Linear viscoelastic properties of the vertex model for epithelial tissues

Epithelial tissues act as barriers and, therefore, must repair themselves, respond to environmental changes and grow without compromising their integrity. Consequently, they exhibit complex viscoelastic rheological behavior where constituent cells actively tune their mechanical properties to change the overall response of the tissue, e.g., from solid-like to fluid-like. Mesoscopic mechanical properties of epithelia are commonly modeled with the vertex model. While previous studies have predominantly focused on the rheological properties of the vertex model at long time scales, we systematically studied the full dynamic range by applying small oscillatory shear and bulk deformations in both solid-like and fluid-like phases for regular hexagonal and disordered cell configurations. We found that the shear and bulk responses in the fluid and solid phases can be described by standard spring-dashpot viscoelastic models. Furthermore, the solid-fluid transition can be tuned by applying pre-deformation to the system. Our study provides insights into the mechanisms by which epithelia can regulate their rich rheological behavior.     

When do meadow vipers (Vipera ursinii) become sexually dimorphic? – ontogenetic patterns of sexual size dimorphisms

Contrary to an increasing number of papers that document sexual dimorphism in size (and/or shape) in adults, studies dealing with sex differences in newborn and juvenile snakes are surprisingly scarce. Data about ontogenetic shifts in sexual dimorphism are generally lacking and hence, it is unclear whether sex differences are set at birth or arise post‐natally. In this study, we analyzed patterns of sexual dimorphism in body size, head dimensions and tail length (TL) among newborn, subadult and adult meadow vipers (Vipera ursinii) from the Bjelasica Mt. in Montenegro. Patterns of sexual size dimorphisms differed among traits. There was no significant difference in head dimension of males and females, but adult snakes were sexually dimorphic in body size. Sexual differences in TL were evident since birth but changed in degree throughout ontogeny. Neonate meadow vipers presented highly significant inter‐litter variation in the sexual dimorphism of all traits we have measured. Such family effects may have an important influence on extent of inter‐sexual differences in snakes and should be included in analyses of sexual dimorphism.     

Value of image cytometry in the subclassification of rhabdomyosarcoma

OBJECTIVE: To test the discriminatory capability of nuclear features in the subclassification of rhabdomyosarcoma (RMS) and especially to differentiate embryonal from alveolar RMS. STUDY DESIGN: The study included 42 patients with RMS. We performed the analysis on Feulgen-stained filtrates of cell suspensions prepared from deparaffinized tissue sections. Image analysis was performed by an automated, high-resolution image cytometer on at least 200 nuclear images. Photometric, morphometric and nuclear texture features were analyzed. Probability density distributions were calculated for each nuclear feature of individual RMS subgroups and compared in order to detect possible differences. RESULTS: There were significant differences between embryonal and alveolar RMS in five nuclear features: DNA index, sphericity, elongation, low_DNA_area and fractall_area. We were able to differentiate between the two main RMS subgroups in 82% of cases on the basis of either sphericity or elongation alone, while the power of differentiation for texture features was 72-79%. CONCLUSION: Differentiation between embryonal and alveolar RMS using one nuclear feature is not an important adjunct to light microscopy. However, the possibility of using a combination of nuclear features would probably increase the discriminatory ability.     

Electrochemical bromination of cholest-5-enes

Four 5,6-unsaturated steroids--3beta-chlorocholest-5-ene (1a), cholesterol (1b) and its acetate (1c) and benzoate (1d)-were subjected to constant current electrolysis (50 mA, 2 F mol(-1)) in an electrolytic cell divided by a ceramic membrane, using a platinum foil as the anode and a graphite stick as the cathode. When electrolysis was carried out in a solution of tetraethylammonium bromide in aprotic solvents (dichloromethane, acetonitrile or acetic anhydride), the addition of electrochemically-generated elemental bromine onto the double bond of the cholesterol derivatives gave their corresponding 5alpha,6beta-dibromosteroids--3beta-chloro-5alpha,6beta-dibromocholestane (2a), 5alpha,6beta-dibromocholestan-3beta-ol (2b), 5alpha,6beta-dibromocholestan-3beta-yl acetate (2c) and 5alpha,6beta-dibromocholestan-3beta-yl benzoate (2d)--as the sole products, and in good yields (58-91%). However, the electrolysis of steroids 1a-c in a solution of tetraethylammonium bromide with methanol as the solvent proceeded to give, in addition to dibromides 2a-c, the corresponding diastereomeric pairs of 5-bromo-6-methoxysteroids: 5alpha-bromo-3beta-chloro-6beta-methoxycholestane (3a) and 5beta-bromo-3beta-chloro-6alpha-methoxycholestane (4a), 5alpha-bromo-6beta-methoxycholestan-3beta-ol (3b) and 5beta-bromo-6alpha-methoxycholestan-3beta-ol (4b) and 5alpha-bromo-6beta-methoxycholestan-3beta-yl acetate (3c) and 5alpha-bromo-6beta-methoxycholestan-3beta-yl acetate (4c). The benzoate 1d was not soluble enough in methanol, even with heating. The products were characterized by physical and spectral data (IR, 1H NMR and 13C NMR). Single crystal X-ray structure determinations of compounds 2a and 3a are also reported.     

Carboxypeptidases cathepsins X and B display distinct protein profile in human cells and tissues

Cathepsin X, a recently discovered lysosomal cysteine protease, shares common structural features and activity properties with cysteine protease cathepsin B. Based on its widespread mRNA distribution in primary tumors and tumor cell lines, a redundant function in tumor progression has been proposed. In this study, we have shown that these two related proteases exhibit different profiles with respect to their protein distribution in cells and tissues and to their possible roles in malignancy. Protein level of cathepsin X did not differ significantly between matched pairs of lung tumor and adjacent lung tissue obtained from patients with lung cancer whereas that of cathepsin B was 9.6-fold higher in tumor compared to adjacent lung tissue. Immunohistochemical analysis of lung tumor cathepsin X revealed very faint staining in tumor cells but positive staining in infiltrated histiocytes, alveolar macrophages, bronchial epithelial cells, and alveolar type II cells. Cathepsin X stained positive also in CD68+ cells in germinal centers of secondary follicles in lymph nodes, corresponding to tingible body macrophages. Two cell lines with proven invasive behavior, MCF-10A neoT and MDA-MB 231, showed positive staining for cathepsin B, but negative for cathepsin X. We showed that the invasive potential of MCF-10A neoT cells can be impaired by specific inhibitor of cathepsin B but not by that of cathepsin X. Cathepsin X was found in large amounts in the pro-monocytic U-937 cell line, in monocytes and in dendritic cells, generated from monocytes in vitro. Our results show that cathepsin X is not involved in degradation of extracellular matrix, a proteolytic event leading to tumor cell invasion and metastasis. Its expression, restricted to immune cells suggests a role in phagocytosis and the regulation of immune response.     

Electrochemical synthesis and X-ray crystal structures of beta-D-2-phenylselenyl-1,3,4,6-tetra-O-acetylglucopyranose and alpha-D-2-phenylselenyl-1,3,4,6-tetra-O-acetylmannopyranose

Electrochemical acetoxyphenylselenation of 3,4-dihydro-2H-pyran and D-3,4,6-tri-O-acetylglucal was studied. The constant current electrolysis (50mA) of dihydropyran and diphenyl diselenide in an acetic acid solution of tetramethylammonium chloride was performed at room temperature in an undivided cell using a graphite anode and an aluminum cathode and yielded trans-DL-2-acetoxy-3-phenylselenyltetrahydropyran (27%), in agreement with Markovnikov's rule. The analysis of the 1H NMR spectral data showed that the acetoxy and phenylselenyl groups adopt axial positions in the most stable conformation of this compound due to the anomeric effect. Under the same conditions D-3,4,6-tri-O-acetylglucal afforded D-2-phenylselenyl-1,3,4,6-tetra-O-acetylglucopyranose and D-2-phenylselenyl-1,3,4,6-tetra-O-acetylmannopyranose, which were separated by column chromatography and isolated in 87% overall yield (isomer ratio 60:40). The structures of these compounds were established by spectral data. Single crystal X-ray structure determinations of the diastereomers are reported.     

Sulfur‐Containing Ferrocenyl Alcohols and Oximes: New Promising Antistaphylococcal Agents

A small library containing four different series of new ferrocene derivatives, 2‐(alkylsulfanyl)‐1‐ferrocenylethan‐1‐ols, 3‐(alkylsulfanyl)‐1‐ferrocenylpropan‐1‐ols, (E)‐ and (Z)‐2‐(alkylsulfanyl)‐1‐ferrocenylethan‐1‐one oximes, and (E)‐ and (Z)‐3‐(alkylsulfanyl)‐1‐ferrocenylpropan‐1‐one oximes (36 different compounds in total) was synthesized starting from ferrocene and the corresponding sulfanyl acids. All compounds were spectrally (IR and NMR) and electrochemically characterized. In general, the obtained compounds were found to exhibit very strong antimicrobial activities (broth microdilution assay) against the tested microorganisms (six common human pathogens). For the majority of the tested compounds, the determined MIC values were either under the 10 μg/ml MIC limit recognized to delimit efficient antimicrobials or were comparable to/lower than those of the used positive controls (tetracycline/nystatin). The most susceptible organism was found to be Staphylococcus aureus with MIC values even reaching 0.001 μg/ml. The presence of ? CH(OH)(CH₂)_nS? and ? CH(?NOH)(CH₂)_nS? (n=1 or 2) structural fragments seems to be essential for the observed strong activity (introduction of hydroxyimino and alcohol functionalities, instead of the keto function, resulted in a more than 10⁵‐fold increase in antistaphylococcal activity in some instances). Nevertheless, a possible influence of the ferrocenyl‐core redox chemistry (Fe²⁺/Fe³⁺) should not be disregarded. The studied alcohols exhibited a reversible one‐electron redox couple at almost the same position as ferrocene, while the hydroxyimino group conjugated with cyclopentadienyl ring considerably shifted the redox potential of the ferrocene unit in oximes.     

Synthesis and antimicrobial activity of some new pyrazole derivatives containing a ferrocene unit

A series of new imines and amines have been synthesized by condensation of 1H-3-ferrocenyl-1-phenylpyrazole-4-carboxaldehyde with the corresponding amines, followed by reduction with sodium borohydride. The synthesized compounds have been screened for their in vitro antimicrobial activity against 11 bacteria and three fungal/yeast strains, using disc diffusion and broth microdilution susceptibility assays. They have shown a wide range of activities, from completely inactive to the highly active compounds.     

Synthesis, characterization, electrochemical studies and antitumor activity of some new chalcone analogues containing ferrocenyl pyrazole moiety

A series of new α,β-unsaturated conjugated ketones containing ferrocenyl pyrazole unit were synthesized and fully characterized by IR and NMR spectroscopy. Electrochemical characterization of subject compounds was performed by means of cyclic voltametry. The in vitro cytotoxic activity of all the synthesized compounds was studied against cervix adenocarcinoma HeLa, melanoma Fem-x and myelogenous leukemia K562 cell lines by the MTT method. Derivative 1l containing 3-pyridyl moiety exhibited a better cytotoxic activity in the cell growth inhibition of K562 cell lines in comparison with cisplatin as a reference compound.     

Moving in the real world: tortoises take the plunge to cross steep steps

Despite exhibiting low velocity and limited agility, many tortoises undertake large scale movements and must overcome various obstacles, notably in populations living in hilly or rocky habitats. Although crucial, studies exploring how tortoises move in complex and irregular environments are scarce. In this context, we examined an important behavioural trait: how tortoises (Testudo hermanni) deal with step‐like obstacles. In their natural habitat, individuals were positioned in a challenging situation: they were placed on a bench approximately 50 cm high, and were observed over a 10‐min period. We compared the behaviour of the tortoises (taking a risk to ‘jump’ or waiting) from two populations living in contrasted habitats: flat versus rugged (crisscrossed by cliffs and rocky steps). Individuals from the flat habitat were reluctant to jump, whereas most tortoises from the rugged habitat jumped. Immature tortoises were less willing to jump compared to larger and more experienced adults. These results suggest that challenging habitats increase boldness. In addition to fundamental findings, these results may have conservation value and assist in improving translocation strategies for endangered tortoise populations. © 2013 The Linnean Society of London