Design principles for riboswitch function

Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence–function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands

Interleukin 7 from Maternal Milk Crosses the Intestinal Barrier and Modulates T- Cell Development in Offspring

Background Breastfeeding protects against illnesses and death in hazardous environments, an effect partly mediated by improved immune function. One hypothesis suggests that factors within milk supplement the inadequate immune response of the offspring, but this has not been able to account for a series of observations showing that factors within maternally derived milk may supplement the development of the immune system through a direct effect on the primary lymphoid organs. In a previous human study we reported evidence suggesting a link between IL-7 in breast milk and the thymic output of infants. Here we report evidence in mice of direct action of maternally-derived IL-7 on T cell development in the offspring. Methods and Findings  We have used recombinant IL-7 labelled with a fluorescent dye to trace the movement in live mice of IL-7 from the stomach across the gut and into the lymphoid tissues. To validate the functional ability of maternally derived IL- 7 we cross fostered IL-7 knock-out mice onto normal wild type mothers. Subsets of thymocytes and populations of peripheral T cells were significantly higher than those found in knock-out mice receiving milk from IL-7 knock-out mothers. Conclusions/Significance Our study provides direct evidence that interleukin 7, a factor which is critical in the development of T lymphocytes, when maternally derived can transfer across the intestine of the offspring, increase T cell production in the thymus and support the survival of T cells in the peripheral secondary lymphoid tissue

NGS-pipe: a flexible, easily extendable, and highly configurable framework for NGS analysis

Next-generation sequencing is now an established method in genomics, and massive amounts of sequencing data are being generated on a regular basis. Analysis of the sequencing data is typically performed by lab-specific in-house solutions, but the agreement of results from different facilities is often small. General standards for quality control, reproducibility, and documentation are missing.; We developed NGS-pipe, a flexible, transparent, and easy-to-use framework for the design of pipelines to analyze whole-exome, whole-genome, and transcriptome sequencing data. NGS-pipe facilitates the harmonization of genomic data analysis by supporting quality control, documentation, reproducibility, parallelization, and easy adaptation to other NGS experiments. https://github.com/cbg-ethz/NGS-pipe [email protected]

Spatial distribution of bivalves in relation to environmental conditions (middle Danube catchment, Hungary)

The spatial distribution of bivalves in relation to environmental conditions was studied along a second- and third order stream – medium-sized river (River Ipoly) – large river (River Danube) continuum in the Hungarian Danube River system. Quantitative samples were collected four times in 2007 and a total of 1662 specimens, belonging to 22 bivalve species were identified. Among these species, two are endangered (Pseudanodonta complanata, Unio crassus) and five are invasive (Dreissena polymorpha, D. rostriformis bugensis, Corbicula fluminea, C. fluminalis, Anodonta woodiana) in Hungary. The higher density presented by Pisidium subtruncatum, P. supinum, P. henslowanum and C. fluminea suggests that these species may have a key role in this ecosystem. Three different faunal groups were distinguished but no significant temporal change was detected. The lowest density and diversity with two species (P. casertanum and P. personatum) occurred in streams. The highest density and diversity was found in the River Ipoly, in the side arms of the Danube and in the main arm of the Danube with sand and silt substrate, being dominated by P. subtruncatum and P. henslowanum. Moderate density and species richness were observed in the main arm of the Danube with pebble and stone substrate, being dominated by C. fluminea and S. rivicola. Ten environmental variables were found to have significant influence on the distribution of bivalves, the strongest explanatory factors being substrate types, current velocity and sedimentological characteristics.The project was financially supported by the Hungarian Scientific Research Fund under the contract No. OTKA T/046180. Special thanks to the DanubeIpoly National Park for the help in field work.info:eu-repo/semantics/publishedVersio

Synthetic biology: Understanding biological design from synthetic circuits

An important aim of synthetic biology is to uncover the design principles of natural biological systems through the rational design of gene and protein circuits. Here, we highlight how the process of engineering biological systems — from synthetic promoters to the control of cell–cell interactions — has contributed to our understanding of how endogenous systems are put together and function. Synthetic biological devices allow us to grasp intuitively the ranges of behaviour generated by simple biological circuits, such as linear cascades and interlocking feedback loops, as well as to exert control over natural processes, such as gene expression and population dynamics

Diagnostische Bedeutung der Proteinbindung von Plasmacortisol, bestimmt durch Dextrangelfiltration

1. Mittels Dextrangelfiltration wurde nach Inkubation von markiertem Cortisol und Plasma der proteingebundene und der sog. freie Anteil (%) des endogenen Plasmacortisols ermittelt und bei gleichzeitiger fluorimetrischer Bestimmung der 11-OHCS auch die Menge proteingebundenen, bzw. sog. freien Cortisols (µg-%) berechnet. 2. Die diagnostische Brauchbarkeit der Methode wurde bei Patienten mit Nebennierenrindeninsuffizienz, mit Hypophysentumoren, nach Hypophysektomie, mit Cushing-Syndrom mit der fluorimetrischen Bestimmung der 11-OHCS verglichen. Die einfache Bestimmung der Cortisolbindung war bei hypophysektomierten Patienten der Bestimmung der 11-OHCS überlegen und entsprach der aufwendigeren ACTH-Belastung. 3. Falsch hohe fluorimetrische 11-OHCS-Spiegel im Plasma unter Spirolacton- oder Oestrogenbehandlung und in der Gravidität lassen sich durch Bestimmung der Cortisolbindung klären. Bei Schilddrüsenüberfunktion war das sog. freie Cortisol im Plasma relativ und absolut vermehrt, bei Schilddrüsenunterfunktion fand sich eine Zunahme des plasmaproteingebundenen Cortisols.1. Following incubation of labeled cortisol and plasma the percentages of protein bound and socalled free endogenous cortisol were determined by means of dextran gel filtration. 2. The diagnostic value of this method was compared with fluorimetric determinations of 11-OHCS for patients with adrenal insufficiency, Cushing-Syndrome, pituitary tumors and after hypophysectomy. In hypophysectomized patients the simple determination of protein bound cortisol was found to correlate well with diagnostic ACTH-infusion tests and to be more sensitive than fluorimetric determinations of 11-OHCS in 9 a.m. plasma. 3. Falsely elevated fluorimetric values of plasma 11-OHCS in patients treated with spirolactone or estrogens, resp. during pregnancy may be recognized through determination of cortisol binding. — In thyrotoxicosis socalled free cortisol was elevated, both relatively and absolutely; in hypothyroidism an increase of protein bound cortisol was found

Simple large wood structures promote hydromorphological heterogeneity and benthic macroinvertebrate diversity in low-gradient rivers

This work has been carried out within the SMART Joint Doctorate Programme ‘Science for the MAnagement of Rivers and their Tidal systems’ funded by the Erasmus Mundus programme of the European Union

Towards a more-than-human approach to tree health

New ways of working and thinking in relation to tree health and plant biosecurity are required. The climate is changing and the number of pests and diseases is increasing. A review of the social science literature on plant health reveals that scholars are not quite sure what this ‘new thinking’ might entail. In this chapter, we begin the process of re-imagining tree health by starting with the trees and our research engagement with them. Trees are acknowledged in this chapter as never static, but rather fluid, shape-shifters, translated across time and space. Health and disease are revealed as relational, and a fixed approach to tree health management won’t work. In a world of rapid change, this way of working is not just relevant for trees

Early detection and surveillance of SARS-CoV-2 genomic variants in wastewater using COJAC

The continuing emergence of SARS-CoV-2 variants of concern and variants of interest emphasizes the need for early detection and epidemiological surveillance of novel variants. We used genomic sequencing of 122 wastewater samples from three locations in Switzerland to monitor the local spread of B.1.1.7 (Alpha), B.1.351 (Beta) and P.1 (Gamma) variants of SARS-CoV-2 at a population level. We devised a bioinformatics method named COJAC (Co-Occurrence adJusted Analysis and Calling) that uses read pairs carrying multiple variant-specific signature mutations as a robust indicator of low-frequency variants. Application of COJAC revealed that a local outbreak of the Alpha variant in two Swiss cities was observable in wastewater up to 13 d before being first reported in clinical samples. We further confirmed the ability of COJAC to detect emerging variants early for the Delta variant by analysing an additional 1,339 wastewater samples. While sequencing data of single wastewater samples provide limited precision for the quantification of relative prevalence of a variant, we show that replicate and close-meshed longitudinal sequencing allow for robust estimation not only of the local prevalence but also of the transmission fitness advantage of any variant. We conclude that genomic sequencing and our computational analysis can provide population-level estimates of prevalence and fitness of emerging variants from wastewater samples earlier and on the basis of substantially fewer samples than from clinical samples. Our framework is being routinely used in large national projects in Switzerland and the UK