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Advances in Human Biology: Combining Genetics and Molecular Biophysics to Pave the Way for Personalized Diagnostics and Medicine  [PDF]
Emil Alexov
Advances in Biology , 2014, DOI: 10.1155/2014/471836
Abstract: Advances in several biology-oriented initiatives such as genome sequencing and structural genomics, along with the progress made through traditional biological and biochemical research, have opened up a unique opportunity to better understand the molecular effects of human diseases. Human DNA can vary significantly from person to person and determines an individual’s physical characteristics and their susceptibility to diseases. Armed with an individual’s DNA sequence, researchers and physicians can check for defects known to be associated with certain diseases by utilizing various databases. However, for unclassified DNA mutations or in order to reveal molecular mechanism behind the effects, the mutations have to be mapped onto the corresponding networks and macromolecular structures and then analyzed to reveal their effect on the wild type properties of biological processes involved. Predicting the effect of DNA mutations on individual’s health is typically referred to as personalized or companion diagnostics. Furthermore, once the molecular mechanism of the mutations is revealed, the patient should be given drugs which are the most appropriate for the individual genome, referred to as pharmacogenomics. Altogether, the shift in focus in medicine towards more genomic-oriented practices is the foundation of personalized medicine. The progress made in these rapidly developing fields is outlined. 1. Introduction The human body is a delicate, self-regulating machine which can respond to its surroundings and internal needs. Such self-regulation involves various processes ranging from processes on atomic and molecular level to processes occurring in organs and tissues. Despite such tremendous complexity, somehow all humans, broadly speaking, are quite similar. However, slight differences in DNA can lead to a multitude of other physical differences. Some of these differences are harmless such as eye and hair color [1], race [2], and skin color [3, 4], while other differences may be disease-associated (see special J. Mol. Biol. issue [5]). The differences among individuals and their susceptibility to diseases are not only due to the single nucleoside polymorphisms (SNPs), but also due to the fact that different individuals have different copy numbers variations (CNVs) for various genes [6–9]. As pointed out by Haraksingh and Snyder [6], the CNVs are perhaps even more important for the humans than the SNPs, a statement supported by other researchers [10–13]. In the end, from the viewpoint of personalized diagnostics and medicine, the most important task is to
The Magellanic Stream to Halo Interface: Processes that shape our nearest gaseous Halo Stream  [PDF]
Lou Nigra,Snezana Stanimirovic,J. S. Gallagher III,Felix J. Lockman,David L. Nidever,Steven R. Majewski
Physics , 2009,
Abstract: Understanding the hydrodynamical processes and conditions at the interface between the Magellanic Stream (MS) and the Galactic halo is critical to understanding the MS and by extension, gaseous tails in other interacting galaxies. These processes operate on relatively small scales and not only help shape this clumpy stream, but also affect the neutral gas dynamics and transfer of mass from the stream to the halo, thus affecting metal enrichment and gas replenishment of the Galaxy. We describe an observational program to place constraints on these processes through high-resolution measurements of HI emission, HI absorption and Halpha emission with unprecedented sensitivity. Methods will include structural analysis, searching for cold gas cores in clumps and analyzing gas kinematics as it transitions to the halo. The latter method includes sophisticated spatial integration techniques to deeply probe the neutral gas, which we apply to a new HI map obtained from the Green Bank Telescope with the highest sensitivity HI observations of the MS to date. We demonstrate that the integration techniques enhance sensitivity even further, thus allowing detection of apparent MS gas components with density approaching that of the Galactic halo.
Constraints on the shape of the Milky Way dark matter halo from the Sagittarius stream  [PDF]
Carlos Vera-Ciro,Amina Helmi
Physics , 2013, DOI: 10.1088/2041-8205/773/1/L4
Abstract: We propose a new model for the dark matter halo of the Milky Way that fits the properties of the stellar stream associated with the Sagittarius dwarf galaxy. Our dark halo is oblate with q_z = 0.9 for r < 10 kpc, and can be made to follow the Law & Majewski model at larger radii. However, we find that the dynamical perturbations induced by the Large Magellanic Cloud on the orbit of Sgr cannot be neglected when modeling its streams. When taken into account, this leads us to constrain the Galaxy's outer halo shape to have minor-to-major axis ratio (c/a)_\Phi = 0.8 and intermediate-to-major axis ratio (b/a)_\Phi = 0.9, in good agreement with cosmological expectations.
New horizons in Biophysics
Elizabeth C Moylan
BMC Biophysics , 2011, DOI: 10.1186/2046-1682-4-1
Abstract: This month PMC Biophysics joins the BMC series of journals as BMC Biophysics. The 'P to B' transition is not some strange quirk of molecular dynamics but the consequence of integrating PhysMath Central journals into Springer and BioMed Central portfolios which has resulted in a very welcome addition to the BMC series. Previously, PMC Biophysics had been published by PhysMath Central but will now be published by BioMed Central - as is the case with all journals in the BMC series. When BioMed Central was founded in 2000, the BMC series of journals were among the first to be launched. Since then, this portfolio of journals have grown rapidly and become well-recognised in the research communities they serve. We are committed to the future of BMC Biophysics and the journal will be in good company among the many successful titles in the BMC series.Under the stewardship of its Editor-in-Chief, Huan-Xiang Zhou, PMC Biophysics was originally launched in 2008 in response to the gathering strength of the open access movement and the multidisciplinary nature of research in biological physics [1]. BMC Biophysics will maintain this ethos, and continue to publish articles in experimental and theoretical aspects of biological processes from the microscopic to macroscopic level. Topics include (but are not limited to) thermodynamics, structural stability and dynamics of biological macromolecules and mesoscale cellular processes. We also welcome studies on membrane biophysics, nucleic acids, signalling and interaction networks and novel biophysical methods. In keeping with recent developments, we have also broadened the scope of the journal to explicitly cover computational and theoretical biophysics.As with the other journals in the BMC-series stable, BMC Biophysics has an international Editorial Board which retains much of the PMC Biophysics Editorial Board with additional new faces [2] and comprises Section Editors, Associate Editors and Editorial Advisors. We are delighted that H
Islands in the Stream: Electromigration-Driven Shape Evolution with Crystal Anisotropy  [PDF]
Philipp Kuhn,Joachim Krug
Physics , 2004,
Abstract: We consider the shape evolution of two-dimensional islands on a crystal surface in the regime where mass transport is exclusively along the island edge. A directed mass current due to surface electromigration causes the island to migrate in the direction of the force. Stationary shapes in the presence of an anisotropic edge mobility can be computed analytically when the capillary effects of the line tension of the island edge are neglected, and conditions for the existence of non-singular stationary shapes can be formulated. In particular, we analyse the dependence of the direction of island migration on the relative orientation of the electric field to the crystal anisotropy, and we show that no stationary shapes exist when the number of symmetry axes is odd. The full problem including line tension is solved by time-dependent numerical integration of the sharp-interface model. In addition to stationary shapes and shape instability leading to island breakup, we also find a regime where the shape displays periodic oscillations.
CURRENT TRENDS IN BIOPHYSICS
Victor,A.Bloomfield
生物物理学报 , 1988,
Abstract: IntroductionBiophysics is an important and vigorous discipline,but one that is sodiverse that it resists easy definition.In its early days,biophysics had strongcontacts with physiology particularly electroyhysiology and muscle physiology,and with radiation biology and photobiology.More recently the discipline hasbecome substantially more molecular,because of major advances in biochemistry,instrumentation,and computer technology.In order to identify the most pro-mising areas for future advance,it is important to identify the areas of grea-test current activity.Methodology
Biophysics software for interdisciplinary education and research  [PDF]
J. M. Deutsch
Physics , 2013, DOI: 10.1119/1.4869198
Abstract: Biophysics is a subject that is spread over many disciplines and transcends the skills and knowledge of the individual student. This makes it challenging both to teach and to learn. Educational materials are described to aid in teaching undergraduates biophysics in an interdisciplinary manner. Projects have been devised on topics that range from x-ray diffraction to the Hodgkin Huxley equations. They are team-based and encourage collaboration. The projects make extensive use of software written in Python/Scipy which can be modified to explore a large range of possible phenomena. The software can also be used in lectures and in the teaching of more traditional biophysics courses.
Systems Biophysics of Gene Expression  [PDF]
Jose M. G. Vilar,Leonor Saiz
Quantitative Biology , 2013, DOI: 10.1016/j.bpj.2013.04.032
Abstract: Gene expression is a central process to any form of life. It involves multiple temporal and functional scales that extend from specific protein-DNA interactions to the coordinated regulation of multiple genes in response to intracellular and extracellular changes. This diversity in scales poses fundamental challenges among traditional approaches to fully understand even the simplest gene expression systems. Recent advances in computational systems biophysics have provided promising avenues to reliably integrate the molecular detail of biophysical process into the system behavior. Here, we review recent advances in the description of gene regulation as a system of biophysical processes that extend from specific protein-DNA interactions to the combinatorial assembly of nucleoprotein complexes. There is now basic mechanistic understanding on how promoters controlled by multiple, local and distal, DNA binding sites for transcription factors can actively control transcriptional noise, cell-to-cell variability, and other properties of gene regulation, including precision and flexibility of the transcriptional responses.
The debut of PMC Biophysics
Huan-Xiang Zhou
BMC Biophysics , 2008, DOI: 10.1186/1757-5036-1-1
Abstract: Firstly, the open access movement is gathering strength. Pioneered by PMC Biophysics's parent company, BioMed Central, open access allows any reader immediate free access to published articles, encouraging the widest possible spread of knowledge. Archiving in multiple repositories ensures the long-term preservation of scientific research, and electronic publication enables the inclusion of multimedia content and the dissemination of raw data - allowing other researchers to exploit them. All these features serve to enhance the impact of published articles.The strength and future success of open access are heralded by two major recent developments. The US National Institutes of Health, the largest public funding agency for biomedical research, now requires that all peer-reviewed journal articles arising from NIH funding be made open access within 12 months of publication. In addition, BioMed Central has recently been acquired by Springer, the world's second largest publisher of scientific journals.The second trend concerns the multidisciplinary nature of research in biological physics.Over the past 40 years, the field of biological physics has been shaped by forces from two directions. On one hand, the study of biological systems has become less and less descriptive and more and more quantitative. It has become more compelling to model biological systems and rationalise or predict behaviours from physical principles, such as in protein folding.On the other hand, it has been discovered time and again that models and techniques developed for simple physical systems eventually become powerful tools for studying biological systems – Born's model for ion solvation and Kramers' rate theory for barrier crossing being classic examples. X-ray crystallography and computer simulations both started from humble beginnings, but are now used to study ever larger biomacromolecular complexes. The end result is that biological physics is now a thriving area for researchers from a wide
The Principle of Stationary Action in Biophysics: Stability in Protein Folding  [PDF]
Walter Simmons,Joel L. Weiner
Quantitative Biology , 2013,
Abstract: Processes that proceed reliably from a variety of initial conditions to a unique final form, regardless of moderately changing conditions, are of obvious importance in biophysics. Protein folding is a case in point. We show that the action principle can be applied directly to study the stability of biological processes. The action principle in classical physics starts with the first variation of the action and leads immediately to the equations of motion. The second variation of the action leads in a natural way to powerful theorems that provide quantitative treatment of stability and focusing and also explain how some very complex processes can behave as though some seemingly important forces drop out. We first apply these ideas to the non-equilibrium states involved in two-state folding. We treat torsional waves and use the action principle to talk about critical points in the dynamics. For some proteins the theory resembles TST. We reach several quantitative and qualitative conclusions. Besides giving an explanation of why TST often works in folding, we find that the apparent smoothness of the energy funnel is a natural consequence of the putative critical points in the dynamics. These ideas also explain why biological proteins fold to unique states and random polymers do not. The insensitivity to perturbations which follows from the presence of critical points explains how folding to a unique shape occurs in the presence of dilute denaturing agents in spite of the fact that those agents disrupt the folded structure of the native state. This paper contributes to the theoretical armamentarium by directing attention to the logical progression from first physical principles to the stability theorems related to catastrophe theory as applied to folding. This can potentially have the same success in biophysics as it has enjoyed in optics.
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