Gelenke,Führungen und Verbindungen

When comparing biological and technical “machine elements” one often finds that they have functional morphological elements in common in a partly amazing way. As these partners on the one side show similar or equal functions, on the other side belong to different realms, theses comparisons are based on classical analogies. Mostly, the technical elements are already well known in detail, while biological elements are discovered repeatedly. In this way, a biotechnical comparison in the first place leads to a better understanding of biological structures, not that much to a bionic improvement of technical ones. In part 1 of this article this is shown by means of ordinary elements such as joints, gliding parts and connections. In part 2 more complex analoga will be compared.     

Transpositionally active episomal hAT elements

Background  

hAT elements and V(D)J recombination may have evolved from a common ancestral transposable element system. Extrachromosomal, circular forms of transposable elements (referred to here as episomal forms) have been reported yet their biological significance remains unknown. V(D)J signal joints, which resemble episomal transposable elements, have been considered non-recombinogenic products of V(D)J recombination and a safe way to dispose of excised chromosomal sequences. V(D)J signal joints can, however, participate in recombination reactions and the purpose of this study was to determine if hobo and Hermes episomal elements are also recombinogenic.     

On technomorphic modelling and classification of biological joints

Summary Biological motion systems are of particular interest to engineers in robotics, prosthetics and micromechanics. Since biological motion systems show a high degree of mobility, smooth movements and minimal deployment of material, the analysis of such systems might help to invent or optimize technical motion systems. To enable the transfer of explanatory techniques, biomechanics and engineering need a shared terminology. Generally, a reference limb, muscles, tendons, a joint and a driven limb are forming two closed mechanisms with different transfer functions. The direction of the forces applied to links is influenced by guiding structures. Movable connections can be constructed by form closure, force closure, and compliance of an anisotropic segment between two rigid segments. Eleven different basic variants of rigid-body joint structures can be classified by the possible relative translatory and rotatory movements in orthogonal co-ordinates. If classified by the form of their rigid parts, biological rigid-body joints (diarthroses) show some similarities to technical joints, but occur in fewer basic variants. The functioning of exoskeletal joints can involve hydrostatic forces, depending on the structure of the rigid elements and the type of linkage between them. Structural classification of biological joints should include at least: 1) degree of freedom (d.o.f.), 2) possible relative movements, 3) variability of d.o.f., 4) restrictions of range of motion, 5) stress in reaction to external forces. From an engineer’s viewpoint, additional features are necessary for structural characterization, including the maintenance of closure and guidance, the geometry and behaviour of contact, geometrical parameters and material properties.     

Saltatory transitions are a naturally occurring property of evolving systems

On the basis of paleological evidence, it has been suggested that biological evolution need not necessarily be characterized by gradual change. Rather, evolutionary history may display saltatory periods of rapid speciation alternating with periods of relative quiescence, the whole dynamic being called punctuated equilibria. The empirical evidence that has been presented in support of this hypothesis has been the object of a vigorous dispute. Mathematical investigations of complex models of biological evolution that contain random elements have demonstrated that these systems can display saltatory behavior. In this paper we address a more abstract question: can saltations occur in the evolution of very simple, deterministic mathematical systems that function in a constant environment? The answer appears to be yes. Saltations appear as a natural dynamical behavior in the evolution of simplistic information processing networks. We stress that these networks do not constitute a model of biological evolution. However, the appearance of saltations in such simple systems suggests that their appearance in a process as complex as biological evolution is not surprising.     

A Multicompartment Approach - Diatoms,Macrophytes, Benthic Macroinvertebrates and Fish - To Assess the Impact of Toxic Industrial Releases on a Small French River

The River Luzou flows through a sandy substrate in the South West of France. According to the results of two assessment surveys, the Water Agency appraised that this river may not achieve the good ecological status by 2015 as required by the Water Framework Directive (2000/60/EC). This ecosystem is impacted by industrial effluents (organic matter, metals and aromatic compounds). In order to assess and characterize the impact, this study aimed to combine a set of taxonomic and non-taxonomic metrics for diatoms, macrophytes, macroinvertebrates and fish along the up- to downstream gradient of the river. Diversity metrics, biological indices, biological and ecological traits were determined for the four biological quality elements (BQE). Various quantitative metrics (biomass estimates) were also calculated for diatom communities. The results were compared to physicochemical analysis. Biological measurements were more informative than physicochemical analysis, in the context of the study. Biological responses indicated both the contamination of water and its intensity. Diversity metrics and biological indices strongly decreased with pollution for all BQE but diatoms. Convergent trait selection with pollution was observed among BQE: reproduction, colonization strategies, or trophic regime were clearly modified at impaired sites. Taxon size and relation to the substrate diverged among biological compartments. Multiple anthropogenic pollution calls for alternate assessment methods of rivers'' health. Our study exemplifies the fact that, in the case of complex contaminations, biological indicators can be more informative for environmental risk, than a wide screening of contaminants by chemical analysis alone. The combination of diverse biological compartments provided a refined diagnostic about the nature (general mode of action) and intensity of the contamination.     

Gene mutation‐based and specific therapies in precision medicine

Precision medicine has been initiated and gains more and more attention from preclinical and clinical scientists. A number of key elements or critical parts in precision medicine have been described and emphasized to establish a systems understanding of precision medicine. The principle of precision medicine is to treat patients on the basis of genetic alterations after gene mutations are identified, although questions and challenges still remain before clinical application. Therapeutic strategies of precision medicine should be considered according to gene mutation, after biological and functional mechanisms of mutated gene expression or epigenetics, or the correspondent protein, are clearly validated. It is time to explore and develop a strategy to target and correct mutated genes by direct elimination, restoration, correction or repair of mutated sequences/genes. Nevertheless, there are still numerous challenges to integrating widespread genomic testing into individual cancer therapies and into decision making for one or another treatment. There are wide‐ranging and complex issues to be solved before precision medicine becomes clinical reality. Thus, the precision medicine can be considered as an extension and part of clinical and translational medicine, a new alternative of clinical therapies and strategies, and have an important impact on disease cures and patient prognoses.     

On the number of experiments required to find the causal structure of complex systems

The need to capture the complexity of biological systems in a simpler formalism is the underlying impetus of biological sciences. Understanding the function of many biological complex systems, such as genetic networks or molecular signalling pathways, requires precise identification of the interactions between their individual components. A number of questions in the study of complex systems are then important-in particular, what can be inferred about the interactions in a complex system from an arbitrary set of experiments, and, what is the minimum number of experiments required to characterize the system? This paper shows that the problem of finding the minimal causal structure of a system based on a set of observations is computationally intractable for even moderately sized systems (it is NP-hard), but a reasonable approximation can be found in a relatively short (polynomial) time. Next, it is shown that the number of experiments required to characterize a complex system grows exponentially with the upper bound on the number of immediate upstream influences of each element, but only logarithmically with the number of elements in the system. This makes it possible to study biological systems with extremely large number of interacting elements and relatively sparse interconnections, such as gene regulatory and cell signalling networks. Finally, the construction of a randomized experimental sequence which achieves this bound is discussed.     

Integrating biological motion: the role of grouping in the perception of point-light actions

The human visual system is highly sensitive to biological motion and manages to organize even a highly reduced point-light stimulus into a vivid percept of human action. The current study investigated to what extent the origin of this saliency of point-light displays is related to its intrinsic Gestalt qualities. In particular, we studied whether biological motion perception is facilitated when the elements can be grouped according to good continuation and similarity as Gestalt principles of perceptual organization. We found that both grouping principles enhanced biological motion perception but their effects differed when stimuli were inverted. These results provide evidence that Gestalt principles of good continuity and similarity also apply to more complex and dynamic meaningful stimuli.     

Model‐guided design of ligand‐regulated RNAi for programmable control of gene expression

Progress in constructing biological networks will rely on the development of more advanced components that can be predictably modified to yield optimal system performance. We have engineered an RNA‐based platform, which we call an shRNA switch, that provides for integrated ligand control of RNA interference (RNAi) by modular coupling of an aptamer, competing strand, and small hairpin (sh)RNA stem into a single component that links ligand concentration and target gene expression levels. A combined experimental and mathematical modelling approach identified multiple tuning strategies and moves towards a predictable framework for the forward design of shRNA switches. The utility of our platform is highlighted by the demonstration of fine‐tuning, multi‐input control, and model‐guided design of shRNA switches with an optimized dynamic range. Thus, shRNA switches can serve as an advanced component for the construction of complex biological systems and offer a controlled means of activating RNAi in disease therapeutics.     

Development of synovial joints

Synovial joints arise through two main processes. In long bone elements, cartilaginous differentiation occurs across the locations of the prospective joints that then segment secondarily. This process occurs through the development of a noncartilaginous region known as the interzone. The interzone becomes an important signaling center to the opposing elements, which can regulate growth through such factors as GDF-5. The interzone also expresses bone morphogenetic proteins (BMPs) and their antagonists, such as noggin. Overexpression of BMPs, or the loss of noggin leads to joint fusions. The interzone also expresses Wnt-14, which appears to be specific for this region in the developing anlagen, and regulates its nonchondrogenic nature. Cavitation of the joint follows, driven by selective high-level synthesis of hyaluronan by interzone cells and presumptive synovial cells. In addition, as the interzone disperses during cavity enlargement, data are now accruing that suggest that both the synovium and articular cartilage develop from this population. Finally, the development of articular cartilage progresses through appositional growth driven by a progenitor/stem cell subpopulation that resides in the articular surface. The individual elements of the skeleton are connected together at regions termed joints or articulations. Classically, there are three broad categories of joints: immovable joints (syntharthroses); mixed articulations, in which the range of movement is limited (amphiarthroses); and the movable, or synovial, joints (diarthroses). This review concentrates on the development of the synovial joints.     

Proteomics in the COVID‐19 Battlefield: First Semester Check‐Up

Proteomics offers a wide collection of methodologies to study biological systems at the finest granularity. Faced with COVID‐19, the most worrying pandemic in a century, proteomics researchers have made significant progress in understanding how the causative virus hijacks the host's cellular machinery and multiplies exponentially, how the disease can be diagnosed, and how it develops, as well as its severity predicted. Numerous cellular targets of potential interest for the development of new antiviral drugs have been documented. Here, the most striking results obtained in the proteomics field over this first semester of the pandemic are presented. The molecular machinery of SARS‐CoV‐2 is much more complex than initially believed, as many post‐translational modifications can occur, leading to a myriad of proteoforms and a broad heterogeneity of viral particles. The interplay of protein–protein interactions, protein abundances, and post‐translational modifications has yet to be fully documented to provide a full picture of this intriguing but lethal biological threat. Proteomics has the potential to provide rapid detection of the SARS‐CoV‐2 virus by mass spectrometry proteotyping, and to further increase the knowledge of severe respiratory syndrome COVID‐19 and its long‐term health consequences.     

DeepQuanTR: MALDI‐MS‐based label‐free quantification of proteins in complex biological samples

The quantification of changes in protein abundance in complex biological specimens is essential for proteomic studies in basic and applied research. Here we report on the development and validation of the DeepQuanTR software for identification and quantification of differentially expressed proteins using LC‐MALDI‐MS. Following enzymatic digestion, HPLC peptide separation and normalization of MALDI‐MS signal intensities to the ones of internal standards, the software extracts peptide features, adjusts differences in HPLC retention times and performs a relative quantification of features. The annotation of multiple peptides to the corresponding parent protein allows the definition of a Protein Quant Value, which is related to protein abundance and which allows inter‐sample comparisons. The performance of DeepQuanTR was evaluated by analyzing 24 samples deriving from human serum spiked with different amounts of four proteins and eight complex samples of vascular proteins, derived from surgically resected human kidneys with cancer following ex vivo perfusion with a reactive ester biotin derivative. The identification and experimental validation of proteins, which were differentially regulated in cancerous lesions as compared with normal kidney, was used to demonstrate the power of DeepQuanTR. This software, which can easily be used with established proteomic methodologies, facilitates the relative quantification of proteins derived from a wide variety of different samples.     

A finite element simulation scheme for biological muscular hydrostats

An explicit finite element scheme is developed for biological muscular hydrostats such as squid tentacles, octopus arms and elephant trunks. The scheme is implemented by embedding muscle fibers in finite elements. In any given element, the fiber orientation can be assigned arbitrarily and multiple muscle directions can be simulated. The mechanical stress in each muscle fiber is the sum of active and passive parts. The active stress is taken to be a function of activation state, muscle fiber shortening velocity and fiber strain; while the passive stress depends only on the strain. This scheme is tested by simulating extension of a squid tentacle during prey capture; our numerical predictions are in close correspondence with existing experimental results. It is shown that the present finite element scheme can successfully simulate more complex behaviors such as torsion of a squid tentacle and the bending behavior of octopus arms or elephant trunks.     

The natural distribution of survival

Great similarities in survival patterns permit the Gompertz and other established equations to describe parts of mortality curves in various species. These patterns appear non-random and invite inference of biological meaning, though no unifying explanation is agreed.Under the theory described here, linear decline of an initial quantity of species or strain-specific redundant reserve interacts with extrinsic hazards via a ‘nested binomial’ model, which is presented both in a simple, four parameter form, and a more complex form that incorporates inter-individual and inter-functional biological variation.This approach demonstrates exponential rises in mortality, late-life deceleration and Strehler-Mildvan correlation. Biological variation within the complex model, specifically in the redundancy decay rate parameter, is shown to generate mortality plateaux, while outlier phenotypes produce mortality decelerations, supporting inter-individual heterogeneity as the cause of these phenomena. The model is robust to large variations in organism complexity, and to broad intra-population hazard variation. Specific parameters appear analogous to observed elements of ageing, and a central role for redundancy depletion provides a context for longevity genes and rapid evolution of increased lifespan.This approach offers a unifying model for a great variety of ageing phenomena across a wide range of species.     

Adaptive velocity-based six degree of freedom load control for real-time unconstrained biomechanical testing

Robotic biomechanics is a powerful tool for further developing our understanding of biological joints, tissues and their repair. Both velocity-based and hybrid force control methods have been applied to biomechanics but the complex and non-linear properties of joints have limited these to slow or stepwise loading, which may not capture the real-time behaviour of joints. This paper presents a novel force control scheme combining stiffness and velocity based methods aimed at achieving six degree of freedom unconstrained force control at physiological loading rates.     

Incidental processing of biological motion

The successful detection of biological motion can have important consequences for survival. Previous studies have demonstrated the ease and speed with which observers can extract a wide range of information from impoverished dynamic displays in which only an actor's joints are visible. Although it has often been suggested that such biological motion processing can be accomplished relatively automatically, few studies have directly tested this assumption by using behavioral methods. Here we used a flanker paradigm to assess how peripheral "to-be-ignored" walkers affect the processing of a central target walker. Our results suggest that task-irrelevant dynamic figures cannot be ignored and are processed to a level where they influence behavior. These findings provide the first direct evidence that complex dynamic patterns can be processed incidentally, a finding that may have important implications for cognitive, neurophysiological, and computational models of biological motion processing.     

Synthesis and Antidiabetic Activity of 5,7‐Dihydroxyflavonoids and Analogs

In a study to evaluate the structural elements essential for the antidiabetic activity of flavonoids, we synthesized two series of flavonoids, 5,7‐dihydroxyflavanones and 5,7‐dihydroxyflavones. In a screening for potential antidiabetic activity, most of the flavonoids showed a remarkable in vitro activity, and compounds 1f, 2d , and 3c were significantly more effective than the positive control, metformin. The biological activity was mainly affected by structural modification at the ring B moiety of the flavonoid skeleton. The results suggest that 5,7‐dihydroxyflavonoids can be considered as promising candidates in the development of new antidiabetic lead compounds.