Extrapolation through hierarchical levels

• 1.1. Translating results from low hierarchical levels to higher orders meets with difficulties with respect to temporal, spatial and organizational scales.
• 2.2. Translating stress effects through hierarchical levels has not yet been possible, thus hampering ecological risk assessment.
• 3.3. Three approaches to link the various levels are described; the energetics, the endpoint and the minimal structure approach.
• 4.4. A concept to integrate these approaches to enable extrapolation of stress effects across hierarchical levels is described.

     

P bodies, stress granules, and viral life cycles

Eukaryotic mRNAs are in a dynamic equilibrium between different subcellular locations. Translating mRNAs can be found in polysomes, mRNAs stalled in translation initiation accumulate in stress granules and mRNAs targeted for degradation or translation repression can accumulate in P bodies. Partitioning of mRNAs between polysomes, stress granules, and P bodies affects rates of translation and mRNA degradation. Host proteins within P bodies and stress granules can enhance or limit viral infection, and some viral RNAs and proteins accumulate in P bodies and/or stress granules. Thus, an important interplay among P bodies, stress granules, and viral life cycles is beginning to emerge.     

Identifying overlapping and hierarchical thematic structures in networks of scholarly papers: a comparison of three approaches

The aim of this paper is to introduce and assess three algorithms for the identification of overlapping thematic structures in networks of papers. We implemented three recently proposed approaches to the identification of overlapping and hierarchical substructures in graphs and applied the corresponding algorithms to a network of 492 information-science papers coupled via their cited sources. The thematic substructures obtained and overlaps produced by the three hierarchical cluster algorithms were compared to a content-based categorisation, which we based on the interpretation of titles, abstracts, and keywords. We defined sets of papers dealing with three topics located on different levels of aggregation: h-index, webometrics, and bibliometrics. We identified these topics with branches in the dendrograms produced by the three cluster algorithms and compared the overlapping topics they detected with one another and with the three predefined paper sets. We discuss the advantages and drawbacks of applying the three approaches to paper networks in research fields.     

Ecologically relevant stress resistance: from microarrays and quantitative trait loci to candidate genes — A research plan and preliminary results using<Emphasis Type="Italic">Drosophila</Emphasis> as a model organism and climatic and genetic stress as model stresses

We aim at studying adaptation to genetic and environmental stress and its evolutionary implications at different levels of biological organization. Stress influences cellular processes, individual physiology, genetic variation at the population level, and the process of natural selection. To investigate these highly connected levels of stress effects, it is advisable - if not critical - to integrate approaches from ecology, evolution, physiology, molecular biology and genetics. To investigate the mechanisms of stress resistance, how resistance evolves, and what factors contribute to and constrain its evolution, we use the well-defined model systems ofDrosophila species, representing both cosmopolitan species such asD. melanogaster with a known genome map, and more specialized and ecologically well described species such as the cactophilicD. buzzatii. Various climate-related stresses are used as model stresses including desiccation, starvation, cold and heat. Genetic stress or genetic load is modelled by studying the consequences of inbreeding, the accumulation of (slightly) deleterious mutations, hybridization or the loss of genetic variability. We present here a research plan and preliminary results combining various approaches: molecular techniques such as microarrays, quantitative trait loci (QTL) analyses, quantitative PCR, ELISA or Western blotting are combined with population studies of resistance to climatic and genetic stress in natural populations collected across climatic gradients as well as in selection lines maintained in the laboratory.     

Prediction of protein kinase-specific phosphorylation sites in hierarchical structure using functional information and random forest

Reversible protein phosphorylation is one of the most important post-translational modifications, which regulates various biological cellular processes. Identification of the kinase-specific phosphorylation sites is helpful for understanding the phosphorylation mechanism and regulation processes. Although a number of computational approaches have been developed, currently few studies are concerned about hierarchical structures of kinases, and most of the existing tools use only local sequence information to construct predictive models. In this work, we conduct a systematic and hierarchy-specific investigation of protein phosphorylation site prediction in which protein kinases are clustered into hierarchical structures with four levels including kinase, subfamily, family and group. To enhance phosphorylation site prediction at all hierarchical levels, functional information of proteins, including gene ontology (GO) and protein–protein interaction (PPI), is adopted in addition to primary sequence to construct prediction models based on random forest. Analysis of selected GO and PPI features shows that functional information is critical in determining protein phosphorylation sites for every hierarchical level. Furthermore, the prediction results of Phospho.ELM and additional testing dataset demonstrate that the proposed method remarkably outperforms existing phosphorylation prediction methods at all hierarchical levels. The proposed method is freely available at http://bioinformatics.ustc.edu.cn/phos_pred/.     

In response to the continuum model for fauna research: a hierarchical, patch-based model of spatial landscape patterns

Models of nature are implicitly influenced by the scale of observation of the processes on which they are founded. The continuum model and the hierarchical patch-based model are two alternate approaches for the spatial modelling of fauna distribution. The continuum model aggregates continuous approximations to individual landscape characteristics, whereas the hierarchical patch-based model constructs a hierarchy in which classifications of landscape characteristics describe an interconnected series of patches. We propose the hierarchical patch-based theory for models of population distributions and landscapes in which the spatial patterns can be effectively represented by mosaics at the variety of levels within the set of individual process models. Given that observations are typically made as points or pixels, and that discrete boundaries exist in both natural and human-modified landscapes, we suggest that the hierarchical patch-based method has many applications in conservation and management.     

A multi‐method approach for analyzing hierarchical genetic structures: a case study with cougars Puma concolor

Genetic data are increasingly used to describe the structure of wildlife populations and to infer landscape influences on functional connectivity. To accomplish this, genetic structure can be described with a multitude of methods that vary in their assumptions, advantages and limitations. While some methods discriminate distinct subpopulations separated by sharp genetic boundaries (i.e. barrier detection or clustering methods), other methods estimate gradient genetic structures using individual‐based genetic distances. We present an analytical framework based on individual ancestry values that combines these different approaches and can be used to a) test for local barriers to gene flow and b) evaluate effects of landscape gradients through individual‐based genetic distances that account for hierarchical genetic structure. We illustrate the approach with a data set of 371 cougars Puma concolor from a 217 000 km² study area in Idaho and western Montana (USA) that were genotyped at 12 microsatellite loci. Results suggest that cougars in the region show a complex, hierarchical genetic structure that is influenced by a local barrier to gene flow (an urban population cluster connected by high traffic volumes), different landscape features (the Snake River Plain, forested habitat), and geographic distance. Our novel approach helped to elucidate the relative influence of these factors on different hierarchical levels of population structure, which was not possible when using either clustering methods or standard genetic distances. Results obtained with our analytical framework highlight the need for multi‐scale management of cougars in the region and show that landscape heterogeneity can create complex genetic structures, even in generalist species with high dispersal capabilities.     

Higher-order structure of chromatin and chromosomes

The linear array of nucleosomes that comprises the primary structure of chromatin is folded and condensed to varying degrees in nuclei and chromosomes forming 'higher order structures'. We discuss the recent findings from novel experimental approaches that have yielded significant new information on the different hierarchical levels of chromatin folding and their functional significance.     

Ecological boundaries in the context of hierarchy theory

Ecological boundaries have been described as being multiscalar or hierarchical entities. However, the concept of the ecological boundary has not been explicitly examined in the context of hierarchy theory. We explore how ecological boundaries might be envisioned as constituents of scalar hierarchical systems. Boundaries may be represented by the surfaces of constituents or as constituents themselves. Where surfaces would correspond to abrupt transition zones, boundary systems might be quite varied depending on hierarchical context. We conclude that hierarchy theory is compatible with a functional vision of ecological boundaries where functions can be largely represented as the processing or filtering of ecological signals. Furthermore, we postulate that emergent ecological boundaries that arise on a new hierarchical level may contribute to the overconnectedness of mature ecosystems. Nevertheless, a thermodynamic approach to the emergence and development of boundary systems does indicate that in many situations, ecological boundaries would persist in time by contributing to the energy production of higher hierarchical levels.     

Classification of key ecological attributes and stresses of biodiversity for ecosystem-based conservation assessments and management

A whole systems thinking approach to conservation has spawned new approaches in adaptive management planning that require a crucial understanding of what is essential for the functionality of ecosystems and the biodiversity they embrace. In this context, the key ecological attributes (KEA) have been introduced as aspects of a conservation target's biology or ecology that, if missing or altered, would lead to the loss of that target over time. Ecological stresses describe the impaired status of KEAs. Whilst for threats, the drivers of stresses, a systematic classification has been suggested and adopted by IUCN, all existing proposals for stresses and KEAs are preliminary. In order to fill the gap and provide conservation analysts and practitioners with a standard terminology supporting adaptive management planning we suggest a first hierarchical framework and comprehensive classification of key ecological attributes and corresponding stresses to biodiversity. Analyzing 22 vulnerability assessments in 13 countries, spread across 5 continents, as well as an extensive literature review, we identified 144 specific KEAs and stresses. These are differentiated and classified according to three hierarchical levels, 11 KEA and stress classes and 42 general KEAs and stresses. Our classification may help with describing and understanding both the natural functionality and also impaired functioning of biodiversity targets, as well as assist with the development of appropriate conservation strategies. The classification of key ecological attributes is presented as a list but it is important to recognize that the diverse array of KEAs and stresses are systemically interrelated across scales.     

Structure prediction of helical transmembrane proteins at two length scales

As the first step toward a multi-scale, hierarchical computational approach for membrane protein structure prediction, the packing of transmembrane helices was modeled at the residue and atom levels, respectively. For predictions at the residue level, the helix-helix and helix-membrane interactions were described by a set of knowledge-based energy functions. For predictions at the atom level, CHARMM19 force field was used. To facilitate the system to overcome energy barriers, the Wang-Landau method was employed, where a random walk is performed in the energy space with a uniform probability. Native-like structures were predicted at both levels for two model systems, each of which consists of two transmembrane helices. Interestingly, consistent results were obtained from simulations at the residue and atom levels for the same system, strongly suggesting the feasibility of a hierarchical approach for membrane protein structure predictions.     

Hierarchical Dragonfly Wing: Microstructure-Biomechanical Behavior Relations

The dragonfly wing,which consists of veins and membrane,is of biological hierarchical material.We observed the cross-sections of longitudinal veins and membrane using Environmental Scanning Electron Microscopy (ESEM).Based on the experiments and previous studies,we described the longitudinal vein and the membrane in terms of two hierarchical levels of organization of composite materials at the micro- and nano-scales.The longitudinal vein of dragonfly wing has a complex sandwich structure with two chitinous shells and a protein layer,and it is considered as the first hierarchical level of the vein.Moreover,the chitinous shells are concentric multilayered structures.Clusters of nano-fibrils grow along the circumferential orientation embedded into the protein layer.It is considered as the second level of the hierarchy.Similarly,the upper and lower epidermises of membrane constitute the first hierarchical level of organization in micro scale.Similar to the vein shell,the membrane epidermises were found to be a paralleled multilayered structure,defined as the second hierarchical level of the membrane.Combining with the mechanical behavior analysis of the dragonfly wing,we concluded that the growth orientation of the hierarchical structure of the longitudinal vein and membrane is relevant to its biomechanical behavior.     

Cortisol as a marker of stress

The review considers the roles cortisol (Crt), dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEA-S) play in the stress response. Age-related, sex-related, and circadian fluctuations in normal conditions and in acute or chronic stress are described for Crt, DHEA, and DHEA-S. The main techniques used to estimate the Crt level in the blood, urine, and saliva are described, and approaches to the interpretation of the results discussed. Special attention is paid to Crt assays in anthropological and psychological studies.     

Micromachined interfaces: new approaches in cell immunoisolation and biomolecular separation

As a novel therapeutic application of microfabrication technology, a micromachined membrane-based biocapsule is described for the transplantation of protein-secreting cells without the need for immunosuppression. This new approach to cell encapsulation is based on microfabrication technology whereby immunoisolation membranes are bulk and surface micromachined to present uniform and well-controlled pore sizes as small as 10 nm, tailored surface chemistries, and precise microarchitecture. Through its ability to achieve highly controlled microarchitectures on size scales relevant to living systems (from microm to nm), microfabrication technology offers unique opportunities to more precisely engineer biocapsules that allow free exchange of the nutrients, waste products, and secreted therapeutic proteins between the host (patient) and implanted cells, but exclude lymphocytes and antibodies that may attack foreign cells. Microfabricated inorganic encapsulation devices may provide biocompatibility, in vivo chemical and mechanical stability, tailored pore geometries, and superior immunoisolation for encapsulated cells over conventional encapsulation approaches. By using microfabrication techniques, structures can be fabricated with spatial features from the sub-micron range up to several millimeters. These multi-scale structures correspond well with hierarchical biological structures, from proteins and sub-cellular organelles to the tissue and organ levels.     

The hierarchical packing of euchromatin domains can be described as multiplicative cascades

The genome is packed into the cell nucleus in the form of chromatin. Biochemical approaches have revealed that chromatin is packed within domains, which group into larger domains, and so forth. Such hierarchical packing is equally visible in super-resolution microscopy images of large-scale chromatin organization. While previous work has suggested that chromatin is partitioned into distinct domains via microphase separation, it is unclear how these domains organize into this hierarchical packing. A particular challenge is to find an image analysis approach that fully incorporates such hierarchical packing, so that hypothetical governing mechanisms of euchromatin packing can be compared against the results of such an analysis. Here, we obtain 3D STED super-resolution images from pluripotent zebrafish embryos labeled with improved DNA fluorescence stains, and demonstrate how the hierarchical packing of euchromatin in these images can be described as multiplicative cascades. Multiplicative cascades are an established theoretical concept to describe the placement of ever-smaller structures within bigger structures. Importantly, these cascades can generate artificial image data by applying a single rule again and again, and can be fully specified using only four parameters. Here, we show how the typical patterns of euchromatin organization are reflected in the values of these four parameters. Specifically, we can pinpoint the values required to mimic a microphase-separated state of euchromatin. We suggest that the concept of multiplicative cascades can also be applied to images of other types of chromatin. Here, cascade parameters could serve as test quantities to assess whether microphase separation or other theoretical models accurately reproduce the hierarchical packing of chromatin.