On the influence of cell shape on dynamic reaction-diffusion polarization patterns.

The distribution of signaling molecules following mechanical or chemical stimulation of a cell defines cell polarization, with regions of high active Cdc42 at the front and low active Cdc42 at the rear. As reaction-diffusion phenomena between signaling molecules, such as Rho GTPases, define the gradient dynamics, we hypothesize that the cell shape influences the maintenance of the "front-to-back" cell polarization patterns. We investigated the influence of cell shape on the Cdc42 patterns using an established computational polarization model. Our simulation results showed that not only cell shape but also Cdc42 and Rho-related (in)activation parameter values affected the distribution of active Cdc42. Despite an initial Cdc42 gradient, the in silico results showed that the maximal Cdc42 concentration shifts in the opposite direction, a phenomenon we propose to call "reverse polarization". Additional in silico analyses indicated that "reverse polarization" only occurred in a particular parameter value space that resulted in a balance between inactivation and activation of Rho GTPases. Future work should focus on a mathematical description of the underpinnings of reverse polarization, in combination with experimental validation using, for example, dedicated FRET-probes to spatiotemporally track Rho GTPase patterns in migrating cells. In summary, the findings of this study enhance our understanding of the role of cell shape in intracellular signaling.

Quantum aspects of torsional vibrations in the HO3H, DO3H and DO3D molecules.

The hydrogen trioxide (HT) molecule HOOOH is 1) a prototype for a class of molecules of the form X(ZY)2 with two equivalent internal tops (ZY) and 2) the second representative of the polyoxides series of the form HOnH (n ≥ 2). Due to this, it is the subject of close attention of researchers. In this paper, we performed a group theory analysis of the torsional and spin states of the HOOOH, DOOOH, and DOOOD molecules. The relationships have been established between the symmetry species of the C2V(M) molecular symmetry group to which the HOOOH and DOOOD molecules belong, and the symmetry species of the C2 and CS point groups to which the equilibrium configurations of trans- and cis-conformers of the above molecules belong, respectively. 2D PES and 2D surfaces of kinematic coefficients related to torsional vibrations of hydroxyl groups were calculated at the complete basis set (CBS) limit by extrapolating the results of calculations at the MP2/cc-pVTZ and MP2/cc-pVQZ levels of theory. For all the three molecules, the energies of the stationary torsional states were computed using the Fourier method for a numerical solution of the 2D vibrational Schrödinger equation. Symmetry species of torsional states and the values of quantum numbers defining the types of torsional vibrations were found by analyzing the torsional wave functions. The selection rules for transitions between torsional states in the dipole approximation were also formulated.

In silico clinical trials for pediatric orphan diseases.

To date poor treatment options are available for patients with congenital pseudarthrosis of the tibia (CPT), a pediatric orphan disease. In this study we have performed an in silico clinical trial on 200 virtual subjects, generated from a previously established model of murine bone regeneration, to tackle the challenges associated with the small, pediatric patient population. Each virtual subject was simulated to receive no treatment and bone morphogenetic protein (BMP) treatment. We have shown that the degree of severity of CPT is significantly reduced with BMP treatment, although the effect is highly subject-specific. Using machine learning techniques we were also able to stratify the virtual subject population in adverse responders, non-responders, responders and asymptomatic. In summary, this study shows the potential of in silico medicine technologies as well as their implications for other orphan diseases.

3D screening device for the evaluation of cell response to different electrospun microtopographies.

Micro- and nano-topographies of scaffold surfaces play a pivotal role in tissue engineering applications, influencing cell behavior such as adhesion, orientation, alignment, morphology and proliferation. In this study, a novel microfabrication method based on the combination of soft-lithography and electrospinning for the production of micro-patterned electrospun scaffolds was proposed. Subsequently, a 3D screening device for electrospun meshes with different micro-topographies was designed, fabricated and biologically validated. Results indicated that the use of defined patterns could induce specific morphological variations in human mesenchymal stem cell cytoskeletal organization, which could be related to differential activity of signaling pathways. STATEMENT OF SIGNIFICANCE: We introduce a novel and time saving method to fabricate 3D micropatterns with controlled micro-architectures on electrospun meshes using a custom made collector and a PDMS mold with the desired topography. A possible application of this fabrication technique is represented by a 3D screening system for patterned electrospun meshes that allows the screening of different scaffold/electrospun parameters on cell activity. In addition, what we have developed in this study could be modularly applied to existing platforms. Considering the different patterned geometries, the cell morphological data indicated a change in the cytoskeletal organization with a close correspondence to the patterns, as shown by phenoplot and boxplot analysis, and might hint at the differential activity of cell signaling. The 3D screening system proposed in this study could be used to evaluate topographies favoring cell alignment, proliferation and functional performance, and has the potential to be upscaled for high-throughput.

[Psycholinguistic study of a special vocabulary used by alcoholics]. / Psikholingvisticheskoe issledovanie spetsial'noi leksiki bol'nykh alkogolizmom.

Twenty-five patients suffering from stage II alcoholism and 20 normal persons were subjected to a psycholinguistic study. The examined were asked to put down words associated with a booze situation. Out of 608 associated words thus derived, only 63 words (10%) turned out to be used by patients and normal persons whereas only 23% of the patients' words were entries of the dictionary of the Russian language. It is concluded that the alcoholic vocabulary of patients may be regarded as a specialized language with a specific contents. It is dominated by the so-called operational words associated with the process of purchasing alcoholic drinks, with the site and amount of booze as well as by the words synonymous to the word to 'knock back'. The alcoholic vocabulary of normal persons was dominated by the words relating to the drinking and companionable themes. The psycholinguistic experiment makes it possible to differentiate between patients and normal persons not only at the group but also at the individual level.