and Materials: In a retrospective single centre study, multiphasic CT examination (with arterial, portal, equilibrium and urographic phases) was performed on 20 patients with clear cell renal carcinomas (14 men and 6 women; mean age 65 years ± 13). Measures of heterogeneity were obtained in post-processing by placing a ROI on the entire tumour and CTTA parameters such as entropy, kurtosis, skewness, mean, mean of positive pixels, and SD of pixel distribution histogram were measured using multiple filter settings. Quantitative data were correlated with the expression of miRNAs obtained from the same cohort of patients: 8 fresh frozen samples and 12 formalin-fixed paraffin-embedded samples (miR-21-5p, miR-210-3p, miR-185-5p, miR-221-3p, miR-145-5p). Both evaluations (miRNAs and CTTA) were performed on tumour tissues as well as on normal cortico-medullar tissues. Analysis of Variance with linear multiple regression model methods were obtained with SPSS statistic software. For all comparisons, statistical significance was assumed p<0.05 Results: We evidenced that CTTA has robust parameters (e.g. entropy, mean, sd) to distinguish normal from pathological tissues. Moreover, a higher coefficient of determination between entropy and miR-21-5p expression (R2 =0,25) was evidenced in tumour tissues as compared to normal tissues (R2 =0,15). Interestingly, excluding four patients with extreme over-expression of miR-21-5p, excellent relation between entropy and miR21-5p levels was found specifically in tumour samples (R2= 0,64; p<0.05). Conclusion: Entropy and miRNA-21-5p show promising correlation in ccRCC; in addiction CTTA features, in particular mean and entropy show a statistically significant increase in ccRCC as compared with normal renal parenchyma