Geneticallyidentical rhesus monkeys would have tremendous utility as models for the study of human disease and would be particularly valuable for vaccine trials and tissue transplantation studies where immune function is important. While advances in nuclear transfer technology may someday enable monkeys to be cloned with some efficiency, embryo splitting may be a more realistic approach to creating pairs of geneticallyidentical monkeys. Although several different approaches to embryo splitting, including blastocyst bisection and blastomere separation, have been used successfully in rodents and domestic species for production of pairs and sets of identical offspring, efforts to create monozygotic twins in rhesus monkeys using these approaches have not met with similar success. Aggregation of split embryos with other types of blastomeres, such as tetraploid and developmentally asynchronous blastomeres, that could potentially increase their cell numbers and developmental competence without contributing to term development has been investigated as an alternative approach to creating monozygotic twin monkeys. The major challenges encountered with respect to the efficient production of monozygotic twins in rhesus monkeys and potential strategies to overcome these challenges are discussed.
UL128-131 or gH/gL/gO (ME and ME-T, respectively, avoided many of the caveats associated with null mutants. Since the viruses are not devoid of either gH/gL/gO or gH/gL/UL128-131, they are theoretically capable of employing physiologically relevant viral entry mechanisms on all cell types, albeit with different efficien- cies. Furthermore, since they are geneticallyidentical viruses, after the initial entry event, replication and plaque spread should be identical. Indeed, plaque sizes and morphologies were indistin- guishable on all cells lacking TetR expression (35). The higher particle-to-PFU ratio of ME than of ME-T on both fibroblasts and epithelial cells indicated that a greater fraction of virions in ME stocks failed to form plaques. Experiments involving PEG-in- duced fusion indicated that these ME virions failed largely because they could not accomplish the fusion event of entry. The fate of nonfusing virions is unclear but may include endocytosis and de- struction within the lysosome. Regardless, these results are incon- sistent with the model that gH/gL/gO and gH/gL/UL128-131 are each sufficient as a herpesvirus core fusion gH/gL for entry into fibroblasts and epithelial cells, respectively. Rather, it is more likely that only gH/gL/gO performs the conserved herpesvirus gH/gL function of promoting gB-mediated membrane fusion during entry into all cell types and gH/gL/UL128-131 provides a distinct, yet necessary, function for entry into select cell types, such as epithelial cells.
The main goal to iden tify genetic differences between genetically highly similar T. cf. atroviride strains LU132 and LU140 by whole genome comparison was successful. A strain-specific molecular marker for T. cf. atroviride LU132 was successfully designed and validated. Further analysis of the polymorphic gene, containing the non-synonymous SNP1, highlighted that even apparently geneticallyidentical strains (1serf mutants) can have different phenotypes and that natural strains with different phenotypes (LU132 and LU140) can be genetically extremely similar. Even though whole genome sequencing is an important tool for fundamental and applied research, the definition of an individual is not exclusively defined by its DNA sequence. In the microbiological context, this creates limitations for molecular strain typing to identify efficient biocontrol strains or pathogens and implies that these techniques should not be applied in isolation but should always be combined with phenotypic characterisation.
Five strains of an unknown, multidrug-resistant coryneform, gram-positive rod were isolated from blood, bronchial aspirate, and abscess specimens. Four of the five strains isolated were highly resistant to antimi- crobial agents, including ␤ -lactams, aminoglycosides, macrolides, quinolones, and tetracyclines, except for glycopeptides. In immunocompromised patients, bacteremia associated with this organism was rapidly fatal. This coryneform bacterium was nonmotile, lipophilic, and nonsaccharolytic. Lack of pyrazinamidase activity differentiated this organism from other lipophilic corynebacteria. Chemotaxonomic studies indicated that this multidrug-resistant coryneform bacterium belongs to the genus Corynebacterium. Comparative 16S rRNA gene sequencing and DNA-DNA hybridization analyses revealed that the five isolates were geneticallyidentical and that they represent a new subline within the genus Corynebacterium, for which we propose the designation Corynebacterium resistens sp. nov. The type strain of Corynebacterium resistens is GTC 2026 T
Although GMO regulations differ in different regions of the world, the ability to construct strains that are geneticallyidentical to strains that were “ selected natu- rally ” or modified using non-GMO technologies demon- strates that simply using a plasmid to construct a strain does not yield a strain that is inherently any more dan- gerous than non-GMO strains. Consider the following hypothetical example: a researcher would like to generate a probiotic bacterium that is resistant to high concentra- tions of human bile. To isolate such a resistant mutant, the cells are plated in the presence of bile, a bile resistant mutant is isolated and its genome is sequenced. A single base pair alteration in the hypothetical gene bilE is iden- tified as the mutation yielding the bile resistant pheno- type. Utilizing SSDR technology, this identical mutation in bilE is constructed in the probiotic organism with the subsequent plasmid containing recT removed. Deep sequencing technology allows us to confirm that no for- eign DNA remains in the cell, and no additional muta- tions have occurred. Thus we have two strains that, by any measure, are genetically 100% identical. If the reason for designating a strain as GMO is for public safety, then there were no reason to believe that in the above example a strain mutated by SSDR would be less safe than a genetic identical non-GMO derivative.
Despite recent major clinical breakthroughs in human cancer immunotherapy including the use of checkpoint inhibitors and engineered T cells, important challenges remain, including determining the sub-populations of patients who will respond and who will experience at times significant toxicities. Although advances in cancer immunotherapy depend on preclinical testing, the majority of in-vivo testing currently relies on geneticallyidentical inbred mouse models which, while offering critical insights regarding efficacy and mechanism of action, also vastly underrepresent the heterogeneity and complex interplay of human immune cells and cancers. Additionally, laboratory mice uncommonly develop spontaneous tumors, are housed under specific-pathogen free conditions which markedly impacts immune development, and incompletely model key aspects of the tumor/immune microenvironment. The canine model represents a powerful tool in cancer immunotherapy research as an important link between murine models and human clinical studies. Dogs represent an attractive outbred combination of companion animals that experience spontaneous cancer development in the setting of an intact immune system. This allows for study of complex immune interactions during the course of treatment while also directly addressing long-term efficacy and toxicity of cancer immunotherapies. However, immune dissection requires access to robust and validated immune assays and reagents as well as appropriate numbers for statistical evaluation. Canine studies will need further optimization of these important mechanistic tools for this model to fulfill its promise as a model for immunotherapy. This review aims to discuss the canine model in the context of existing preclinical cancer immunotherapy models to evaluate both its advantages and limitations, as well as highlighting its growth as a powerful tool in the burgeoning field of both human and veterinary immunotherapy.
Perfect synchrony corresponds to a form of dimension reduction, since the net- work is effectively replaced by a single self-coupled neuron. However, the stability of this state depends on the linearisation of the full dynamics around it. In this paper we use another form of dimension reduction, the Watanabe/Strogatz (WS) ansatz [9, 10], applicable to all-to-all coupled networks of identical phase oscillators. For the ansatz to be applicable, the velocity field of an oscillator has to contain only the first harmonics of the phase variable. The theta neuron [11, 12] is such a model oscillator. The derivation of a network of coupled phase oscillators from a general weakly- coupled network of oscillators is well known [7, 13, 14]. Unlike those derivations, the equation for a theta neuron, involving just one phase variable, is the normal form of a saddle-node-on-a-circle (SNIC) bifurcation, and will thus describe all neurons undergoing this bifurcation, at least in some neighbourhood in a parameter space of the bifurcation. Such a bifurcation leads to the neuron being of Type I [15, 16], i.e. capable of firing at arbitrarily low frequencies.
As the search deepened, the topic evolved from GM food labeling issues to public safety after it was discovered that new GM food labeling laws were becoming effective in Connecticut on October 1, 2013, with bills in other states in the works. It should be noted that food labeling does not guarantee public safety, but provides one measure that empowers the public to make informed choices for themselves and their families. Based on these findings, the search focus then became the safety assurance of genetically modified salmon. Additional sources were pulled from the original articles identified by the initial literature search findings listed in Appendix A. The review of these additional sources revealed that there are many public health issues under debate regarding GM foods, including environmental, health, and regulatory
We have considered a set of identical twin brothers who were born with the same genetic structures. It is assumed that, after the birth, they reside and grow up in two different locations, and under different environmental conditions. One of them, say A, lives in a polluted environment and under external stresses, but brother B does not.
Of prime importance and long overdue is an inclusive discussion on the appropriate testable, scientific hypoth- eses and methodologies that are supportive of the provi- sions and tasks formulated by the EU legal framework on risk assessment of GM organisms. The EU law is based on the axiom that risks, which may be caused by GM organisms, cannot be a priori-deducted from ex- perience with existing organisms. Due to their genomic and evolutionary novelty, specific laws regulate the test- ing in the open environment and the market approval process of GM organisms since 1990. Therefore, the EU Directive 2001/18 on the deliberate release into the en- vironment of genetically modified organisms clearly states as a ‘General Principle’ for environmental risk as- sessment that ‘identified characteristics of the GMO and its use which have the potential to cause adverse effects should be compared to those presented by the non- modified organism from which it is derived and its use under corresponding situations’. Nowhere does this Directive or the Regulation (EC) No 1829/2003 on gen- etically modified food and feed suggest that GM organ- isms also need to be compared to unrelated control organisms in the context of risk assessment (see Regulation
Dispersion of the activities from the activity pool to the identical processors and then schedules them efficiently is an interesting problem area for researchers. The most important thing is developing a quick and efficient heuristic algorithm so that the variance limit of waiting time should be minimized. The main focus of this paper is developing an efficient and quick solution for such problem when the size of the activity grows up exponentially. When the activity grows exponentially then the problems are known as hardest form of combinatorial optimization problem and belong to NP-hard class. Finding an exact solution (i.e. schedule) is really impossible for these categories of problem in polynomial time. Hence heuristic conspire is the only way for finding solutions.