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Complex system in biology

Olivia Angelin-Bonnet, Patrick J Biggs, Matthieu Vignes
Modelling gene regulatory networks requires not only a thorough understanding of the biological system depicted, but also the ability to accurately represent this system from a mathematical perspective. Throughout this chapter, we aim to familiarize the reader with the biological processes and molecular factors at play in the process of gene expression regulation. We first describe the different interactions controlling each step of the expression process, from transcription to mRNA and protein decay. In the second section, we provide statistical tools to accurately represent this biological complexity in the form of mathematical models...
2019: Methods in Molecular Biology
Christopher A Penfold, Iulia Gherman, Anastasiya Sybirna, David L Wild
Gaussian process dynamical systems (GPDS) represent Bayesian nonparametric approaches to inference of nonlinear dynamical systems, and provide a principled framework for the learning of biological networks from multiple perturbed time series measurements of gene or protein expression. Such approaches are able to capture the full richness of complex ODE models, and can be scaled for inference in moderately large systems containing hundreds of genes. Related hierarchical approaches allow for inference from multiple datasets in which the underlying generative networks are assumed to have been rewired, either by context-dependent changes in network structure, evolutionary processes, or synthetic manipulation...
2019: Methods in Molecular Biology
Alex White, Matthieu Vignes
Biological networks are a very convenient modeling and visualization tool to discover knowledge from modern high-throughput genomics and post-genomics data sets. Indeed, biological entities are not isolated but are components of complex multilevel systems. We go one step further and advocate for the consideration of causal representations of the interactions in living systems. We present the causal formalism and bring it out in the context of biological networks, when the data is observational. We also discuss its ability to decipher the causal information flow as observed in gene expression...
2019: Methods in Molecular Biology
Katherine E Liu
Despite the productivity of basic cancer research, cancer continues to be a health burden to society because this research has not yielded corresponding clinical applications. Many proposed solutions to this dilemma have revolved around implementing organizational and policy changes related to cancer research. Here I argue for a different solution: a new conceptualization of causation in cancer. Neither the standard molecular biomarker approaches nor evolutionary biology approaches to cancer fully capture its complex causal dynamics, even when considered jointly...
2018: Biological Theory
Boya Wang, Chris Thachuk, Andrew D Ellington, Erik Winfree, David Soloveichik
Artificially designed molecular systems with programmable behaviors have become a valuable tool in chemistry, biology, material science, and medicine. Although information processing in biological regulatory pathways is remarkably robust to error, it remains a challenge to design molecular systems that are similarly robust. With functionality determined entirely by secondary structure of DNA, strand displacement has emerged as a uniquely versatile building block for cell-free biochemical networks. Here, we experimentally investigate a design principle to reduce undesired triggering in the absence of input (leak), a side reaction that critically reduces sensitivity and disrupts the behavior of strand displacement cascades...
December 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
Yingying Zhang, Luhui Wang, Yanan Wang, Yafei Dong
The development of efficient and convenient strategy without involving enzyme or complex nanomaterial for the micro molecules detection has profound meaning in the diagnosis of diseases. Herein, taking the advantages of the strong affinity of aptamer and catalyzed hairpin assembly, we develop a new non-label optical amplified strategy for thrombin detection in this work. To support both biological inquiry and technological innovation, thermodynamic models are introduced to predict the minimum energy secondary structure of interacting nucleic acid strands and calculate the partition function and equilibrium concentration for complexes in our system...
December 3, 2018: Computational Biology and Chemistry
EunJin Bang, Bonggi Lee, Sang-Gyun Noh, Dae Hyun Kim, Hee Jin Jung, Sugyeong Ha, Byung Pal Yu, Hae Young Chung
Aging is a complex and progressive process characterized by physiological and functional decline with time that increases susceptibility to diseases. Aged-related functional change is accompanied by a low-grade, unresolved chronic inflammation as a major underlying mechanism. In order to explain aging in the context of chronic inflammation, a new integrative concept on age-related chronic inflammation is necessary that encompasses much broader and wider characteristics of cells, tissues, organs, systems, and interactions between immune and non-immune cells, metabolic and non-metabolic organs...
December 14, 2018: BMB Reports
Jyung Mean Son, Changhan Lee
Aging is accompanied by a time-dependent progressive deterioration of multiple factors of the cellular system. The past several decades have witnessed major leaps in our understanding of the biological mechanism of aging using dietary, genetic, pharmacological, and physical interventions. Metabolic processes, including nutrient sensing pathways and mitochondrial function, have emerged as prominent regulators of aging. Mitochondria have been considered to play a key role largely due to their production of reactive oxygen species (ROS), resulting in DNA damage that accumulates over time and ultimately causes cellular failure...
December 14, 2018: BMB Reports
Alexandra C Tuggle, Jeffrey H Cohen, Douglas E Crews
BACKGROUND: Immigration is a disruptive event with multiple implications for health. Stressors, including family separation, acculturation, job insecurity, restricted mobility, sojourns, dangerous border crossings, stigmatization, and marginalization, shape immigrant health in ways we are only beginning to untangle. Around the world, there are over 200 million international migrants. In 2015, there were 43.2 million immigrants living in the US, 26.8% of whom were born in Mexico. Investigating how stress affects health among migrants facilitates better understanding of their experiences...
December 13, 2018: Journal of Physiological Anthropology
Santosh Jagadeeshan, Alyssa K Gomes, Rama S Singh
Maternal mortality remains one of the leading causes of death in women of reproductive age in developing countries, and a major concern in some developed countries. It is puzzling why such a condition has not been reduced in frequency, if not eliminated, in the course of evolution. Maternal mortality is a complex phenomenon caused by several physiological and physical factors. Among the physical factors, maternal mortality due to fetopelvic disproportion remains controversial. Several explanations including evolution of bipedal locomotion, rapid brain growth, and nutritional changes and life style changes in settler communities have been proposed...
December 13, 2018: Reproductive Sciences
Sergey Milikisiyants, Maxim A Voinov, Antonin Marek, Morteza Jafarabadi, Jing Liu, Rong Han, Shenlin Wang, Alex I Smirnov
Over the past decades pulsed electron-electron double resonance (PELDOR), often called double electron-electron resonance (DEER), became one of the major spectroscopic tools for measurements of nanometer-scale distances and distance distributions in non-crystalline biological and chemical systems. The method is based on detecting the amplitude of the primary (3-pulse DEER) or refocused (4-pulse DEER) spin echo for the so-called "observer" spins when the other spins coupled to the former by a dipolar interaction are flipped by a "pump" pulse at another EPR frequency...
December 5, 2018: Journal of Magnetic Resonance
Kathryn Regan, Devynn Wulstein, Hannah Rasmussen, Ryan McGorty, Rae M Robertson-Anderson
Crowding plays a key role in the transport and conformations of biological macromolecules. Gene therapy, viral infection, and transfection require DNA to traverse the crowded cytoplasm, including the cytoskeletal network of filamentous proteins. Given the complexity of cellular crowding, the dynamics of biological molecules can be highly dependent on the spatiotemporal scale probed. We present a powerful platform that spans molecular and cellular scales by coupling single-molecule conformational tracking (SMCT) and selective-plane illumination differential dynamic microscopy (SPIDDM)...
December 13, 2018: Soft Matter
Mark Benhaim, Kelly K Lee, Miklos Guttman
Structural biology has provided a fundamental understanding of protein structure and mechanistic insight into their function. However, high-resolution structures alone are insufficient for a complete understanding of protein behavior. Higher energy conformations, conformational changes, and subtle structural fluctuations that underlie the proper function of proteins are often difficult to probe using traditional structural approaches. Solution state structural techniques are needed to interrogate the dynamic nature of proteins under native conditions...
December 12, 2018: Protein and Peptide Letters
Losiana Nayak, Abhijit Dasgupta, Ritankar Das, Kuntal Ghosh, Rajat K De
The human brain and its temporal behavior correlated with development, structure, and function is a complex natural system even for its own kind. Coding and automation are necessary for modeling, analyzing and understanding the 86.1 +/- 8.1 +/- billion neurons, an almost equal number of non-neuronal glial cells, and the neuronal networks of the human brain comprising about 100 trillion connections. 'Computational neuroscience' which is heavily dependent on biology, physics, mathematics and computation addresses such problems while the archival, retrieval and merging of the huge amount of generated data in the form of clinical records, scientific literature, and specialized databases are carried out by 'neuroinformatics' approaches...
December 2018: Journal of Biosciences
Márcia S Pereira, Inês Alves, Manuel Vicente, Ana Campar, Mariana C Silva, Nuno A Padrão, Vanda Pinto, Ângela Fernandes, Ana M Dias, Salomé S Pinho
The immune system is highly controlled and fine-tuned by glycosylation, through the addition of a diversity of carbohydrates structures (glycans) to virtually all immune cell receptors. Despite a relative backlog in understanding the importance of glycans in the immune system, due to its inherent complexity, remarkable findings have been highlighting the essential contributions of glycosylation in the regulation of both innate and adaptive immune responses with important implications in the pathogenesis of major diseases such as autoimmunity and cancer...
2018: Frontiers in Immunology
Francesca Nerattini, Luca Tubiana, Chiara Cardelli, Valentino Bianco, Christoph Dellago, Ivan Coluzza
Molecular recognition is a critical process for many biological functions and consists in non-covalent binding of different molecules, such as protein-protein, antigen-antibody and many others. The host-guest molecules involved often show a shape complementarity, and one of the leading specification for molecular recognition is that the interaction must be selective, i.e. the host should strongly bind to one selected guest and poorly, if at all, to all other biomolecules. Our work focuses on the role played by the chemical heterogeneity and the steric compatibility on the selectivity power of the binding site between two proteins...
December 11, 2018: Journal of Chemical Theory and Computation
Xian Liu, Daniel P Evatt, Bradley E Belsher
Introduction: Since the 1991 Gulf War, mental health conditions of military Service members have received increasing public attention and are a major focus for the U.S. government. A substantial proportion of military health research has been devoted to examining the pattern of change over time in mental health symptoms and diagnostic status among Service members. Unfortunately, many researchers continue to use somewhat obsolete methods to analyze trends and transitions in mental health, despite advances in statistical methodology that permit attention to the unique features inherent in longitudinal data...
December 7, 2018: Military Medicine
G Baiocco, G Babini, S Barbieri, J Morini, W Friedland, C Villagrasa, H Rabus, A Ottolenghi
Ionizing radiation is a peculiar perturbation when it comes to damage to biological systems: it proceeds through discrete energy depositions, over a short temporal scale and a spatial scale critical for subcellular targets as DNA, whose damage complexity determines the outcome of the exposure. This lies at the basis of the success of track structure (and nanodosimetry) and microdosimetry in radiation biology. However, such reductionist approaches cannot account for the complex network of interactions regulating the overall response of the system to radiation, particularly when effects are manifest at the supracellular level and involve long times...
December 11, 2018: Radiation Protection Dosimetry
Gabe Nagy, Dusan Veličković, Rosalie K Chu, Alyssa A Carrell, David J Weston, Yehia M Ibrahim, Christopher R Anderton, Richard D Smith
We demonstrate the coupling of liquid extraction surface analysis (LESA) to structures for lossless ion manipulations in conjunction with serpentine ultralong path with extending routing (SLIM SUPER) ion mobility-mass spectrometry (IM-MS) for the unambiguous annotation of important isomeric glycoforms in carbon-fixing communities.
December 7, 2018: Chemical Communications: Chem Comm
Jingkun Lu, Yuchong Hu, Lechun Wang, Yuewu Wang, Shengsang Na, Jian Wang, Yuhui Shun, Xiaoqin Wang, Peifeng Xue, Pengwei Zhao, Liping Su
GuangZao and RouDouKou ( Fructus Choerospondiatis and Nutmeg , FCN) are one of the most common herb pairs in traditional Mongolian medicine for the treatment of coronary heart disease (CHD). However, evidence for the protective effect of FCN is limited, and its underlying mechanism of action remains unclear. The present study employed a network pharmacology approach to identify the potentially active ingredients and synergistic effects of the herb pair FCN as traditional Mongolian medicine. We predicted the targets of all available FCN ingredients with PharmMapper, SWISS, and SuperPred Server and clustered CHD-related targets from the DrugBank and the OMIM database...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
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