Towards the First Principles in Biology and Cancer: New Vistas in Computational Systems Biology of Cancer

These days many leading scientists argue for a new paradigm for cancer research and propose a complex systems-view of cancer supported by empirical evidence. As an example, Thea Newman (2021) has applied “the lessons learned from physical systems to a critique of reductionism in medical research, with an emphasis on cancer”. It is the understanding of this author that the mesoscale constructs that combine the bottom-up as well as top-down approaches, are very close to the concept of emergence. The mesoscale constructs can be said to be those effective components through which the system allows itself to be understood. A short list of basic concepts related to life/biology fundamentals are first introduced to demonstrate a lack of emphasis on these matters in literature. It is imperative that physical and chemical approaches are introduced and incorporated in biology to make it more conceptually sound, quantitative, and based on the first principles. Non-equilibrium thermodynamics is the only tool currently available for making progress in this direction. A brief outline of systems biology, the discovery of emergent properties, and metabolic modeling are introduced in the second part. Then, different cancer initiation concepts are reviewed, followed by application of non-equilibrium thermodynamics in the metabolic and genomic analysis of initiation and development of cancer, stressing the endogenous network hypothesis (ENH). Finally, extension of the ENH is suggested to include a cancer niche (exogenous network hypothesis). It is expected that this will lead to a unifying systems–biology approach for a future combination of the analytical and synthetic arms of two major hypotheses of cancer models (SMT and TOFT).

Laboratory exploration of mineral precipitates from Europa's subsurface ocean

The precipitation of hydrated phases from a chondrite-like Na–Mg–Ca–SO4–Cl solution is studied using in situ synchrotron X-ray powder diffraction, under rapid- (360 K h−1, T = 250–80 K, t = 3 h) and ultra-slow-freezing (0.3 K day−1, T = 273–245 K, t = 242 days) conditions. The precipitation sequence under slow cooling initially follows the predictions of equilibrium thermodynamics models. However, after ∼50 days at 245 K, the formation of the highly hydrated sulfate phase Na2Mg(SO4)2·16H2O, a relatively recent discovery in the Na2Mg(SO4)2–H2O system, was observed. Rapid freezing, on the other hand, produced an assemblage of multiple phases which formed within a very short timescale (≤4 min, ΔT = 2 K) and, although remaining present throughout, varied in their relative proportions with decreasing temperature. Mirabilite and meridianiite were the major phases, with pentahydrite, epsomite, hydrohalite, gypsum, blödite, konyaite and loweite also observed. Na2Mg(SO4)2·16H2O was again found to be present and increased in proportion relative to other phases as the temperature decreased. The results are discussed in relation to possible implications for life on Europa and application to other icy ocean worlds.

A case study of non-Fourier heat conduction using internal variables and GENERIC

Applying simultaneously the methodology of non-equilibrium thermodynamics with internal variables (NET-IV) and the framework of General Equation for the Non-Equilibrium Reversible–Irreversible Coupling (GENERIC), we demonstrate that, in heat conduction theories, entropy current multipliers can be interpreted as relaxed state variables. Fourier’s law and its various extensions—the Maxwell–Cattaneo–Vernotte, Guyer–Krumhansl, Jeffreys type, Ginzburg–Landau (Allen–Cahn) type and ballistic–diffusive heat conduction equations—are derived in both formulations. Along these lines, a comparison of NET-IV and GENERIC is also performed. Our results may pave the way for microscopic/multiscale understanding of beyond-Fourier heat conduction and open new ways for numerical simulations of heat conduction problems.

Equilibrium thermodynamics and the genesis of protein–protein complexes in cells

It is often thought that the structural complexity of living organisms places Life outside the laws of Physics. According to the Second Law of Thermodynamics, inanimate matter tends towards ever-increasing randomness. Most thermodynamic studies on the living system are course-grained in the sense that it is the whole organism which is considered and they lack microscopic details. In these studies, as the living system is an open system, non-linear thermodynamics have been used. This requires that a number of assumptions be made concerning the living system itself, which may not be correct in organisms living under natural environmental conditions. In the present study, we depart from this approach and use a fine-grained analysis of the genesis of subcellular protein complex structures. The analysis is performed in terms of classical equilibrium thermodynamics using the acquired knowledge of protein/protein interactions. In this way, it is demonstrated that the spontaneous creation of ordered subcellular structures occurs in accordance with the Second Law of Thermodynamics. We specifically consider the simple example of protein dimer and trimer formation from its monomer components, both in vitro and with chaperone assistance in vivo. The entropy decrease associated with protein complex assembly, on which the continuing debate is founded, is shown to be a relatively small component in the overall and positive entropy increase. Graphic abstract