scholarly journals Towards an integrated experimental–theoretical approach for assessing the mechanistic basis of hair and feather morphogenesis

2012 ◽  
Vol 2 (4) ◽  
pp. 433-450 ◽  
Author(s):  
K. J. Painter ◽  
G. S. Hunt ◽  
K. L. Wells ◽  
J. A. Johansson ◽  
D. J. Headon
Keyword(s):  
Pattern Formation ◽  
Theoretical Approach ◽  
Spatial Patterning ◽  
Biological Processes ◽  
Chemical Basis ◽  
Alan Turing ◽  
Theoretical Approaches ◽  
Simple Demonstration ◽  
Mechanistic Basis ◽  
Elegant Solution

In his seminal 1952 paper, ‘The Chemical Basis of Morphogenesis’, Alan Turing lays down a milestone in the application of theoretical approaches to understand complex biological processes. His deceptively simple demonstration that a system of reacting and diffusing chemicals could, under certain conditions, generate spatial patterning out of homogeneity provided an elegant solution to the problem of how one of nature's most intricate events occurs: the emergence of structure and form in the developing embryo. The molecular revolution that has taken place during the six decades following this landmark publication has now placed this generation of theoreticians and biologists in an excellent position to rigorously test the theory and, encouragingly, a number of systems have emerged that appear to conform to some of Turing's fundamental ideas. In this paper, we describe the history and more recent integration between experiment and theory in one of the key models for understanding pattern formation: the emergence of feathers and hair in the skins of birds and mammals.

scholarly journals Macromolecule Translocation in a Nanopore: Center of Mass Drift–Diffusion over an Entropic Barrier

2019 ◽  
Author(s):  
Z. E. Dell ◽  
M. Muthukumar
Keyword(s):  
Single Molecule ◽  
Theoretical Approach ◽  
Center Of Mass ◽  
Diffusion Constant ◽  
Hydrodynamic Interactions ◽  
Biological Processes ◽  
Theoretical Approaches ◽  
Direct Interpretation ◽  
Synthetic Macromolecules ◽  
A Chain

ABSTRACTMany fundamental biological processes involve moving macromolecules across membranes, through nanopores, in a process called translocation. Such motion is necessary for gene expression and regulation, tissue formation, and viral infection. Furthermore, in recent years nanopore technologies have been developed for single molecule detection of biological and synthetic macromolecules, which have been most notably employed in next generation DNA sequencing devices. Many successful theories have been established, which calculate the entropic barrier required to elongate a chain during translocation. However, these theories are at the level of the translocation coordinate (number of forward steps) and thus lack a clear connection to experiments and simulations. Furthermore, the proper diffusion coefficient for such a coordinate is unclear. In order to address these issues, we propose a center of mass (CM) theory for translocation. We start with the entropic barrier approach and show that the translocation coordinate is equivalent to the center of mass of the chain, providing a direct interpretation of previous theoretical studies. We thus recognize that the appropriate dynamics is given by CM diffusion, and calculate the appropriate diffusion constant (Rouse or Zimm) as the chain translocates. We illustrate our theoretical approach with a planar nanopore geometry and calculate some characteristic dynamical predictions. Our main result is the connection between the translocation coordinate and the chain CM, however, we also find that the translocation time is sped up by 1–2 orders of magnitude if hydrodynamic interactions are present. Our approach can be extended to include the details included in previous translocation theories. Most importantly this work provides a direct connection between theoretical approaches and experiments or simulations.SIGNIFICANCEMacromolecule motion through nanopores is critical for many biological processes, and has been recently employed for nucleic acid sequencing. Despite this, direct theoretical understandings of translocation are difficult to evaluate due to the introduction of the translocation coordinate. In this manuscript, we propose a theory for translocation written at the center of mass level of the polymer chain. This theoretical approach is more easily compared to experimental and simulation results, and additionally allows one to accurately account for hydrodynamic interactions on the macromolecule dynamics.

scholarly journals Biochemistry: one molecule at a time

2021 ◽  
Vol 65 (1) ◽  
pp. 1-3
Author(s):  
Dominika T. Gruszka
Keyword(s):  
Complex Networks ◽  
Single Molecule ◽  
Population Level ◽  
Early Career ◽  
Molecular Heterogeneity ◽  
Biological Processes ◽  
Biological Macromolecule ◽  
Exciting Field ◽  
Early Career Researchers ◽  
Mechanistic Basis

Abstract Biological processes are orchestrated by complex networks of molecules. Conventional approaches for studying the action of biomolecules operate on a population level, averaging out any inhomogeneities within the ensemble. Investigating one biological macromolecule at a time allows researchers to directly probe individual behaviours, and thus characterise the intrinsic molecular heterogeneity of the system. Single-molecule methods have unravelled unexpected modes of action for many seemingly well-characterised biomolecules and often proved instrumental in understanding the intricate mechanistic basis of biological processes. This collection of reviews aims to showcase how single-molecule techniques can be used to address important biological questions and to inspire biochemists to ‘zoom in’ to the population and probe individual molecular behaviours, beyond the ensemble average. Furthermore, this issue of Essays in Biochemistry is the very first written and edited entirely by early career researchers, and so it also highlights the strength, diversity and excellence of the younger generation single-molecule scientists who drive this exciting field of research forward.

scholarly journals Variety of theoretical approaches to legal interpretation

2021 ◽  
pp. 109-114
Author(s):  
A. Yе. Shevchenko ◽  
S. V. Kudin
Keyword(s):  
Social Relations ◽  
Theoretical Approach ◽  
Special Kind ◽  
Integrative Approach ◽  
Legal Interpretation ◽  
True Nature ◽  
Theoretical Approaches ◽  
The Will ◽  
The Subject ◽  
The Law

The article explores the variety of theoretical approaches to legal interpretation. It has been determined that the variety of approaches to legal interpretation is due to the complexity of the nature of the origin of this phenomenon, the conditions for the development of post-non-classical science, and the recent influence of the paradigm of comparism, which assumes pluralism of opinions and ideas in legal research. It was found that in modern science there are four traditional theoretical approaches to the essence of legal interpretation. It has been determined that the content of the first approach is revealed within the framework of legal hermeneutics through a number of categories. The essence of the second approach (formal dogmatic or static) is expressed in the fact that the subject of interpretation must strictly and rigorously follow the letter of the law, establish only the meaning of the normative legal act, which the lawmaking body enshrined in it at the time of the publication of the act. That is why normative legal acts cannot, through interpretation, adapt to the changing economic, social, political, cultural internal and external conditions of public life. It is proved that the essence of the dynamic theoretical approach lies in the fact that the subject of legal interpretation adapts the normative legal act to the changes that occur in various social relations. It was found that there is a contradiction between the dynamic and static approaches in legal interpretation, which is reflected in the traditionally called objective and subjective theories of interpretation. According to the subjective theory, the purpose of legal interpretation is to establish the «will of the legislator», and according to the objective theory – to establish the «will of the law». It has been substantiated that the essence of the activity approach is that interpretation is considered as a special kind of legal activity aimed at understanding and clarifying the content of legal texts. The authors of this article point out that in order to establish the true nature of legal interpretation, the methodological foundations of the study should be presented much broader and more diverse, and not be limited only to traditional approaches. When studying it, a comprehensive, integrative approach is needed, which, based on the relevance of interdisciplinary relationships, would include logical, language (linguistic), philosophical, sociological, psychological, axiological (value), ethical, legal, historical, economic, political, mathematical and other substantiation of legal interpretation. Keywords: diversity, theoretical approach, legal interpretation, interpretive practice, integrative approach

scholarly journals Mechanics unlocks the morphogenetic puzzle of interlocking bivalved shells

2019 ◽  
Vol 117 (1) ◽  
pp. 43-51 ◽  
Author(s):  
Derek E. Moulton ◽  
Alain Goriely ◽  
Régis Chirat
Keyword(s):  
Pattern Formation ◽  
Growth Process ◽  
Shell Growth ◽  
Point Of View ◽  
Mathematical Framework ◽  
Bivalve Mollusks ◽  
Modeling Framework ◽  
Mechanistic Basis ◽  
Developmental Point ◽  
Rigid Shell

Brachiopods and mollusks are 2 shell-bearing phyla that diverged from a common shell-less ancestor more than 540 million years ago. Brachiopods and bivalve mollusks have also convergently evolved a bivalved shell that displays an apparently mundane, yet striking feature from a developmental point of view: When the shell is closed, the 2 valve edges meet each other in a commissure that forms a continuum with no gaps or overlaps despite the fact that each valve, secreted by 2 mantle lobes, may present antisymmetric ornamental patterns of varying regularity and size. Interlocking is maintained throughout the entirety of development, even when the shell edge exhibits significant irregularity due to injury or other environmental influences, which suggests a dynamic physical process of pattern formation that cannot be genetically specified. Here, we derive a mathematical framework, based on the physics of shell growth, to explain how this interlocking pattern is created and regulated by mechanical instabilities. By close consideration of the geometry and mechanics of 2 lobes of the mantle, constrained both by the rigid shell that they secrete and by each other, we uncover the mechanistic basis for the interlocking pattern. Our modeling framework recovers and explains a large diversity of shell forms and highlights how parametric variations in the growth process result in morphological variation. Beyond the basic interlocking mechanism, we also consider the intricate and striking multiscale-patterned edge in certain brachiopods. We show that this pattern can be explained as a secondary instability that matches morphological trends and data.

Ion Channel Permeation and Selectivity

2019 ◽  
Author(s):  
Juan J. Nogueira ◽  
Ben Corry
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Ion Selectivity ◽  
Ionic Currents ◽  
Biological Processes ◽  
Ion Permeation ◽  
Voltage Gated ◽  
Physical Mechanisms ◽  
Theoretical Approaches ◽  
Mechanistic Insight

Many biological processes essential for life rely on the transport of specific ions at specific times across cell membranes. Such exquisite control of ionic currents, which is regulated by protein ion channels, is fundamental for the proper functioning of the cells. It is not surprising, therefore, that the mechanism of ion permeation and selectivity in ion channels has been extensively investigated by means of experimental and theoretical approaches. These studies have provided great mechanistic insight but have also raised new questions that are still unresolved. This chapter first summarizes the main techniques that have provided significant knowledge about ion permeation and selectivity. It then discusses the physical mechanisms leading to ion permeation and the explanations that have been proposed for ion selectivity in voltage-gated potassium, sodium, and calcium channels.

A “Global Theory of Federalism”: The Nature and Challenges of a Federal State

2005 ◽  
Vol 6 (10) ◽  
pp. 1297-1318 ◽  
Author(s):  
Anna Gamper
Keyword(s):  
Theoretical Approach ◽  
Constitutional Law ◽  
Federal State ◽  
Common Denominator ◽  
Global Theory ◽  
Theoretical Approaches ◽  
Interdisciplinary Character ◽  
Or Economics ◽  
Definition Of ◽  
Concrete Concept

Innumerable attempts have been made to explore the theoretical nature of federalism. Due to the long history, worldwide existence and interdisciplinary character of federalism, a plethora of literature has been written on the topic. Yet, these endeavours have not even resulted in a clear and commonly used definition of the term. Surely, it is one of the great dilemmas of this field of research that despite so much discussion, there is no settled common denominator of ‘federalism'. Whereas practical studies and exchange of experience between the various federal systems offer a more conventional research arena, comparative theoretical approaches are much more seldom. This is not the least because of the tremendous semantic challenges of a comparative theoretical approach. At first glance, it is sometimes difficult to understand the terminology of federalism, the meaning of which differs according to the perspectives of constitutional law, political science or economics. Even more difficulty arises when the substance of federal theories is discussed. Again, differences between theories may be due to different academic approaches, particularly between understanding federalism as an overall principle or as a more concrete concept of a federal state and, in particular, whether the constituent units of a federal state are states, and, if states, whether they are sovereign.

scholarly journals Turing's theory of morphogenesis of 1952 and the subsequent discovery of the crucial role of local self-enhancement and long-range inhibition

2012 ◽  
Vol 2 (4) ◽  
pp. 407-416 ◽  
Author(s):  
Hans Meinhardt
Keyword(s):  
Pattern Formation ◽  
De Novo ◽  
Molecular Genetic ◽  
Stable State ◽  
Nonlinear Interactions ◽  
Alan Turing ◽  
Component Systems ◽  
Genetic Level ◽  
Reaction Schemes

In his pioneering work, Alan Turing showed that de novo pattern formation is possible if two substances interact that differ in their diffusion range. Since then, we have shown that pattern formation is possible if, and only if, a self-enhancing reaction is coupled with an antagonistic process of longer range. Knowing this crucial condition has enabled us to include nonlinear interactions, which are required to design molecularly realistic interactions. Different reaction schemes and their relation to Turing's proposal are discussed and compared with more recent observations on the molecular–genetic level. The antagonistic reaction may be accomplished by an inhibitor that is produced in the activated region or by a depletion of a component that is used up during the self-enhancing reaction. The autocatalysis may be realized by an inhibition of an inhibition. Activating molecules can be processed into molecules that have an inhibiting function; patterning of the Wnt pathway is proposed to depend on such a mechanism. Three-component systems, as discussed in Turing's paper, are shown to play a major role in the generation of highly dynamic patterns that never reach a stable state.

scholarly journals Decoding of position in the developing neural tube from antiparallel morphogen gradients

Science ◽  
2017 ◽  
Vol 356 (6345) ◽  
pp. 1379-1383 ◽  
Author(s):  
Marcin Zagorski ◽  
Yoji Tabata ◽  
Nathalie Brandenberg ◽  
Matthias P. Lutolf ◽  
Gašper Tkačik ◽  
...  
Keyword(s):  
Pattern Formation ◽  
Cell Fate ◽  
Neural Tube ◽  
Target Gene ◽  
Ex Vivo ◽  
Data Link ◽  
Cell Fate Decisions ◽  
Morphogen Gradients ◽  
Positional Identity ◽  
Mechanistic Basis

Like many developing tissues, the vertebrate neural tube is patterned by antiparallel morphogen gradients. To understand how these inputs are interpreted, we measured morphogen signaling and target gene expression in mouse embryos and chick ex vivo assays. From these data, we derived and validated a characteristic decoding map that relates morphogen input to the positional identity of neural progenitors. Analysis of the observed responses indicates that the underlying interpretation strategy minimizes patterning errors in response to the joint input of noisy opposing gradients. We reverse-engineered a transcriptional network that provides a mechanistic basis for the observed cell fate decisions and accounts for the precision and dynamics of pattern formation. Together, our data link opposing gradient dynamics in a growing tissue to precise pattern formation.

scholarly journals Theoretical approaches towards the steps of nongovernmental actors in world politics: global paradiplomacy of the Iraqi Kurdistan (KRI).

2021 ◽  
pp. 31-41
Author(s):  
Dalsooz Jalal Hussein
Keyword(s):  
International Relations ◽  
Theoretical Approach ◽  
International Politics ◽  
World Politics ◽  
Political Actors ◽  
Theoretical Approaches ◽  
Iraqi Kurdistan ◽  
State Actor ◽  
The Subject ◽  
State Actors

This article presents a theoretical approach towards the global political steps of non-state actors. Particular attention is given to a number of theories of international relations, such as neorealism, international liberalism, and constructivism, which are able to encompass current global actions of non-state political actors. For a clearer perspective on the subject matter, the article employs the example of Iraqi Kurdistan (KRI); as a non-state actor, KRI has recently become a vivid example for the theories of international relations. The conclusion is made that security, economy, culture, religion and identity are the key and post powerful instruments of non-state actors of international politics. The example of KRI demonstrates that international relations of non-state actors focus on security, economy and culture, as well as serve as the instruments of interaction with both, state and non-state actors. The article reviews such activity within the framework of neorealism, international liberalism, and constructivism. It is underlines that the example of Iraqi Kurdistan (KRI) fully meets all the criteria of a non-state actor of international politics. It is also a brilliant example for the theories of international relations.

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