979 research outputs found
Fluctuations in Polymer Translocation
We investigate a model of chaperone-assisted polymer translocation through a
nanopore in a membrane. Translocation is driven by irreversible random
sequential absorption of chaperone proteins that bind to the polymer on one
side of the membrane. The proteins are larger than the pore and hence the
backward motion of the polymer is inhibited. This mechanism rectifies Brownian
fluctuations and results in an effective force that drags the polymer in a
preferred direction. The translocated polymer undergoes an effective biased
random walk and we compute the corresponding diffusion constant. Our methods
allow us to determine the large deviation function which, in addition to
velocity and diffusion constant, contains the entire statistics of the
translocated length.Comment: 20 pages, 6 figure
Computational and Biological Analogies for Understanding Fine-Tuned Parameters in Physics
In this philosophical paper, we explore computational and biological
analogies to address the fine-tuning problem in cosmology. We first clarify
what it means for physical constants or initial conditions to be fine-tuned. We
review important distinctions such as the dimensionless and dimensional
physical constants, and the classification of constants proposed by
Levy-Leblond. Then we explore how two great analogies, computational and
biological, can give new insights into our problem. This paper includes a
preliminary study to examine the two analogies. Importantly, analogies are both
useful and fundamental cognitive tools, but can also be misused or
misinterpreted. The idea that our universe might be modelled as a computational
entity is analysed, and we discuss the distinction between physical laws and
initial conditions using algorithmic information theory. Smolin introduced the
theory of "Cosmological Natural Selection" with a biological analogy in mind.
We examine an extension of this analogy involving intelligent life. We discuss
if and how this extension could be legitimated.
Keywords: origin of the universe, fine-tuning, physical constants, initial
conditions, computational universe, biological universe, role of intelligent
life, cosmological natural selection, cosmological artificial selection,
artificial cosmogenesis.Comment: 25 pages, Foundations of Science, in pres
Maintenance of respiratory control in mitochondria after rate zonal centrifugation
The respiratory control of rat liver mitochondria is lost when they are subjected to rate zonal centrifugation in a sucrose gradient (8.0% to 46.6%, w/w) at values for ω 2 t necessary for resolution. High sucrose concentration and high ω 2 t are both responsible. Respiratory control can be maintained in iso-osmotic Ficoll + 8.3% sucrose media, and after zonal centrifugation in such media at values of ω 2 t sufficient for resolution.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44800/1/10863_2005_Article_BF01539061.pd
The compositional and evolutionary logic of metabolism
Metabolism displays striking and robust regularities in the forms of
modularity and hierarchy, whose composition may be compactly described. This
renders metabolic architecture comprehensible as a system, and suggests the
order in which layers of that system emerged. Metabolism also serves as the
foundation in other hierarchies, at least up to cellular integration including
bioenergetics and molecular replication, and trophic ecology. The
recapitulation of patterns first seen in metabolism, in these higher levels,
suggests metabolism as a source of causation or constraint on many forms of
organization in the biosphere.
We identify as modules widely reused subsets of chemicals, reactions, or
functions, each with a conserved internal structure. At the small molecule
substrate level, module boundaries are generally associated with the most
complex reaction mechanisms and the most conserved enzymes. Cofactors form a
structurally and functionally distinctive control layer over the small-molecule
substrate. Complex cofactors are often used at module boundaries of the
substrate level, while simpler ones participate in widely used reactions.
Cofactor functions thus act as "keys" that incorporate classes of organic
reactions within biochemistry.
The same modules that organize the compositional diversity of metabolism are
argued to have governed long-term evolution. Early evolution of core
metabolism, especially carbon-fixation, appears to have required few
innovations among a small number of conserved modules, to produce adaptations
to simple biogeochemical changes of environment. We demonstrate these features
of metabolism at several levels of hierarchy, beginning with the small-molecule
substrate and network architecture, continuing with cofactors and key conserved
reactions, and culminating in the aggregation of multiple diverse physical and
biochemical processes in cells.Comment: 56 pages, 28 figure
Single-molecule experiments in biological physics: methods and applications
I review single-molecule experiments (SME) in biological physics. Recent
technological developments have provided the tools to design and build
scientific instruments of high enough sensitivity and precision to manipulate
and visualize individual molecules and measure microscopic forces. Using SME it
is possible to: manipulate molecules one at a time and measure distributions
describing molecular properties; characterize the kinetics of biomolecular
reactions and; detect molecular intermediates. SME provide the additional
information about thermodynamics and kinetics of biomolecular processes. This
complements information obtained in traditional bulk assays. In SME it is also
possible to measure small energies and detect large Brownian deviations in
biomolecular reactions, thereby offering new methods and systems to scrutinize
the basic foundations of statistical mechanics. This review is written at a
very introductory level emphasizing the importance of SME to scientists
interested in knowing the common playground of ideas and the interdisciplinary
topics accessible by these techniques. The review discusses SME from an
experimental perspective, first exposing the most common experimental
methodologies and later presenting various molecular systems where such
techniques have been applied. I briefly discuss experimental techniques such as
atomic-force microscopy (AFM), laser optical tweezers (LOT), magnetic tweezers
(MT), biomembrane force probe (BFP) and single-molecule fluorescence (SMF). I
then present several applications of SME to the study of nucleic acids (DNA,
RNA and DNA condensation), proteins (protein-protein interactions, protein
folding and molecular motors). Finally, I discuss applications of SME to the
study of the nonequilibrium thermodynamics of small systems and the
experimental verification of fluctuation theorems. I conclude with a discussion
of open questions and future perspectives.Comment: Latex, 60 pages, 12 figures, Topical Review for J. Phys. C (Cond.
Matt
Systems protobiology:Origin of life in lipid catalytic networks
Life is that which replicates and evolves, but there is no consensus on how life emerged. We advocate a systems protobiology view, whereby the first replicators were assemblies of spontaneously accreting, heterogeneous and mostly non-canonical amphiphiles. This view is substantiated by rigorous chemical kinetics simulations of the graded autocatalysis replication domain (GARD) model, based on the notion that the replication or reproduction of compositional information predated that of sequence information. GARD reveals the emergence of privileged non-equilibrium assemblies (composomes), which portray catalysis-based homeostatic (concentration-preserving) growth. Such a process, along with occasional assembly fission, embodies cell-like reproduction. GARD pre-RNA evolution is evidenced in the selection of different composomes within a sparse fitness landscape, in response to environmental chemical changes. These observations refute claims that GARD assemblies (or other mutually catalytic networks in the metabolism first scenario) cannot evolve. Composomes represent both a genotype and a selectable phenotype, anteceding present-day biology in which the two are mostly separated. Detailed GARD analyses show attractor-like transitions from random assemblies to self-organized composomes, with negative entropy change, thus establishing composomes as dissipative systemstextemdashhallmarks of life. We show a preliminary new version of our model, metabolic GARD (M-GARD), in which lipid covalent modifications are orchestrated by non-enzymatic lipid catalysts, themselves compositionally reproduced. M-GARD fills the gap of the lack of true metabolism in basic GARD, and is rewardingly supported by a published experimental instance of a lipid-based mutually catalytic network. Anticipating near-future far-reaching progress of molecular dynamics, M-GARD is slated to quantitatively depict elaborate protocells, with orchestrated reproduction of both lipid bilayer and lumenal content. Finally, a GARD analysis in a whole-planet context offers the potential for estimating the probability of life's emergence. The invigorated GARD scrutiny presented in this review enhances the validity of autocatalytic sets as a bona fide early evolution scenario and provides essential infrastructure for a paradigm shift towards a systems protobiology view of life's origin
On decoding and rewriting genomes: a psychoanalytical reading of a scientific revolution
In various documents the view emerges that contemporary biotechnosciences are currently experiencing a scientific revolution: a massive increase of pace, scale and scope. A significant part of the research endeavours involved in this scientific upheaval is devoted to understanding and, if possible, ameliorating humankind: from our genomes up to our bodies and brains. New developments in contemporary technosciences, such as synthetic biology and other genomics and “post-genomics” fields, tend to blur the distinctions between prevention, therapy and enhancement. An important dimension of this development is “biomimesis”: i.e. the tendency of novel technologies and materials to mimic or plagiarize nature on a molecular and microscopic level in order to optimise prospects for the embedding of technological artefacts in natural systems such as human bodies and brains. In this paper, these developments are read and assessed from a psychoanalytical perspective. Three key concepts from psychoanalysis are used to come to terms with what is happening in research laboratories today. After assessing the general profile of the current revolution in this manner, I will focus on a particular case study, a line of research that may serve as exemplification of the vicissitudes of contemporary technosciences, namely viral biomaterials. Viral life forms can be genetically modified (their genomes can be rewritten) in such a manner that they may be inserted in human bodies in order to produce substances at specific sites such as hormones (testosterone), neurotransmitters (dopamine), enzymes (insulin) or bone and muscle tissue. Notably, certain target groups such as top athletes, soldiers or patients suffering from degenerative diseases may become the pioneers serving as research subjects for novel applications. The same technologies can be used for various purposes ranging from therapy up to prevention and enhancement
Two approaches to the study of the origin of life.
This paper compares two approaches that attempt to explain the origin of life, or biogenesis. The more established approach is one based on chemical principles, whereas a new, yet not widely known approach begins from a physical perspective. According to the first approach, life would have begun with - often organic - compounds. After having developed to a certain level of complexity and mutual dependence within a non-compartmentalised organic soup, they would have assembled into a functioning cell. In contrast, the second, physical type of approach has life developing within tiny compartments from the beginning. It emphasises the importance of redox reactions between inorganic elements and compounds found on two sides of a compartmental boundary. Without this boundary, ¿life¿ would not have begun, nor have been maintained; this boundary - and the complex cell membrane that evolved from it - forms the essence of life
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