Evolving Gene Regulatory Networks with Mobile DNA Mechanisms

This paper uses a recently presented abstract, tuneable Boolean regulatory network model extended to consider aspects of mobile DNA, such as transposons. The significant role of mobile DNA in the evolution of natural systems is becoming increasingly clear. This paper shows how dynamically controlling network node connectivity and function via transposon-inspired mechanisms can be selected for in computational intelligence tasks to give improved performance. The designs of dynamical networks intended for implementation within the slime mould Physarum polycephalum and for the distributed control of a smart surface are considered.Comment: 7 pages, 8 figures. arXiv admin note: substantial text overlap with arXiv:1303.722

On the evolution of Boolean networks for computation: A guide RNA mechanism

© 2015 Taylor & Francis. There is a growing body of work within computational intelligence which explores the use of representations inspired by the genetic regulatory networks of biological cells. This paper uses a recently presented abstract, tunable model of such networks to investigate how their design through simulated evolution is affected through the ability to dynamically rewire connectivity. The contextual editing of transcribed RNA by other molecules such that the form of the final product differs from that specified in the corresponding DNA sequence is ubiquitous. It is here shown that a guide RNA-inspired editing mechanism can be selected for under various scenarios

On Natural Genetic Engineering: Structural Dynamism in Random Boolean Networks

This short paper presents an abstract, tunable model of genomic structural change within the cell lifecycle and explores its use with simulated evolution. A well-known Boolean model of genetic regulatory networks is extended to include changes in node connectivity based upon the current cell state, e.g., via transposable elements. The underlying behaviour of the resulting dynamical networks is investigated before their evolvability is explored using a version of the NK model of fitness landscapes. Structural dynamism is found to be selected for in non-stationary environments and subsequently shown capable of providing a mechanism for evolutionary innovation when such reorganizations are inherited

Network and Algebraic Topology of Influenza Evolution

Evolution is a force that has molded human existence since its divergence from chimpanzees about 5.4 million years ago. In that same amount of time, an influenza virus, which replicates every six hours, would have undergone an equivalent number of generations over only a hundred years. The fast replication times of influenza, coupled with its high mutation rate, make the virus a perfect model to study real-time evolution at a mega-Darwin scale, more than a million times faster than human evolution. While recent developments in high-throughput sequencing provide an optimal opportunity to dissect their genetic evolution, a concurrent growth in computational tools is necessary to analyze the large influx of complex genomic data. In my thesis, I present novel computational methods to examine different aspects of influenza evolution. I first focus on seasonal influenza, particularly the problems that hamper public health initiatives to combat the virus. I introduce two new approaches: 1. The q2-coefficient, a method of quantifying pathogen surveillance, and 2. FluGraph, a technique that employs network topology to track the spread of seasonal influenza around the world. The second chapter of my thesis examines how mutations and reassortment combine to alter the course of influenza evolution towards pandemic formation. I highlight inherent deficiencies in the current phylogenetic paradigm for analyzing evolution and offer a novel methodology based on algebraic topology that comprehensively reconstructs both vertical and horizontal evolutionary events. I apply this method to viruses, with emphasis on influenza, but foresee broader application to cancer cells, bacteria, eukaryotes, and other taxa

New Advances on Zika Virus Research

Zika virus (ZIKV) is a mosquito-borne member of the Flaviviridae family that historically has been associated with mild febrile illness. However, the recent outbreaks in Brazil in 2015 and its rapid spread throughout South and Central America and the Caribbean, together with its association with severe neurological disorders—including fetal microcephaly and Guillain-Barré syndrome in adults—have changed the historic perspective of ZIKV. Currently, ZIKV is considered an important public health concern that has the potential to affect millions of people worldwide. The significance of ZIKV in human health and the lack of approved vaccines and/or antiviral drugs to combat ZIKV infection have triggered a global effort to develop effective countermeasures to prevent and/or treat ZIKV infection. In this Special Issue of Viruses, we have assembled a collection of 32 research and review articles that cover the more recent advances on ZIKV molecular biology, replication and transmission, virus–host interactions, pathogenesis, epidemiology, vaccine development, antivirals, and viral diagnosis

Improving Vaccine Design For Viral Diseases Using Modified Antigens And Vectors

Two of the principal challenges facing vaccine design today are how to generate protective antibody responses against viruses that have evolved sophisticated strategies to evade the humoral immune system and how to more rapidly and effectively produce vaccines to address emerging epidemics. In this regard, we explored multiple strategies to improve vaccine design for HIV-1 and Zika virus. In one approach, we derived CD4-independent variants of HIV-1 envelope (Env) with the hypothesis that such Envs would expose conserved epitopes that may be targets of protective, non-neutralizing antibodies. We characterized the biological and structural properties of two CD4-independent Env clones and found that they exhibited significantly greater exposure of a relatively conserved, linear epitope in the second variable loop (V2) that had previously been associated with decreased risk of infection in a clinical HIV-1 vaccine trial. This epitope was significantly more immunogenic in mice and nonhuman primates and, intriguingly, was associated with more rapid development of antibody-dependent cell-mediated cytotoxicity. In another approach, we designed mutations in the cytoplasmic tail of HIV-1 Env that were predicted to increase its cell surface expression and thus its immunogenicity in a vaccinia prime-protein boost vaccine protocol. We found that the highest level of surface expression was mediated by Envs with truncated cytoplasmic tails, and this was associated with higher levels of binding and neutralizing antibodies after vaccinia primes and protein boosts, respectively. These two studies revealed that modifications to HIV-1 Env immunogens are able to influence both the quality and magnitude of desirable antibody responses. Finally, we used a newly developed vaccine platform based on nucleoside-modified mRNA to design a vaccine against Zika virus. This vaccine, encoding the surface prM and E proteins, was potently immunogenic and elicited high and sustained titers of neutralizing antibodies in mice and nonhuman primates following a single intradermal immunization. We observed rapid and durable protection from Zika virus infection in mice and a high level of protection in monkeys challenged five weeks after vaccination. This vaccine thus represents a promising candidate for clinical use in controlling the spread of Zika virus

International Conference on Mathematical Analysis and Applications in Science and Engineering – Book of Extended Abstracts

The present volume on Mathematical Analysis and Applications in Science and Engineering - Book of Extended Abstracts of the ICMASC’2022 collects the extended abstracts of the talks presented at the International Conference on Mathematical Analysis and Applications in Science and Engineering – ICMA2SC'22 that took place at the beautiful city of Porto, Portugal, in June 27th-June 29th 2022 (3 days). Its aim was to bring together researchers in every discipline of applied mathematics, science, engineering, industry, and technology, to discuss the development of new mathematical models, theories, and applications that contribute to the advancement of scientific knowledge and practice. Authors proposed research in topics including partial and ordinary differential equations, integer and fractional order equations, linear algebra, numerical analysis, operations research, discrete mathematics, optimization, control, probability, computational mathematics, amongst others. The conference was designed to maximize the involvement of all participants and will present the state-of- the-art research and the latest achievements.info:eu-repo/semantics/publishedVersio

Bibliometric Studies and Worldwide Research Trends on Global Health

Global health, conceived as a discipline, aims to train, research and respond to problems of a transboundary nature, in order to improve health and health equity at the global level. The current worldwide situation is ruled by globalization, and therefore the concept of global health involves not only health-related issues, but also those related to the environment and climate change. Therefore, in this Special Issue, the problems related to global health have been addressed from a bibliometric approach in four main areas: environmental issues, diseases, health, education and society