Dynamics of complex systems is often driven by large and intricate networks of microscopic interactions, whose sheer size obfuscates understanding. With limited experimental data, many parameters of ...such dynamics are unknown, and thus detailed, mechanistic models risk overfitting and making faulty predictions. At the other extreme, simple ad hoc models often miss defining features of the underlying systems. Here we develop an approach that instead constructs phenomenological, coarse-grained models of network dynamics that automatically adapt their complexity to the available data. Such adaptive models produce accurate predictions even when microscopic details are unknown. The approach is computationally tractable, even for a relatively large number of dynamical variables. Using simulated data, it correctly infers the phase space structure for planetary motion, avoids overfitting in a biological signalling system and produces accurate predictions for yeast glycolysis with tens of data points and over half of the interacting species unobserved.
Species are considered the fundamental unit in many ecological and evolutionary analyses, yet accurate, complete, accessible taxonomic frameworks with which to identify them are often unavailable to ...researchers. In such cases DNA sequence-based species delimitation has been proposed as a means of estimating species boundaries for further analysis. Several methods have been proposed to accomplish this. Here we present a Bayesian implementation of an evolutionary model-based method, the general mixed Yule-coalescent model (GMYC). Our implementation integrates over the parameters of the model and uncertainty in phylogenetic relationships using the output of widely available phylogenetic models and Markov-Chain Monte Carlo (MCMC) simulation in order to produce marginal probabilities of species identities.
We conducted simulations testing the effects of species evolutionary history, levels of intraspecific sampling and number of nucleotides sequenced. We also re-analyze the dataset used to introduce the original GMYC model. We found that the model results are improved with addition of DNA sequence and increased sampling, although these improvements have limits. The most important factor in the success of the model is the underlying phylogenetic history of the species under consideration. Recent and rapid divergences result in higher amounts of uncertainty in the model and eventually cause the model to fail to accurately assess uncertainty in species limits.
Our results suggest that the GMYC model can be useful under a wide variety of circumstances, particularly in cases where divergences are deeper, or taxon sampling is incomplete, as in many studies of ecological communities, but that, in accordance with expectations from coalescent theory, rapid, recent radiations may yield inaccurate results. Our implementation differs from existing ones in two ways: it allows for the accounting for important sources of uncertainty in the model (phylogenetic and in parameters specific to the model) and in the specification of informative prior distributions that can increase the precision of the model. We have incorporated this model into a user-friendly R package available on the authors' websites.
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Reactive oxygen species (ROS) are a family of molecules that are continuously generated, transformed and consumed in all living organisms as a consequence of aerobic life. The traditional view of ...these reactive oxygen metabolites is one of oxidative stress and damage that leads to decline of tissue and organ systems in aging and disease. However, emerging data show that ROS produced in certain situations can also contribute to physiology and increased fitness. This Perspective provides a focused discussion on what factors lead ROS molecules to become signal and/or stress agents, highlighting how increasing knowledge of the underlying chemistry of ROS can lead to advances in understanding their disparate contributions to biology. An important facet of this emerging area at the chemistry-biology interface is the development of new tools to study these small molecules and their reactivity in complex biological systems.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Several states, including Israel and the United States, have put decapitation tactics, which seek to kill or capture leaders of terrorist organizations, at the forefront of their counterterrorism ...efforts. The vast majority of scholarly work on decapitation suggests, however, that leadership decapitation is ineffective at best and counterproductive at worst. Contrary to this conventional wisdom, leadership decapitation significantly increases the mortality rate of terrorist groups, although the results indicate that the effect of decapitation decreases with the age of the group, even to a point where it may have no effect at all. This finding helps to explain the previously perplexing mixed record of decapitation effectiveness. Terrorist groups are especially susceptible to leadership decapitation because their organizational characteristics (they are violent, clandestine, and values based) amplify the difficulties of leadership succession. Additionally, in contrast to the conventional wisdom regarding the durability of terrorist groups, politically relevant terrorist groups (defined as those with at least four attacks including one attack resulting in a fatality) endure significantly longer than previously believed.
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BFBNIB, INZLJ, IZUM, KILJ, NMLJ, NUK, ODKLJ, PILJ, PNG, SAZU, UL, UM, UPUK, ZRSKP
There is an urgent need for antiviral agents that treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We screened a library of 1900 clinically safe drugs against OC43, a ...human beta coronavirus that causes the common cold, and evaluated the top hits against SARS-CoV-2. Twenty drugs significantly inhibited replication of both viruses in cultured human cells. Eight of these drugs inhibited the activity of the SARS-CoV-2 main protease, 3CLpro, with the most potent being masitinib, an orally bioavailable tyrosine kinase inhibitor. X-ray crystallography and biochemistry show that masitinib acts as a competitive inhibitor of 3CLpro. Mice infected with SARS-CoV-2 and then treated with masitinib showed >200-fold reduction in viral titers in the lungs and nose, as well as reduced lung inflammation. Masitinib was also effective in vitro against all tested variants of concern (B.1.1.7, B.1.351, and P.1).
•Precise rare earth pyrochlore structural and thermo-mechanical data obtained.•Experimental results and density functional theory calculations compared.•Insights obtained into rare earth bonding and ...hybridization in pyrochlores.•Thermal expansion results obtained for use in nuclear waste-form design.•Structural/bonding results obtained that are pertinent to radiation damage studies.
Rare-earth titanates, RE2Ti2O7 (where RE=a rare-earth) with the pyrochlore structure continue to be investigated for use as potential stable host materials for nuclear and actinide-rich wastes. Accordingly, the present work is directed towards the elucidation of the fundamental structural, physical, and thermochemical properties of this class of compounds. Single-crystals of the rare earth pyrochlores were synthesized using a high-temperature flux technique and were subsequently characterized using single-crystal X-ray diffraction. The cubic lattice parameters display an approximately linear correlation with the RE-site cation radius. Theoretical calculations of the lattice constants and bond lengths of the subject materials were carried out using density functional theory, and the results are compared to the experimental values. The Sm and Eu titanates exhibit a covalency increase between the REO8 and TiO6 polyhedral resulting in a deviation from the increasing linear lattice parameter through the transition series. Gd2Ti2O7 with the 4f7 half-filled f-orbital Gd3+ sub-shell exhibits the lowest 48f oxygen positional parameter. The coefficient of thermal expansion for the rare-earth titanate series is approximately linear, and it has a range of 10.1–11.2×10−6°C−1. Raman spectroscopy indicated that the ∼530cm−1 peak associated with the Ti–O stretching mode follows a general trend of decreasing frequency with increasing RE reduced mass.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The nonlinearity of dynamics in systems biology makes it hard to infer them from experimental data. Simple linear models are computationally efficient, but cannot incorporate these important ...nonlinearities. An adaptive method based on the S-system formalism, which is a sensible representation of nonlinear mass-action kinetics typically found in cellular dynamics, maintains the efficiency of linear regression. We combine this approach with adaptive model selection to obtain efficient and parsimonious representations of cellular dynamics. The approach is tested by inferring the dynamics of yeast glycolysis from simulated data. With little computing time, it produces dynamical models with high predictive power and with structural complexity adapted to the difficulty of the inference problem.
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How to fail at species delimitation Carstens, Bryan C.; Pelletier, Tara A.; Reid, Noah M. ...
Molecular ecology,
September 2013, Volume:
22, Issue:
17
Journal Article
Peer reviewed
Open access
Species delimitation is the act of identifying species‐level biological diversity. In recent years, the field has witnessed a dramatic increase in the number of methods available for delimiting ...species. However, most recent investigations only utilize a handful (i.e. 2–3) of the available methods, often for unstated reasons. Because the parameter space that is potentially relevant to species delimitation far exceeds the parameterization of any existing method, a given method necessarily makes a number of simplifying assumptions, any one of which could be violated in a particular system. We suggest that researchers should apply a wide range of species delimitation analyses to their data and place their trust in delimitations that are congruent across methods. Incongruence across the results from different methods is evidence of either a difference in the power to detect cryptic lineages across one or more of the approaches used to delimit species and could indicate that assumptions of one or more of the methods have been violated. In either case, the inferences drawn from species delimitation studies should be conservative, for in most contexts it is better to fail to delimit species than it is to falsely delimit entities that do not represent actual evolutionary lineages.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Several compounds extracted from spices and herbs exhibit antiviral effects in vitro, suggesting potential pharmacological uses. Curcumin, a component of turmeric, has been used as a food additive ...and herbal supplement due to its potential medicinal properties. Previously, curcumin exhibited antiviral properties against several viruses, including dengue virus and hepatitis C virus, among others. Here, we describe the antiviral effect of curcumin on Zika and chikungunya viruses, two mosquito-borne outbreak viruses. Both viruses responded to treatment of cells with up to 5 μM curumin without impacting cellular viability. We observed that direct treatment of virus with curcumin reduced infectivity of virus in a dose- and time-dependent manner for these enveloped viruses, as well as vesicular stomatitis virus. In contrast, we found no change in infectivity for Coxsackievirus B3, a non-enveloped virus. Derivatives of curcumin also exhibited antiviral activity against enveloped viruses. Further examination revealed that curcumin interfered with the binding of the enveloped viruses to cells in a dose-dependent manner, though the integrity of the viral RNA was maintained. Together, these results expand the family of viruses sensitive to curcumin and provide a mechanism of action for curcumin's effect on these enveloped viruses.
•Curcumin inhibits Zika and chikungunya virus replication in human cells.•Curcumin acts at an early step in virus infection.•Virus incubated with curcumin loses infectivity.•Curcumin interferes with virus-cell binding.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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