Transmembrane signalling by a bionic receptor: biological input and output, chemical mechanism of signal transduction

Signal transduction through sealed biological membranes is among the most important evolutionary achievements. Herein, we focus on the development of artificial signal transduction mechanisms and engineer a bionic receptor with capacity of transduction of biological signals across biological membranes using tools of chemistry. The bionic receptor described in this work exhibits similarity with the natural counterpart in the most essential characteristics: in having an exofacial ligand for signal capture, in being membrane anchored, and in featuring a releasable secondary messenger molecule, which performs enzyme activation in the endo volume. The main difference with the natural receptors is that signal transduction across the lipid bilayer was performed using the tools of organic chemistry, namely a self-immolative linker. The highest novelty of our work is that the artificial signalling cascade designed herein achieved transmembrane activation of enzymatic activity, as is the hallmark of activity by natural signalling receptors.

Culture systems influence the physiological performance of the soft coral Sarcophyton glaucum

There is an urgent need to develop means of ex situ biobanking and biopreserving corals and other marine organisms whose habitats have been compromised by climate change and other anthropogenic stressors. To optimize laboratory growth of soft corals in a way that could also benefit industry (e.g., aquarium trade), three culture systems were tested herein with Sarcophyton glaucum: (1) a recirculating aquaculture system (RAS) without exogenous biological input (RAS−B), (2) a RAS with “live” rocks and an exogenous food supply (RAS+B), and (3) a simple flow-through system (FTS) featuring partially filtered natural seawater. In each system, the effects of two levels of photosynthetically active radiation (100 or 200 μmol quanta m−2 s−1) and flow velocity (5 or 15 cm s−1) were assessed, and a number of soft coral response variables were measured. All cultured corals survived the multi-month incubation, yet those of the RAS−B grew slowly and even paled; however, once they were fed (RAS−B modified to RAS+B), their pigmentation increased, and their oral discs readily expanded. Light had a more pronounced effect in the RAS−B system, while flow affected certain coral response variables in the FTS tanks; there were few effects of light or flow in the RAS+B system, potentially highlighting the importance of heterotrophy. Unlike the ceramic pedestals of the FTS, those of the RAS+B did not regularly become biofouled by algae. In concert with the aforementioned physiological findings, we therefore recommend RAS+B systems as a superior means of biopreservating and biobanking soft corals.

On the Quantitative Tripartite Allocation of the Atmospheric Vapor, Oqtav

The quantitative distribution of AVM into three distinguished vapor endmembers is lacking in the literature. This work fills such a gap. The isotope ratio, δ18OL, of rainwater in Winter, and artificial condensates in Summer, gave the 18OV contents of the AVMs at temperature-dependent equilibrium, downtown Cairo city, Nile Delta apex. We used our models, TIMAM, CLAW, and SIGNALS to process the δ18OV and the commensurate S values in several AVM data sets for determining the percent and mass contributions of three moisture origins and their temporal waveforms. The proportions revealed the Marine vapor dominance, followed by Evapotranspiration contribution. By far, the free Troposphere source showed a slight input. The quota of each constituent manifests a delayed waveform vs. the δ18OV influx, which shows a diurnal peak and a nocturnal tunnel. The moderate ET percent inputs in Winter, and by daytime, impose significant AVM 18O enrichment. In contrast, the high Maritime vapor inputs in Summer, and by night, stand behind the depleted AVM 18O content. The relationship between the mass input of each source and the AVM isotope ratio show significant dispersion for the negative trend of the diurnal-nocturnal Marine vapor in the two seasons. Such a high scattering is due to the mingling of the diurnal northern wind-gust convection (marked by low Marine vapor input) and the nocturnal steady advection (characterized by high Marine vapor input). Marine vapor waveform has a 12-hour time-lag by the intertwining of turbulent diurnal transmission, and steady nocturnal transport, via the long trajectory (180 km) from the Mediterranean coast to Cairo. In contrast, the relationships between ET mass input and AVM isotope ratio, on the one hand, and between the Troposphere vapor mass input and AVM isotope ratio, on the other hand, manifest low-dispersion positive and negative regressions, respectively. Such a low dispersion is due to short transport pathway, narrow range of the biological input (that increases only during daytime), and Troposphere downdraft (moving northward in Winter but southward in Summer). The ET waveform has a Zero-hour time-lag, like that of the Troposphere vapor. Albeit the low S value of the Troposphere vapor, its impact on the AVM isotopic depletion is significant due to its extremely shallow 18O content. The Troposphere input increase, at low S values of the AVM, is related to regional drought, as expected. The high S values, of Marine and biotic origins, usually go with temperature apogees, especially in Summer, as anticipated. The used models help in improving the time-series simulation of evaporation runs, since using seasonal δ18OV and S markers is better than using a snapshot. The ternary-vapor-source allocation procedure is a breakthrough in isotope hydrology. This thoroughly useful procedure will prove its ultimate benefits when the users get CRDS laser-controlled devices for the continuous measurements of the isotopic ratios in the local AVMs.

Scambi fushi tarazu: A Musical Representation of a Drosophila Gene Expression Pattern

The term Bio-Art has entered common usage to describe the interaction between the arts and the biological sciences. Although Bio-Art implies that Bio-Music would be one of its obvious sub-disciplines, the latter term has been much less frequently used. Nevertheless, there has been no shortage of projects that have brought together music and the biological sciences. Most of these projects have allowed the biological data to dictate to a large extent the sound produced, for instance the translation of genome or protein sequences into musical phrases, and therefore may be regarded as process compositions. Here I describe a Bio-Music process composition that derives its biological input from a visual representation of the expression pattern of the gene fushi tarazu in the Drosophila embryo. An equivalent pattern is constructed from the Scambi portfolio of short electronic music fragments created by Henri Pousseur in the 1950s. This general form of the resulting electronic composition follows that of the fushi tarazu pattern, while satisfying the rules of the Scambi compositional framework devised by Pousseur. The range and flexibility of Scambi make it ideally suited to other Bio-Music projects wherever there is a requirement, or desire, to build larger sonic structures from small units.

Exploring biological data: Mappings between ontology- and cluster-based representations

Ontologies and hierarchical clustering are both important tools in biology and medicine to study high-throughput data such as transcriptomics and metabolomics data. Enrichment of ontology terms in the data is used to identify statistically overrepresented ontology terms, giving insight into relevant biological processes or functional modules. Hierarchical clustering is a standard method to analyze and visualize data to find relatively homogeneous clusters of experimental data points. Both methods support the analysis of the same data set but are usually considered independently. However, often a combined view is desired: visualizing a large data set in the context of an ontology under consideration of a clustering of the data. This article proposes new visualization methods for this task. They allow for interactive selection and navigation to explore the data under consideration as well as visual analysis of mappings between ontology- and cluster-based space-filling representations. In this context, we discuss our approach together with specific properties of the biological input data and identify features that make our approach easily usable for domain experts.

Analysis of bidirectional pattern synchrony of concentration-secretion pairs: implementation in the human testicular and adrenal axes

The hypothalamo-pituitary-testicular and hypothalamo-pituitary-adrenal axes are prototypical coupled neuroendocrine systems. In the present study, we contrasted in vivo linkages within and between these two axes using methods without linearity assumptions. We examined 11 young (21–31 yr) and 8 older (62–74 yr) men who underwent frequent (every 2.5 min) blood sampling overnight for paired measurement of LH and testosterone and 35 adults (17 women and 18 men; 26–77 yr old) who underwent adrenocorticotropic hormone (ACTH) and cortisol measurements every 10 min for 24 h. To mirror physiological interactions, hormone secretion was first deconvolved from serial concentrations with a waveform-independent biexponential elimination model. Feedforward synchrony, feedback synchrony, and the difference in feedforward-feedback synchrony were quantified by the cross-approximate entropy (X-ApEn) statistic. These were applied in a forward (LH concentration template, examining pattern recurrence in testosterone secretion), reverse (testosterone concentration template, examining pattern recurrence in LH secretion), and differential (forward minus reverse) manner, respectively. Analogous concentration-secretion X-ApEn estimates were calculated from ACTH-cortisol pairs. X-ApEn, a scale- and model-independent measure of pattern reproducibility, disclosed 1) greater testosterone-LH feedback coordination than LH-testosterone feedforward synchrony in healthy men and significant and symmetric erosion of both feedforward and feedback linkages with aging; 2) more synchronous ACTH concentration-dependent feedforward than feedback drive of cortisol secretion, independent of gender and age; and 3) enhanced detection of bidirectional physiological regulation by in vivo pairwise concentration-secretion compared with concentration-concentration analyses. The linking of relevant biological input to output signals and vice versa should be useful in the dissection of the reciprocal control of neuroendocrine systems or even in the analysis of other nonendocrine networks.

Significance and Implementation of RBE Variations in Proton Beam Therapy

Key to radiation therapy is to apply a high tumor-destroying dose while protecting healthy tissue, especially near organs at risk. To optimize treatment for ion therapy not the dose but the dose multiplied by the relative biological effectiveness (RBE) is decisive. Proton therapy has been based on the use of a generic RBE, which is applied to all treatments independent of dose/fraction, position in the spread-out Bragg peak (SOBP), initial beam energy or the particular tissue. Dependencies of the RBE on various physical and biological properties are disregarded. The variability of RBE in clinical situations is believed to be within 10–20%. This is in the same range of effects that receive high attention these days, i.e., patient set-up uncertainties, organ motion effects, and dose calculation accuracy all affecting proton as well as conventional radiation therapy. Elevated RBE values can be expected near the edges of the target, thus probably near critical structures. This is because the edges show lower doses and, depending on the treatment plan, may be identical with the beam's distal edge, where dose is deposited in part by high-LET protons. We assess the rationale for the continued use of a generic RBE and whether the magnitude of RBE variation with treatment parameters is small relative to our abilities to determine RBE's. Two aspects have to be considered. Firstly, the available information from experimental studies and secondly, our ability to calculate RBE values for a given treatment plan based on parameters extracted from such experiments. We analyzed published RBE values for in vitro and in vivo endpoints. The values for cell survival in vitro indicate a substantial spread between the diverse cell lines. The average value at mid SOBP over all dose levels is ≈ 1.2 in vitro and ≈ 1.1 in vivo. Both in vitro and in vivo data indicate a statistically significant increase in RBE for lower doses per fraction, which is much smaller for in vivo systems. The experimental in vivo data indicate that continued employment of a generic RBE value of 1.1 is reasonable. At present, there seems to be too much uncertainty in the RBE value for any human tissue to propose RBE values specific for tissue, dose/fraction, etc. There is a clear need for prospective assessments of normal tissue reactions in proton irradiated patients and determinations of RBE values for several late responding tissues in animal systems, especially as a function of dose in the range of 1–4 Gy. However, there is a measurable increase in RBE over the terminal few mm of the SOBP, which results in an extension of the bio-effective range of the beam of a few mm. This needs to be considered in treatment planning, particularly for single field plans or for an end of range in or close to a critical structure. To assess our ability to calculate RBE values we studied two approaches, which are both based on the track structure theory of radiation action. RBE calculations are difficult since both the physical input parameters, i.e., LET distributions, and, even more so, the biological input parameters, i.e., local cellular response, have to be known with high accuracy. Track structure theory provides a basis for predicting dose-response curves for particle irradiation. However, designed for heavy ion applications the models show weaknesses in the prediction of proton radiation effects. We conclude that, at present, RBE modeling in treatment planning involves significant uncertainties. To incorporate RBE variations in treatment planning there has to be a reliable biological model to calculate RBE values based on the physical characteristics of the radiation field and based on well-known biological input parameters. In order to do detailed model calculations more experimental data, in particular for in vivo endpoints, are needed.