Origin of electroneutrality in living system

Mapping Intimacies ◽

10.1101/2021.09.21.461264 ◽

2021 ◽

Author(s):

Amir Akbari ◽

Bernhard O. Palsson

Keyword(s):

Lipid Membranes ◽

Evolutionary Biology ◽

Building Blocks ◽

Living System ◽

Membrane Potentials ◽

Transport Systems ◽

Chemical Transformations ◽

Charged Surfaces ◽

Ion Distributions ◽

Nonequilibrium States

AbstractIdentifying the first chemical transformations, from which life emerged is a central problem in the theories of life’s origins. These reactions would likely have been self-sustaining and self-reproductive before the advent of complex biochemical pathways found in modern organisms to synthesize lipid membranes, enzymes, or nucleic acids. Without lipid membranes and enzymes, exceedingly low concentrations of the organic intermediates of early metabolic cycles in protocells would have significantly hindered evolvability. To address this problem, we propose a mechanism, where a positive membrane potential elevates the concentration of the organic intermediates. In this mechanism, positively charged surfaces of protocell membranes due to accumulation of transition metals generate positive membrane potentials. We compute steady-state ion distributions and determine their stability in a protocell model to identify the key factors constraining achievable membrane potentials. We find that (i) violation of electroneutrality is necessary to induce nonzero membrane potentials; (ii) strategies that generate larger membrane potentials can destabilize ion distributions; and (iii) violation of electroneutrality enhances osmotic pressure and diminishes reaction efficiency, thereby driving the evolution of lipid membranes, specialized ion channels, and active transport systems.SignificanceThe building blocks of life are constantly synthesized and broken down through concurrent cycles of chemical transformations. Tracing these reactions back 4 billion years to their origins has been a long-standing goal of evolutionary biology. The first metabolic cycles at the origin of life must have overcome several obstacles to spontaneously start and sustain their nonequilibrium states. Notably, maintaining the concentration of organic intermediates at high levels needed to support their continued operation and subsequent evolution would have been particularly challenging in primitive cells lacking evolutionarily tuned lipid membranes and enzymes. Here, we propose a mechanism, in which the concentration of organic intermediates could have been elevated to drive early metabolic cycles forward in primitive cells with ion-permeable porous membranes under prebiotic conditions and demonstrate its feasibility in a protocell model from first principles.

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Perception, Expression, and Social Function of Pain: A Human Ethological View

Science in Context ◽

10.1017/s0269889700001885 ◽

1995 ◽

Vol 8 (1) ◽

pp. 31-46 ◽

Cited By ~ 9

Author(s):

Wulf Schiefenhövel

Keyword(s):

Evolutionary Biology ◽

Well Being ◽

Building Blocks ◽

Field Work ◽

The Body ◽

Human Interaction ◽

Small Children ◽

Body Postures ◽

Culture Independent ◽

Health And Well Being

The ArgumentPain has important biomedical socioanthropological, semiotic, and other facets. In this contribution pain and the experssion of pain are looked at from the perspective of evolutionary biology, utilizing, among others, cross-cultural data from field work in Melanesia.No other being cares for sick and suffering conspecifics in the way humans do. Notwithstanding aggression and neglect, common in all cultures, human societies can be characterized as empathic, comforting, and promoting the health and well-being of their members. One important stimulus triggering this caring response in others is the expression of pain. The nonverbal channel of communication, particularly certain universal — i.e., culture-independent facial expressions, gestures, and body postures, convey much of the message from the painstricken person to the group.These behaviors signal the person's physical and psychical pain, sadness, grief, and despair in ways very similar to the signs given by infants and small children: the body loses tonus and sinks or drops to the ground, the gestures are those of helplessness. Pain and grief may be so strong that control is lost not only over the body's posture but also over the mind's awareness. In such cases the afflicted person may carry out actions endangering himself or others. In general, these behavior patterns resemble those of infants in situations of distress and danger, and it is not surprising that the response of the members of the group is basically parental: taking care, assisting and consoling.Perceptive and behavioral patterns which developed in the course of avian and mammalian phylogeny to serve the well-being of the young have proven, as was shown by Eibl-Eibesfeldt (1989), to be powerful building blocks for actions in other spheres of human interaction. Love is one such field, the reactions to a conspecific suffering pain is another.

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Bioenzymatic and Chemical Derivatization of Renewable Fatty Acids

Biomolecules ◽

10.3390/biom9100566 ◽

2019 ◽

Vol 9 (10) ◽

pp. 566 ◽

Cited By ~ 1

Author(s):

Akula ◽

Kwon

Keyword(s):

Large Scale ◽

Dicarboxylic Acids ◽

Cost Effective ◽

Building Blocks ◽

Synthetic Methods ◽

Aqueous Alcohol ◽

Chemical Transformations ◽

Hydroxycarboxylic Acids ◽

Escherichia Coli Cells ◽

Catalyzed Oxidation

In addition to our previous efforts toward bioenzymatic and chemical transformations of ricinoleic acid and oleic acid to their corresponding ,-dicarboxylic acids via their ester intermediates driven in Escherichia coli cells, several efficient oxidation conditions were investigated and optimized for the conversion of -hydroxycarboxylic acids to ,-dicarboxylic acids. Pd/C-catalyzed oxidation using NaBH4 in a basic aqueous alcohol and Ni(II) salt-catalyzed oxidation using aqueous sodium hypochlorite were considered to be excellent as a hybrid reaction for three successive chemical reactions (hydrogenation, hydrolysis, and oxidation) and an eco-friendly, cost-effective, and practical approach, respectively. Omega-hydroxycarboxylic acids and -aminocarboxylic acid were also easily prepared as useful building blocks for plastics or bioactive compounds from the bioenzymatically driven ester intermediate. The scope of the developed synthetic methods can be utilized for large-scale synthesis and various derivatizations.

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Functional phosphorus-based π-conjugated systems: Structural diversity without multistep synthesis

Pure and Applied Chemistry ◽

10.1351/pac200779020201 ◽

2007 ◽

Vol 79 (2) ◽

pp. 201-212 ◽

Cited By ~ 24

Author(s):

Muriel Hissler ◽

Christophe Lescop ◽

Régis Réau

Keyword(s):

Structural Diversity ◽

Building Blocks ◽

Transition Metal Ions ◽

Organic Light Emitting Diodes ◽

Supramolecular Organization ◽

Chemical Transformations ◽

Light Emitting ◽

Conjugated Systems ◽

Multistep Synthesis ◽

Organic Light

The synthesis and properties of linear π-conjugated systems incorporating phosphole rings are described. Their supramolecular organization in the solid state can be controlled either by chemical modifications or coordination to transition metals of the phosphorus atom. Furthermore, chemical transformations of the phosphole ring allow organizing these P-chromophores in 3D assemblies exhibiting σ-π conjugation or in organometallic ferrocene-like derivatives. Phosphole-pyridine-containing π-conjugated chromophores act as P,N-chelates toward transition-metal ions, giving rise to mono- and di-nuclear complexes. The specific properties of these complexes make them valuable materials for organic light-emitting diodes (OLEDs) and interesting building blocks for the tailoring of π-conjugated systems.

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Construction of membrane-bound artificial cells using microfluidics: a new frontier in bottom-up synthetic biology

Biochemical Society Transactions ◽

10.1042/bst20160052 ◽

2016 ◽

Vol 44 (3) ◽

pp. 723-730 ◽

Cited By ~ 45

Author(s):

Yuval Elani

Keyword(s):

Synthetic Biology ◽

High Throughput ◽

Lipid Membranes ◽

Spatial Organization ◽

Building Blocks ◽

Artificial Cells ◽

Bottom Up ◽

Grand Challenges ◽

New Frontier ◽

Membrane Bound

The quest to construct artificial cells from the bottom-up using simple building blocks has received much attention over recent decades and is one of the grand challenges in synthetic biology. Cell mimics that are encapsulated by lipid membranes are a particularly powerful class of artificial cells due to their biocompatibility and the ability to reconstitute biological machinery within them. One of the key obstacles in the field centres on the following: how can membrane-based artificial cells be generated in a controlled way and in high-throughput? In particular, how can they be constructed to have precisely defined parameters including size, biomolecular composition and spatial organization? Microfluidic generation strategies have proved instrumental in addressing these questions. This article will outline some of the major principles underpinning membrane-based artificial cells and their construction using microfluidics, and will detail some recent landmarks that have been achieved.

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CRISPR interference as low burden logic inverters in synthetic circuits: characterization and tuning

10.1101/2020.08.03.234096 ◽

2020 ◽

Cited By ~ 1

Author(s):

Massimo Bellato ◽

Angelica Frusteri Chiacchiera ◽

Elia Salibi ◽

Michela Casanova ◽

Davide De Marchi ◽

...

Keyword(s):

Rational Design ◽

Building Blocks ◽

Living System ◽

Context Dependency ◽

Heterologous Protein Expression ◽

Bacterial Cells ◽

Crispr Interference ◽

In Vivo Assays ◽

Load Effects

AbstractThe rational design of complex biological systems through the interconnection of single functional building blocks is hampered by many unpredictability sources; this is mainly due to the tangled context-dependency behavior of those parts once placed into an intrinsically complex living system. Among others, the finite amount of translational resources in prokaryotic cells leads to load effects in heterologous protein expression. As a result, hidden interactions among protein synthesis rates arise, leading to unexpected and counterintuitive behaviors. To face this issue in rational design of synthetic circuits in bacterial cells, CRISPR interference is here evaluated as genetic logic inverters with low translational resource usage, compared with traditional transcriptional regulators. This system has been studied and characterized in several circuit configurations. Each module composing the circuit architecture has been optimized in order to meet the desired specifications, and its reduced metabolic load has been eventually demonstrated via in-vivo assays.

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Efficient Hit-to-Lead Searching of Kinase Inhibitor Chemical Space via Computational Fragment Merging

10.1101/2021.06.01.446684 ◽

2021 ◽

Author(s):

Grigorii V. Andrianov ◽

Wern Juin Gabriel Ong ◽

Ilya Serebriiskii ◽

John Karanicolas

Keyword(s):

Kinase Inhibitors ◽

Kinase Inhibitor ◽

Chemical Space ◽

Early Stage ◽

Building Blocks ◽

Lead Optimization ◽

Chemical Transformations ◽

Interaction Energies ◽

The Individual ◽

New Compounds

In early stage drug discovery, the stage of hit-to-lead optimization (or "hit expansion") entails starting from a newly-identified active compound, and improving its potency or other properties. Traditionally this process relies on synthesizing and evaluating a series of analogs to build up structure-activity relationships. Here, we describe a computational strategy focused on kinase inhibitors, intended to expedite the process of identifying analogs with improved potency. Our protocol begins from an inhibitor of the target kinase, and generalizes the synthetic route used to access it. By searching for commercially-available replacements for the individual building blocks used to make the parent inhibitor, we compile an enumerated library of compounds that can be accessed using the same chemical transformations; these huge libraries can exceed many millions - or billions - of compounds. Because the resulting libraries are much too large for explicit virtual screening, we instead consider alternate approaches to identify the top-scoring compounds. We find that contributions from individual substituents are well-described by a pairwise additivity approximation, provided that the corresponding fragments position their shared core in precisely the same way relative to the binding site. This key insight allows us to determine which fragments are suitable for merging into a single new compounds, and which are not. Further, the use of the pairwise approximation allows interaction energies to be assigned to each compound in the library, without the need for any further structure-based modeling: interaction energies instead can be reliably estimated from the energies of the component fragments. We demonstrate this protocol using libraries built from five representative kinase inhibitors drawn from the literature, which target four different kinases: CDK9, CHK1, CDK2, and ACK1. In each example, the enumerated library includes additional analogs reported by the original study to have activity, and these analogs are successfully prioritized within the library. We envision that the insights from this work can facilitate the rapid assembly and screening of increasingly large libraries for focused hit-to-lead optimization. To enable adoption of these methods and to encourage further analyses, we disseminate the computational tools needed to deploy this protocol.

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Available Technologies and Materials for Waste Cooking Oil Recycling

Processes ◽

10.3390/pr8030366 ◽

2020 ◽

Vol 8 (3) ◽

pp. 366 ◽

Cited By ~ 9

Author(s):

Alberto Mannu ◽

Sebastiano Garroni ◽

Jesus Ibanez Porras ◽

Andrea Mele

Keyword(s):

Chemical Engineering ◽

Raw Materials ◽

Building Blocks ◽

Waste Cooking Oil ◽

Added Value ◽

Special Focus ◽

Chemical Transformations ◽

Oil Processing ◽

Physical Treatments ◽

Cooking Oils

Recently, the interest in converting waste cooking oils (WCOs) to raw materials has grown exponentially. The driving force of such a trend is mainly represented by the increasing number of WCO applications, combined with the definition, in many countries, of new regulations on waste management. From an industrial perspective, the simple chemical composition of WCOs make them suitable as valuable chemical building blocks, in fuel, materials, and lubricant productions. The sustainability of such applications is sprightly related to proper recycling procedures. In this context, the development of new recycling processes, as well as the optimization of the existing ones, represents a priority for applied chemistry, chemical engineering, and material science. With the aim of providing useful updates to the scientific community involved in vegetable oil processing, the current available technologies for WCO recycling are herein reported, described, and discussed. In detail, two main types of WCO treatments will be considered: chemical transformations, to exploit the chemical functional groups present in the waste for the synthesis of added value products, and physical treatments as extraction, filtration, and distillation procedures. The first part, regarding chemical synthesis, will be connected mostly to the production of fuels. The second part, concerning physical treatments, will focus on bio-lubricant production. Moreover, during the description of filtering procedures, a special focus will be given to the development and applicability of new materials and technologies for WCO treatments.

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Simple Building Blocks for Complex Chemical Transformations: Mimicking Early Metabolism

10.26226/morressier.614222345a6b32ccbe1480c9 ◽

2021 ◽

Author(s):

Antara Reja

Keyword(s):

Building Blocks ◽

Chemical Transformations ◽

Complex Chemical

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Special Issue on Cybernetic City Transport Systems and Technologies

Journal of Robotics and Mechatronics ◽

10.20965/jrm.2010.p0683 ◽

2010 ◽

Vol 22 (6) ◽

pp. 683-684

Author(s):

Ljubo Vlacic ◽

Toshio Fukuda ◽

Yasuhisa Hasegawa ◽

Michel Parent

Keyword(s):

Building Blocks ◽

Detection Algorithm ◽

Operational Performance ◽

Transport Systems ◽

Shape Estimation ◽

Sustainable Mobility ◽

Dual Mode ◽

Road Infrastructure ◽

Traffic Lights ◽

Road Testing

The publication of this issue was driven by the vision that, in the not too distant future, Cybernetic Transport Systems (CTS) will be seen on city roads and dedicated infrastructures. TheWorld Council for Sustainability has projected that CTS will be seen in cities in as early as 2030 (Mobility 2030: Meeting the Challenges to Sustainability; World Business Council for Sustainable Mobility, July 2004). CTS are based on fully automated driverless urban road vehicles (CyberCars). They can also be based on Dual-Mode Vehicles (DMV) - conventional vehicles with Advanced Driver Assistance Technology (ADAT) and capable of driverless driving, on request by a driver. ADAT covers electronic and software products that assist drivers in driving. DMV assumes that a driver is not in control of the vehicle at all times but is fully responsible for vehicle operation throughout. Both CyberCars and DMVs co-operate through vehicle-to-vehicle and vehicle-to-infrastructure communication links thus enabling cybernetic transport to achieve higher traffic flows and improve network efficiency. Main CTS building blocks are CyberCars and/or Dual Mode Vehicles, Road Infrastructure Elements and CTS Traffic Management & Control Centre. These four blocks are interconnected, integrated and made interoperable through Communication Architecture and Protocols, and Operational Safety & Reliability Certification Procedures. A variety of CTS concepts have been prototyped and evaluated within the scope of projects such as: (i) Toyota’s Intelligent Multimode Transportation System (http://www.expo2005.or.jp/en/technology/imts.html); (ii) the CyberCars (http://www.cybercars.org); CyberMove (http://www.cybermove.org); (iii) CityMobil (http://www.citymobil-project.eu/); (iv) Safespot (http://www.safespot-eu.org/); (v) CVIS (http://www.cvisproject.org); (vi) Group Rapid Transit (http://www.2getthere.eu/Group Transit). The figure above shows a CTS prototyped by the CyberCars-2 Project Consortium. An extensive infield, i.e., on-road testing of operational performance of co-operative cybernetic transport solutions was conducted at several road tracks, the last being held at La Rochelle, France, in September 2008. This issue addresses a broad spectrum of theoretical and implementational topics related to CTS development and deployment including: • Cooperative Cybernetic Transport System Architecture • Real-time Decision Making by driverless vehicles • On-road testing of operational performance of CTS • Road-Crossing Landmarks Detection algorithm • Landmark Shape Detection algorithm • Road Shape Estimation algorithm, and • Vehicle-to-road infrastructure (traffic lights) communication solutions. In addition, this issue presents papers that deal with ADAT and analyses: • Acceptability and Usability of a Parking Assistance System for Elderly Drivers • Relationships between Car Accidents and a Driver’s Physiology and Psychology • 2D Localization in Urban Environment, and • Sustainability and Reusability aspects of Common Robotic Technology components. We hope you enjoy the issue!

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