The complexes: RhCl(P-N)(THP), where P-N is P,N-chelated o-diphenylphosphino-N,N-dimethylaniline and THP is tris(hydroxymethyl)phosphine, and RhCl[(O)P-N][THP(O)] containing O-bonded phosphine oxides

The complex RhCl(P-N)(THP) (1) is synthesized under argon from RhCl(cod)(THP) and P-N, and is structurally characterized; P-N = P,N-chelated o-diphenylphosphino-N,N-dimethylaniline, THP = tris(hydroxymethyl)phosphine, and cod = 1,5-cyclo-octadiene. The corresponding synthesis in air yields RhCl[(O)P-N][THP(O)] (2), containing O-bonded phosphine oxide ligands.     

TinkerCell: modular CAD tool for synthetic biology

Background

Synthetic biology brings together concepts and techniques from engineering and biology. In this field, computer-aided design (CAD) is necessary in order to bridge the gap between computational modeling and biological data. Using a CAD application, it would be possible to construct models using available biological "parts" and directly generate the DNA sequence that represents the model, thus increasing the efficiency of design and construction of synthetic networks.

Results

An application named TinkerCell has been developed in order to serve as a CAD tool for synthetic biology. TinkerCell is a visual modeling tool that supports a hierarchy of biological parts. Each part in this hierarchy consists of a set of attributes that define the part, such as sequence or rate constants. Models that are constructed using these parts can be analyzed using various third-party C and Python programs that are hosted by TinkerCell via an extensive C and Python application programming interface (API). TinkerCell supports the notion of a module, which are networks with interfaces. Such modules can be connected to each other, forming larger modular networks. TinkerCell is a free and open-source project under the Berkeley Software Distribution license. Downloads, documentation, and tutorials are available at http://www.tinkercell.com.

Conclusion

An ideal CAD application for engineering biological systems would provide features such as: building and simulating networks, analyzing robustness of networks, and searching databases for components that meet the design criteria. At the current state of synthetic biology, there are no established methods for measuring robustness or identifying components that fit a design. The same is true for databases of biological parts. TinkerCell's flexible modeling framework allows it to cope with changes in the field. Such changes may involve the way parts are characterized or the way synthetic networks are modeled and analyzed computationally. TinkerCell can readily accept third-party algorithms, allowing it to serve as a platform for testing different methods relevant to synthetic biology.     

Phylogeography and founder effect of the endangered Corsican red deer (<Emphasis Type="Italic">Cervus elaphus corsicanus</Emphasis>)

Red deer (n = 149) from eight geographical locations, including the endangered endemic populations from the Tyrrhenian islands (Sardinia and Corsica), were analysed at eight polymorphic microsatellite loci. Two questions were addressed: (1) Is there a founder effect in the Corsican population, which was reintroduced to the island using Sardinian deer after the species’ extinction on Corsica? (2) What is the origin of the Tyrrhenian or Corsican red deer (Cervus elaphus corsicanus)? Our results showed signs of a founder effect for the red deer on Corsica in that these deer showed differentiation from the Sardinian population as measured by F_ST values, assignment tests (with and without a priori definition of populations) and individual-based dendrograms. Genetic variability, however, did not differ significantly between the two populations. With respect to the phylogeography of C. e. corsicanus we found that both deer from North-Africa and Mesola on the Italian mainland were genetically close to the Corsican red deer, but phylogenetic trees based on genetic distances were only poorly supported statistically. Among all populations studied the Mesola red deer showed the lowest distance values from Corsican red deer and yielded allele frequencies that were more similar to those of C. e. corsicanus than were those of North-African red deer. These results are in line with recent palaeontological and archaeozoological findings which suggest that the Corsican red deer is derived from small Italian red deer introduced from the mainland to Sardinia and Corsica during the Late Neolithic and just before the beginning of Classical Antiquity, respectively. They also suggest a possible recent introduction of Tyrrhenian red deer to North-Africa (rather than the other way around), thus accounting for the close genetic relationship (especially based on mitochondrial DNA) that has repeatedly been found between C. e. corsicanus and C. e. barbarus.     

Skin homeostasis during inflammation: a role for nerve growth factor

The skin is a neuroendocrine immune organ in which many different molecules operate in autocrine-paracrine manner to guarantee tissue homeostatsis in physiological and pathophysiological conditions. In this paper we examined NGF and p75 receptor expression in the skin, during CFA induced inflammation, in a time-course study. We also examined cutaneus innervation and proliferation, by means of immunohistochemistry and quantitative image analysis, RT-PCR and Western blot. Spontaneous and evoked pain-behavior was also measured in experimental rats. The main results can be summarized as follows: 1). a peripheral sensory neuropathy develops in this condition, as indicated by thermal hyperalgesia, thus leading to a sensory denervation of the hind-paw skin as indicated by disappearance of CGRP and PGP9.5-IR fibers; 2). NGF and p75 expression (mRNA and protein) increases in the skin (keratinocytes) in the acute phase of CFA inflammation; 3). at this stage, a higher proliferative activity is observed in the skin, as defined by the expression of cell cycle-associated protein Ki67; 4). in the long-lasting chronic phase there is a further up-regulation of NFG and p75 expression in the skin; 5). trkA mRNA expression inversely correlates with p75 and NGF mRNA expression. These results suggest that CFA chronic inflammation evolves from inflammation to a small fibers sensory neuropathy and NGF seems to play a role in both events.     

Mouse early embryos obtained by natural breeding or in vitro fertilization display a differential sensitivity to extremely low-frequency electromagnetic fields

We have investigated the sensitivity of pre-implantation embryos obtained by natural breeding (NB) or in vitro fertilization (IVF) to extremely low-frequency magnetic fields (ELF-MF). Fertilized eggs obtained by NB were removed from mothers 12h after mating and cultured in vitro for 5 days under continuous ELF-MF exposure (constant strength of 50Hz and various intensities, i.e. 60, 120 and 220 microT). Alternatively, zygotes obtained by IVF were subjected to ELF-MF exposure (50Hz, 60 microT), starting 12h after IVF for 5 days. We found that ELF-MF exposure causes a small yet significant (P<0.05) decrease in the survival rate of NB-derived embryos at the latest stages of pre-implantation development, i.e. the eight cell-to-blastocyst transition. In embryos exposed to the highest field intensity (220 microT), the effect became apparent somewhat earlier. When IVF-derived embryos were exposed to ELF-MF, the reduction in the rate of embryo survival was more pronounced and the difference from controls was more significant (P<0.01). Moreover, the decreased survival rate in IVF embryos became apparent as early as the first cleavage and persisted throughout pre-implantation. These results suggest that IVF-derived embryos are more sensitive than NB-generated embryos to ELF-MF, and that this sensitivity occurs earlier in development.     

Oscillatory dynamics arising from competitive inhibition and multisite phosphorylation

There have been a growing number of observations of oscillating protein levels (p53 and NFkB) in eukaryotic signalling pathways. This has resulted in a renewed interest in the mechanism by which such oscillations might occur. Recent computational work has shown that a multisite phosphorylation mechanism such as that found in the MAPK cascade can theoretically exhibit bistability. The bistable behavior was shown to arise from sequestration and saturation mechanisms for the enzymes that catalyse the multisite phosphorylation cycle. These effects generate the positive feedback necessary for bistability. In this paper we describe two kinds of oscillatory dynamics which can occur in a network by which, both use such bistable multisite phosphorylated cycles. In the first example, the fully phosphorylated form of the phosphorylated cycle represses the production of the kinase, which carries out the phosphorylation of the unphosphorylated states of the cycle. The dynamics of this system leads to a relaxation oscillator. In the second example, we consider a cascade of two cycles, in which the fully phosphorylated form of the kinase, in the first cycle, phosphorylates the unphosphorylated forms in the second cycle. A feedback loop, by which the fully phosphorylated form of the second cycle inhibits the kinase step in the first cycle is also present. In this case we obtain a ring oscillator. Both these networks illustrate the versatility of the multisite bistable network.     

Regenerative medicine and liver injury: what role for bone marrow derived stem cells?

In recent years, great interest has been aroused by the discovery of the ability of adult stem cells to contribute to regeneration processes and repair of damaged tissues. In particular, bone marrow derived stem cells (BMSCs), the most well known population of multipotent stem cells in adults, have been shown to be able to generate many different committed cellular types. In this review, we systematically organize the numerous hypotheses emerging from the most recent studies, in animal and humans, which evaluated the potentiality of BMSCs to contribute to tissue repair in different types of liver damage. Our aim is to give scientists and clinicians who are interested in regenerative medicine the rational basis for planning future studies on stem cell therapy for liver diseases.