High Throughput Method to Quantify Anterior-Posterior Polarity of T-Cells and Epithelial Cells

The virologic synapse (VS), which is formed between a virus-infected and uninfected cell, plays a central role in the transmission of certain viruses, such as HIV and HTLV-1. During VS formation, HTLV-1-infected T-cells polarize cellular and viral proteins toward the uninfected T-cell. This polarization resembles anterior-posterior cell polarity induced by immunological synapse (IS) formation, which is more extensively characterized than VS formation and occurs when a T-cell interacts with an antigen-presenting cell. One measure of cell polarity induced by both IS or VS formation is the repositioning of the microtubule organizing center (MTOC) relative to the contact point with the interacting cell. Here we describe an automated, high throughput system to score repositioning of the MTOC and thereby cell polarity establishment. The method rapidly and accurately calculates the angle between the MTOC and the IS for thousands of cells. We also show that the system can be adapted to score anterior-posterior polarity establishment of epithelial cells. This general approach represents a significant advancement over manual cell polarity scoring, which is subject to experimenter bias and requires more time and effort to evaluate large numbers of cells

Systems Biology in ELIXIR: modelling in the spotlight

info:eu-repo/semantics/publishedVersio

Whole genome sequencing,molecular typing and in vivovirulence of OXA-48-producingEscherichia coli isolates includingST131 H30-Rx, H22 and H41subclones

Carbapenem-resistant Enterobacteriaceae, including the increasingly reported OXA-48 Escherichia coli producers, are an emerging public health threat worldwide. Due to their alarming detection in our healthcare setting and their possible presence in the community, seven OXA-48-producing, extraintestinal pathogenic E. coli were analysed by whole genome sequencing as well as conventional tools, and tested for in vivo virulence. As a result, five E. coli OXA-48-producing subclones were detected (O25:H4-ST131/PST43-fimH30-virotype E; O25:H4-ST131/PST9-fimH22-virotype D5, O16:H5-ST131/ PST506-fimH41; O25:H5-ST83/PST207 and O9:H25-ST58/PST24). Four ST131 and one ST83 isolates satisfied the ExPEC status, and all except the O16:H5 ST131 isolate were UPEC. All isolates exhibited local inflammatory response with extensive subcutaneous necrosis but low lethality when tested in a mouse sepsis model. The blaOXA-48 gene was located in MOBP131/IncL plasmids (four isolates) or within the chromosome (three ST131 H30-Rx isolates), carried by Tn1999-like elements. All, except the ST83 isolate, were multidrug-resistant, with additional plasmids acting as vehicles for the spread of various resistance genes. This is the first study to analyse the whole genome sequences of blaOXA-48-positive ST131, ST58 and ST83 E. coli isolates in conjunction with experimental data, and to evaluate the in vivo virulence of blaOXA-48 isolates, which pose an important challenge to patient management

Systems Biology in ELIXIR: modelling in the spotlight

In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR\u27s future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives

The dynamic stability and nonlinear resonance of a flexible connecting rod: Continuous parameter model

The transverse vibrations of a flexible connecting rod in an otherwise rigid slider-crank mechanism are considered. An analytical approach using the method of multiple scales is adopted and particular emphasis is placed on nonlinear effects which arise from finite deformations. Several nonlinear resonances and instabilities are investigated, and the influences of important system parameters on these resonances are examined in detail.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43330/1/11071_2004_Article_BF00162233.pd

Drug-target identification in COVID-19 disease mechanisms using computational systems biology approaches

IntroductionThe COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing. MethodsExtensive community work allowed an impressive step forward in building interfaces between Systems Biology tools and platforms. Our framework can link biomolecules from omics data analysis and computational modelling to dysregulated pathways in a cell-, tissue- or patient-specific manner. Drug repurposing using text mining and AI-assisted analysis identified potential drugs, chemicals and microRNAs that could target the identified key factors.ResultsResults revealed drugs already tested for anti-COVID-19 efficacy, providing a mechanistic context for their mode of action, and drugs already in clinical trials for treating other diseases, never tested against COVID-19. DiscussionThe key advance is that the proposed framework is versatile and expandable, offering a significant upgrade in the arsenal for virus-host interactions and other complex pathologies

SBML Level 3: an extensible format for the exchange and reuse of biological models

Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction-based models and packages that extend the core with features suited to other model types including constraint-based models, reaction-diffusion models, logical network models, and rule-based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single-cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution

Wpływ warunków fermentacji brzeczki piwnej na poziom produktów metabolizmu drożdży

The pressure fermentation as well as the classic fermentation at at 7° to 9.5°C and at the lowered temperature of 6° to 8.2°C were used. The physiological parameters of the test variants' yeast as compared to the control test revealed substantial worsening. The content of dead yeast cells in the sediment after pressure fermentation grew higher and their autolysis resulted in a considerable quantitative increase in nitrogen compounds. Depletion of the yeast sediment during fermentation tends to reduce this negative phenomenon. The beer from yeast sediment revealed growing quantities of esters, alcohols and products of desorption.Przeprowadzono badania nad wpływem metody fermentacji, temperatury i czasu trwania procesu na stan fizjologiczny drożdży i związany z nim poziom niektórych produktów przemiany materii drożdży w piwie oddzielonym z gęstwy drożdżowej. Stosowano brzeczkę słodową filtrowaną, którą szczepiono drożdżami Bratislava w dawce 0,5 l gęstwy/hl. Badania wykonano w układzie warunków fermentacji klasycznej w temperaturze 7-9,5°C średnio 8,5°C i w temperaturze obniżonej 6-8,5°C średnio 7,2°C oraz fermentacji ciśnieniowej w temperaturze 11-16°C pod ciśnieniem 0,7-1,8 atn. Z pierwszej próby ciśnieniowej oddzielano gęstwę drożdżową po 3 dobach fermentacji, natomiast z drugiej próby po zakończeniu procesu, tzn. po 4 dniach. Młode piwo leżakowano w temperaturze 0-2°C i ciśnieniu 0,8 atn w ciągu 10 dni. Gęstwę drożdżową zebraną po fermentacji przechowywano w temperaturze 0-2°C w ciągu 1 doby, po czym oddzielano piwo metodą wirowania. Skład chemiczny piwa z gęstwy porównywano ze składem piwa młodego. Ponadto przedstawiono charakterystykę fizykochemiczną i organoleptyczną produktu końcowego. Stwierdzono, że podczas fermentacji ciśnieniowej wskutek wyższej temperatury procesu, przemiany metaboliczne i zjawiska adsorpcji składników brzeczki przebiegają znacznie intensywniej niż w czasie fermentacji prowadzonej metodą klasyczną. Wyższy jest stopień wykorzystania składników azotowych brzeczki, a jednocześnie zwiększa się synteza lotnych produktów fermentacji, w tym głównie alkoholi amylowych, aldehydu octowego i octanu etylowego. Pogorszenie stanu fizjologicznego, obniżenie żywotności drożdży po fermentacji ciśnieniowej jest przyczyną znacznego wzrostu pH i ilości związków azotowych i alkoholu etylowego oraz nasilenia się zjawisk desorpcji składników goryczkowych, polifenoli i substancji barwnych w piwie z gęstwy drożdżowej. Niekorzystne zmiany w składzie chemicznym tego piwa mogą być częściowo zmniejszone przez oddzielenie drożdży osadzonych na dnie fermentorów jeszcze w czasie trwania procesu fermentacji, a nie dopiero po jej zakończeniu. Stosowanie niższych temperatur procesu, powodujące przedłużone deformowanie brzeczki w porównaniu z fermentacją klasyczną, powoduje zmniejszenie ogólnej aktywności metabolicznej drożdży wyrażające się mniejszą asymilacją aminokwasów i syntezą lotnych produktów fermentacji. W piwie oddzielonym z gęstwy drożdżowej, wskutek procesów autolizy drożdży i zjawisk desorpcji następuje wzrost ilości substancji azotowych, goryczkowych, barwnych, polifenoli, octanu etylowego oraz wartości pH