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Progress in Biophysics and Molecular Biology

Roland G Huber, Jan K Marzinek, Daniel A Holdbrook, Peter J Bond
Viral pathogens are a significant source of human morbidity and mortality, and have a major impact on societies and economies around the world. One of the challenges inherent in targeting these pathogens with drugs is the tight integration of the viral life cycle with the host's cellular machinery. However, the reliance of the virus on the host cell replication machinery is also an opportunity for therapeutic targeting, as successful entry- and exit-inhibitors have demonstrated. An understanding of the extracellular and intracellular structure and dynamics of the virion - as well as of the entry and exit pathways in host and vector cells - is therefore crucial to the advancement of novel antivirals...
October 17, 2016: Progress in Biophysics and Molecular Biology
Eann A Patterson, Maurice P Whelan
Computational models in biology and biomedical science are often constructed to aid people's understanding of phenomena or to inform decisions with socioeconomic consequences. Model credibility is the willingness of people to trust a model's predictions and is often difficult to establish for computational biology models. A 3 × 3 matrix has been proposed to allow such models to be categorised with respect to their testability and epistemic foundation in order to guide the selection of an appropriate process of validation to supply evidence to establish credibility...
October 1, 2016: Progress in Biophysics and Molecular Biology
David McKinnon, Barbara Rosati
Evolution has acted to shape the action potential in different regions of the heart in order to produce a maximally stable and efficient pump. This has been achieved by creating regional differences in ion channel expression levels within the heart as well as differences between equivalent cardiac tissues in different species. These region- and species-dependent differences in channel expression are established by regulatory evolution, evolution of the regulatory mechanisms that control channel expression levels...
October 1, 2016: Progress in Biophysics and Molecular Biology
Igor N Berezovsky, Enrico Guarnera, Zejun Zheng
Study of the hierarchy of domain structure with alternative sets of domains and analysis of discontinuous domains, consisting of remote segments of the polypeptide chain, raised a question about the minimal structural unit of the protein domain. The hypothesis on the decisive role of the polypeptide backbone in determining the elementary units of globular proteins have led to the discovery of closed loops. It is reviewed here how closed loops form the loop-n-lock structure of proteins, providing the foundation for stability and designability of protein folds/domain and underlying their co-translational folding...
September 30, 2016: Progress in Biophysics and Molecular Biology
Lizhe Zhu, Hanlun Jiang, Fu Kit Sheong, Xuefeng Cui, Yanli Wang, Xin Gao, Xuhui Huang
At the core of RNA interference, the Argonaute proteins (Ago) load and utilize small guide nucleic acids to silence mRNAs or cleave foreign nucleic acids in a sequence specific manner. In recent years, based on extensive structural studies of Ago and its interaction with the nucleic acids, considerable progress has been made to reveal the dynamic aspects of various Ago-mediated processes. Here we review these novel insights into the guide-strand loading, duplex unwinding, and effects of seed mismatch, with a focus on two representative Agos, the human Ago 2 (hAgo2) and the bacterial Thermus thermophilus Ago (TtAgo)...
September 30, 2016: Progress in Biophysics and Molecular Biology
C O S Sorzano, J Vargas, J Otón, V Abrishami, J M de la Rosa-Trevín, J Gómez-Blanco, J L Vilas, R Marabini, J M Carazo
Fourier Shell Correlation, Spectral Signal-to-Noise Ratio, Fourier Neighbour Correlation, and Differential Phase Residual are different measures that have been proposed over time to determine the spatial resolution achieved by a certain 3D reconstruction. Estimates of B-factors to describe the reduction in signal-to-noise ratio with increasing resolution is also a useful parameter. All these concepts are interrelated and different thresholds have been given for each one of them. However, the problem of resolution assessment in 3DEM is still far from settled and preferences are normally adopted in order to choose the "correct" threshold...
September 22, 2016: Progress in Biophysics and Molecular Biology
Xinchang Zhang, Qiangsong Wang, Zongming Wan, Jianyu Li, Lu Liu, Xizheng Zhang
Casein kinase 2-interacting protein 1 (CKIP-1) is a negative regulator for bone formation. CKIP-1 knockout (KO) mice are very important for research on countermeasures to bone loss induced by space microgravity. Under simulated microgravity, the bone metabolism of CKIP-1 KO mice was different than that of wild-type (WT) mice. Many experiments all showed that the KO mice had significantly enhanced ossification in the tail suspension conditions, and the differences were closely related to the time the mice were exposed to the microgravity environment...
September 22, 2016: Progress in Biophysics and Molecular Biology
Togo Shimozawa, Erisa Hirokawa, Fuyu Kobirumaki-Shimozawa, Kotaro Oyama, Seine A Shintani, Takako Terui, Yasuharu Kushida, Seiichi Tsukamoto, Teruyuki Fujii, Shin'ichi Ishiwata, Norio Fukuda
The cardiac pump function is a result of a rise in intracellular Ca(2+) and the ensuing sarcomeric contractions [i.e., excitation-contraction (EC) coupling] in myocytes in various locations of the heart. In order to elucidate the heart's mechanical properties under various settings, cardiac imaging is widely performed in today's clinical as well as experimental cardiology by using echocardiogram, magnetic resonance imaging and computed tomography. However, because these common techniques detect local myocardial movements at a spatial resolution of ∼100 μm, our knowledge on the sub-cellular mechanisms of the physiology and pathophysiology of the heart in vivo is limited...
September 21, 2016: Progress in Biophysics and Molecular Biology
Ira S Cohen, Richard T Mathias
No abstract text is available yet for this article.
September 16, 2016: Progress in Biophysics and Molecular Biology
Philip Turner, Laurent Nottale
Based on laboratory based growth of plant-like structures from inorganic materials, we present new theory for the emergence of plant structure at a range of scales dictated by levels of ionization, which can be traced directly back to proteins transcribed from genetic code and their interaction with external sources of charge in real plants. Beyond a critical percolation threshold, individual charge induced quantum potentials merge to form a complex, interconnected geometric web, creating macroscopic quantum potentials, which lead to the emergence of macroscopic quantum processes...
September 14, 2016: Progress in Biophysics and Molecular Biology
Julie M J Laffy, Tihomir Dodev, Jamie A Macpherson, Catherine Townsend, Hui Chun Lu, Deborah Dunn-Walters, Franca Fraternali
Human B cells produce antibodies, which bind to their cognate antigen based on distinct molecular properties of the antibody CDR loop. We have analysed a set of 10 antibodies showing a clear difference in their binding properties to a panel of antigens, resulting in two subsets of antibodies with a distinct binding phenotype. We call the observed binding multiplicity 'promiscuous' and selected physico-chemical CDRH3 characteristics and conformational preferences may characterise these promiscuous antibodies...
September 14, 2016: Progress in Biophysics and Molecular Biology
Zhimin Li, Charles Shang
A model of growth control system suggests that the organizers in embryogenesis continue to exist and partially retain their function after embryogenesis. The organizers are the macroscopic singular points of the morphogen gradient and bioelectric fields. They have higher metabolic rate, higher density of gap junctions and stem cells than the surrounding tissue. The growth control model predicts that the organizers are likely to exist at the extreme points of surface or interface curvature of the body. Changes in bioelectric field at organizers precede the morphological and anatomical changes in morphogenesis and pathogenesis...
September 12, 2016: Progress in Biophysics and Molecular Biology
Douglas B Kell, Etheresia Pretorius
The chief and largely terminal element of normal blood clotting is considered to involve the polymerisation of the mainly α-helical fibrinogen to fibrin, with a binding mechanism involving 'knobs and holes' but with otherwise little change in protein secondary structure. We recognise, however, that extremely unusual mutations or mechanical stressing can cause fibrinogen to adopt a conformation containing extensive β-sheets. Similarly, prions can change morphology from a largely α-helical to largely β-sheet conformation, and the latter catalyses both the transition and the self-organising polymerisation of the β-sheet structures...
August 20, 2016: Progress in Biophysics and Molecular Biology
Maël Montévil, Lucia Speroni, Carlos Sonnenschein, Ana M Soto
In multicellular organisms, relations among parts and between parts and the whole are contextual and interdependent. These organisms and their cells are ontogenetically linked: an organism starts as a cell that divides producing non-identical cells, which organize in tri-dimensional patterns. These association patterns and cells types change as tissues and organs are formed. This contextuality and circularity makes it difficult to establish detailed cause and effect relationships. Here we propose an approach to overcome these intrinsic difficulties by combining the use of two models; 1) an experimental one that employs 3D culture technology to obtain the structures of the mammary gland, namely, ducts and acini, and 2) a mathematical model based on biological principles...
August 17, 2016: Progress in Biophysics and Molecular Biology
Maël Montévil, Matteo Mossio, Arnaud Pocheville, Giuseppe Longo
Darwin introduced the concept that random variation generates new living forms. In this paper, we elaborate on Darwin's notion of random variation to propose that biological variation should be given the status of a fundamental theoretical principle in biology. We state that biological objects such as organisms are specific objects. Specific objects are special in that they are qualitatively different from each other. They can undergo unpredictable qualitative changes, some of which are not defined before they happen...
August 13, 2016: Progress in Biophysics and Molecular Biology
Matteo Mossio, Maël Montévil, Giuseppe Longo
In the search of a theory of biological organisms, we propose to adopt organization as a theoretical principle. Organization constitutes an overarching hypothesis that frames the intelligibility of biological objects, by characterizing their relevant aspects. After a succinct historical survey on the understanding of organization in the organicist tradition, we offer a specific characterization in terms of closure of constraints. We then discuss some implications of the adoption of organization as a principle and, in particular, we focus on how it fosters an original approach to biological stability, as well as and its interplay with variation...
August 10, 2016: Progress in Biophysics and Molecular Biology
Ana M Soto, Giuseppe Longo, Paul-Antoine Miquel, Maël Montevil, Matteo Mossio, Nicole Perret, Arnaud Pocheville, Carlos Sonnenschein
Organisms, be they uni- or multi-cellular, are agents capable of creating their own norms; they are continuously harmonizing their ability to create novelty and stability, that is, they combine plasticity with robustness. Here we articulate the three principles for a theory of organisms proposed in this issue, namely: the default state of proliferation with variation and motility, the principle of variation and the principle of organization. These principles profoundly change both biological observables and their determination with respect to the theoretical framework of physical theories...
August 4, 2016: Progress in Biophysics and Molecular Biology
Chaohua Zhu, Gang Guo, Qiqi Ma, Fengjuan Zhang, Funing Ma, Dao Xiao, Xiaolin Yang, Ming Sun
Surface layers, referred to simply as S-layers, are the two-dimensional crystalline arrays of protein or glycoprotein subunits on cell surface. They are one of the most common outermost envelope components observed in prokaryotic organisms (Archaea and Bacteria). Over the past decades, S-layers have become an issue of increasing interest due to their ubiquitousness, special features and functions. Substantial work in this field provides evidences of an enormous diversity in S-layers. This paper reviews and illustrates the diversity from several different aspects, involving the S-layer-carrying strains, the structure of S-layers, the S-layer proteins and genes, as well as the functions of S-layers...
August 3, 2016: Progress in Biophysics and Molecular Biology
Carlos Sonnenschein, Ana Soto
For a century, the somatic mutation theory (SMT) has been the prevalent theory to explain carcinogenesis. According to the SMT, cancer is a cellular problem, and thus, the level of organization where it should be studied is the cellular level. Additionally, the SMT proposes that cancer is a problem of the control of cell proliferation and assumes that proliferative quiescence is the default state of cells in metazoa. In 1999, a competing theory, the tissue organization field theory (TOFT), was proposed. In contraposition to the SMT, the TOFT posits that cancer is a tissue-based disease whereby carcinogens (directly) and mutations in the germ-line (indirectly) alter the normal interactions between the diverse components of an organ, such as the stroma and its adjacent epithelium...
August 3, 2016: Progress in Biophysics and Molecular Biology
Logan R Myler, Ilya J Finkelstein
DNA double-strand breaks (DSBs) disrupt the physical and genetic continuity of the genome. If unrepaired, DSBs can lead to cellular dysfunction and malignant transformation. Homologous recombination (HR) is a universally conserved DSB repair mechanism that employs the information in a sister chromatid to catalyze error-free DSB repair. To initiate HR, cells assemble the resectosome: a multi-protein complex composed of helicases, nucleases, and regulatory proteins. The resectosome nucleolytically degrades (resects) the free DNA ends for downstream homologous recombination...
August 3, 2016: Progress in Biophysics and Molecular Biology
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