Simplivariate models: uncovering the underlying biology in functional genomics data

One of the first steps in analyzing high-dimensional functional genomics data is an exploratory analysis of such data. Cluster Analysis and Principal Component Analysis are then usually the method of choice. Despite their versatility they also have a severe drawback: they do not always generate simple and interpretable solutions. On the basis of the observation that functional genomics data often contain both informative and non-informative variation, we propose a method that finds sets of variables containing informative variation. This informative variation is subsequently expressed in easily interpretable simplivariate components.We present a new implementation of the recently introduced simplivariate models. In this implementation, the informative variation is described by multiplicative models that can adequately represent the relations between functional genomics data. Both a simulated and two real-life metabolomics data sets show good performance of the method.     

Some examples of persistence in epidemiological models

The aim of this short note is to illustrate how an abstract result by Fonda about persistence in dynamical systems can be easily applied to some epidemiological models.     

The first examples of benzidinium cations templated low-dimensional molybdates

For the first time, use of benzidine as a structure-directing agent has resulted in the crystallization of two novel organic/inorganic hybrid molybdates under hydrothermal condition (180 °C and autogenous pressure). The presence of monoprotonated benzidinium ions in aqueous molybdate solution appears to engineer two new hybrid solids: one-dimensional chains in [H₂NC₁₂H₈NH₃]₂Mo₂O₇, 1 (a = 5.9686, b = 7.0761 and c = 14.3293 Å, α = 77.17°, β = 85.25° and γ = 88.56°; and Z = 2) and two-dimensional step-wise layered molybdate [H₂NC₁₂H₈NH₃]₂Mo₅O₁₆, 2 (a = 5.6843, b = 14.3024 and c = 19.4787Å, α = 108.1°, β = 98.4° and γ = 90.0°; , Z = 2). 1 is an unusual solid wherein the anionic chains are charge compensated by counter cations which also act as ligands to the metal and 2 is a new layered molybdate built of MoO₅ square pyramids and MoO₆ octahedra.     

Toxicokinetic models as predictive tools in biomonitoring metals in zooplankton: a synthesis of ideas

The objective of the present study was to evaluate previously reported compartment models as a predictive tool, in particular, to investigate the potential of nonlinear predictions in case of saturation of the uptake process. Examples supporting this idea are presented for the amphipods Gammarus oceanicus from northern Norway and Themisto abyssorum from the Greenland Sea as well as for the copepod Calanoides acutus from the Weddell Sea. A further objective was to investigate verification of model parameters with independent experimental observations, aided by the statistical analysis of the results. This can be regarded as a first step toward a meta-analysis. While modeling results obtained for T. abyssorum in 1993 underestimated observed uptake of Pb and Cu in independent experiments (1999) in the same species, a good agreement was encountered between models obtained for T. abyssorum in 1993 and experimental data obtained for Themisto libellula (1999). Furthermore, a fairly good agreement was found between modeling results obtained for Pb in Calanus hyperboreus from the Greenland Sea (1993) and experimental data obtained for C. acutus (1999). Therefore, the biological species cannot be regarded as a “natural” unit in biomonitoring studies without further evaluation (viz. calibration as biomonitor), while even samples of animals belonging to different species may serve as such a unit, allowing for a comparison of bioaccumulation on large temporal and spatial scales. Finally, the concept of the sensitivity of zooplankton organisms for biomonitoring was elaborated in detail. These procedures involve analytical and experimental variability and model simulations based on previously derived parameters of compartment models. The minimal increments in exposure concentrations estimated in this way were 0.4–1.2 μg Pb l⁻¹ for T. abyssorum, T. libellula, C. hyperboreus, and C. acutus. Corresponding results for Cu varied to a greater extent: 4–9 μg l⁻¹ for the amphipods and 1–5 μg l⁻¹ for the copepods. A correction of these values is proposed, taking into account the ratios of experimental (kinetic) and field bioconcentration factors; this yields exposure concentrations close to those reported for natural seawater. Guest editors: U. M. Azeiteiro, I. Jenkinson & M. J. Pereira Plankton Studies     

COVID-19: From pathogenesis models to the first drug trials

The number of people infected with SARS-CoV-2, and sadly dying from COVID-19, has exploded, and so the amount of literature on the novel coronavirus and the disease it causes has increased proportionately. The case numbers in some countries are beyond the epidemic peak, but the uncertainty about a second wave keeps politicians and societies under pressure. Appropriate decision-making and winning support from the population depends on precise scientific information rather than leaving the field to scaremongers of all proveniences. This mini-review is an update of earlier reports (Brüssow, Microb Biotechnol 2020a;13:607; Brüssow, Microb Biotechnol 2020b; https://doi.org/10.1111/1751-7915.13592 ).     

Inferring phenomenological models of first passage processes

Biochemical processes in cells are governed by complex networks of many chemical species interacting stochastically in diverse ways and on different time scales. Constructing microscopically accurate models of such networks is often infeasible. Instead, here we propose a systematic framework for building phenomenological models of such networks from experimental data, focusing on accurately approximating the time it takes to complete the process, the First Passage (FP) time. Our phenomenological models are mixtures of Gamma distributions, which have a natural biophysical interpretation. The complexity of the models is adapted automatically to account for the amount of available data and its temporal resolution. The framework can be used for predicting behavior of FP systems under varying external conditions. To demonstrate the utility of the approach, we build models for the distribution of inter-spike intervals of a morphologically complex neuron, a Purkinje cell, from experimental and simulated data. We demonstrate that the developed models can not only fit the data, but also make nontrivial predictions. We demonstrate that our coarse-grained models provide constraints on more mechanistically accurate models of the involved phenomena.     

Enlarged occlusal surfaces on first molars due to severe attrition and hypercementosis: examples from prehistoric coastal populations of Texas

During an examination of prehistoric samples from the Texas coast, individuals consistently exhibited a suite of traits on the first molars that included severe wear, hypercementosis, and resorption of the buccal margin of the alveolus. The occlusal surface of the tooth was worn below the cervical margin, with the subsequent incorporation of the buccal surface of the buccal roots into the occlusal plane. This expanded occlusal surface, which extends the buccal surface beyond the normal edge of the tooth, is composed of a combination of original enamel, secondary dentin, and cementum. There is a marked rounding of the buccal aspect of the occlusal surface. These conditions were noted in both maxillary and mandibular first molars. The resorption of alveolar bone surrounding the buccal roots resembles resorption associated with periodontal infection and is thought to be the result of severe levels of stress being applied to this portion of the dentition.     

Costs of memory: ideas and predictions

Studies on the ecology of animal memory have focused on the benefits of memory while implicitly assuming that there are costs as well. Here I discuss probable costs of memory by relying on knowledge from molecular biology and physiology, which indicates that the maintenance of accurate information in animals is an active and costly process of maintenance and repair. Redundancy probably plays a key role in ensuring a high level of accuracy; its cost is in terms of additional tissue, which increases body mass and energetic expenditure. Examining the magnitude and cost of redundancy at the neurobiological and behavioral levels can help us understand the cost of memory in particular and cognitive abilities in general.     

Probiotics and health: new facts and ideas

Many trials on probiotics are now published that use established methods to demonstrate their clinical efficacy. Convincing progress has been made in the field of inflammatory bowel disease and allergy prevention in infants. Experimental studies show clear differences (and even sometimes opposite effects) between apparently closely related probiotics and suggest new mechanisms for the observed effects, such as immunostimulation by bacterial DNA and interaction with Toll-like receptors and dendritic cells in the gastrointestinal tract.     

Staining of macromolecules: possible mechanisms and examples

This review is based on a presentation given at the Biological Stain Commission meeting in June 2008. I discuss staining as an interaction between dye, solvent, and biological macromolecules. Most staining takes place in water, where the physico-chemical properties of the macromolecules are particularly important. Staining from aqueous solution is summarized. The first step is diffusion–ion exchange, which builds up the dye ion concentration close to the appropriately charged tissue constituents. While charge interactions are important for selectivity and build-up of dye ions around specific tissue and cell constituents, they have in most cases little to do with actual dye binding. The next step, actual binding, is predominantly between aromatic and other non-polar parts of the dye and corresponding groups in the tissue constituent. This results in a reduction of the total hydrophobic area exposed to water, hence the term hydrophobic interaction. Because dye binding is predominantly by dispersive forces, the larger the aromatic dye system and the fewer the number of charges on the dye, the greater the substantivity or affinity. Some relatively straightforward anionic or cationic one-step staining systems are discussed also. These include amyloid staining with Congo red, elastin staining with orceins, collagen staining with picrofuchsin, DNA–RNA staining with methyl green-pyronin Y, acid heteroglycan staining with Alcian blue, and metachromatic staining.     

Discrete-time travelling waves: Ecological examples

Integrodifference equations are discrete-time models that possess many of the attributes of continuous-time reaction-diffusion equations. They arise naturally in population biology as models for organisms with discrete nonoverlapping generations and well-defined growth and dispersal stages. I examined the varied travelling waves that arise in some simple ecologically-interesting integrodifference equations. For a scalar equation with compensatory growth, I observed only simple travelling waves. For carefully chosen redistribution kernels, one may derive the speed and approximate the shape of the observed waveforms. A model with overcompensation exhibited flip bifurcations and travelling cycles in addition to simple travelling waves. Finally, a simple predator-prey system possessed periodic wave trains and a variety of travelling waves.     

Picornaviral processing: some new ideas

Mature picornaviral proteins are derived by progressive, post-translational cleavage of a giant precursor polyprotein. At least three viral-encoded proteolytic activities are involved in the processing. The first cleavage takes place while the polyprotein is still nascent on a ribosome. In poliovirus, this event is probably catalyzed by peptide 2A, a protein from the middle portion of the genome. Most subsequent processing is effected by viral protease 3C, a thiol-type enzyme, responsible for eight to ten self-cleaving and autocatalytic reactions within the polyprotein. The final proteolytic processing event, maturation of the VPO peptide, may occur by a novel, autocatalytic, serine-type mechanism, where viral RNA serves as proton-acceptor during the cleavage reaction.     

Efficient information visualization in LCA: approach and examples

Aim, Scope and Background  The data-intensive nature of life cycle assessment (LCA), even for non-complex products, quickly leads to the utilization of various methods of representing the data in forms other than written characters. Up until now, traditional representations of life cycle inventory (LCI) data and environmental impact analysis (EIA) results have usually been based on 2D and 3D variants of simple tables, bar charts, pie charts and x/y graphs. However, these representation methods do not sufficiently address aspects such as representation of life cycle inventory information at a glance, filtering out data while summarizing the filtered data (so as to reduce the information load), and representation of data errors and uncertainty. Main Features  This new information representation approach with its glyph-based visualization method addresses the specific problems outlined above, encountered when analyzing LCA and EIA related information. In particular, support for multi-dimensional information representation, reduction of information load, and explicit data feature propagation are provided on an interactive, computer-aided basis. Results  Three-dimensional, interactive geometric objects, so called OM-glyphs, were used in the visualization method introduced, to represent LCA-related information in a multi-dimensional information space. This representation is defined by control parameters, which in turn represent spatial, geometric and retinal properties of glyphs and glyph formations. All relevant analysis scenarios allowed and valid can be visualized. These consist of combinations of items for the material and energy inventories, environmental items, life cycle phases and products, or their parts and components. Individual visualization scenarios, once computed and rendered on a computer screen, can then interactively be modified in terms of visual viewpoint, size, spatial location and detail of data represented, as needed. This helps to increase speed, efficiency and quality of the assessment performance, while at the same time considerably reducing mental load due to the more structured manner in which information is represented to the human expert. Conclusions  The previous paper in this series discussed the motivation for a new approach to efficient information visualization in LCA and introduced the essential basic principles. This second paper offers more insight into and discussion on technical details and the framework developed. To provide a means for better understanding the visualization method presented, examples have been given. The main purpose of the examples, as already indicated, is to demonstrate and make transparent the mapping of LCA related data and their contexts to glyph parameters. Those glyph parameters, in turn, are used to generate a novel form of sophisticated information representation which is transparent, clear and compact, features which cannot be achieved with any traditional representation scheme. Outlook  Final technical details of this approach and its framework will be presented and discussed in the next paper. Theoretical and practical issues related to the application of this visualization method to the computed life cycle inventory data of an actual industrial product will also be discussed in this next paper.