Publications

FAIRDOMHub: a repository and collaboration environment for sharing systems biology research.

Abstract (Expand)

The FAIRDOMHub is a repository for publishing FAIR (Findable, Accessible, Interoperable and Reusable) Data, Operating procedures and Models (https://fairdomhub.org/) for the Systems Biology community. … It is a web-accessible repository for storing and sharing systems biology research assets. It enables researchers to organize, share and publish data, models and protocols, interlink them in the context of the systems biology investigations that produced them, and to interrogate them via API interfaces. By using the FAIRDOMHub, researchers can achieve more effective exchange with geographically distributed collaborators during projects, ensure results are sustained and preserved and generate reproducible publications that adhere to the FAIR guiding principles of data stewardship.

Authors: K. Wolstencroft, O. Krebs, J. L. Snoep, N. J. Stanford, F. Bacall, M. Golebiewski, R. Kuzyakiv, Q. Nguyen, S. Owen, S. Soiland-Reyes, J. Straszewski, D. D. van Niekerk, A. R. Williams, L. Malmstrom, B. Rinn, W. Muller, C. Goble

Date Published: 3rd Dec 2016

Publication Type: Not specified

Genome reduction boosts heterologous gene expression in Pseudomonas putida.

Abstract (Expand)

BACKGROUND: The implementation of novel platform organisms to be used as microbial cell factories in industrial applications is currently the subject of intense research. Ongoing efforts include the … adoption of Pseudomonas putida KT2440 variants with a reduced genome as the functional chassis for biotechnological purposes. In these strains, dispensable functions removed include flagellar motility (1.1% of the genome) and a number of open reading frames expected to improve genotypic and phenotypic stability of the cells upon deletion (3.2% of the genome). RESULTS: In this study, two previously constructed multiple-deletion P. putida strains were systematically evaluated as microbial cell factories for heterologous protein production and compared to the parental bacterium (strain KT2440) with regards to several industrially-relevant physiological traits. Energetic parameters were quantified at different controlled growth rates in continuous cultivations and both strains had a higher adenosine triphosphate content, increased adenylate energy charges, and diminished maintenance demands than the wild-type strain. Under all the conditions tested the mutants also grew faster, had enhanced biomass yields and showed higher viability, and displayed increased plasmid stability than the parental strain. In addition to small-scale shaken-flask cultivations, the performance of the genome-streamlined strains was evaluated in larger scale bioreactor batch cultivations taking a step towards industrial growth conditions. When the production of the green fluorescent protein (used as a model heterologous protein) was assessed in these cultures, the mutants reached a recombinant protein yield with respect to biomass up to 40% higher than that of P. putida KT2440. CONCLUSIONS: The two streamlined-genome derivatives of P. putida KT2440 outcompeted the parental strain in every industrially-relevant trait assessed, particularly under the working conditions of a bioreactor. Our results demonstrate that these genome-streamlined bacteria are not only robust microbial cell factories on their own, but also a promising foundation for further biotechnological applications.

Authors: S. Lieder, P. I. Nikel, V. de Lorenzo, R. Takors

Date Published: 19th Apr 2015

Publication Type: Not specified

Modeling the cell division cycle: cdc2 and cyclin interactions.

Abstract (Expand)

The proteins cdc2 and cyclin form a heterodimer (maturation promoting factor) that controls the major events of the cell cycle. A mathematical model for the interactions of cdc2 and cyclin is constructed. … Simulation and analysis of the model show that the control system can operate in three modes: as a steady state with high maturation promoting factor activity, as a spontaneous oscillator, or as an excitable switch. We associate the steady state with metaphase arrest in unfertilized eggs, the spontaneous oscillations with rapid division cycles in early embryos, and the excitable switch with growth-controlled division cycles typical of nonembryonic cells.

Author: J. J. Tyson

Date Published: 15th Aug 1991

Publication Type: Not specified

Schemes of flux control in a model of Saccharomyces cerevisiae glycolysis.

Abstract (Expand)

We used parameter scanning to emulate changes to the limiting rate for steps in a fitted model of glucose-derepressed yeast glycolysis. Three flux-control regimes were observed, two of which were under … the dominant control of hexose transport, in accordance with various experimental studies and other model predictions. A third control regime in which phosphofructokinase exerted dominant glycolytic flux control was also found, but it appeared to be physiologically unreachable by this model, and all realistically obtainable flux control regimes featured hexose transport as a step involving high flux control.

Authors: L. Pritchard, D. B. Kell

Date Published: No date defined

Publication Type: Not specified

Can yeast glycolysis be understood in terms of in vitro kinetics of the constituent enzymes? Testing biochemistry.

Abstract (Expand)

This paper examines whether the in vivo behavior of yeast glycolysis can be understood in terms of the in vitro kinetic properties of the constituent enzymes. In nongrowing, anaerobic, compressed … Saccharomyces cerevisiae the values of the kinetic parameters of most glycolytic enzymes were determined. For the other enzymes appropriate literature values were collected. By inserting these values into a kinetic model for glycolysis, fluxes and metabolites were calculated. Under the same conditions fluxes and metabolite levels were measured. In our first model, branch reactions were ignored. This model failed to reach the stable steady state that was observed in the experimental flux measurements. Introduction of branches towards trehalose, glycogen, glycerol and succinate did allow such a steady state. The predictions of this branched model were compared with the empirical behavior. Half of the enzymes matched their predicted flux in vivo within a factor of 2. For the other enzymes it was calculated what deviation between in vivo and in vitro kinetic characteristics could explain the discrepancy between in vitro rate and in vivo flux.

Authors: B. Teusink, J. Passarge, C. A. Reijenga, E. Esgalhado, C. C. van der Weijden, M. Schepper, M. C. Walsh, B. M. Bakker, K. van Dam, H. V. Westerhoff, J. L. Snoep

Date Published: No date defined

Publication Type: Not specified

Construction and validation of a detailed kinetic model of glycolysis in Plasmodium falciparum.

Abstract (Expand)

UNLABELLED: The enzymes in the Embden-Meyerhof-Parnas pathway of Plasmodium falciparum trophozoites were kinetically characterized and their integrated activities analyzed in a mathematical model. For … validation of the model, we compared model predictions for steady-state fluxes and metabolite concentrations of the hexose phosphates with experimental values for intact parasites. The model, which is completely based on kinetic parameters that were measured for the individual enzymes, gives an accurate prediction of the steady-state fluxes and intermediate concentrations. This is the first detailed kinetic model for glucose metabolism in P. falciparum, one of the most prolific malaria-causing protozoa, and the high predictive power of the model makes it a strong tool for future drug target identification studies. The modelling workflow is transparent and reproducible, and completely documented in the SEEK platform, where all experimental data and model files are available for download. DATABASE: The mathematical models described in the present study have been submitted to the JWS Online Cellular Systems Modelling Database (http://jjj.bio.vu.nl/database/penkler). The investigation and complete experimental data set is available on SEEK (10.15490/seek.1. INVESTIGATION: 56).

Authors: G. Penkler, F. du Toit, W. Adams, M. Rautenbach, D. C. Palm, D. D. van Niekerk, J. L. Snoep

Date Published: No date defined

Publication Type: Not specified

Targeting glycolysis in the malaria parasite Plasmodium falciparum.

Abstract (Expand)

UNLABELLED: Glycolysis is the main pathway for ATP production in the malaria parasite Plasmodium falciparum and essential for its survival. Following a sensitivity analysis of a detailed kinetic model … for glycolysis in the parasite, the glucose transport reaction was identified as the step whose activity needed to be inhibited to the least extent to result in a 50% reduction in glycolytic flux. In a subsequent inhibitor titration with cytochalasin B, we confirmed the model analysis experimentally and measured a flux control coefficient of 0.3 for the glucose transporter. In addition to the glucose transporter, the glucokinase and phosphofructokinase had high flux control coefficients, while for the ATPase a small negative flux control coefficient was predicted. In a broader comparative analysis of glycolytic models, we identified a weakness in the P. falciparum pathway design with respect to stability towards perturbations in the ATP demand. DATABASE: The mathematical model described here has been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.bio.vu.nl/database/vanniekerk1. The SEEK-study including the experimental data set is available at DOI 10.15490/seek.1. INVESTIGATION: 56 (http://dx.doi.org/10.15490/seek.1. INVESTIGATION: 56).

Authors: D. D. van Niekerk, G. P. Penkler, F. du Toit, J. L. Snoep

Date Published: No date defined

Publication Type: Not specified

Quantitative analysis of drug effects at the whole-body level: a case study for glucose metabolism in malaria patients.

Abstract (Expand)

We propose a hierarchical modelling approach to construct models for disease states at the whole-body level. Such models can simulate effects of drug-induced inhibition of reaction steps on the whole-body … physiology. We illustrate the approach for glucose metabolism in malaria patients, by merging two detailed kinetic models for glucose metabolism in the parasite Plasmodium falciparum and the human red blood cell with a coarse-grained model for whole-body glucose metabolism. In addition we use a genome-scale metabolic model for the parasite to predict amino acid production profiles by the malaria parasite that can be used as a complex biomarker.

Authors: J. L. Snoep, K. Green, J. Eicher, D. C. Palm, G. Penkler, F. du Toit, N. Walters, R. Burger, H. V. Westerhoff, D. D. van Niekerk

Date Published: No date defined

Publication Type: Not specified

Comparison of Three Xylose Pathways in Pseudomonas putida KT2440 for the Synthesis of Valuable Products

Abstract (Expand)

Pseudomonas putida KT2440 is a well-established chassis in industrial biotechnology. To increase the substrate spectrum, we implemented three alternative xylose utilization pathways, namely the Isomerase, … Weimberg, and Dahms pathways. The synthetic operons contain genes from Escherichia coli and Pseudomonas taiwanensis. For isolating the Dahms pathway in P. putida KT2440 two genes (PP_2836 and PP_4283), encoding an endogenous enzyme of the Weimberg pathway and a regulator for glycolaldehyde degradation, were deleted. Before and after adaptive laboratory evolution, these strains were characterized in terms of growth and synthesis of mono-rhamnolipids and pyocyanin. The engineered strain using the Weimberg pathway reached the highest maximal growth rate of 0.30 h−1. After adaptive laboratory evolution the lag phase was reduced significantly. The highest titers of 720mg L−1 mono-rhamnolipids and 30mg L−1 pyocyanin were reached by the evolved strain using the Weimberg or an engineered strain using the Isomerase pathway, respectively. The different stoichiometries of the three xylose utilization pathways may allow engineering of tailored chassis for valuable bioproduct synthesis.

Authors: Isabel Bator, Andreas Wittgens, Frank Rosenau, Till Tiso, Lars M. Blank

Date Published: 17th Jan 2020

Publication Type: Not specified

Yeast-Based Biosynthesis of Natural Products From Xylose.

Abstract (Expand)

Xylose is the second most abundant sugar in lignocellulosic hydrolysates. Transformation of xylose into valuable chemicals, such as plant natural products, is a feasible and sustainable route to … industrializing biorefinery of biomass materials. Yeast strains, including Saccharomyces cerevisiae, Scheffersomyces stipitis, and Yarrowia lipolytica, display some paramount advantages in expressing heterologous enzymes and pathways from various sources and have been engineered extensively to produce natural products. In this review, we summarize the advances in the development of metabolically engineered yeasts to produce natural products from xylose, including aromatics, terpenoids, and flavonoids. The state-of-the-art metabolic engineering strategies and representative examples are reviewed. Future challenges and perspectives are also discussed on yeast engineering for commercial production of natural products using xylose as feedstocks.

Authors: J. Zha, M. Yuwen, W. Qian, X. Wu

Date Published: 22nd Feb 2021

Publication Type: Journal

Competing G protein-coupled receptor kinases balance G protein and beta-arrestin signaling.

Abstract (Expand)

Seven-transmembrane receptors (7TMRs) are involved in nearly all aspects of chemical communications and represent major drug targets. 7TMRs transmit their signals not only via heterotrimeric G proteins … but also through beta-arrestins, whose recruitment to the activated receptor is regulated by G protein-coupled receptor kinases (GRKs). In this paper, we combined experimental approaches with computational modeling to decipher the molecular mechanisms as well as the hidden dynamics governing extracellular signal-regulated kinase (ERK) activation by the angiotensin II type 1A receptor (AT(1A)R) in human embryonic kidney (HEK)293 cells. We built an abstracted ordinary differential equations (ODE)-based model that captured the available knowledge and experimental data. We inferred the unknown parameters by simultaneously fitting experimental data generated in both control and perturbed conditions. We demonstrate that, in addition to its well-established function in the desensitization of G-protein activation, GRK2 exerts a strong negative effect on beta-arrestin-dependent signaling through its competition with GRK5 and 6 for receptor phosphorylation. Importantly, we experimentally confirmed the validity of this novel GRK2-dependent mechanism in both primary vascular smooth muscle cells naturally expressing the AT(1A)R, and HEK293 cells expressing other 7TMRs.

Authors: D. Heitzler, G. Durand, N. Gallay, A. Rizk, S. Ahn, J. Kim, J. D. Violin, L. Dupuy, C. Gauthier, V. Piketty, P. Crepieux, A. Poupon, F. Clement, F. Fages, R. J. Lefkowitz, E. Reiter

Date Published: 26th Jun 2012

Publication Type: Journal

Functional characterization of GNAS mutations found in patients with pseudohypoparathyroidism type Ic defines a new subgroup of pseudohypoparathyroidism affecting selectively Gsalpha-receptor interaction.

Abstract (Expand)

Pseudohypoparathyroidism type Ia (PHPIa) is caused by GNAS mutations leading to deficiency of the alpha-subunit of stimulatory G proteins (Gsalpha) that mediate signal transduction of G protein-coupled … receptors via cAMP. PHP type Ic (PHPIc) and PHPIa share clinical features of Albright hereditary osteodystrophy (AHO); however, in vitro activity of solubilized Gsalpha protein is normal in PHPIc but reduced in PHPIa. We screened 32 patients classified as PHPIc for GNAS mutations and identified three mutations (p.E392K, p.E392X, p.L388R) in four unrelated families. These and one novel mutation associated with PHPIa (p.L388P) were introduced into a pcDNA3.1(-) expression vector encoding Gsalpha wild-type and expressed in a Gsalpha-null cell line (Gnas(E2-/E2-) ). To investigate receptor-mediated cAMP accumulation, we stimulated the endogenous expressed beta(2) -adrenergic receptor, or the coexpressed PTH or TSH receptors, and measured the synthesized cAMP by RIA. The results were compared to receptor-independent cholera toxin-induced cAMP accumulation. Each of the mutants associated with PHPIc significantly reduced or completely disrupted receptor-mediated activation, but displayed normal receptor-independent activation. In contrast, PHPIa associated p.L388P disrupted both receptor-mediated activation and receptor-independent activation. We present a new subgroup of PHP that is caused by Gsalpha deficiency and selectively affects receptor coupling functions of Gsalpha.

Authors: S. Thiele, L. de Sanctis, R. Werner, J. Grotzinger, C. Aydin, H. Juppner, M. Bastepe, O. Hiort

Date Published: 14th Apr 2011

Publication Type: Journal

Characterization of a PTH1R missense mutation responsible for Jansen type metaphyseal chondrodysplasia.

Abstract (Expand)

Parathyroid hormone and parathyroid hormone-related peptide (PTHrP), and its receptor (PTH1R) play an important role in differentiation of bone and cartilage in the developing stages. Constitutive … dimers of PTH1R are believed to be dissociated by ligand binding, and monomeric PTH1R is capable of activating G protein. Jansen type metaphyseal chondrodysplasia is caused by missense mutations in PTH1R, which are constitutively active even without the presence of the ligands. However, the underlying pathomechanisms remained largely unknown. In this study, we have attempted to further characterize a PTH1R missense mutation H223R responsible for Jansen type metaphyseal chondrodysplasia. cDNAs encoding wild-type (Wt)- and H223R mutant (Mut)-PTH1R were transfected into HEK293T cells, and as a consequence of western blots, both the Wt- and Mut-PTH1R proteins showed several fragments between 55 and 65 kDa in size, while the patterns of N-glycosylation were distinct between them. Then we hypothesized that the Mut-PTH1R might physically interact with the Wt-PTH1R, leading to affect the downstream cAMP accumulation. Co-immunoprecipitation assays clearly showed that interaction occurred not only between the Wt-PTH1R themselves, but also between the Wt- and Mut-PTH1R. Furthermore, we performed CRE reporter assays to investigate cAMP accumulation. Constitutive, ligand-independent cAMP accumulation was observed in HEK293T cells expressing the Mut-PTH1R. Interestingly, there was a statistically lower constitutive activity in HEK293T cells co-expressing the Wt- and Mut-PTH1R proteins. Summarizing, it seems likely that Mut-PTH1R may be, at least in part, co-localized with Wt-PTH1R by forming a heterodimer, leading to affect the function to each other.

Authors: J. Shimomura-Kuroki, M. Farooq, T. Sekimoto, N. Amizuka, Y. Shimomura

Date Published: 11th May 2016

Publication Type: Journal

Identification of novel hits as highly prospective dual agonists for mu and kappa opioid receptors: an integrated in silico approach

Abstract

Not specified

Authors: Indrani Bera, Mrinal Vishwas Marathe, Pavan V. Payghan, Nanda Ghoshal

Date Published: 25th Jan 2018

Publication Type: Journal

Structural dynamics bridge the gap between the genetic and functional levels of GPCRs.

Abstract (Expand)

G protein-coupled receptors (GPCRs) are implicated in nearly all physiological processes in the human body and represent an important drug targeting class. The genes encoding the different GPCR (sub)types … determine their specific functionality, which can be altered by natural genetic variants and isoforms. Deciphering the molecular link between sequence diversity and its functional consequences is a current challenge and critical for the comprehension of the physiological response of GPCRs. It requires a global understanding of how protein sequence translates into protein structure, how this impacts the structural motions of the protein, and, finally, how all these factors determine the receptor functionality. Here, we discuss available resources and state-of-the-art computational approaches to address this question.

Authors: M. Torrens-Fontanals, T. M. Stepniewski, D. E. Gloriam, J. Selent

Date Published: 27th May 2021

Publication Type: Journal

Computational characterization of the glutamate receptor antagonist perampanel and its close analogs: density functional exploration of conformational space and molecular docking study

Abstract (Expand)

Perampanel approved by FDA in 2012 is a first-in-class antiepileptic drug which inhibits α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor currents. It is markedly more active than … many of its close analogs, and the reasons for this activity difference are not quite clear. Recent crystallographic studies allowed the authors to identify the location of its binding site. Unfortunately, the resolution is low, and the detailed description of perampanel binding mode is still in part speculative. Here we provide a detailed DFT-level conformational analysis of perampanel in a vacuum and in the solvents, mimicking the protein environment, followed by quantum theory of atoms in molecules (QTAIM), non-covalent interactions (NCI), and natural bond orbital (NBO) analyses. The findings indicate the electrostatic nature of the intramolecular interactions which contribute to energy differences of the conformations in a vacuum whereas the increase of dielectric constant leads to the energy equalization of conformations. Based on these results, the docking study was performed to investigate possible binding modes of perampanel and its close analogs in AMPA receptors. The influence of the pyridine nitrogen and cyano group position was explained based on the results of conformational analysis and molecular docking. These findings may contribute to the design of novel antiepileptic drugs and the development of novel approaches to treat neurodegenerative diseases and major depressive disorder.

Authors: Abdul-Akim D. Guseynov, Sergey A. Pisarev, Dmitry A. Shulga, Vladimir A. Palyulin, Maxim V. Fedorov, Dmitry S. Karlov

Date Published: 1st Oct 2019

Publication Type: Journal

Biased Ligands Differentially Shape the Conformation of the Extracellular Loop Region in 5-HT2B Receptors.

Abstract (Expand)

G protein-coupled receptors are linked to various intracellular transducers, each pathway associated with different physiological effects. Biased ligands, capable of activating one pathway over another, … are gaining attention for their therapeutic potential, as they could selectively activate beneficial pathways whilst avoiding those responsible for adverse effects. We performed molecular dynamics simulations with known beta-arrestin-biased ligands like lysergic acid diethylamide and ergotamine in complex with the 5-HT2B receptor and discovered that the extent of ligand bias is directly connected with the degree of closure of the extracellular loop region. Given a loose allosteric coupling of extracellular and intracellular receptor regions, we delineate a concept for biased signaling at serotonin receptors, by which conformational interference with binding pocket closure restricts the signaling repertoire of the receptor. Molecular docking studies of biased ligands gathered from the BiasDB demonstrate that larger ligands only show plausible docking poses in the ergotamine-bound structure, highlighting the conformational constraints associated with bias. This emphasizes the importance of selecting the appropriate receptor conformation on which to base virtual screening workflows in structure-based drug design of biased ligands. As this mechanism of ligand bias has also been observed for muscarinic receptors, our studies provide a general mechanism of signaling bias transferable between aminergic receptors.

Authors: K. Denzinger, T. N. Nguyen, T. Noonan, G. Wolber, M. Bermudez

Date Published: 20th Dec 2020

Publication Type: Journal

Residue-level determinants of angiopoietin-2 interactions with its receptor Tie2.

Abstract (Expand)

We combined computational and experimental methods to interrogate the binding determinants of angiopoietin-2 (Ang2) to its receptor tyrosine kinase (RTK) Tie2-a central signaling system in angiogenesis, … inflammation, and tumorigenesis. We used physics-based electrostatic and surface-area calculations to identify the subset of interfacial Ang2 and Tie2 residues that can affect binding directly. Using random and site-directed mutagenesis and yeast surface display (YSD), we validated these predictions and identified additional Ang2 positions that affected receptor binding. We then used burial-based calculations to classify the larger set of Ang2 residues that are buried in the Ang2 core, whose mutations can perturb the Ang2 structure and thereby affect interactions with Tie2 indirectly. Our analysis showed that the Ang2-Tie2 interface is dominated by nonpolar contributions, with only three Ang2 and two Tie2 residues that contribute electrostatically to intermolecular interactions. Individual interfacial residues contributed only moderately to binding, suggesting that engineering of this interface will require multiple mutations to reach major effects. Conversely, substitutions in substantially buried Ang2 residues were more prevalent in our experimental screen, reduced binding substantially, and are therefore more likely to have a deleterious effect that might contribute to oncogenesis. Computational analysis of additional RTK-ligand complexes, c-Kit-SCF and M-CSF-c-FMS, and comparison to previous YSD results, further show the utility of our combined methodology.

Authors: A. Bakhman, E. Rabinovich, T. Shlamkovich, N. Papo, M. Kosloff

Date Published: 7th Dec 2018

Publication Type: Journal

Bioinformatics strategies for taxonomy independent binning and visualization of sequences in shotgun metagenomics.

Abstract (Expand)

One of main steps in a study of microbial communities is resolving their composition, diversity and function. In the past, these issues were mostly addressed by the use of amplicon sequencing of a … target gene because of reasonable price and easier computational postprocessing of the bioinformatic data. With the advancement of sequencing techniques, the main focus shifted to the whole metagenome shotgun sequencing, which allows much more detailed analysis of the metagenomic data, including reconstruction of novel microbial genomes and to gain knowledge about genetic potential and metabolic capacities of whole environments. On the other hand, the output of whole metagenomic shotgun sequencing is mixture of short DNA fragments belonging to various genomes, therefore this approach requires more sophisticated computational algorithms for clustering of related sequences, commonly referred to as sequence binning. There are currently two types of binning methods: taxonomy dependent and taxonomy independent. The first type classifies the DNA fragments by performing a standard homology inference against a reference database, while the latter performs the reference-free binning by applying clustering techniques on features extracted from the sequences. In this review, we describe the strategies within the second approach. Although these strategies do not require prior knowledge, they have higher demands on the length of sequences. Besides their basic principle, an overview of particular methods and tools is provided. Furthermore, the review covers the utilization of the methods in context with the length of sequences and discusses the needs for metagenomic data preprocessing in form of initial assembly prior to binning.

Authors: K. Sedlar, K. Kupkova, I. Provaznik

Date Published: 17th Dec 2016

Publication Type: Journal

Cultivar-specific transcriptome and pan-transcriptome reconstruction of tetraploid potato.

Abstract (Expand)

Although the reference genome of Solanum tuberosum Group Phureja double-monoploid (DM) clone is available, knowledge on the genetic diversity of the highly heterozygous tetraploid Group Tuberosum, … representing most cultivated varieties, remains largely unexplored. This lack of knowledge hinders further progress in potato research. In conducted investigation, we first merged and manually curated the two existing partially-overlapping DM genome-based gene models, creating a union of genes in Phureja scaffold. Next, we compiled available and newly generated RNA-Seq datasets (cca. 1.5 billion reads) for three tetraploid potato genotypes (cultivar Desiree, cultivar Rywal, and breeding clone PW363) with diverse breeding pedigrees. Short-read transcriptomes were assembled using several de novo assemblers under different settings to test for optimal outcome. For cultivar Rywal, PacBio Iso-Seq full-length transcriptome sequencing was also performed. EvidentialGene redundancy-reducing pipeline complemented with in-house developed scripts was employed to produce accurate and complete cultivar-specific transcriptomes, as well as to attain the pan-transcriptome. The generated transcriptomes and pan-transcriptome represent a valuable resource for potato gene variability exploration, high-throughput omics analyses, and breeding programmes.

Authors: M. Petek, M. Zagorscak, Z. Ramsak, S. Sanders, S. Tomaz, E. Tseng, M. Zouine, A. Coll, K. Gruden

Date Published: 24th Jul 2020

Publication Type: Journal

EnzymeML-a data exchange format for biocatalysis and enzymology.

Abstract (Expand)

EnzymeML is an XML-based data exchange format that supports the comprehensive documentation of enzymatic data by describing reaction conditions, time courses of substrate and product concentrations, … the kinetic model, and the estimated kinetic constants. EnzymeML is based on the Systems Biology Markup Language, which was extended by implementing the STRENDA Guidelines. An EnzymeML document serves as a container to transfer data between experimental platforms, modeling tools, and databases. EnzymeML supports the scientific community by introducing a standardized data exchange format to make enzymatic data findable, accessible, interoperable, and reusable according to the FAIR data principles. An application programming interface in Python supports the integration of software tools for data acquisition, data analysis, and publication. The feasibility of a seamless data flow using EnzymeML is demonstrated by creating an EnzymeML document from a structured spreadsheet or from a STRENDA DB database entry, by kinetic modeling using the modeling platform COPASI, and by uploading to the enzymatic reaction kinetics database SABIO-RK.

Authors: J. Range, C. Halupczok, J. Lohmann, N. Swainston, C. Kettner, F. T. Bergmann, A. Weidemann, U. Wittig, S. Schnell, J. Pleiss

Date Published: 11th Dec 2021

Publication Type: Journal

A star-PEG-heparin hydrogel platform to aid cell replacement therapies for neurodegenerative diseases.

Abstract (Expand)

Biofunctional matrices for in vivo tissue engineering strategies must be modifiable in both biomolecular composition and mechanical characteristics. To address this challenge, we present a modular … system of biohybrid hydrogels based on covalently cross-linked heparin and star-shaped poly(ethylene glycols) (star-PEG) in which network characteristics can be gradually varied while heparin contents remain constant. Mesh size, swelling and elastic moduli were shown to correlate well with the degree of gel component cross-linking. Additionally, secondary conversion of heparin within the biohybrid gels allowed the covalent attachment of cell adhesion mediating RGD peptides and the non-covalent binding of soluble mitogens such as FGF-2. We applied the biohybrid gels to demonstrate the impact of mechanical and biomolecular cues on primary nerve cells and neural stem cells. The results demonstrate the cell type-specific interplay of synergistic signaling events and the potential of biohybrid materials to selectively stimulate cell fate decisions. These findings suggest important future uses for this material in cell replacement based-therapies for neurodegenerative diseases.

Authors: U. Freudenberg, A. Hermann, P. B. Welzel, K. Stirl, S. C. Schwarz, M. Grimmer, A. Zieris, W. Panyanuwat, S. Zschoche, D. Meinhold, A. Storch, C. Werner

Date Published: 30th Jun 2009

Publication Type: Journal

Stimuli-responsive hydrogels in drug delivery and tissue engineering

Abstract

Not specified

Authors: Nikhil Sood, Ankur Bhardwaj, Shuchi Mehta, Abhinav Mehta

Date Published: 23rd Mar 2016

Publication Type: Journal

The contributions of Prof. Kenneth F. O'Driscoll to radical copolymerization kinetics

Abstract

Not specified

Authors: Robin A. Hutchinson, Bert Klumperman, Gregory T. Russell, Alexander M. Van Herk

Date Published: 1st Apr 2022

Publication Type: Journal

Evaluation of Pharmacokinetic and Toxicological Parameters of Arnica Tincture after Dermal Application In Vivo

Abstract (Expand)

Cutaneous leishmaniasis (CL) is classified as a neglected tropical disease by the World Health Organization. As the standard drugs for the treatment of this disease suffer from severe unwanted effects, …anted effects, new effective and safe therapeutic options are required. In our previous work, Arnica tincture showed promising antileishmanial effects in vitro and in vivo. For the potential treatment of human CL patients with Arnica tincture, data on the pharmacokinetic properties of the bioactive, antileishmanial compounds (the sesquiterpene lactone (STL) helenalin and its derivatives) are needed. Therefore, we studied the in vivo absorption of the bioactive compounds after the dermal application of Arnica tincture in rats. Moreover, we analyzed the blood plasma, urine, and feces of the animals by ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS). Although the majority (84%) of the applied STLs (1.0 mg) were absorbed, the concentrations in the plasma, urine, and feces were below the limit of detection (0.3 ng/mL) in the samples for UHPLC-HRMS analysis. This result may be explained by extensive metabolism and slow permeation accompanied by the accumulation of STLs in the skin, as described in our previous work. Accordingly, the plasma concentration of STLs after the topical application of Arnica tincture was very far from a dose where toxicity could be expected. Additionally, tests for corrosive or irritant activity as well as acute and repeated-dose dermal toxicity did not show any positive results after the administration of the amounts of Arnica tincture that would be needed for the treatment of CL. Consequently, in the treatment of CL patients with Arnica tincture, no toxic effects are expected, other than the known sensitization potential of the STLs.

Authors: Franziska M. Jürgens, Sara M. Robledo, Thomas J. Schmidt

Date Published: 1st Nov 2022

Publication Type: Journal

Data management and data enrichment for systems biology projects.

Abstract (Expand)

Collecting, curating, interlinking, and sharing high quality data are central to de.NBI-SysBio, the systems biology data management service center within the de.NBI network (German Network for … Bioinformatics Infrastructure). The work of the center is guided by the FAIR principles for scientific data management and stewardship. FAIR stands for the four foundational principles Findability, Accessibility, Interoperability, and Reusability which were established to enhance the ability of machines to automatically find, access, exchange and use data. Within this overview paper we describe three tools (SABIO-RK, Excemplify, SEEK) that exemplify the contribution of de.NBI-SysBio services to FAIR data, models, and experimental methods storage and exchange. The interconnectivity of the tools and the data workflow within systems biology projects will be explained. For many years we are the German partner in the FAIRDOM initiative (http://fair-dom.org) to establish a European data and model management service facility for systems biology.

Authors: U. Wittig, M. Rey, A. Weidemann, W. Muller

Date Published: 10th Nov 2017

Publication Type: Journal

A new granulation method for compressed tablets [proceedings].

Abstract

Not specified

Author: M. H. Rubinstein

Date Published: 1st Dec 1976

Publication Type: Journal

EnzymeML: seamless data flow and modeling of enzymatic data.

Abstract (Expand)

The design of biocatalytic reaction systems is highly complex owing to the dependency of the estimated kinetic parameters on the enzyme, the reaction conditions, and the modeling method. Consequently, … reproducibility of enzymatic experiments and reusability of enzymatic data are challenging. We developed the XML-based markup language EnzymeML to enable storage and exchange of enzymatic data such as reaction conditions, the time course of the substrate and the product, kinetic parameters and the kinetic model, thus making enzymatic data findable, accessible, interoperable and reusable (FAIR). The feasibility and usefulness of the EnzymeML toolbox is demonstrated in six scenarios, for which data and metadata of different enzymatic reactions are collected and analyzed. EnzymeML serves as a seamless communication channel between experimental platforms, electronic lab notebooks, tools for modeling of enzyme kinetics, publication platforms and enzymatic reaction databases. EnzymeML is open and transparent, and invites the community to contribute. All documents and codes are freely available at https://enzymeml.org .

Authors: S. Lauterbach, H. Dienhart, J. Range, S. Malzacher, J. D. Sporing, D. Rother, M. F. Pinto, P. Martins, C. E. Lagerman, A. S. Bommarius, A. V. Host, J. M. Woodley, S. Ngubane, T. Kudanga, F. T. Bergmann, J. M. Rohwer, D. Iglezakis, A. Weidemann, U. Wittig, C. Kettner, N. Swainston, S. Schnell, J. Pleiss

Date Published: 10th Feb 2023

Publication Type: Journal

Position paper on management of personal data in environment and health research in Europe.

Abstract (Expand)

Management of datasets that include health information and other sensitive personal information of European study participants has to be compliant with the General Data Protection Regulation (GDPR, … Regulation (EU) 2016/679). Within scientific research, the widely subscribed'FAIR' data principles should apply, meaning that research data should be findable, accessible, interoperable and re-usable. Balancing the aim of open science driven FAIR data management with GDPR compliant personal data protection safeguards is now a common challenge for many research projects dealing with (sensitive) personal data. In December 2020 a workshop was held with representatives of several large EU research consortia and of the European Commission to reflect on how to apply the FAIR data principles for environment and health research (E&H). Several recent data intensive EU funded E&H research projects face this challenge and work intensively towards developing solutions to access, exchange, store, handle, share, process and use such sensitive personal data, with the aim to support European and transnational collaborations. As a result, several recommendations, opportunities and current limitations were formulated. New technical developments such as federated data management and analysis systems, machine learning together with advanced search software, harmonized ontologies and data quality standards should in principle facilitate the FAIRification of data. To address ethical, legal, political and financial obstacles to the wider re-use of data for research purposes, both specific expertise and underpinning infrastructure are needed. There is a need for the E&H research data to find their place in the European Open Science Cloud. Communities using health and population data, environmental data and other publicly available data have to interconnect and synergize. To maximize the use and re-use of environment and health data, a dedicated supporting European infrastructure effort, such as the EIRENE research infrastructure within the ESFRI roadmap 2021, is needed that would interact with existing infrastructures.

Authors: G. Eva, G. Liese, B. Stephanie, H. Petr, M. Leslie, V. Roel, V. Martine, B. Sergi, H. Mette, J. Sarah, R. M. Laura, S. Arnout, A. S Morris, T. Jan, T. Xenia, V. Nina, V. E. Koert, R. Sylvie, S. Greet

Date Published: 14th Jun 2022

Publication Type: Journal

A new granulation method for compressed tablets [proceedings].

Abstract

Not specified

Author: M. H. Rubinstein

Date Published: 1st Dec 1976

Publication Type: Journal

Metabolome plasticity in 241 Arabidopsis thaliana accessions reveals evolutionary cold adaptation processes.

Abstract (Expand)

Acclimation and adaptation of metabolism to a changing environment are key processes for plant survival and reproductive success. In the present study, 241 natural accessions of Arabidopsis (Arabidopsis … thaliana) were grown under two different temperature regimes, 16 degrees C and 6 degrees C, and growth parameters were recorded, together with metabolite profiles, to investigate the natural genome x environment effects on metabolome variation. The plasticity of metabolism, which was captured by metabolic distance measures, varied considerably between accessions. Both relative growth rates and metabolic distances were predictable by the underlying natural genetic variation of accessions. Applying machine learning methods, climatic variables of the original growth habitats were tested for their predictive power of natural metabolic variation among accessions. We found specifically habitat temperature during the first quarter of the year to be the best predictor of the plasticity of primary metabolism, indicating habitat temperature as the causal driver of evolutionary cold adaptation processes. Analyses of epigenome- and genome-wide associations revealed accession-specific differential DNA-methylation levels as potentially linked to the metabolome and identified FUMARASE2 as strongly associated with cold adaptation in Arabidopsis accessions. These findings were supported by calculations of the biochemical Jacobian matrix based on variance and covariance of metabolomics data, which revealed that growth under low temperatures most substantially affects the accession-specific plasticity of fumarate and sugar metabolism. Our findings indicate that the plasticity of metabolic regulation is predictable from the genome and epigenome and driven evolutionarily by Arabidopsis growth habitats.

Authors: J. Weiszmann, D. Walther, P. Clauw, G. Back, J. Gunis, I. Reichardt, S. Koemeda, J. Jez, M. Nordborg, J. Schwarzerova, I. Pierides, T. Nagele, W. Weckwerth

Date Published: 22nd Sep 2023

Publication Type: Journal

Change in the kinetics of sulphacetamide tissue distribution in Walker tumor-bearing rats.

Abstract (Expand)

The effect of Walker tumor on sulphacetamide distribution was studied in rats 21 days after tumor implantation in a hind leg. After oral administration of sulphacetamide (5 and 20 min), the concentration … of the drug was found to be lower in the plasma and liver of tumor-bearing rats when compared with that of control group. However, 90 min after sulphacetamide administration, the concentration of the drug in these same tissues was found to be higher in tumor-bearing rats than in control animals. Whereas the tumor had no apparent effect on sulphacetamide concentration in the brain, drug concentrations in the fat tissue of tumor-bearing rats were constantly higher than those of control animals. These changes in sulphacentamide disposition kinetics could be explained in part by delay in gastrointestinal absorption of the drug. Contrary to what was observed after oral administration, constantly higher drug concentrations were found in the plasma of tumor-bearing rats after iv injection of sulphacetamide. Furthermore, the half-life of sulphacetamide in these same animals was much higher than in control animals. It is concluded that, in Walker tumor-bearing rats, there are changes in the kinetics of sulphacetamide which are functions of the route of administration of the drug.

Authors: D. Nadeau, C. Marchand

Date Published: 1st Nov 1975

Publication Type: Journal

Prediction and analysis of redox-sensitive cysteines using machine learning and statistical methods.

Abstract (Expand)

Reactive oxygen species are produced by a number of stimuli and can lead both to irreversible intracellular damage and signaling through reversible post-translational modification. It is unclear which … factors contribute to the sensitivity of cysteines to redox modification. Here, we used statistical and machine learning methods to investigate the influence of different structural and sequence features on the modifiability of cysteines. We found several strong structural predictors for redox modification. Sensitive cysteines tend to be characterized by higher exposure, a lack of secondary structure elements, and a high number of positively charged amino acids in their close environment. Our results indicate that modified cysteines tend to occur close to other post-translational modifications, such as phosphorylated serines. We used these features to create models and predict the presence of redox-modifiable cysteines in human mitochondrial complex I as well as make novel predictions regarding redox-sensitive cysteines in proteins.

Authors: M. Kessler, I. Wittig, J. Ackermann, I. Koch

Date Published: 27th Jul 2021

Publication Type: Journal

Thermodynamic parameters of reactions involving E. Coli, a review

Abstract

Not specified

Editor:

Date Published: No date defined

Publication Type: Journal

Digitoxin metabolism by rat liver microsomes.

Abstract

Not specified

Authors: A. Schmoldt, H. F. Benthe, G. Haberland

Date Published: 1st Sep 1975

Publication Type: Journal

Chloroplast-Specific in Vivo Ca 2+ Imaging Using Yellow Cameleon Fluorescent Protein Sensors Reveals Organelle-Autonomous Ca 2+ Signatures in the Stroma

Abstract

Not specified

Authors: Giovanna Loro, Stephan Wagner, Fabrizio Gandolfo Doccula, Smrutisanjita Behera, Stefan Weinl, Joerg Kudla, Markus Schwarzländer, Alex Costa, Michela Zottini

Date Published: 2nd Aug 2016

Publication Type: Journal

Solvent Selection in Homogeneous Catalysis—Optimization of Kinetics and Reaction Performance

Abstract

Not specified

Authors: Fabian Huxoll, Froze Jameel, Jonas Bianga, Thomas Seidensticker, Matthias Stein, Gabriele Sadowski, Dieter Vogt

Date Published: 15th Jan 2021

Publication Type: Journal

Virtually identical does not mean exactly identical: Discrepancy in energy metabolism between glucose and fructose fermentation influences the reproductive potential of yeast cells.

Abstract (Expand)

The physiological efficiency of cells largely depends on the possibility of metabolic adaptations to changing conditions, especially on the availability of nutrients. Central carbon metabolism has an … essential role in cellular function. In most cells is based on glucose, which is the primary energy source, provides the carbon skeleton for the biosynthesis of important cell macromolecules, and acts as a signaling molecule. The metabolic flux between pathways of carbon metabolism such as glycolysis, pentose phosphate pathway, and mitochondrial oxidative phosphorylation is dynamically adjusted by specific cellular economics responding to extracellular conditions and intracellular demands. Using Saccharomyces cerevisiae yeast cells and potentially similar fermentable carbon sources i.e. glucose and fructose we analyzed the parameters concerning the metabolic status of the cells and connected with them alteration in cell reproductive potential. Those parameters were related to the specific metabolic network: the hexose uptake - glycolysis and activity of the cAMP/PKA pathway - pentose phosphate pathway and biosynthetic capacities - the oxidative respiration and energy generation. The results showed that yeast cells growing in a fructose medium slightly increased metabolism redirection toward respiratory activity, which decreased pentose phosphate pathway activity and cellular biosynthetic capabilities. These differences between the fermentative metabolism of glucose and fructose, lead to long-term effects, manifested by changes in the maximum reproductive potential of cells.

Authors: R. Maslanka, S. Bednarska, R. Zadrag-Tecza

Date Published: 14th May 2024

Publication Type: Journal

Pyruvate kinase: Function, regulation and role in cancer.

Abstract (Expand)

Pyruvate kinase is an enzyme that catalyzes the conversion of phosphoenolpyruvate and ADP to pyruvate and ATP in glycolysis and plays a role in regulating cell metabolism. There are four mammalian … pyruvate kinase isoforms with unique tissue expression patterns and regulatory properties. The M2 isoform of pyruvate kinase (PKM2) supports anabolic metabolism and is expressed both in cancer and normal tissue. The enzymatic activity of PKM2 is allosterically regulated by both intracellular signaling pathways and metabolites; PKM2 thus integrates signaling and metabolic inputs to modulate glucose metabolism according to the needs of the cell. Recent advances have increased our understanding of metabolic regulation by pyruvate kinase, raised new questions, and suggested the possibility of non-canonical PKM2 functions to regulate gene expression and cell cycle progression via protein-protein interactions and protein kinase activity. Here we review the structure, function, and regulation of pyruvate kinase and discuss how these properties enable regulation of PKM2 for cell proliferation and tumor growth.

Authors: W. J. Israelsen, M. G. Vander Heiden

Date Published: 17th Aug 2015

Publication Type: Journal

Streptosporangium minutum sp. nov., isolated from garden soil exposed to microwave radiation

Abstract

Not specified

Authors: Marilize Le Roes-Hill, Kim Durrell, Alaric Prins, Paul R. Meyers

Date Published: 1st Jun 2018

Publication Type: Journal

Keratinases as Versatile Enzymatic Tools for Sustainable Development

Abstract (Expand)

To reduce anthropological pressure on the environment, the implementation of novel technologies in present and future economies is needed for sustainable development. The food industry, with dairy and …with dairy and meat production in particular, has a significant environmental impact. Global poultry production is one of the fastest-growing meat producing sectors and is connected with the generation of burdensome streams of manure, offal and feather waste. In 2020, the EU alone produced around 3.2 million tonnes of poultry feather waste composed primarily of keratin, a protein biopolymer resistant to conventional proteolytic enzymes. If not managed properly, keratin waste can significantly affect ecosystems, contributing to environmental pollution, and pose a serious hazard to human and livestock health. In this article, the application of keratinolytic enzymes and microorganisms for promising novel keratin waste management methods with generation of new value-added products, such as bioactive peptides, vitamins, prion decontamination agents and biomaterials were reviewed.

Authors: Marcin Sypka, Iga Jodłowska, Aneta M. Białkowska

Date Published: 1st Dec 2021

Publication Type: Journal

Network- and enrichment-based inference of phenotypes and targets from large-scale disease maps

Abstract (Expand)

Abstract Complex diseases are inherently multifaceted, and the associated data are often heterogeneous, making linking interactions across genes, metabolites, RNA, proteins, cellular functions, and …s, cellular functions, and clinically relevant phenotypes a high-priority challenge. Disease maps have emerged as knowledge bases that capture molecular interactions, disease-related processes, and disease phenotypes with standardized representations in large-scale molecular interaction maps. Various tools are available for disease map analysis, but an intuitive solution to perform in silico experiments on the maps in a wide range of contexts and analyze high-dimensional data is currently missing. To this end, we introduce a two-dimensional enrichment analysis (2DEA) approach to infer downstream and upstream elements through the statistical association of network topology parameters and fold changes from molecular perturbations. We implemented our approach in a plugin suite for the MINERVA platform, providing an environment where experimental data can be mapped onto a disease map and predict potential regulatory interactions through an intuitive graphical user interface. We show several workflows using this approach and analyze two RNA-seq datasets in the Atlas of Inflammation Resolution (AIR) to identify enriched downstream processes and upstream transcription factors. Our work improves the usability of disease maps and increases their functionality by facilitating multi-omics data integration and exploration.

Authors: Matti Hoch, Suchi Smita, Konstantin Cesnulevicius, David Lescheid, Myron Schultz, Olaf Wolkenhauer, Shailendra Gupta

Date Published: 1st Dec 2022

Publication Type: Journal

Digitoxin metabolism by rat liver microsomes.

Abstract

Not specified

Authors: A. Schmoldt, H. F. Benthe, G. Haberland

Date Published: 1st Sep 1975

Publication Type: Journal

A Saccharomyces cerevisiae mutant unable to convert glucose to glucose-6-phosphate accumulates excessive glucose in the endoplasmic reticulum due to core oligosaccharide trimming.

Abstract (Expand)

D-Glucose is the preferred carbon and energy source for most eukaryotic cells. Immediately following its uptake, glucose is rapidly phosphorylated to glucose-6-phosphate (Glc-6-P). The yeast Saccharomyces … cerevisiae has three enzymes (Hxk1p, Hxk2p, and Glk1p) that convert glucose to Glc-6-P. In the present study, we found that yeast mutants lacking any two of these enzymes retain the ability to efficiently convert glucose to Glc-6-P and thus maintain a low level of cellular glucose. However, a mutant strain lacking all three glucose-phosphorylating enzymes contained up to 225-fold more intracellular glucose than normal. Drugs that inhibit the synthesis or the trimming of the lipid-linked core oligosaccharide Glu(3)Man(9)GlcNac(2) effectively reduced the accumulation of glucose. Similarly, mutations that block the addition of glucose residues to the core oligosaccharide moiety, such as alg5Delta or alg6Delta, also diminished glucose accumulation. These results indicate that the intracellular glucose accumulation observed in the glucose phosphorylation mutant results primarily from the trimming of glucose residues from core oligosaccharide chains within the endoplasmic reticulum (ER). Consistent with this conclusion, both [(14)C]glucose exchange and subcellular fractionation experiments indicate that much of the accumulated glucose is retained within an intracellular compartment, suggesting that the efficient transport of glucose from the ER to the cytosol in yeast may be coupled to its rephosphorylation to Glc-6-P. The high level of cellular glucose was associated with an increased level of protein glycation and the release of glucose into the culture medium via its transit through the secretory pathway. Finally, we also found that the accumulation of glucose may lead to a subtle alteration in ion homeostasis, particularly Ca(2+) uptake. This suggests that this mutant strain may serve as a useful model to study the consequences of excessive glucose accumulation and protein glycation.

Authors: A. Miseta, M. Tokes-Fuzesi, D. P. Aiello, D. M. Bedwell

Date Published: 11th Jun 2003

Publication Type: Journal

Spawning time in adult polar cod ( Boreogadus saida ) altered by crude oil exposure, independent of food availability

Abstract

Not specified

Authors: Leah C. Strople, Ireen Vieweg, Fekadu Yadetie, Derrick Kwame Odei, Anders Thorsen, Odd André Karlsen, Anders Goksøyr, Lisbet Sørensen, Antonio Sarno, Bjørn Henrik Hansen, Marianne Frantzen, Øyvind J. Hansen, Velmurugu Puvanendran, Jasmine Nahrgang

Date Published: 3rd Jul 2023

Publication Type: Journal

Bacterial laccase-like multicopper oxidases in delignification and detoxification processes

Abstract

Not specified

Authors: Marilize Le Roes-Hill, Alaric Prins, Mayowa Agunbiade

Date Published: 2024

Publication Type: Journal

The Synthesis Rates of Total Liver Protein and Plasma Albumin Determined Simultaneously In Vivo In Humans

Abstract (Expand)

Although the metabolism of liver–derived plasma proteins such as albumin has been extensively studied, human hepatic protein synthesis as a whole has not been well characterized, because a reproducible … a whole has not been well characterized, because a reproducible model for obtaining human liver tissue has not been available. In this study, the fractional synthesis rates of total liver protein and albumin in vivo were determined simultaneously in nine subjects undergoing elective laparoscopic cholecystectomy. l–[2H5]phenylalanine (45 mg/kg body wt) was administered for 10 minutes intravenously. Blood samples were collected at regular intervals for 90 minutes and a liver biopsy specimen was taken at 35 ± 7 minutes. The enrichments of plasma free phenylalanine, plasma albumin, and total liver protein were measured with gas chromatography mass spectrometry (GC–MS). The fractional synthesis rate (FSR) of total liver protein was 24.7 ± 3.1 %/d (mean ± SD), and that of albumin was 5.9 ±1.2%/d. The amount of albumin synthesized per day (absolute synthesis rate, ASR) was 109 ± 21 mg/kg body wt. No correlation between FSR of total liver protein and ASR of albumin was found. It is concluded that the technique of obtaining liver tissue specimens during laparoscopic surgery may serve as a human in vivo model to study total liver protein synthesis. The fractional synthesis rate of total liver proteins (stationary and exported), equals approximately 25% of the liver protein content daily. Within the range of values of this study, the absolute synthesis rate of albumin was not correlated to the fractional synthesis rate of total liver protein.

Authors: H. Barle, B. Nyberg, P. Essén, K. Andersson, M. A. McNurlan, J. Wernerman, P. J. Garlick

Date Published: 1997

Publication Type: Journal

Making Sense of "Nonsense" and More: Challenges and Opportunities in the Genetic Code Expansion, in the World of tRNA Modifications.

Abstract (Expand)

The evolutional development of the RNA translation process that leads to protein synthesis based on naturally occurring amino acids has its continuation via synthetic biology, the so-called rational … bioengineering. Genetic code expansion (GCE) explores beyond the natural translational processes to further enhance the structural properties and augment the functionality of a wide range of proteins. Prokaryotic and eukaryotic ribosomal machinery have been proven to accept engineered tRNAs from orthogonal organisms to efficiently incorporate noncanonical amino acids (ncAAs) with rationally designed side chains. These side chains can be reactive or functional groups, which can be extensively utilized in biochemical, biophysical, and cellular studies. Genetic code extension offers the contingency of introducing more than one ncAA into protein through frameshift suppression, multi-site-specific incorporation of ncAAs, thereby increasing the vast number of possible applications. However, different mediating factors reduce the yield and efficiency of ncAA incorporation into synthetic proteins. In this review, we comment on the recent advancements in genetic code expansion to signify the relevance of systems biology in improving ncAA incorporation efficiency. We discuss the emerging impact of tRNA modifications and metabolism in protein design. We also provide examples of the latest successful accomplishments in synthetic protein therapeutics and show how codon expansion has been employed in various scientific and biotechnological applications.

Authors: O. M. Lateef, M. O. Akintubosun, O. T. Olaoba, S. O. Samson, M. Adamczyk

Date Published: 15th Jan 2022

Publication Type: Journal

Growth and metabolism of adult polar cod (Boreogadus saida) in response to dietary crude oil

Abstract

Not specified

Authors: Jasmine Nahrgang, Morgan L. Bender, Sonnich Meier, Jordan Nechev, Jørgen Berge, Marianne Frantzen

Date Published: 1st Sep 2019

Publication Type: Journal

The role of the anterior lateral eyes in the vision-based behaviour of jumping spiders

Abstract (Expand)

SUMMARY Jumping spiders, or salticids, sample their environment using a combination of two types of eyes. The forward-facing pair of ‘principal’ eyes have narrow fields of view, but exceptional spatial …w, but exceptional spatial resolution, while the two or three pairs of ‘secondary’ eyes have wide fields of view and function especially well as motion analysers. Motion detected by the secondary eyes may elicit an orienting response, whereupon the object of interest is examined further using the high-acuity principal eyes. The anterior lateral (AL) eyes are particularly interesting, as they are the only forward-facing pair of secondary eyes. In this study, we aimed to determine characteristics of stimuli that elicit orienting responses mediated by the AL eyes. After covering all eyes except the AL eyes, we measured orienting responses to dot stimuli that varied in size and contrast, and moved at different speeds. We found that all stimulus parameters had significant effects on orientation propensity. When tethered flies were used as prey, we found that visual information from the AL eyes alone was sufficient to elicit stalking behaviour. These results suggest that, in terms of overall visual processing, the relevance of spatial vision in the AL eyes has been underestimated in the literature. Our results also show that female spiders are significantly more responsive than males. We found that hunger caused similar increases in orientation propensity in the two sexes, but females responded more often than males both when sated and when hungry. A higher propensity by females to orient toward moving objects may be related to females tending to experience higher nutritional demands than males.

Authors: Daniel B. Zurek, Alan J. Taylor, Christopher S. Evans, Ximena J. Nelson

Date Published: 15th Jul 2010

Publication Type: Journal

Review of Key Elements in Developing a Common Data Model for Rare Diseases: Identifying Common Success Factors.

Abstract (Expand)

This paper explores key success factors for the development and implementation of a Common Data Model (CDM) for Rare Diseases (RDs) focusing on the European context. Several challenges hinder RD care … and research in diagnosis, treatment, and research, including data fragmentation, lack of standardisation, and Interoperability (IOP) issues within healthcare information systems. We identify key issues and recommendations for an RD-CDM, drawing on international guidelines and existing infrastructure, to address organisational, consensus, interoperability, usage, and secondary use challenges. Based on these, we analyse the importance of balancing the scope and IOP of a CDM to cater to the unique requirements of RDs while ensuring effective data exchange and usage across systems. In conclusion, a well-designed RD-CDM can bridge gaps in RD care and research, enhance patient care and facilitate international collaborations.

Authors: A. S. L. Graefe, F. Rehburg, M. Hubner, S. Thun, O. Beyan

Date Published: 22nd Aug 2024

Publication Type: Proceedings

A liver digital twin for in silico testing of cellular and inter-cellular mechanisms in regeneration after drug-induced damage

Abstract

Not specified

Authors: Jieling Zhao, Ahmed Ghallab, Reham Hassan, Steven Dooley, Jan Georg Hengstler, Dirk Drasdo

Date Published: 1st Feb 2024

Publication Type: Journal

Gene regulatory network inference in the era of single-cell multi-omics

Abstract

Not specified

Authors: Pau Badia-i-Mompel, Lorna Wessels, Sophia Müller-Dott, Rémi Trimbour, Ricardo O. Ramirez Flores, Ricard Argelaguet, Julio Saez-Rodriguez

Date Published: 1st Nov 2023

Publication Type: Journal

Guided interactive image segmentation using machine learning and color-based image set clustering

Abstract (Expand)

Abstract Motivation Over the last decades, image processing and analysis have become one of the key technologies in systems biology and medicine. The quantification of anatomical structures and dynamic …The quantification of anatomical structures and dynamic processes in living systems is essential for understanding the complex underlying mechanisms and allows, i.e. the construction of spatio-temporal models that illuminate the interplay between architecture and function. Recently, deep learning significantly improved the performance of traditional image analysis in cases where imaging techniques provide large amounts of data. However, if only a few images are available or qualified annotations are expensive to produce, the applicability of deep learning is still limited. Results We present a novel approach that combines machine learning-based interactive image segmentation using supervoxels with a clustering method for the automated identification of similarly colored images in large image sets which enables a guided reuse of interactively trained classifiers. Our approach solves the problem of deteriorated segmentation and quantification accuracy when reusing trained classifiers which is due to significant color variability prevalent and often unavoidable in biological and medical images. This increase in efficiency improves the suitability of interactive segmentation for larger image sets, enabling efficient quantification or the rapid generation of training data for deep learning with minimal effort. The presented methods are applicable for almost any image type and represent a useful tool for image analysis tasks in general. Availability and implementation The presented methods are implemented in our image processing software TiQuant which is freely available at tiquant.hoehme.com. Supplementary information Supplementary data are available at Bioinformatics online.

Authors: Adrian Friebel, Tim Johann, Dirk Drasdo, Stefan Hoehme

Date Published: 1st Oct 2022

Publication Type: Journal

Non-Invasive Detection of Fibrotic NASH in NAFLD Patients with Low or Intermediate FIB-4

Abstract (Expand)

Background: Non-alcoholic steatohepatitis (NASH) and fibrosis are the main prognostic factors in non-alcoholic fatty liver disease (NAFLD). The FIB-4 score has been suggested as an initial test for the …l test for the exclusion of progressed fibrosis. However, increasing evidence suggests that also NASH patients with earlier fibrosis stages are at risk of disease progression, emphasizing the need for improved non-invasive risk stratification. Methods: We evaluated whether the apoptosis biomarker M30 can identify patients with fibrotic NASH despite low or intermediate FIB-4 values. Serum M30 levels were assessed by ELISA, and FIB-4 was calculated in an exploration (n = 103) and validation (n = 100) cohort of patients with histologically confirmed NAFLD. Results: The majority of patients with low FIB-4 (cut-off value < 1.3) in the exploration cohort revealed increased M30 levels (>200 U/L) and more than 80% of them had NASH, mostly with fibrosis. NASH was also detected in all patients with intermediate FIB-4 (1.3 to 2.67) and elevated M30, from which ~80% showed fibrosis. Importantly, in the absence of elevated M30, most patients with FIB-4 < 1.3 and NASH showed also no fibrosis. Similar results were obtained in the validation cohort. Conclusions: The combination of FIB-4 with M30 enables a more reliable identification of patients at risk for progressed NAFLD and might, therefore, improve patient stratification.

Authors: Katharina John, Martin Franck, Sherin Al Aoua, Monika Rau, Yvonne Huber, Joern M. Schattenberg, Andreas Geier, Matthias J. Bahr, Heiner Wedemeyer, Klaus Schulze-Osthoff, Heike Bantel

Date Published: 1st Aug 2022

Publication Type: Journal

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