Platinum(II)-Acyclovir Complexes: Synthesis, Antiviral and Antitumour Activity

A platinum(II) complex with the antiviral drug acyclovir was synthesized and its antiviral and anticancer properties were investigated in comparison to those of acyclovir and cisplatin. The platinum-acyclovir complex maintained the antiviral activity of the parent drug acyclovir, though showing a minor efficacy on a molar basis (ID50  =   7.85 and 1.02 μΜ for platinum-acyclovir and cisplatin, respectively). As anticancer agent, the platinum-acyclovir complex was markedly less potent than cisplatin on a mole-equivalent basis, but it was as effective as cisplatin when equitoxic dosages were administered in vivo to P388 leukaemia-bearing mice (%T/C = 209 and 211 for platinum-acyclovir and cisplatin, respectively). The platinum-acyclovir complex was also active against a cisplatin-resistant subline of the P388 leukaemia (%T/C = 140), thus suggesting a different mechanism of action. The DNA interaction properties (sequence specificity and interstrand cross-linking ability) of platinum-acyclovir were also investigated in comparison to those of cisplatin and [Pt(dien)Cl]+, an antitumour-inactive platinum-triamine compound. The results of this study point to a potential new drug endowed, at the same time, with antiviral and anticancer activity and characterized by DNA interaction properties different from those of cisplatin

The structure of uniform discrete defective crystals

In the continuum context, a uniform crystal has dislocation density tensor constant in space. A simple iteration procedure generates an infinite set of points which is associated with uniform defective crystals. When certain necessary conditions are satisfied, there is a minimum (non-zero) separation of points in this set, so the set is discrete. We describe the structure of such sets explicitly, and show in particular that any such set is either a simple lattice or a 4-lattice

The vasa regulatory region mediates germline expression and maternal transmission of proteins in the malaria mosquito Anopheles gambiae: a versatile tool for genetic control strategies

<p>Abstract</p> <p>Background</p> <p>Germline specific promoters are an essential component of potential vector control strategies which function by genetic drive, however suitable promoters are not currently available for the main human malaria vector <it>Anopheles gambiae</it>.</p> <p>Results</p> <p>We have identified the <it>Anopheles gambiae vasa</it>-like gene and found its expression to be specifically localized to both the male and female gonads in adult mosquitoes. We have functionally characterised using transgenic reporter lines the regulatory regions required for driving transgene expression in a pattern mirroring that of the endogenous <it>vasa </it>locus. Two reporter constructs indicate the existence of distinct <it>vasa </it>regulatory elements within the 5' untranslated regions responsible not only for the spatial and temporal but also for the sex specific germline expression. <it>vasa </it>driven eGFP expression in the ovary of heterozygous mosquitoes resulted in the progressive accumulation of maternal protein and transcript in developing oocytes that were then detectable in all embryos and neonatal larvae.</p> <p>Conclusion</p> <p>We have characterized the <it>vasa </it>regulatory regions that are not only suited to drive transgenes in the early germline of both sexes but could also be utilized to manipulate the zygotic genome of developing embryos via maternal deposition of active molecules. We have used computational models to show that a homing endonuclease-based gene drive system can function in the presence of maternal deposition and describe a novel non-invasive control strategy based on early <it>vasa </it>driven homing endonuclease expression.</p

In vitro evaluation of antiviral and virucidal activity of a high molecular weight hyaluronic acid.

BACKGROUND: hyaluronic acid (HA), a non-sulphated glycosaminoglycan, is present in synovial fluid, vitreous humour serum and many connective tissues. Pharmaceutical preparations of HA are used in clinical practice for wound healing, joint pain, kerato-conjunctivitis, asthma, mouth care, oesophageal-reflux, and gastritis. Moreover, it is used as a filler to counteract ageing and facial lipoatrophy. Our study aims at investigating the in vitro antiviral activity of a high molecular weight HA.METHODS: the MTT test was used to rule out the potential toxic effects of HA on the different cell lines used in the antiviral assays. The antiviral activity of HA against Coxsackievirus B5, Herpes simplex virus-1, Mumps virus, Adenovirus-5, Influenza Virus A/H1N1, Human Herpesvirus-6, Porcine Parvovirus, Porcine Reproductive and Respiratory Syndrome Virus was assessed by virus yield assays.RESULTS: the most effective inhibition was observed against Coxsackievirus B5, with 3Log reduction of the virus yield at 4mg/ml, and a reduction of 3.5Log and 2Log, at 2mg/ml and 1mg/ml, respectively: the selectivity index was 16. Mumps virus was highly inhibited too showing a reduction of 1.7Log at 1mg/ml and 1Log at 4mg/ml and 2mg/ml (selectivity index = 12). The selectivity index for Influenza Virus was 12 with the highest inhibition (1Log) observed at 4mg/ml. Herpes simplex virus-1 and Porcine Parvovirus were mildly inhibited, whereas no antiviral activity was observed with respect to Adenovirus-5, Human Herpesvirus-6, Porcine Reproductive and Respiratory Syndrome Virus. No HA virucidal activity was ever observed against any of the viruses tested. Kinetic experiments showed that both Coxsackievirus B5 and Herpes simplex virus-1 replication were consistently inhibited, not influenced by the time of HA addition, during the virus replication cycle.CONCLUSIONS: the spectrum of the antiviral activity exhibited by HA against both RNA and DNA viruses, known to have different structures (with or without envelope) and replication strategies, suggests a non specific mechanism of action, probably involving cell membrane-virus interaction steps. The results of the kinetic experiments support this hypothesis

Elastic symmetries of defective crystals

I construct discrete and continuous crystal structures that are compatible with a given choice of dislocation density tensor, and (following Mal’cev) provide a canonical form for these discrete structures. The symmetries of the discrete structures extend uniquely to symmetries of corresponding continuous structures—I calculate these symmetries explicitly for a particular choice of dislocation density tensor and deduce corresponding constraints on energy functions which model defective crystals

Rotational symmetries of crystals with defects

I use the theory of Lie groups/algebras to discuss the symmetries of crystals with uniform distributions of defects

On the Interface Formation Model for Dynamic Triple Lines

This paper revisits the theory of Y. Shikhmurzaev on forming interfaces as a continuum thermodynamical model for dynamic triple lines. We start with the derivation of the balances for mass, momentum, energy and entropy in a three-phase fluid system with full interfacial physics, including a brief review of the relevant transport theorems on interfaces and triple lines. Employing the entropy principle in the form given in [Bothe & Dreyer, Acta Mechanica, doi:10.1007/s00707-014-1275-1] but extended to this more general case, we arrive at the entropy production and perform a linear closure, except for a nonlinear closure for the sorption processes. Specialized to the isothermal case, we obtain a thermodynamically consistent mathematical model for dynamic triple lines and show that the total available energy is a strict Lyapunov function for this system

Geometrical structure of two-dimensional crystals with non-constant dislocation density

We outline mathematical methods which seem to be necessary in order to discuss crystal structures with non-constant dislocation density tensor(ddt) in some generality. It is known that, if the ddt is constant (in space), then material points can be identified with elements of a certain Lie group, with group operation determined in terms of the ddt - the dimension of the Lie group equals that of the ambient space in which the body resides, in that case. When the ddt is non-constant, there is also a relevant Lie group (given technical assumptions), but the dimension of the group is strictly greater than that of the ambient space. The group acts on the set of material points, and there is a non-trivial isotropy group associated with the group action. We introduce and discuss the requisite mathematical apparatus in the context of Davini's model of defective crystals, and focus on a particular case where the ddt is such that a three dimensional Lie group acts on a two dimensional crystal state - this allows us to construct corresponding discrete structures too

A classification of the symmetries of uniform discrete defective crystals

Crystals which have a uniform distribution of defects are endowed with a Lie group description which allows one to construct an associated discrete structure. These structures are in fact the discrete subgroups of the ambient Lie group. The geometrical symmetries of these structures can be computed in terms of the changes of generators of the discrete subgroup which preserve the discrete set of points. Here a classification of the symmetries for the discrete subgroups of a particular class of three-dimensional solvable Lie group is presented. It is a fact that there are only three mathematically distinct types of Lie groups which model uniform defective crystals, and the calculations given here complete the discussion of the symmetries of the corresponding discrete structures. We show that those symmetries corresponding to automorphisms of the discrete subgroups extend uniquely to symmetries of the ambient Lie group and we regard these symmetries as (restrictions of) elastic deformations of the continuous defective crystal. Other symmetries of the discrete structures are classified as ‘inelastic’ symmetries

Gebiss: an ImageJ plugin for the specification of ground truth and the performance evaluation of 3D segmentation algorithms.

Background: Image segmentation is a crucial step in quantitative microscopy that helps to define regions of tissues, cells or subcellular compartments. Depending on the degree of user interactions, segmentation methods can be divided into manual, automated or semi-automated approaches. 3D image stacks usually require automated methods due to their large number of optical sections. However, certain applications benefit from manual or semi-automated approaches. Scenarios include the quantification of 3D images with poor signal-to-noise ratios or the generation of so-called ground truth segmentations that are used to evaluate the accuracy of automated segmentation methods. Results: We have developed Gebiss; an ImageJ plugin for the interactive segmentation, visualisation and quantification of 3D microscopic image stacks. We integrated a variety of existing plugins for threshold-based segmentation and volume visualisation. Conclusions: We demonstrate the application of Gebiss to the segmentation of nuclei in live Drosophila embryos and the quantification of neurodegeneration in Drosophila larval brains. Gebiss was developed as a cross-platform ImageJ plugin and is freely available on the web at http://imaging.bii.a-star.edu.sg/projects/gebiss