Non-viral approaches to gene therapy

Several advances in non-viral gene transfer technology have been reported over the past year. Cationic lipids have been successfully used to deliver genes in vivo, providing a clear alternative to recombinant viruses. In addition, investigators have demonstrated that direct application of DNA via injection or particle bombardment can be used for vaccination. Analysis of the mechanisms employed by viruses to invade cells has demonstrated a crucial role for membrane-active proteins or peptides in the entry process. Several non-viral systems that include membrane-active elements are now available

Viral systems : a new bio-inspired optimisation approach

The paper presents a new approach to deal with combinatorial problems. It makes use of a biological analogy inspired by the performance of viruses. The replication mechanism, as well as the hosts’ infection processes is used to generate a metaheuristic that allows the obtention of valuable results. The viral system (VS) theoretical context is described and it is applied to a library of medium-to-large-sized cases of the Steiner problem for which the optimal solution is known. The method is compared with the metaheuristics that have provided the best results for the Steiner problem. The VS provides better solutions than genetic algorithms and certain tabu search approaches. For the most sophisticated tabu search approaches (the best metaheuristic approximations to the Steiner problem solution) VS provides solutions of similar quality

Viral system algorithm: foundations and comparison between selective and massive infections

This paper presents a guided and deep introduction to Viral Systems (VS), a novel bio-inspired methodology based on a natural biological process taking part when the organism has to give a response to an external infection. VS has proven to be very efficient when dealing with problems of high complexity. The paper discusses on the foundations of viral systems, presents the main pseudocodes that need to be implemented and illustrates the methodology application. A comparison between VS and other metaheuristics, as well between different VS approaches is presented. Finally trends and new research opportunities are presented for this bio-inspired methodology

The Role of Viral Systems in Nutrient Cycling

The Te Arawa/Rotorua lakes located in the central North Island of New Zealand have significant cultural, historic, social and economic value. Anthropogenic changes in land use have led to a decline in water quality in some lakes. A number of lakes have accelerated eutrophication with recurring cyanobacterial blooms and periods of bottom-water anoxia. Whilst there has been extensive research undertaken on phytoplankton dynamics in freshwater lakes there is little information on the abundance and activity of viral-like particles (VLPs) and bacteria. VLPs are the most abundant biological entities in aquatic environments and play an important role in carbon and nutrient cycling, reproducing either by cell lysis or replication in the host cell. Bacterial community structure is thought to be closely linked to the viral community and bacterial taxa have a key role in biochemical cycling in freshwater systems. Two Te Arawa/Rotorua monomictic lakes differing in their trophic status; oligotrophic Lake Tikitapu and eutrophic Lake Okaro, were sampled over a 12-month period at the surface (epilimnion) and bottom (hypolimnion) and through a discrete layer of the thermocline during stratification. The thermocline is a region where there may be steep clines in physiochemical parameters (e.g., dissolved oxygen) which may strongly affect the distribution of, and environmental factors that influence, prokaryotes, protozoa and viruses. Physiochemical variables, nutrients, microbiological and molecular analyses were undertaken on samples in order to compare and contrast changes occurring within and between the two lakes. Both lakes were strongly stratified for c. 8 months from September 2009 to June 2010 as indicated by Schmidt stability values > 1, which contributed to well-lit but nutrient-limited surface waters for phytoplankton productivity. With increasing duration of stratification a deep chlorophyll maximum formed in both lakes with Chlorophyta and Euglenophyta the dominant phytoplankton. Viral-like particle abundance in both lakes exceeded bacterial abundance by a factor of c. 100, with maximum VLP and bacterial abundances in both lakes c. 10⁸ cells mL-¹ and 10⁶ cells mL-¹, respectively. Bacterial abundance in both lakes was similar in the epilimnion and hypolimnion during stratification with the exception of a peak (2 x 10⁷ cells mL-¹) in the epilimnion of Lake Okaro in February 2010 (and in the hypolimnion (9.74 x 10⁶ cells mL-¹) in March 2010 of in Lake Tikitapu. Viral-like particle abundance was variable but the epilimnion and hypolimnion tracked in both lakes between August 2009 and January 2010 after which Lake Okaro epilimnion and hypolimnion remained steady with Lake Tikitapu hypolimnion showing considerably higher VLP abundance than the epilimnion before tracking together in June 2010. The abundance of the following bacterial functional genes was monitored through the study; nifH (encoding the nitrogenase reductase protein), dsrA (encoding the sulphate reductase protein), mcrA (encoding the methyl coenzyme M reductase protein), amoA (encoding the ammonium oxidising protein and nosZ (encoding for the nitrous oxide reductase protein). The occurrence of the nifH gene correlated with increased abundance of cyanobacteria capable of fixing nitrogen in the epilimnion of both lakes while the dsrA gene was more abundant in Lake Okaro, likely due to higher organic matter concentrations and greater duration and spatial extent of reducing conditions in that lake. Abundance of mcrA was expected to be high in the anoxic waters of the nutrient rich sediment of Lake Okaro but there was very low abundance. The amoA genes were detected when concentrations of ammonium were elevated in the bottom waters of both lakes. Both lakes showed the presence nosZ genes with high abundance occurring in Lake Okaro in December 2009 through all levels and also in December 2009 in Lake Tikitapu in the epilimnion and hypolimnion. With denitrification reliant on the availability of nitrate (NO3-N) and dissolved organic carbon levels and performed by obligate and facultative anaerobes, conditions need to be precise for the process to occur

A viral system to optimise the daily drayage problem

The intermodal transport chain can become more efficient by means of a good organisation of the drayage movements. Drayage in intermodal container terminals involves the pick up or delivery of containers at customer locations, and the main objective is normally the assignment of transportation tasks to the different vehicles, often with the presence of time windows. This paper focuses on a new approach to tackle the daily drayage problem by the use of viral system (VS). VS is a novel bio-inspired approach that makes use of a virus-infection biological analogy that is producing very satisfactory results when dealing with complex problems with huge feasibility region.Unión Europea TEC2013-47286-C3-3-

Penerapan Algoritma Viral System Pada Single-Machine Total Weighted Tardiness Problem

Single Machine Total Weighted Tardiness Problem (SMTWTP) merupakan permasalahan klasik kombinatorial yang dikenal np-hard. Pada penelitian ini, suatu algoritma yang relatif baru yang terinspirasi dari sistem replikasi virus yang disebut sebagai Viral Systems digunakan untuk menyelesaikan permasalahan tersebut. Algoritma dengan proses pencarian terdiri dari Neighborhood dan mutasi tersebut memiliki delapan parameter. Penelitian ini menerapkan algoritma Viral Systems pada SMTWTP. Pengujian dilakukan untuk menganalisa parameter dan performansi algoritma dalam penyelesaian permasalahan. Hasil eksperimen menunjukkan bahwa setiap parameter memberikan pengaruh masing-masing terhadap algoritma dalam sisi hasil dan waktu komputasi. Eksperimen terhadap set data 40 pekerjaan, 50 pekerjaan, dan 100 pekerjaan menampilkan hasil bahwa algoritma dapat menyelesaikan 235 solusi optimal dari 275 permasalaha

Transient Pulse Formation in Jasmonate Signaling Pathway

The jasmonate (JA) signaling pathway in plants is activated as defense response to a number of stresses like attacks by pests or pathogens and wounding by animals. Some recent experiments provide significant new knowledge on the molecular detail and connectivity of the pathway. The pathway has two major components in the form of feedback loops, one negative and the other positive. We construct a minimal mathematical model, incorporating the feedback loops, to study the dynamics of the JA signaling pathway. The model exhibits transient gene expression activity in the form of JA pulses in agreement with experimental observations. The dependence of the pulse amplitude, duration and peak time on the key parameters of the model is determined computationally. The deterministic and stochastic aspects of the pathway dynamics are investigated using both the full mathematical model as well as a reduced version of it. We also compare the mechanism of pulse formation with the known mechanisms of pulse generation in some bacterial and viral systems

Adaptive evolution of transcription factor binding sites

The regulation of a gene depends on the binding of transcription factors to specific sites located in the regulatory region of the gene. The generation of these binding sites and of cooperativity between them are essential building blocks in the evolution of complex regulatory networks. We study a theoretical model for the sequence evolution of binding sites by point mutations. The approach is based on biophysical models for the binding of transcription factors to DNA. Hence we derive empirically grounded fitness landscapes, which enter a population genetics model including mutations, genetic drift, and selection. We show that the selection for factor binding generically leads to specific correlations between nucleotide frequencies at different positions of a binding site. We demonstrate the possibility of rapid adaptive evolution generating a new binding site for a given transcription factor by point mutations. The evolutionary time required is estimated in terms of the neutral (background) mutation rate, the selection coefficient, and the effective population size. The efficiency of binding site formation is seen to depend on two joint conditions: the binding site motif must be short enough and the promoter region must be long enough. These constraints on promoter architecture are indeed seen in eukaryotic systems. Furthermore, we analyse the adaptive evolution of genetic switches and of signal integration through binding cooperativity between different sites. Experimental tests of this picture involving the statistics of polymorphisms and phylogenies of sites are discussed.Comment: published versio

Tools for Controlling Activity of Neural Circuits Can Boost Gastrointestinal Research

We thank Prof U. G. Knaus and T. C. Collin for critical reading of the manuscript. GA is supported by the European Crohn's and Colitis Organization (ECCO) (J/15/2) and by the National Childrens' Research Centre (K/12/1). GD is supported by the University of Aberdeen Wellcome Trust Institutional Support Fund (105625/Z/14Z).Peer reviewedPublisher PD

The iscom structure as an immune enhancing moiety: experience with viral systems.

Review, Tutoria