Representing and analysing molecular and cellular function in the computer

Determining the biological function of a myriad of genes, and understanding how they interact to yield a living cell, is the major challenge of the post genome-sequencing era. The complexity of biological systems is such that this cannot be envisaged without the help of powerful computer systems capable of representing and analysing the intricate networks of physical and functional interactions between the different cellular components. In this review we try to provide the reader with an appreciation of where we stand in this regard. We discuss some of the inherent problems in describing the different facets of biological function, give an overview of how information on function is currently represented in the major biological databases, and describe different systems for organising and categorising the functions of gene products. In a second part, we present a new general data model, currently under development, which describes information on molecular function and cellular processes in a rigorous manner. The model is capable of representing a large variety of biochemical processes, including metabolic pathways, regulation of gene expression and signal transduction. It also incorporates taxonomies for categorising molecular entities, interactions and processes, and it offers means of viewing the information at different levels of resolution, and dealing with incomplete knowledge. The data model has been implemented in the database on protein function and cellular processes 'aMAZE' (http://www.ebi.ac.uk/research/pfbp/), which presently covers metabolic pathways and their regulation. Several tools for querying, displaying, and performing analyses on such pathways are briefly described in order to illustrate the practical applications enabled by the model

Thermodynamics of a Colloidal Particle in a Time-Dependent Non-Harmonic Potential

We study the motion of an overdamped colloidal particle in a time-dependent non-harmonic potential. We demonstrate the first law-like balance between applied work, exchanged heat, and internal energy on the level of a single trajectory. The observed distribution of applied work is distinctly non-Gaussian in good agreement with numerical calculations. Both the Jarzynski relation and a detailed fluctuation theorem are verified with good accuracy

In silico identification of NF-kappaB-regulated genes in pancreatic beta-cells

BACKGROUND: Pancreatic beta-cells are the target of an autoimmune attack in type 1 diabetes mellitus (T1DM). This is mediated in part by cytokines, such as interleukin (IL)-1β and interferon (IFN)-γ. These cytokines modify the expression of hundreds of genes, leading to beta-cell dysfunction and death by apoptosis. Several of these cytokine-induced genes are potentially regulated by the IL-1β-activated transcription factor (TF) nuclear factor (NF)-κB, and previous studies by our group have shown that cytokine-induced NF-κB activation is pro-apoptotic in beta-cells. To identify NF-κB-regulated gene networks in beta-cells we presently used a discriminant analysis-based approach to predict NF-κB responding genes on the basis of putative regulatory elements. RESULTS: The performance of linear and quadratic discriminant analysis (LDA, QDA) in identifying NF-κB-responding genes was examined on a dataset of 240 positive and negative examples of NF-κB regulation, using stratified cross-validation with an internal leave-one-out cross-validation (LOOCV) loop for automated feature selection and noise reduction. LDA performed slightly better than QDA, achieving 61% sensitivity, 91% specificity and 87% positive predictive value, and allowing the identification of 231, 251 and 580 NF-κB putative target genes in insulin-producing INS-1E cells, primary rat beta-cells and human pancreatic islets, respectively. Predicted NF-κB targets had a significant enrichment in genes regulated by cytokines (IL-1β or IL-1β + IFN-γ) and double stranded RNA (dsRNA), as compared to genes not regulated by these NF-κB-dependent stimuli. We increased the confidence of the predictions by selecting only evolutionary stable genes, i.e. genes with homologs predicted as NF-κB targets in rat, mouse, human and chimpanzee. CONCLUSION: The present in silico analysis allowed us to identify novel regulatory targets of NF-κB using a supervised classification method based on putative binding motifs. This provides new insights into the gene networks regulating cytokine-induced beta-cell dysfunction and death

Tunability of Critical Casimir Interactions by Boundary Conditions

We experimentally demonstrate that critical Casimir forces in colloidal systems can be continuously tuned by the choice of boundary conditions. The interaction potential of a colloidal particle in a mixture of water and 2,6-lutidine has been measured above a substrate with a gradient in its preferential adsorption properties for the mixture's components. We find that the interaction potentials at constant temperature but different positions relative to the gradient continuously change from attraction to repulsion. This demonstrates that critical Casimir forces respond not only to minute temperature changes but also to small changes in the surface properties.Comment: 4 figures; http://www.iop.org/EJ/article/0295-5075/88/2/26001/epl_88_2_26001.htm

Generalized Newton-Cartan geometries for particles and strings

We discuss the generalized Newton-Cartan geometries that can serve as gravitational background fields for particles and strings. In order to enable us to define affine connections that are invariant under all the symmetries of the structure group, we describe torsionful geometries with independent torsion tensors. A characteristic feature of the non-Lorentzian geometries we consider is that some of the torsion tensors are so-called ‘intrinsic torsion’ tensors. Setting some components of these intrinsic torsion tensors to zero leads to constraints on the geometry. For both particles and strings, we discuss various such constraints that can be imposed consistently with the structure group symmetries. In this way, we reproduce several results in the literature.</p

Online monitoring the isomerization of an azobenzene-based dendritic bolaamphiphile using ion mobility-mass spectrometry

Ion mobility-mass spectrometry was used to obtain detailed information about the kinetics of the light-induced cis/trans isomerization process of a new supramolecular azobenzene-based bolaamphiphile. Further experiments revealed that the investigated light-induced structural transition dramatically influences the aggregation behaviour of the molecule

Restoring soil functionality in degraded areas of organic vineyards - Preliminary results of the ReSolVe project in the French vineyards

Degraded soil areas in vineyards are associated with problems in vine health, grape production and quality. Different causes for soil degradation are possible such as poor organic matter content, lower plant nutrient availability, pH, water deficiency, soil compaction / lower oxygenation… The aim of this preliminary study is to assess soil functionality (OM decomposition), biodiversity through mesofauna diversity and consequences for vine growth and quality

Huge impact of compressive strain on phase transition temperatures in epitaxial ferroelectric KxNa1-xNbO3 thin films

We present a study in which ferroelectric phase transition temperatures in epitaxial KxNa1-xNbO3 films are altered systematically by choosing different (110)-oriented rare-earth scandate substrates and by variation of the potassium to sodium ratio. Our results prove the capability to continuously shift the ferroelectric-to-ferroelectric transition from the monoclinic MC to orthorhombic c-phase by about 400 °C via the application of anisotropic compressive strain. The phase transition was investigated in detail by monitoring the temperature dependence of ferroelectric domain patterns using piezoresponse force microscopy and upon analyzing structural changes by means of high resolution X-ray diffraction including X-ray reciprocal space mapping. Moreover, the temperature evolution of the effective piezoelectric coefficient d33,f was determined using double beam laser interferometry, which exhibits a significant dependence on the particular ferroelectric phase. © 2019 Author(s)

Unveiling Glycerolipid Fragmentation by Cryogenic Infrared Spectroscopy

Mass spectrometry is routinely employed for structure elucidation of molecules. Structural information can be retrieved from intact molecular ions by fragmentation; however, the interpretation of fragment spectra is often hampered by poor understanding of the underlying dissociation mechanisms. For example, neutral headgroup loss from protonated glycerolipids has been postulated to proceed via an intramolecular ring closure but the mechanism and resulting ring size have never been experimentally confirmed. Here we use cryogenic gas-phase infrared (IR) spectroscopy in combination with computational chemistry to unravel the structures of fragment ions and thereby shed light on elusive dissociation mechanisms. Using the example of glycerolipid fragmentation, we study the formation of protonated five-membered dioxolane and six-membered dioxane rings and show that dioxolane rings are predominant throughout different glycerolipid classes and fragmentation channels. For comparison, pure dioxolane and dioxane ions were generated from tailor-made dehydroxyl derivatives inspired by natural 1,2- and 1,3-diacylglycerols and subsequently interrogated using IR spectroscopy. Furthermore, the cyclic structure of an intermediate fragment occurring in the phosphatidylcholine fragmentation pathway was spectroscopically confirmed. Overall, the results contribute substantially to the understanding of glycerolipid fragmentation and showcase the value of vibrational ion spectroscopy to mechanistically elucidate crucial fragmentation pathways in lipidomics