<abstract> <p>The present article includes data on the possible selective cytotoxic effect of extract of <italic>Ribes nigrum</italic> L. growing at high Armenian landscape. For this purpose, different non-cancer (microglial BV-2 wild type (<italic>Wt</italic>), acyl-CoA oxidase 1 (ACOX1) deficient (<italic>Acox1<sup>−/−</sup></italic>) and cancer (human colon adenocarcinoma HT29 and human breast cancer MCF7) cell lines were applied. <italic>R. nigrum</italic> leaf ethanol extract showed a growth inhibition effect towards HT29 and MCF7 cells started from 6 h of treatment at the concentration of 0.5 mg/mL DW. The lowest concentration (0.125 mg/mL DW) of the investigated extract expressed cytotoxicity after 72 hours following cancer cell treatment. In contrast to the cancer cells, in the case of the tested non-cancer cells, cytotoxic effect was not observed at the applied concentrations. The extract sub-cytotoxic concentration, in this case, was reported to be the 1 mg/mL DW. Further investigations are needed to confirm the selective cytotoxicity and possible action mechanisms of the leaf extract of <italic>R. nigrum</italic>.</p> </abstract>

<abstract> <p>In the presented work, we aimed to investigate the antioxidant and possible neuroprotective capacity of extract of the aerial parts of <italic>Hypericum alpestre</italic>, found in high altitude Armenian landscape. The neuroprotective activity was evaluated using BV-2 wild type (WT) cells and acyl-CoA oxidase 1 (ACOX1) deficient (<italic>Acox1<sup>-/-</sup></italic>) microglial cell lines. In the chemical-based tests, <italic>H. alpestre</italic> extract showed high antioxidant activity, which was maintained even after heat treatment at 121 °C for 30 min. MTT test showed that the sub-cytotoxic concentration of investigated extracts for both microglial cell lines was 40 µg/mL. There were no significant changes in catalase activity during all period of treatment in both cell lines, meanwhile, SOD activity increased (up to 30%) in WT cells during the 48 h treatment. Increase of SOD activity (up to 50%) in Acox<sup>-/-</sup> cells was observed under the 24 h treatment. Significant modulation in activity of palmitoyl-CoA oxidase 1 was noticed only during the 48 h treatment of WT microglial cells. These results evidenced the pro-oxidant activity of the investigated extract. This finding can serve as a basis for further evaluation of plant extracts influence on cancer cell lines.</p> </abstract>

<abstract> <p>Recently the understanding of complex biological systems has been increased considering the important interplay among different scholars coming from different applied sciences such as mathematics, physics and information sciences. As known, the modeling of a complex system requires the analysis of the different interactions occurring among the different components of the system. Moreover, the analysis of a complex system can be performed at different scales; usually the microscopic, the mesoscopic and the macroscopic scales are the most representation scales. However, a multiscale approach is required. A unified approach that takes into account the different phenomena occurring at each observation scale is the desire of this century. This editorial article deals with the topic of this special issue, which is devoted to the new developments in the multiscale modeling of complex biological systems with special attention to the interplay between different scholars.</p> </abstract>

<abstract> <p>The recent developments in the fields of mathematics and computer sciences have allowed a more accurate description of the dynamics of some biological systems. On the one hand new mathematical frameworks have been proposed and employed in order to gain a complete description of a biological system thus requiring the definition of complicated mathematical structures; on the other hand computational models have been proposed in order to give both a numerical solution of a mathematical model and to derive computation models based on cellular automata and agents. Experimental methods are developed and employed for a quantitative validation of the modeling approaches. This editorial article introduces the topic of this special issue which is devoted to the recent advances and future perspectives of the mathematical and computational frameworks proposed in biosciences.</p> </abstract>

<abstract> <p>In the last years, cryogenic-electron microscopy (cryo-EM) underwent the most impressive improvement compared to other techniques used in structural biology, such as X-ray crystallography and NMR. Electron microscopy was invented nearly one century ago but, up to the beginning of the last decades, the 3D maps produced through this technique were poorly detailed, justifying the term “blobbology” to appeal to cryo-EM. Recently, thanks to a new generation of microscopes and detectors, more efficient algorithms, and easier access to computational power, single particles cryo-EM can routinely produce 3D structures at resolutions comparable to those obtained with X-ray crystallography. However, unlike X-ray crystallography, which needs crystallized proteins, cryo-EM exploits purified samples in solution, allowing the study of proteins and protein complexes that are hard or even impossible to crystallize. For these reasons, single-particle cryo-EM is often the first choice of structural biologists today. Nevertheless, before starting a cryo-EM experiment, many drawbacks and limitations must be considered. Moreover, in practice, the process between the purified sample and the final structure could be trickier than initially expected. Based on these observations, this review aims to offer an overview of the principal technical aspects and setups to be considered while planning and performing a cryo-EM experiment.</p> </abstract>

Three elastin peptides derived from a peculiar elastin sequence (exon 30) were investigated by Infra-red spectroscopy (IRTF), differential scanning calorimetry (DSC) and dielectric spectroscopy (DDS) to clarify the relationship between structural organization and physical properties of these peptides in the solid state. If a great majority of elastin derived peptides form organized structures, only few are able to coacervate, and only one, that is encoded by Exon 30, gives rise to an irreversible precipitation into amyloid fibers. The peptides studied in this work are constituted by 17, 18 or 22 amino acids whose sequences are contained in the longer exon 30. They all contain the XGGZG sequence (where X, Z = V, L) previously suspected to be responsible for amyloid formation in elastin peptides. Two of them gave rise to amyloid fibers while the other one was able to coacervate. In this work we attempted to correlate vibrational, thermal and dielectric behavior of these peptides in the solid state with the propensity to lead to reversible or irreversible aggregation in vivo.

This paper is devoted to a mathematical proof of the continuous dependence on the initial data for the discrete thermostatted kinetic framework, for all T > 0. This is a versatile model for describing the time-evolution of a biological complex system which is composed by a large number of interacting entities, called active particles, and is subjected to an external force field due to the environment. A thermostat term is introduced in order to keep the 2nd-order moment of the system, corresponding to the physical global activation energy, constant in time. This model is expressed by a system of nonlinear ordinary differential equations with quadratic nonlinearity.

Differential scanning calorimetry and FITR analyses allowed to investigate the role of URG7 (up-regulated gene clone 7) protein involved in the development of hepatocellular carcinoma induced by hepatitis B virus infection, on the physical structure both of lysates of human hepatoblastoma cells (HepG2) stressed with tunicamycin and α-synuclein, one of the proteins associated with neurogenerative diseases. The protein-water interfacial region was identified and correlated with protein structure. DSC results confirm through the interfacial water behavior that URG7 is able to act in two ways: it maintains the interfacial water stability and controls the mobile fraction level, thereby the flexibility and the protein folding. The mobile water phase increases strongly for cells exposed to α-synuclein, demonstrating an important influence on water hydration. FTIR results evidenced an increase of about 30% of cross β structures in cells exposed to α-synuclein, associated with aggregated proteins. In stress conditions, URG7 was able to maintain the same fraction of mobile water as untreated cells. URG7 was able to restore the water reorientation ability around the complex lysate system and reduced abnormal protein folding.

This editorial deals with the topic of the special issue devoted to the modeling of complex biological systems. The development of theoretical frameworks and specific models for complex biological systems has recently gained much attention and an interplay among different scholars has emerged thus allowing the possibility to develop a multidisciplinary and a multiscale approach.

Chromatin is a complex multi-scale structure composed of DNA wrapped around nucleosomes. The compaction state is finely regulated mainly by epigenetic marks present not only on nucleosomes but also on the DNA itself. The most studied DNA post-transcriptional modification is 5-methylcytosine (5-mC). Methylation of the cytosine at CpG islands localized at the promoter is associated with repression of transcription. On the contrary, enrichment of 5-hydroxymethylcytosine (5-hmC), one of the oxidation products of 5-mC by TET (ten-eleven translocation) enzymes, on promoters and enhancers promotes transcription activation. Recently, a new role of 5-hmC has been proposed in the context of DNA repair. 5-hmC was found to be enriched at DNA lesions and knockdown of TET led to impaired repair efficiency. Here, we review our current knowledge regarding the role of the regulation of the 5-mC/5-hmC balance by TET enzymes in the context of transcription modulation as well as DNA repair processes. In a final section, we speculate on the potential involvement of TET proteins in DNA repair mechanisms associated with transcription activation.

The cohabitation of lipids and proteins in the plasma membrane of mammalian cells is controlled by specific biochemical and biophysical rules. Lipids may be either constitutively tightly bound to cell-surface receptors (non-annular lipids) or less tightly attached to the external surface of the protein (annular lipids). The latter are exchangeable with surrounding bulk membrane lipids on a faster time scale than that of non-annular lipids. Not only do non-annular lipids bind to membrane proteins through stereoselective mechanisms, they can also help membrane receptors acquire (or maintain) a functional 3D structure. Cholesterol is the prototype of membrane lipids that finely controls the 3D structure and function of receptors. However, several other lipids such as sphingolipids may also modulate the function of membrane proteins though conformational adjustments. All these concepts are discussed in this review in the light of representative examples taken from the literature.

We propose a new strategy to evaluate adhesion strength at the single cell level. This approach involves variable-angle total internal reflection fluorescence microscopy to monitor in real time the topography of cell membranes, i.e. a map of the membrane/substrate separation distance. According to the Boltzmann distribution, both potential energy profile and dissociation energy related to the interactions between the cell membrane and the substrate were determined from the membrane topography. We have highlighted on glass substrates coated with poly-L-lysine and fibronectin, that the dissociation energy is a reliable parameter to quantify the adhesion strength of MDA-MB-231 motile cells.

This review addresses the question of fluorescent detection of ordered membrane (micro) domains in living (cultured) cells, with a “practical” point of view since the situation is much more complicated than for studying model membranes. We first briefly recall the bases of model membrane structural organization involving liquid-ordered and -disordered phases, and the main features of their counterparts in cell membranes that are the various microdomains. We then emphasize the utility of the fluorescent probes derived from cholesterol, and delineate the respective advantages, limitations and drawbacks of the existing ones. In particular, besides their intra-membrane behavior, their relevant characteristics should integrate their different cellular fates for membrane turn-over, trafficking and metabolism, in order to evaluate and improve their efficiency for in-situ probing membrane microdomains in the cell physiology context. Finally, at the present stage, it appears that Bdp-Chol and Pyr-met-Chol display well complementary properties, allowing to use them in combination to improve the reliability of the current experimental approaches. But the field is still open, and there remains much work to perform in this research area.

As the main grain legume consumed worldwide, the common bean (Phaseolus vulgaris) is generally considered as a model for food legumes. The mitochondrial voltage-dependent anion-selective channel (VDAC) is the major transport pathway for inorganic ions, metabolites, and tRNA, and consequently it controls the exchange of these compounds between the cytoplasm and the mitochondrion. Two VDAC isoforms of Phaseolus coccineus have been investigated experimentally. However, plant VDACs are known to belong to a small multigenic family of variable size. Here, we combine available experimental as well as genomic and transcriptomic data to identify and characterize the VDAC family of Phaseolus vulgaris. To this aim, we review the current state of our knowledge of Phaseolus VDAC functional and structural properties. The genomic and transcriptomic data available for the putative VDACs of Phaseolus vulgaris are studied using bioinformatics approach including homology modelling. The obtained results indicate that five out of the seven putative VDAC encoding sequences (named PvVDAC1–5) share strongly conserved motifs and structural homology with known VDACs. Notably, PvVDAC4 and PvVDAC5 are very close to the two abundant and characterized experimentally VDAC isoforms purified from Phaseolus coccineus mitochondria.

The dynamics of spontaneous capillary flow of Newtonian fluids is well-known and can be predicted by the Lucas-Washburn-Rideal (LWR) law. However a wide variety of viscoelastic fluids such as alginate, xanthan and blood, does not exhibit the same Newtonian behavior.In this work we consider the Herschel-Bulkley (HB) rheological model and Navier-Stokes equation to derive a generic expression that predicts the capillary flow of non-Newtonian fluids. The Herschel-Bulkley rheological model encompasses a wide variety of fluids, including the Power-law fluids (also called Ostwald fluids), the Bingham fluids and the Newtonian fluids. It will be shown that the proposed equation reduces to the Lucas-Washburn-Rideal law for Newtonian fluids and to the Weissenberg-Rabinowitsch-Mooney (WRM) law for power-law fluids. Although HB model cannot reduce to Casson’s law, which is often used to model whole blood rheology, HB model can fit the whole blood rheology with the same accuracy.Our generalized expression for the capillary flow of non-Newtonian fluid was used to accurately fit capillary flow of whole blood. The capillary filling of a cylindrical microchannel by whole blood was monitored. The blood first exhibited a Newtonian behavior, then after 7 cm low shear stress and rouleaux formation made LWR fails to fit the data: the blood could not be considered as Newtonian anymore. This non-Newtonian behavior was successfully fit by the proposed equation.

The dynamics of spontaneous capillary flow of Newtonian fluids is well-known and can be predicted by the Lucas-Washburn-Rideal (LWR) law. However a wide variety of viscoelastic fluids such as alginate, xanthan and blood, does not exhibit the same Newtonian behavior.In this work we consider the Herschel-Bulkley (HB) rheological model and Navier-Stokes equation to derive a generic expression that predicts the capillary flow of non-Newtonian fluids. The Herschel-Bulkley rheological model encompasses a wide variety of fluids, including the Power-law fluids (also called Ostwald fluids), the Bingham fluids and the Newtonian fluids. It will be shown that the proposed equation reduces to the Lucas-Washburn-Rideal law for Newtonian fluids and to the Weissenberg-Rabinowitsch-Mooney (WRM) law for power-law fluids. Although HB model cannot reduce to Casson’s law, which is often used to model whole blood rheology, HB model can fit the whole blood rheology with the same accuracy.Our generalized expression for the capillary flow of non-Newtonian fluid was used to accurately fit capillary flow of whole blood. The capillary filling of a cylindrical microchannel by whole blood was monitored. The blood first exhibited a Newtonian behavior, then after 7 cm low shear stress and rouleaux formation made LWR fails to fit the data: the blood could not be considered as Newtonian anymore. This non-Newtonian behavior was successfully fit by the proposed equation.

In eukaryotes, chromatin is coated with epigenetic marks which induce differential gene expression profiles and eventually lead to different cellular phenotypes. One of the challenges of contemporary cell biology is to relate the wealth of epigenomic data with the observed physical properties of chromatin. In this study, we present a polymer physics framework that takes into account the sizes of epigenomic domains. We build a model of chromatin as a block copolymer made of domains with various sizes. This model produces a rich set of conformations which is well explained by finite-size scaling analysis of the coil-globule transition of epigenomic domains. Our results suggest that size-dependent folding of epigenomic domains may be a crucial physical mechanism able to provide chromatin with tissue-specific folding states, these being associated with differential gene expression.

Chromatin has a complex, dynamic architecture in the interphase nucleus, which regulates the accessibility of the underlying DNA and plays a key regulatory role in all the cellular functions using DNA as a template, such as replication, transcription or DNA damage repair. Here, we review the recent progresses in the understanding of the interplay between chromatin architecture and DNA repair mechanisms. Several reports based on live cell fluorescence imaging show that the activation of the DNA repair machinery is associated with major changes in the compaction state and the mobility of chromatin. We discuss the functional consequences of these changes in yeast and mammals in the light of the different repair pathways utilized by these organisms. In the final section of this review, we show how future developments in high-resolution light microscopy and chromatin modelling by polymer physics should contribute to a better understanding of the relationship between the structural changes in chromatin and the activity of the repair processes.

ATP-dependent chromatin remodeling is the active displacement of nucleosomes along or off DNA induced by chromatin remodeling complexes. This key process of gene regulation in eukaryote organisms has recently been argued to be controlled by a kinetic proofreading mechanism. In this paper we present a discussion of the current understanding of this process. We review the case of gene repression via heterochromatin formation by remodelers from the ISWI family and then discuss the activation of the IFN-β gene, where the displacement of the nucleosome is initiated by histone tail acetylations by the enzyme GCN5 which are required for the recruitment of SWI-SNF remodelers. We quantify the speci city of the acetylation step in the remodeling process by peptide docking simulations.