Proteolytic clipping of histone tails: the emerging role of histone proteases in regulation of various biological processes

Chromatin is a dynamic DNA scaffold structure that responds to a variety of external and internal stimuli to regulate the fundamental biological processes. Majority of the cases chromatin dynamicity is exhibited through chemical modifications and physical changes between DNA and histones. These modifications are reversible and complex signaling pathways involving chromatin-modifying enzymes regulate the fluidity of chromatin. Fluidity of chromatin can also be impacted through irreversible change, proteolytic processing of histones which is a poorly understood phenomenon. In recent studies, histone proteolysis has been implicated as a regulatory process involved in the permanent removal of epigenetic marks from histones. Activities responsible for clipping of histone tails and their significance in various biological processes have been observed in several organisms. Here, we have reviewed the properties of some of the known histone proteases, analyzed their significance in biological processes and have provided future directions.     

Phenomenon of Life: Between Equilibrium and Non-Linearity

A model of ordering applicable to biological evolution is presented. It is shown that a steady state (more precisely approaching to a steady state) system of irreversible processes, under conditions of disproportionation of entropy, produces a lower-entropy product, that is, ordering. The ordering is defined as restricting of degrees of freedom: freedom of motion, interactions etc. The model differs from previous ones in that it relates the ordering to processes running not far from equilibrium, described in the linear field of non-equilibrium thermodynamics. It is shown that a system, which includes adenosine triphosphate (ATP) to adenosine diphosphate (ADP) conversion meets the demands of the physical model: it provides energy maintaining steady state conditions, and hydrolysis of ATP proceeding with consumption of water can be tightly conjugated with the most important reactions of synthesis of organic polymers (peptides, nucleotide chains etc.), which proceed with release of water. For these and other reasons ATP seems to be a key molecule of prebiotic evolution. It is argued that the elementary chemical reaction proceeding under control of an enzyme is not necessarily far from equilibrium. The experimental evidence supporting this idea, is presented. It is based on isotope data. Carbon isotope distribution in biochemical systems reveals regularity, which is inherent to steady state systems of chemical reactions, proceeding not far from equilibrium. In living organisms this feature appears at the statistical level, as many completely irreversible and non-linear processes occur in organisms. However not-far-from-equilibrium reactions are inherent to biochemical systems as a matter of principle. They are reconcilable with biochemical behavior. Extant organisms are highly evolved entities which, however, show in their basis the same features, as the simplest chemical systems must have had been involved in the origin of life. Some consequences following from the model, which may be significant for understanding the origin of life and the mechanism of biological evolution, are pointed out.     

Phosphatidylserine exposure in living cells

Abstract

P4-ATPases, a subfamily of P-type ATPases, translocate cell membrane phospholipids from the exoplasmic/luminal leaflet to the cytoplasmic leaflet to generate and maintain membrane lipid asymmetry. Exposure of phosphatidylserine (PS) in the exoplasmic leaflet is well known to transduce critical signals for apoptotic cell clearance and platelet coagulation. PS exposure is also involved in many other biological processes, including myoblast and osteoclast fusion, and the immune response. Moreover, mounting evidence suggest that PS exposure is critical for neuronal regeneration and degeneration. In apoptotic cells, PS exposure is induced by irreversible activation of scramblases and inactivation of P4-ATPases. However, how PS is reversibly exposed and restored in viable cells during other biological processes remains poorly understood. In the present review, we discuss the physiological significance of reversible PS exposure in living cells, and the putative roles of flippases, floppases, and scramblases.     

Measuring “Unmeasurable” Folding Kinetics of Proteins by Single-Molecule Force Spectroscopy

Folding and unfolding are fundamental biological processes in cell and are important for the biological functions of proteins. Characterizing the folding and unfolding kinetics of proteins is important for understanding the energetic landscape leading to the active native conformations of these molecules. However, the thermal or chemical-induced unfolding of many proteins is irreversible in vitro, precluding characterization of the folding kinetics of such proteins, just as it is impossible to “un-boil” an egg. Irreversible unfolding often manifests as irreversible aggregation of unfolded polypeptide chains, which typically occurs between denatured protein molecules in response to the exposure of hydrophobic residues to solvent. An example of such a protein where thermal denaturation results in irreversible aggregation is the β-1,4 endoxylanase from Bacillus circulans (BCX). Here, we report the use of single-molecule atomic force microscopy to directly measure the folding kinetics of BCX in vitro. By mechanically unfolding BCX, we essentially allowed only one unfolded molecule to exist in solution at a given time, effectively eliminating the possibility for aggregation. We found that BCX can readily refold back to the native state, allowing us to measure its folding kinetics for the first time. Our results demonstrate that single-molecule force-spectroscopy-based methods can adequately tackle the challenge of “un-boiling eggs”, providing a general methodology to characterize the folding kinetics of many proteins that suffer from irreversible denaturation and thus cannot be characterized using traditional equilibrium methodologies.     

Concept of the "physiological age" of animals and its application to ixodid ticks

The definition "physiological age" of animals has been revised. A new definition has been formulated on the basis of V. N. Beklemishev's (1962) and Ju. S. Balashov's (1962) theses as follows: physiological age of animals (= biological) is an extent of general irreversible morphophysiological change of organism during its whole life and determined by the accumulation of irreversible changes as a result of its normal vital activity. This definition is equivalent to that of "biological ages" of man. The contents of this definition is enlarged and the possibility of its use for different animals including their males is unified. On the basis of the general concept this definition is specified in regard to ixodid ticks: physiological age of hungry ixodid tick is an extent of general irreversible morpholophysiological change of its organism during the whole life and determined by the state of reserve nutrient and excretory substances. According to the amount of reserve and excretory substances in the organism of ixodid tick we distinguish 4 main physiological ages: new-born, young, mature and old which reflect general biological regularity of age development of animals.     

Twelve testable hypotheses on the geobiology of weathering

Critical Zone (CZ) research investigates the chemical, physical, and biological processes that modulate the Earth's surface. Here, we advance 12 hypotheses that must be tested to improve our understanding of the CZ: (1) Solar-to-chemical conversion of energy by plants regulates flows of carbon, water, and nutrients through plant-microbe soil networks, thereby controlling the location and extent of biological weathering. (2) Biological stoichiometry drives changes in mineral stoichiometry and distribution through weathering. (3) On landscapes experiencing little erosion, biology drives weathering during initial succession, whereas weathering drives biology over the long term. (4) In eroding landscapes, weathering-front advance at depth is coupled to surface denudation via biotic processes. (5) Biology shapes the topography of the Critical Zone. (6) The impact of climate forcing on denudation rates in natural systems can be predicted from models incorporating biogeochemical reaction rates and geomorphological transport laws. (7) Rising global temperatures will increase carbon losses from the Critical Zone. (8) Rising atmospheric P(CO2) will increase rates and extents of mineral weathering in soils. (9) Riverine solute fluxes will respond to changes in climate primarily due to changes in water fluxes and secondarily through changes in biologically mediated weathering. (10) Land use change will impact Critical Zone processes and exports more than climate change. (11) In many severely altered settings, restoration of hydrological processes is possible in decades or less, whereas restoration of biodiversity and biogeochemical processes requires longer timescales. (12) Biogeochemical properties impart thresholds or tipping points beyond which rapid and irreversible losses of ecosystem health, function, and services can occur.     

Effect of substrate competition in kinetic models of metabolic networks

Substrate competition can be found in many types of biological processes, ranging from gene expression to signal transduction and metabolic pathways. Although several experimental and in silico studies have shown the impact of substrate competition on these processes, it is still often neglected, especially in modelling approaches. Using toy models that exemplify different metabolic pathway scenarios, we show that substrate competition can influence the dynamics and the steady state concentrations of a metabolic pathway. We have additionally derived rate laws for substrate competition in reversible reactions and summarise existing rate laws for substrate competition in irreversible reactions.     

Direct detection of proteins adsorbed on synthetic materials by matrix-assisted laser desorption ionization-mass spectrometry.

The irreversible accumulation of biological material on synthetic surfaces ("biofouling") adversely affects for instance contact lenses, implantable biomedical devices, biosensors, water purification, transport and storage systems, and marine structures. It is shown here that proteins adsorbed on contact lenses can be detected directly, rapidly, and conveniently, with high sensitivity, by matrix-assisted laser desorption ionization (MALDI)-mass spectrometry. This new approach allows detection of minor (and major) proteinaceous constituents of biofouled layers on samples retrieved from clinical usage and in vitro protein adsorption studies, at levels substantially below monolayer coverage. Identification of the detected biological molecules can be done by comparison of the detected mass peaks with known protein molecular masses or with spectra recorded of pure compounds or by separate biochemical assays. The MALDI mass spectra recorded on different contact lenses contain peaks assignable to lysozyme and a number of smaller proteins. Such sensitive characterization of the early stages of biofouling enhances the understanding of protein/materials interactions and assists in designing guided strategies toward control of biological adsorption processes.     

Biomathematics on the Basis of Thermodynamics

Mathematical terms as e.g. total differential and partial derivative play a specific role in classic thermodynamics. In this connection we ask for the existence of a thermodynamical biomathematics in consequence of the large biological importance of the thermodynamics of irreversible processes in open systems. In spite of our present limited knowledge we answer this question positive by means of theoretical considerations and practical examples.     

细菌和藻类的粘附行为及其生态学意义

生活在水中的细菌和藻类粘附到物理和生物表面是一种普遍现象(Ｆｌｅｔｃｈｅｒ,1979ｂ;1980)。一根木头,一块洁净的玻璃板放入水中后表面很快被细菌和藻类占据。从水中捞起的植物碎屑表面布满细菌和藻类等生物。浮游甲壳动物和轮虫表面为绿藻和鞭毛藻等密集粘附后,原表面色泽被掩饰而表现为绿色。对细菌和藻类粘附行为的研究在很早以前就已开始,至今人们在这方面获得了相当多的认识,本文就其中的某些研究结果予以介绍。1　细菌和藻类的粘附过程细菌和藻类的粘附是一个分阶段进行的过程。最初的粘附是可逆的。在这个阶段,细菌和藻类与被粘附…     

On the role of chemical systems in the microphysical aspects of primary genetic mechanisms

It is pointed out that two fundamentally different views of primary genetic processes occur in the literature which are frequently confused. The first is a true communication-theoretic view, which regards the genetic apparatus as containing a real information-source and a transducer which converts that information to useful form. The second view is generally expressed as a template scheme based on the Watson-Crick model; it is shown that in this model there is actually no such thing as genetic information in a communication-theoretic sense. Both views are then discussed on the basis of microphysical principles developed in previous work of the author (Bull. Math. Biophysics,22, 227–255, 1960) in an attempt to find which approach is in closer accord with the biological facts. It is shown that, if the communication-theoretic view is correct, then the information-bearing object must act as a “catalyst,” but it is pointed out that the type of catalysis involved must be of a fundamentally different nature than that occurring in familiar enzyme-catalyzed reactions. On the basis of general considerations of irreversible changes in microphysical measuring systems, it is shown that any type of template must suffer a gradual and irreversible denaturation, which seems to make it unlikely that a template could play a primary role in fundamental genetic processes. This research was supported by the United States Air Force through the Air Force Office of Scientific Research of the Air Research and Development Command, under Contract AF 49(638)-917.     

Peptide-based covalent inhibitors of protein–protein interactions

Protein–protein interactions (PPI) are involved in all cellular processes and many represent attractive therapeutic targets. However, the frequently rather flat and large interaction areas render the identification of small molecular PPI inhibitors very challenging. As an alternative, peptide interaction motifs derived from a PPI interface can serve as starting points for the development of inhibitors. However, certain proteins remain challenging targets when applying inhibitors with a competitive mode of action. For that reason, peptide-based ligands with an irreversible binding mode have gained attention in recent years. This review summarizes examples of covalent inhibitors that employ peptidic binders and have been tested in a biological context.     

New irreversible adenosine A(1) antagonists based on FSCPX

FSCPX (1) and its amide analogue (2) have been reported to exhibit potent and selective irreversible antagonism of the A(1) adenosine receptor (A(1)AR) when used in in vitro biological preparations. In order to obtain an irreversible A(1)AR antagonist with improved stability, analogues of FSCPX incorporating the chemoreactive 4-(fluorosulfonyl)phenyl moiety separated from the xanthine pharmacophore by a ketone linkage were explored. Compounds 4a-c exhibited improved affinity for the A(1)AR and concentration-dependent irreversible binding to the A(1)AR.     

Immune memory,immune oblivion: A lesson from Funes the memorious

We commonly think of the immune system as having a memory. However, memory is always accompanied by a complementary process of oblivion. Is there immune oblivion? In this theoretical paper, I address this question and suggest that oblivion is an integral aspect of memorization. In this context, I suggest that immune memory is an orchestration of reversible and irreversible processes of biological computation through feedback loops. Drawing on the linguistic metaphor, I inquire into the implications of this idea for a better understanding of immune memory and immune deficiency among the elderly.     

Immune memory, immune oblivion: a lesson from Funes the memorious

We commonly think of the immune system as having a memory. However, memory is always accompanied by a complementary process of oblivion. Is there immune oblivion? In this theoretical paper, I address this question and suggest that oblivion is an integral aspect of memorization. In this context, I suggest that immune memory is an orchestration of reversible and irreversible processes of biological computation through feedback loops. Drawing on the linguistic metaphor, I inquire into the implications of this idea for a better understanding of immune memory and immune deficiency among the elderly.     

Overview on the developments of microbial fuel cells

Microbial fuel cells (MFCs) are a promising technology for electricity production from a variety of materials, such as natural organic matter, complex organic waste or renewable biomass, and can be advantageously combined with applications in wastewater treatment. The problem with MFCs is that they are technically still very far from attaining acceptable levels of power output, since the performance of this type of fuel cells is affected by limitations based on irreversible reactions and processes occurring both on the anode and cathode side. However, in the last years, there has been a growing amount of work on MFCs which managed to increase power outputs by an order of magnitude.The present review article discusses a number of biological and engineering aspects related to improvement of MFC performance including the effect of important parameters, such as pH, temperature, feed rate, shear stress and organic load. The recent progresses on scale-up MFC are summarized and the different modelling approaches to describe the different biological and transport phenomena in MFCs are also provided.     

Discovery of a new inhibitor lead of adenovirus proteinase: steps toward selective, irreversible inhibitors of cysteine proteinases

Using the computer docking program EUDOC, in silico screening of a chemical database for inhibitors of human adenovirus cysteine proteinase (hAVCP) identified 2,4,5,7-tetranitro-9-fluorenone that selectively and irreversibly inhibits hAVCP in a two-step reaction: reversible binding (Ki = 3.09 microM) followed by irreversible inhibition (ki = 0.006 s(-1)). The reversible binding is due to molecular complementarity between the inhibitor and the active site of hAVCP, which confers the selectivity of the inhibitor. The irreversible inhibition is due to substitution of a nitro group of the inhibitor by the nearby Cys122 in the active site of hAVCP. These findings suggest a new approach to selective, irreversible inhibitors of cysteine proteinases involved in normal and abnormal physiological processes ranging from embryogenesis to apoptosis and pathogen invasions.     

Oligosaccharide microarrays fabricated on aminooxyacetyl functionalized glass surface for characterization of carbohydrate-protein interaction

Carbohydrate-protein interactions play important biological roles in biological processes. But there is a lack of high-throughput methods to elucidate recognition events between carbohydrates and proteins. This paper reported a convenient and efficient method for preparing oligosaccharide microarrays, wherein the underivatized oligosaccharide probes were efficiently immobilized on aminooxyacetyl functionalized glass surface by formation of oxime bonding with the carbonyl group at the reducing end of the suitable carbohydrates via irreversible condensation. Prototypes of carbohydrate microarrays containing 10 oligosaccharides were fabricated on aminooxyacetyl functionalized glass by robotic arrayer. Utilization of the prepared carbohydrate microarrays for the characterization of carbohydrate-protein interaction reveals that carbohydrates with different structural features selectively bound to the corresponding lectins with relative binding affinities that correlated with those obtained from solution-based assays. The limit of detection (LOD) for lectin ConA on the fabricated carbohydrate microarrays was determined to be approximately 0.008 microg/mL. Inhibition experiment with soluble carbohydrates also demonstrated that the binding affinities of lectins to different carbohydrates could be analyzed quantitatively by determining IC(50) values of the soluble carbohydrates with the carbohydrate microarrays. This work provides a simple procedure to prepare carbohydrate microarray for high-throughput parallel characterization of carbohydrate-protein interaction.