Mathematical modelling identifies conditions for maintaining and escaping feedback control in the intestinal epithelium.

The intestinal epithelium is one of the fastest renewing tissues in mammals. It shows a hierarchical organisation, where intestinal stem cells at the base of crypts give rise to rapidly dividing transit amplifying cells that in turn renew the pool of short-lived differentiated cells. Upon injury and stem-cell loss, cells can also de-differentiate.

A dynamic clamp protocol to artificially modify cell capacitance.

Dynamics of excitable cells and networks depend on the membrane time constant, set by membrane resistance and capacitance. Whereas pharmacological and genetic manipulations of ionic conductances of excitable membranes are routine in electrophysiology, experimental control over capacitance remains a challenge. Here, we present capacitance clamp, an approach that allows electrophysiologists to mimic a modified capacitance in biological neurons via an unconventional application of the dynamic clamp technique.

The simulation experiment description markup language (SED-ML): language specification for level 1 version 4.

Computational simulation experiments increasingly inform modern biological research, and bring with them the need to provide ways to annotate, archive, share and reproduce the experiments performed. These simulations increasingly require extensive collaboration among modelers, experimentalists, and engineers. The Minimum Information About a Simulation Experiment (MIASE) guidelines outline the information needed to share simulation experiments.

Pharmacokinetics of Caffeine: A Systematic Analysis of Reported Data for Application in Metabolic Phenotyping and Liver Function Testing.

Caffeine is by far the most ubiquitous psychostimulant worldwide found in tea, coffee, cocoa, energy drinks, and many other beverages and food. Caffeine is almost exclusively metabolized in the liver by the cytochrome P-450 enzyme system to the main product paraxanthine and the additional products theobromine and theophylline. Besides its stimulating properties, two important applications of caffeine are metabolic phenotyping of cytochrome P450 1A2 (CYP1A2) and liver function testing.

Resident memory CD4 T lymphocytes mobilize from bone marrow to contribute to a systemic secondary immune reaction.

Resident memory T lymphocytes (T ) of epithelial tissues and the Bm protect their host tissue. To what extent these cells are mobilized and contribute to systemic immune reactions is less clear. Here, we show that in secondary immune reactions to the measles-mumps-rubella (MMR) vaccine, CD4 T are mobilized into the blood within 16 to 48 h after immunization in humans.

Contagion dynamics in self-organized systems of self-propelled agents.

We investigate the susceptible-infectious-recovered contagion dynamics in a system of self-propelled particles with polar alignment. Using agent-based simulations, we analyze the outbreak process for different combinations of the spatial parameters (alignment strength and Peclet number) and epidemic parameters (infection-lifetime transmissibility and duration of the individual infectious period). We show that the emerging spatial features strongly affect the contagion process.

Synergies of Multiple Zeitgebers Tune Entrainment.

Circadian rhythms are biological rhythms with a period close to 24 h. They become entrained to the Earth's solar day different periodic cues, so-called zeitgebers. The entrainment of circadian rhythms to a single zeitgeber was investigated in many mathematical clock models of different levels of complexity, ranging from the Poincaré oscillator and the Goodwin model to biologically more detailed models of multiple transcriptional translational feedback loops.

Acoustic and visual stimuli combined promote stronger responses to aerial predation in fish.

Bird predation poses a strong selection pressure on fish. Since birds must enter the water to catch fish, a combination of visual and mechano-acoustic cues (multimodal) characterize an immediate attack, while single cues (unimodal) may represent less dangerous disturbances. We investigated whether fish could use this information to distinguish between non-threatening and dangerous events and adjust their antipredator response to the perceived level of risk.

Fish waves as emergent collective antipredator behavior.

The collective behavior of animals has attracted considerable attention in recent years, with many studies exploring how local interactions between individuals can give rise to global group properties. The functional aspects of collective behavior are less well studied, especially in the field, and relatively few studies have investigated the adaptive benefits of collective behavior in situations where prey are attacked by predators. This paucity of studies is unsurprising because predator-prey interactions in the field are difficult to observe.

Analysis of more than 20,000 injuries in European professional football by using a citizen science-based approach: An opportunity for epidemiological research?

Objectives: It has been claimed that analyses of large datasets from publicly accessible, open-collaborated ("citizen science-based") online databases may provide additional insight into the epidemiology of injuries in professional football. However, this approach comes with major limitations, raising critical questions about the current trend of utilizing citizen science-based data. Therefore, we aimed to determine if citizen science-based health data from a popular online database on professional football players can be used for epidemiological research, i.

A Computational Analysis in a Cohort of Parkinson's Disease Patients and Clock-Modified Colorectal Cancer Cells Reveals Common Expression Alterations in Clock-Regulated Genes.

Increasing evidence suggests a role for circadian dysregulation in prompting disease-related phenotypes in mammals. Cancer and neurodegenerative disorders are two aging related diseases reported to be associated with circadian disruption. In this study, we investigated a possible effect of circadian disruption in Parkinson's disease (PD) and colorectal cancer (CRC).

Physiologically Based Modeling of the Effect of Physiological and Anthropometric Variability on Indocyanine Green Based Liver Function Tests.

Accurate evaluation of liver function is a central task in hepatology. Dynamic liver function tests (DLFT) based on the time-dependent elimination of a test substance provide an important tool for such a functional assessment. These tests are used in the diagnosis and monitoring of liver disease as well as in the planning of hepatobiliary surgery.

Prediction of Survival After Partial Hepatectomy Using a Physiologically Based Pharmacokinetic Model of Indocyanine Green Liver Function Tests.

The evaluation of hepatic function and functional capacity of the liver are essential tasks in hepatology as well as in hepatobiliary surgery. Indocyanine green (ICG) is a widely applied test compound that is used in clinical routine to evaluate hepatic function. Important questions for the functional evaluation with ICG in the context of hepatectomy are how liver disease such as cirrhosis alters ICG elimination, and if postoperative survival can be predicted from preoperative ICG measurements.

Hebbian plasticity in parallel synaptic pathways: A circuit mechanism for systems memory consolidation.

Systems memory consolidation involves the transfer of memories across brain regions and the transformation of memory content. For example, declarative memories that transiently depend on the hippocampal formation are transformed into long-term memory traces in neocortical networks, and procedural memories are transformed within cortico-striatal networks. These consolidation processes are thought to rely on replay and repetition of recently acquired memories, but the cellular and network mechanisms that mediate the changes of memories are poorly understood.

Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function.

Liver resection causes marked perfusion alterations in the liver remnant both on the organ scale (vascular anatomy) and on the microscale (sinusoidal blood flow on tissue level). These changes in perfusion affect hepatic functions via direct alterations in blood supply and drainage, followed by indirect changes of biomechanical tissue properties and cellular function. Changes in blood flow impose compression, tension and shear forces on the liver tissue.

Phases and homogeneous ordered states in alignment-based self-propelled particle models.

We study a set of models of self-propelled particles that achieve collective motion through similar alignment-based dynamics, considering versions with and without repulsive interactions that do not affect the heading directions. We explore their phase space within a broad range of values of two nondimensional parameters (coupling strength and Peclet number), characterizing their polarization and degree of clustering. The resulting phase diagrams display equivalent, similarly distributed regions for all models with repulsion.

Neuroblastoma signalling models unveil combination therapies targeting feedback-mediated resistance.

Very high risk neuroblastoma is characterised by increased MAPK signalling, and targeting MAPK signalling is a promising therapeutic strategy. We used a deeply characterised panel of neuroblastoma cell lines and found that the sensitivity to MEK inhibitors varied drastically between these cell lines. By generating quantitative perturbation data and mathematical modelling, we determined potential resistance mechanisms.

Finding disease outbreak locations from human mobility data.

Unlabelled: Finding the origin location of an infectious disease outbreak quickly is crucial in mitigating its further dissemination. Current methods to identify outbreak locations early on rely on interviewing affected individuals and correlating their movements, which is a manual, time-consuming, and error-prone process. Other methods such as contact tracing, genomic sequencing or theoretical models of epidemic spread offer help, but they are not applicable at the onset of an outbreak as they require highly processed information or established transmission chains.

Neural optimization: Understanding trade-offs with Pareto theory.

Nervous systems, like any organismal structure, have been shaped by evolutionary processes to increase fitness. The resulting neural 'bauplan' has to account for multiple objectives simultaneously, including computational function, as well as additional factors such as robustness to environmental changes and energetic limitations. Oftentimes these objectives compete, and quantification of the relative impact of individual optimization targets is non-trivial.

Specifications of standards in systems and synthetic biology: status and developments in 2021.

This special issue of the contains updated specifications of COMBINE standards in systems and synthetic biology. The 2021 special issue presents four updates of standards: Synthetic Biology Open Language Visual Version 2.3, Synthetic Biology Open Language Visual Version 3.

Susceptibility rhythm to bacterial endotoxin in myeloid clock-knockout mice.

Local circadian clocks are active in most cells of our body. However, their impact on circadian physiology is still under debate. Mortality by endotoxic (LPS) shock is highly time-of-day dependent and local circadian immune function such as the cytokine burst after LPS challenge has been assumed to be causal for the large differences in survival.

Mortality, Risk Factors and Risk Assessment after Periprosthetic Femoral Fractures-A Retrospective Cohort Study.

Periprosthetic femoral fracture (PFF) is a devastating complication. Here, the authors aimed to determine the influence of the timing of surgery as a risk factor for mortality and poor postoperative outcome in patients suffering from PFF. A retrospective descriptive analysis of patients treated for PFF between January 2010 and March 2018 was performed.

A mathematical model of the circadian clock and drug pharmacology to optimize irinotecan administration timing in colorectal cancer.

Scheduling anticancer drug administration over 24 h may critically impact treatment success in a patient-specific manner. Here, we address personalization of treatment timing using a novel mathematical model of irinotecan cellular pharmacokinetics and -dynamics linked to a representation of the core clock and predict treatment toxicity in a colorectal cancer (CRC) cellular model. The mathematical model is fitted to three different scenarios: mouse liver, where the drug metabolism mainly occurs, and two human colorectal cancer cell lines representing an experimental system for human colorectal cancer progression.

Dose-response functions and surrogate models for exploring social contagion in the Copenhagen Networks Study.

Spreading dynamics and complex contagion processes on networks are important mechanisms underlying the emergence of critical transitions, tipping points and other non-linear phenomena in complex human and natural systems. Increasing amounts of temporal network data are now becoming available to study such spreading processes of behaviours, opinions, ideas, diseases and innovations to test hypotheses regarding their specific properties. To this end, we here present a methodology based on dose-response functions and hypothesis testing using surrogate data models that randomise most aspects of the empirical data while conserving certain structures relevant to contagion, group or homophily dynamics.