Co-Complexes-Based Self-Oscillating Gels Driven by the Belousov-Zhabotinsky Reaction.

We report the synthesis of novel cobalt complexes-based catalysts designed for the oscillatory Belousov-Zhabotinsky (BZ) reaction. For the first time, we introduce cobalt complex-based self-oscillating gels that demonstrate autonomous color oscillations within a BZ reagent solution, functioning without the need for any external stimuli. We created acrylamide-based self-oscillating gels containing immobilized tris(2,2'-bipyridine)cobalt(II) or tris(1,10-phenanthroline)cobalt(II) complexes and gels containing covalently bound (5-acrylamido-1,10-phenanthroline)bis(2,2'-bipyridine)cobalt(II), (5-acrylamido-1,10-phenanthroline)bis(1,10-phenanthroline) cobalt(II), or tris(5-acrylamido-1,10-phenanthroline)cobalt(II) complexes. When the BZ reaction takes place within the gels, it results in the observation of moving chemical waves and reversible color changes. We believe that Co-complexes-based self-oscillating gels have potential applications in the design of soft actuators and chemical devices for signal processing.

Leveraging Accelerometer Data for Lameness Detection in Dairy Cows: A Longitudinal Study of Six Farms in Germany.

Lameness in dairy cows poses a significant challenge to improving animal well-being and optimizing economic efficiency in the dairy industry. To address this, employing automated animal surveillance for early lameness detection and prevention through activity sensors proves to be a promising strategy. In this study, we analyzed activity (accelerometer) data and additional cow-individual and farm-related data from a longitudinal study involving 4860 Holstein dairy cows on six farms in Germany during 2015-2016. We designed and investigated various statistical models and chose a logistic regression model with mixed effects capable of detecting lameness with a sensitivity of 77%. Our results demonstrate the potential of automated animal surveillance and hold the promise of significantly improving lameness detection approaches in dairy livestock.

Accessing Properties of Molecular Compounds Involved in Cellular Metabolic Processes with Electron Paramagnetic Resonance, Raman Spectroscopy, and Differential Scanning Calorimetry.

In this work, we review some physical methods of macroscopic experiments, which have been recently argued to be promising for the acquisition of valuable characteristics of biomolecular structures and interactions. The methods we focused on are electron paramagnetic resonance spectroscopy, Raman spectroscopy, and differential scanning calorimetry. They were chosen since it can be shown that they are able to provide a mutually complementary picture of the composition of cellular envelopes (with special attention paid to mycobacteria), transitions between their molecular patterning, and the response to biologically active substances (reactive oxygen species and their antagonists-antioxidants-as considered in our case study).

Establishing Compliance between Spectral, Colourimetric and Photometric Indicators in Resazurin Reduction Test.

The resazurin reduction test is one of the basic tests for bacterial culture viability and drug resistance endorsed by the World Health Organisation. At the same time, conventional spectrophotometric and spectrofluorimetric methods demand rather bulky and expensive equipment. This induces a challenge for developing simpler approaches to sensor systems that are portable and applicable in resource-limited settings. In this work, we address two such alternative approaches, based on the colour processing of the microbiological plate's photographic images and single-channel photometry with a recently developed portable microbiological analyser. The key results consist of establishing a sequential linear correspondence between the concentration of resorufin produced due to the reduction of resazurin by viable bacteria as determined by the UV-Vis studies, the intensity of the a* channel of the CIE L*a*b* colour space and the transmitted light intensity registered by a luxmeter under the LED illumination with a yellow colour filter. This route is illustrated with the chemical system "Hydrazine hydrate - resazurin", isolating the target colour change-inducing reaction and the test of determining the minimal inhibition concentration of the antibacterial first-line drug isoniazid acting on the culture of the H37Rv strain of M. tuberculosis.

An Improved Diagnostic of the Mycobacterium tuberculosis Drug Resistance Status by Applying a Decision Tree to Probabilities Assigned by the CatBoost Multiclassifier of Matrix Metalloproteinases Biomarkers.

In this work, we discuss an opportunity to use a set of the matrix metalloproteinases MMP-1, MMP-8, and MMP-9 and the tissue inhibitor TIMP, the concentrations of which can be easily obtained via a blood test from patients suffering from tuberculosis, as the biomarker for a fast diagnosis of the drug resistance status of Mycobacterium tuberculosis. The diagnostic approach is based on machine learning with the CatBoost system, which has been supplied with additional postprocessing. The latter refers not only to the simple probabilities of ML-predicted outcomes but also to the decision tree-like procedure, which takes into account the presence of strict zeros in the primary set of probabilities. It is demonstrated that this procedure significantly elevates the accuracy of distinguishing between sensitive, multi-, and extremely drug-resistant strains.

Transport in the Brain Extracellular Space: Diffusion, but Which Kind?

The mechanisms of transport of substances in the brain parenchyma have been a hot topic in scientific discussion in the past decade. This discussion was triggered by the proposed glymphatic hypothesis, which assumes a directed flow of cerebral fluid within the parenchyma, in contrast to the previous notion that diffusion is the main mechanism. However, when discussing the issue of "diffusion or non-diffusion", much less attention was given to the question that diffusion itself can have a different character. In our opinion, some of the recently published results do not fit into the traditional understanding of diffusion. In this regard, we outline the relevant new theoretical approaches on transport processes in complex random media such as concepts of diffusive diffusivity and time-dependent homogenization, which expands the understanding of the forms of transport of substances based on diffusion.

Ensemble density-dependent synchronization of mycobacterial growth: BACTEC MGIT 960 fluorescence-based analysis and mathematical modelling of coupled biophysical and chemical processes.

This study presents an analysis of M. tuberculosis growth data obtained using the BACTEC MGIT 960 system and respective mathematical models. The system is based on the detection of a decrease in oxygen level in the broth due to the bacterial respiration. It is shown that recordings sampled with a 1 hour rate provide an opportunity to distinguish between the oxygen consumption of growing cells and active cells division when the density of micro-organisms is sufficient to enter into the synchronized division mode. More specifically, the growth of culture is continuous only with large initial dilutions; otherwise, there are jumps between different growth stages with a time interval of 13-15 h. The combination of the oxygen-quenching kinetics for an analytic reagent and the population growth kinetics resulted in a mathematical model, which consists of mixing Verhulst's and Gompertz's models. The parameters of such mixing and switching between the models' prevalences are discussed with respect to oxygen uptake reactions reflected in the changes in the experimentally registered fluorescence level.

Protein-Ligand Dissociation Rate Constant from All-Atom Simulation.

Dissociation of a ligand isoniazid from a protein catalase was investigated using all-atom molecular dynamics (MD) simulations. Random acceleration MD (τ-RAMD) was used, in which a random artificial force applied to the ligand facilitates its dissociation. We have suggested a novel approach to extrapolate such obtained dissociation times to the zero-force limit assuming never before attempted universal exponential dependence of the bond strength on the applied force, allowing direct comparison with experimentally measured values. We have found that our calculated dissociation time was equal to 36.1 s with statistically significant values distributed in the interval of 0.2-72.0 s, which quantitatively matches the experimental value of 50 ± 8 s despite the extrapolation over 9 orders of magnitude in time.

Bi-logistic model for disease dynamics caused by Mycobacterium tuberculosis in Russia.

In this work, we explore epidemiological dynamics by the example of tuberculosis in Russian Federation. It has been shown that the epidemiological dynamics correlates linearly with the virulence of Mycobacterium tuberculosis during the period 1987-2012. To construct an appropriate model, we have analysed (using LogLet decomposition method) epidemiological World Health Organization (WHO) data (period 1980-2014) and obtained, as result of their integration, a curve approximated by a bi-logistic function. This fact allows a subdivision of the whole population into parts, each of them satisfies the Verhulst-like models with different constant virulences introduced into each subsystem separately. Such a subdivision could be interconnected with the heterogeneous structure of mycobacterial population that has a high ability of adaptation to the host and strong mutability.

Ordinary differential equations and Boolean networks in application to modelling of 6-mercaptopurine metabolism.

We consider two approaches to modelling the cell metabolism of 6-mercaptopurine, one of the important chemotherapy drugs used for treating acute lymphocytic leukaemia: kinetic ordinary differential equations, and Boolean networks supplied with one controlling node, which takes continual values. We analyse their interplay with respect to taking into account ATP concentration as a key parameter of switching between different pathways. It is shown that the Boolean networks, which allow avoiding the complexity of general kinetic modelling, preserve the possibility of reproducing the principal switching mechanism.

Inhibitory and excitatory pulse coupling of two frequency-different chemical oscillators with time delay.

Dynamical regimes of two pulse coupled non-identical Belousov-Zhabotinsky oscillators have been studied experimentally as well as theoretically with the aid of ordinary differential equations and phase response curves both for pure inhibitory and pure excitatory coupling. Time delay τ between a spike in one oscillator and perturbing pulse in the other oscillator plays a significant role for the phase relations of synchronous regimes of the 1:1 and 1:2 resonances. Birhythmicity between anti-phase and in-phase oscillations for inhibitory pulse coupling as well as between 1:2 and 1:1 resonances for excitatory pulse coupling have also been found. Depending on the ratio of native periods of oscillations T2/T1, coupling strength, and time delay τ, such resonances as 1:1 (with different phase locking), 2:3, 1:2, 2:5, 1:3, 1:4, as well as complex oscillations and oscillatory death are observed.

Two pulse-coupled non-identical, frequency-different BZ oscillators with time delay.

Two non-identical, frequency-different pulse-coupled oscillators with time delay have been systematically studied using four-variable model of the Belousov-Zhabotinsky (BZ) reaction at mutual inhibitory, mutual excitatory, and mixed excitatory-inhibitory types of coupling. Different resonances like 1 : 2, 2 : 3, 1 : 3, etc., as well as complex rhythms and abrupt changes between them occur depending on the coupling strengths, time delay, and frequency ratio. Analogously to in-phase and anti-phase oscillations for 1 : 1 resonance, a similar phase locking exists for 1 : 2 resonance in the case of inhibitory coupling. For excitatory coupling, a bursting regime is found. The number of spikes in a single burst can be tuned by both the frequency ratio and time delay. For excitatory-inhibitory coupling, a region where one oscillator is suppressed (OS zone) has been found. Boundary of the OS zone depends on the frequency ratio. For weakly coupled oscillators, Farey sequence has been found for excitatory-inhibitory and mutual excitatory coupling.