Mitotic slippage in non-cancer cells induced by a microtubule disruptor,disorazole C<Subscript>1</Subscript>

Background

Disorazoles are polyene macrodiolides isolated from a myxobacterium fermentation broth. Disorazole C₁ was newly synthesized and found to depolymerize microtubules and cause mitotic arrest. Here we examined the cellular responses to disorazole C₁ in both non-cancer and cancer cells and compared our results to vinblastine and taxol.

Results

In non-cancer cells, disorazole C₁ induced a prolonged mitotic arrest, followed by mitotic slippage, as confirmed by live cell imaging and cell cycle analysis. This mitotic slippage was associated with cyclin B degradation, but did not require p53. Four assays for apoptosis, including western blotting for poly(ADP-ribose) polymerase cleavage, microscopic analyses for cytochrome C release and annexin V staining, and gel electrophoresis examination for DNA laddering, were conducted and demonstrated little induction of apoptosis in non-cancer cells treated with disorazole C₁. On the contrary, we observed an activated apoptotic pathway in cancer cells, suggesting that normal and malignant cells respond differently to disorazole C₁.

Conclusion

Our studies demonstrate that non-cancer cells undergo mitotic slippage in a cyclin B-dependent and p53-independent manner after prolonged mitotic arrest caused by disorazole C₁. In contrast, cancer cells induce the apoptotic pathway after disorazole C₁ treatment, indicating a possibly significant therapeutic window for this compound.

     

Bis[4‐(dimethylamino)pyridine‐κN1]silver(I) nitrate dihydrate

The title compound, [Ag(C₇H₁₀N₂)₂]NO₃·2H₂O or [Ag(dmap)₂]NO₃·2H₂O, where dmap is 4‐(dimethylamino)pyridine, has a distorted linear coordination geometry around the Ag^I ion. A novel pattern of water–nitrate hydrogen‐bonded anionic strands is formed in the c direction, with the cationic [Ag(dmap)₂]⁺ monomers trapped between them. The Ag^I ion and the nitrate group atoms, as well as the water molecules (including the H atoms), are on a crystallographic mirror plane (Wyckoff position 4a). The influence of bulky methyl substituents in position 4 of the 4‐(dimethylamino)pyridine ligand on packing is discussed. The absolute structure was determined unequivocally.     

A remark on the range of elementary operators

Let L(H) denote the algebra of all bounded linear operators on a separable infinite dimensional complex Hilbert space H into itself. Given A ∈ L(H), we define the elementary operator Δ _A : L(H) → L(H) by Δ _A (X) = AXA − X. In this paper we study the class of operators A ∈ L(H) which have the following property: ATA = T implies AT*A = T* for all trace class operators T ∈ C ₁(H). Such operators are termed generalized quasi-adjoints. The main result is the equivalence between this character and the fact that the ultraweak closure of the range of Δ _A is closed under taking adjoints. We give a characterization and some basic results concerning generalized quasi-adjoints operators.     

Vector subspaces and operators with the Stone condition

We introduce the notion of an operating function on a subset of a F{\Phi} -algebra E. Then we use this notion to generalize results from Huijsmans and de Pagter (Proc. Lond. Math. Soc. 48:161–174, 1984) about the connection between vector subspaces and subalgebras of E. In the second part we investigate the analogous problem for operators.     

A Mathematical Programming Based Procedure for Breast Cancer Classification

In this paper we propose a new procedure for classification based on a hybrid approach. The classification problem is solved by minimizing the distance between the components of each clusters and the centers of the clusters. The determination of the cluster centers is therefore a critical step in our approach and was addressed used the k-means algorithm. Once the centers of each class are determined, the rule of center neighbourhood is applied to assign an element to a class using mathematical programming. The implementation of our hybrid approach was validated on benchmark datasets and applied to an original biological dataset on 84 breast cancer tumours. Each tumour was measured for five parameters corresponding to the expression of five biomarkers (proteins). The obtained classification was discussed using biological knowledge and classical clinical experts’ classification of breast tumors.     

Three-dimensional thermal shock problem of generalized thermoelastic half-space

A three-dimensional model of the generalized thermoelasticity with one relaxation time is established. The resulting non-dimensional coupled equations together with the Laplace and double Fourier transforms techniques are applied to a specific problem of a half space subjected to thermal shock and traction free surface. The inverses of Fourier transforms and Laplace transforms are obtained numerically by using the complex inversion formula of the transform together with Fourier expansion techniques. Numerical results for the temperature, thermal stress, strain and displacement distributions are represented graphically.     

Variational principle of fractional order generalized thermoelasticity

Recently, Youssef constructed a new theory of fractional order generalized thermoelasticity by taking into account the theory of heat conduction in deformable bodies, which depends upon the idea of the Riemann–Liouville fractional integral operator. In this paper, the variational theorem is obtained for the generalized thermoelasticity model for a homogeneous and isotropic body.     

On the distribution function with respect to conditional expectation on Riesz spaces

The notion of distribution function with respect to a conditional expectation is defined and studied in the framework of Riesz spaces.     

The effect of chemical composition on microfibrillar cellulose films from wood pulps: water interactions and physical properties for packaging applications

The interactions with water and the physical properties of microfibrillated celluloses (MFCs) and associated films generated from wood pulps of different yields (containing extractives, lignin, and hemicelluloses) have been investigated. MFCs were produced by combining mechanical refining and a high pressure treatment using a homogenizer. The produced MFCs were characterized by morphology analysis, water retention, hard-to-remove water content, and specific surface area. Regardless of chemical composition, processing to convert macrofibrils to microfibrils resulted in a decrease in water adsorption and water vapor transmission rate, both important properties for food packaging applications. After homogenization, MFCs with high lignin content had a higher water vapor transmission rate, even with a higher initial contact angle, hypothesized to be due to large hydrophobic pores in the film. A small amount of paraffin wax, less than 10%, reduced the WVTR to a similar value as low density polyethylene. Hard-to-remove water content correlated with specific surface area up to approximately 50 m²/g, but not with water retention value. The drying rate of the MFCs increased with the specific surface area. Hornified fibers from recycled paper also have the potential to be used as starting materials for MFC production as the physical and optical properties of the films were similar to the films from virgin fibers. In summary, the utilization of lignin containing MFCs resulted in unique properties and should reduce MFC production costs by reducing wood, chemical, and energy requirements.