|1.||Adimy M., Chekroun A., Kaźmierczak B., Traveling waves in a coupled reaction–diffusion and difference model of hematopoiesis, Journal of Differential Equations, ISSN: 0022-0396, DOI: 10.1016/j.jde.2016.12.009, Vol.262, No.7, pp.4085-4128, 2017|
Adimy M., Chekroun A., Kaźmierczak B.
, Traveling waves in a coupled reaction–diffusion and difference model of hematopoiesis
, Journal of Differential Equations
, ISSN: 0022-0396
, DOI: 10.1016/j.jde.2016.12.009
, Vol.262, No.7, pp.4085-4128, 2017
The formation and development of blood cells is a very complex process, called hematopoiesis. This process involves a small population of cells called hematopoietic stem cells (HSCs). The HSCs are undifferentiated cells, located in the bone marrow before they become mature blood cells and enter the blood stream. They have a unique ability to produce either similar cells (self-renewal), or cells engaged in one of different lineages of blood cells: red blood cells, white cells and platelets (differentiation). The HSCs can be either in a proliferating or in a quiescent phase. In this paper, we distinguish between dividing cells that enter directly to the quiescent phase and dividing cells that return to the proliferating phase to divide again. We propose a mathematical model describing the dynamics of HSC population, taking into account their spatial distribution. The resulting model is a coupled reaction–diffusion equation and difference equation with delay. We study the existence of monotone traveling wave fronts and the asymptotic speed of spread.
Hematopoiesis, Age-structured population, Reaction–diffusion system with delay, Difference equation, Traveling wave front, Asymptotic speed of spread
|2.||Kochańczyk M., Kocieniewski P., Kozłowska E., Jaruszewicz-Błońska J., Sparta B., Pargett M., Albeck J.G., Hlavacek W.S., Lipniacki T., Relaxation oscillations and hierarchy of feedbacks in MAPK signaling, Scientific Reports, ISSN: 2045-2322, DOI: 10.1038/srep38244, Vol.7, No.38244, pp.1-15, 2017|Kochańczyk M.
, Kocieniewski P.
, Kozłowska E., Jaruszewicz-Błońska J.
, Sparta B., Pargett M., Albeck J.G., Hlavacek W.S., Lipniacki T.
, Relaxation oscillations and hierarchy of feedbacks in MAPK signaling
, Scientific Reports
, ISSN: 2045-2322
, DOI: 10.1038/srep38244
, Vol.7, No.38244, pp.1-15, 2017
We formulated a computational model for a MAPK signaling cascade downstream of the EGF receptor to investigate how interlinked positive and negative feedback loops process EGF signals into ERK pulses of constant amplitude but dose-dependent duration and frequency. A positive feedback loop involving RAS and SOS, which leads to bistability and allows for switch-like responses to inputs, is nested within a negative feedback loop that encompasses RAS and RAF, MEK, and ERK that inhibits SOS via phosphorylation. This negative feedback, operating on a longer time scale, changes switch-like behavior into oscillations having a period of 1 hour or longer. Two auxiliary negative feedback loops, from ERK to MEK and RAF, placed downstream of the positive feedback, shape the temporal ERK activity profile but are dispensable for oscillations. Thus, the positive feedback introduces a hierarchy among negative feedback loops, such that the effect of a negative feedback depends on its position with respect to the positive feedback loop. Furthermore, a combination of the fast positive feedback involving slow-diffusing membrane components with slower negative feedbacks involving faster diffusing cytoplasmic components leads to local excitation/global inhibition dynamics, which allows the MAPK cascade to transmit paracrine EGF signals into spatially non-uniform ERK activity pulses.
MAPK signaling, Oscillations, Mathematical modelling
|3.||Varga A., Ehrenreiter K., Aschenbrenner B., Kocieniewski P., Kochańczyk M., Lipniacki T., Baccarini M., RAF1/BRAF dimerization integrates the signal from RAS to ERK and ROKα, Science Signaling, ISSN: 1945-0877, DOI: 10.1126/scisignal.aai8482, Vol.10, No.469, pp.eaai8482-1-11, 2017|
Varga A., Ehrenreiter K., Aschenbrenner B., Kocieniewski P.
, Kochańczyk M.
, Lipniacki T.
, Baccarini M., RAF1/BRAF dimerization integrates the signal from RAS to ERK and ROKα
, Science Signaling
, ISSN: 1945-0877
, DOI: 10.1126/scisignal.aai8482
, Vol.10, No.469, pp.eaai8482-1-11, 2017
Downstream of growth factor receptors and of the guanine triphosphatase (GTPase) RAS, heterodimers of the serine/threonine kinases BRAF and RAF1 are critical upstream kinases and activators of the mitogen-activated protein kinase (MAPK) module containing the mitogen-activated and extracellular signal–regulated kinase kinase (MEK) and their targets, the extracellular signal–regulated kinase (ERK) family. Either direct or scaffold protein–mediated interactions among the components of the ERK module (the MAPKKKs BRAF and RAF1, MEK, and ERK) facilitate signal transmission. RAF1 also has essential functions in the control of tumorigenesis and migration that are mediated through its interaction with the kinase ROKα, an effector of the GTPase RHO and regulator of cytoskeletal rearrangements. We combined mutational and kinetic analysis with mathematical modeling to show that the interaction of RAF1 with ROKα is coordinated with the role of RAF1 in the ERK pathway. We found that the phosphorylated form of RAF1 that interacted with and inhibited ROKα was generated during the interaction of RAF1 with the ERK module. This mechanism adds plasticity to the ERK pathway, enabling signal diversification at the level of both ERK and RAF. Furthermore, by connecting ERK activation with the regulation of ROKα and cytoskeletal rearrangements by RAF1, this mechanism has the potential to precisely coordinate the proper timing of proliferation with changes in cell shape, adhesion, or motility.
MAPK pathway, kinase RAF, protein isoform, phosphorylation, mathematical modeling
|4.||Urbanek O., Sajkiewicz P., Pierini F., Czerkies M., Kołbuk D., Structure and properties of polycaprolactone/chitosan nonwovens tailored by solvent systems, Biomedical Materials, ISSN: 1748-6041, DOI: 10.1088/1748-605X/aa5647, Vol.12, No.1, pp.015020-1-12, 2017|Urbanek O.
, Sajkiewicz P.
, Pierini F.
, Czerkies M.
, Kołbuk D.
, Structure and properties of polycaprolactone/chitosan nonwovens tailored by solvent systems
, Biomedical Materials
, ISSN: 1748-6041
, DOI: 10.1088/1748-605X/aa5647
, Vol.12, No.1, pp.015020-1-12, 2017
Electrospinning of chitosan blends is a reasonable idea to prepare fibre mats for biomedical applications. Synthetic and natural components provide, for example, appropriate mechanical strength and biocompatibility, respectively. However, solvent characteristics and the polyelectrolyte nature of chitosan influence the spinnability of these blends. In order to compare the effect of solvent on polycaprolactone/chitosan fibres, two types of the most commonly used solvent systems were chosen, namely 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and acetic acid (AA)/formic acid (FA). Results obtained by various experimental methods clearly indicated the effect of the solvent system on the structure and properties of electrospun polycaprolactone/chitosan fibres. Viscosity measurements confirmed different polymer–solvent interactions. Various molecular interactions resulting in different macromolecular conformations of chitosan influenced its spinnability and properties. HFIP enabled fibres to be obtained whose average diameter was less than 250 nm while maintaining the brittle and hydrophilic character of the nonwoven, typical for the chitosan component. Spectroscopy studies revealed the formation of chitosan salts in the case of the AA/FA solvent system. Chitosan salts visibly influenced the structure and properties of the prepared fibre mats. The use of AA/FA caused a reduction of Young's modulus and wettability of the proposed blends. It was confirmed that wettability, mechanical properties and the antibacterial effect of polycaprolactone/chitosan fibres may be tailored by selecting an appropriate solvent system. The MTT cell proliferation assay revealed an increase of cytotoxicity to mouse fibroblasts in the case of 25% w/w of chitosan in electrospun nonwovens.
chitosan, electrospinning, PCL/chitosan fibres, solvent system, chitosan salts
|5.||Lanzi M., Salatelli E., Di-Nicola F.P., Zuppiroli L., Pierini F., A new photocrosslinkable oligothiophene for organic solar cells with enhanced stability, MATERIALS CHEMISTRY AND PHYSICS, ISSN: 0254-0584, DOI: 10.1016/j.matchemphys.2016.10.034, Vol.186, pp.98-107, 2017|
Lanzi M., Salatelli E., Di-Nicola F.P., Zuppiroli L., Pierini F.
, A new photocrosslinkable oligothiophene for organic solar cells with enhanced stability
, MATERIALS CHEMISTRY AND PHYSICS
, ISSN: 0254-0584
, DOI: 10.1016/j.matchemphys.2016.10.034
, Vol.186, pp.98-107, 2017
A novel thiophenic tetramer containing a cinnamate group in the side chain with a functionalization degree of 50% is reported. The tetramer was obtained by means of a simple and straightforward procedure involving the functionalization of a p-methoxyphenoxy substituted thiophenic precursor, which led to a soluble product with a good yield. The oligomer was fully characterized from a structural and chemical point of view and employed for the fabrication of small molecule organic solar cells exploiting the bulk heterojunction (BHJ) architecture. The presence of an UV-light sensitive group in the tetramer allowed the photocrosslinking of tetramer/PCBM blends, giving high values of photocurrent and conversion efficiency for the exposed samples. Moreover, the UV-treated devices showed improved stability, even upon heating for three days at 130 °C, thus confirming that photocrosslinking can strongly reduce phase segregation under severe operational conditions.
Electronic materials, Polymers, Fullerenes, Nanostructures, Electrical characterization, Semiconductors