From chimeras to extensive chaos in networks of heterogeneous Kuramoto oscillator populations.

Populations of coupled oscillators can exhibit a wide range of complex dynamical behavior, from complete synchronization to chimera and chaotic states. We can, thus, expect complex dynamics to arise in networks of such populations. Here, we analyze the dynamics of networks of populations of heterogeneous mean-field coupled Kuramoto-Sakaguchi oscillators and show that the instability that leads to chimera states in a simple two-population model also leads to extensive chaos in large networks of coupled populations.

Open problems in synthetic multicellularity.

Multicellularity is one of the major evolutionary transitions, and its rise provided the ingredients for the emergence of a biosphere inhabited by complex organisms. Over the last decades, the potential for bioengineering multicellular systems has been instrumental in interrogating nature and exploring novel paths to regeneration, disease, cognition, and behaviour. Here, we provide a list of open problems that encapsulate many of the ongoing and future challenges in the field and suggest conceptual approaches that may facilitate progress.

Biochemically plausible models of habituation for single-cell learning.

The ability to learn is typically attributed to animals with brains. However, the apparently simplest form of learning, habituation, in which a steadily decreasing response is exhibited to a repeated stimulus, is found not only in animals but also in single-cell organisms and individual mammalian cells. Habituation has been codified from studies in both invertebrate and vertebrate animals as having ten characteristic hallmarks, seven of which involve a single stimulus.

Physiological cost of antibiotic resistance: Insights from a ribosome variant in bacteria.

Antibiotic-resistant ribosome variants arise spontaneously in bacterial populations; however, their impact on the overall bacterial physiology remains unclear. We studied the naturally arising antibiotic-resistant L22* ribosome variant of and identified a Mg-dependent physiological cost. Coculture competition experiments show that Mg limitation hinders the growth of the L22* variant more than the wild type (WT), even under antibiotic pressure.

Biological computation through recurrence.

One of the defining features of living systems is their adaptability to changing environmental conditions. This requires organisms to extract temporal and spatial features of their environment, and use that information to compute the appropriate response. In the last two decades, a growing body of work, mainly coming from the machine learning and computational neuroscience fields, has shown that such complex information processing can be performed by recurrent networks.

Modeling the impact of neuromorphological alterations in Down syndrome on fast neural oscillations.

Cognitive disorders, including Down syndrome (DS), present significant morphological alterations in neuron architectural complexity. However, the relationship between neuromorphological alterations and impaired brain function is not fully understood. To address this gap, we propose a novel computational model that accounts for the observed cell deformations in DS.

A multiscale sensorimotor model of experience-dependent behavior in a minimal organism.

To survive in ever-changing environments, living organisms need to continuously combine the ongoing external inputs they receive, representing present conditions, with their dynamical internal state, which includes influences of past experiences. It is still unclear in general, however 1) how this happens at the molecular and cellular levels and 2) how the corresponding molecular and cellular processes are integrated with the behavioral responses of the organism. Here, we address these issues by modeling mathematically a particular behavioral paradigm in a minimal model organism, namely chemotaxis in the nematode C.

Multiscale networks in multiple sclerosis.

Complex diseases such as Multiple Sclerosis (MS) cover a wide range of biological scales, from genes and proteins to cells and tissues, up to the full organism. In fact, any phenotype for an organism is dictated by the interplay among these scales. We conducted a multilayer network analysis and deep phenotyping with multi-omics data (genomics, phosphoproteomics and cytomics), brain and retinal imaging, and clinical data, obtained from a multicenter prospective cohort of 328 patients and 90 healthy controls.

Parametric modeling of mechanical effects on circadian oscillators.

Circadian rhythms are archetypal examples of nonlinear oscillations. While these oscillations are usually attributed to circuits of biochemical interactions among clock genes and proteins, recent experimental studies reveal that they are also affected by the cell's mechanical environment. Here, we extend a standard biochemical model of circadian rhythmicity to include mechanical effects in a parametric manner.

Shared Proteins and Pathways of Cardiovascular and Cognitive Diseases: Relation to Vascular Cognitive Impairment.

One of the primary goals of systems medicine is the detection of putative proteins and pathways involved in disease progression and pathological phenotypes. Vascular cognitive impairment (VCI) is a heterogeneous condition manifesting as cognitive impairment resulting from vascular factors. The precise mechanisms underlying this relationship remain unclear, which poses challenges for experimental research.

Single-cell Bayesian deconvolution.

Individual cells exhibit substantial heterogeneity in protein abundance and activity, which is frequently reflected in broad distributions of fluorescently labeled reporters. Since all cellular components are intrinsically fluorescent to some extent, the observed distributions contain background noise that masks the natural heterogeneity of cellular populations. This limits our ability to characterize cell-fate decision processes that are key for development, immune response, tissue homeostasis, and many other biological functions.

On time: developmental timing within and across species.

Organisms across species differ in the relative size and complexity of their tissues to serve the specific purposes of the host. Correct timing is a crucial ingredient in the development of tissues, as reaching the right size and complexity requires a careful balance between cellular proliferation and differentiation. Premature or delayed differentiation, for instance, can result in tissue imbalance, malformation or malfunction.

Mechanical control of the mammalian circadian clock via YAP/TAZ and TEAD.

Autonomous circadian clocks exist in nearly every mammalian cell type. These cellular clocks are subjected to a multilayered regulation sensitive to the mechanochemical cell microenvironment. Whereas the biochemical signaling that controls the cellular circadian clock is increasingly well understood, mechanisms underlying regulation by mechanical cues are largely unknown.

The computational capabilities of many-to-many protein interaction networks.

Many biological circuits comprise sets of protein variants that interact with one another in a many-to-many, or promiscuous, fashion. These architectures can provide powerful computational capabilities that are especially critical in multicellular organisms. Understanding the principles of biochemical computations in these circuits could allow more precise control of cellular behaviors.

Complex spatiotemporal oscillations emerge from transverse instabilities in large-scale brain networks.

Spatiotemporal oscillations underlie all cognitive brain functions. Large-scale brain models, constrained by neuroimaging data, aim to trace the principles underlying such macroscopic neural activity from the intricate and multi-scale structure of the brain. Despite substantial progress in the field, many aspects about the mechanisms behind the onset of spatiotemporal neural dynamics are still unknown.

A Genome-Wide Functional Screen Identifies Enhancer and Protective Genes for Amyloid Beta-Peptide Toxicity.

Alzheimer's disease (AD) is known to be caused by amyloid β-peptide (Aβ) misfolded into β-sheets, but this knowledge has not yet led to treatments to prevent AD. To identify novel molecular players in Aβ toxicity, we carried out a genome-wide screen in , using a library of 5154 gene knock-out strains expressing Aβ. We identified 81 mammalian orthologue genes that enhance Aβ toxicity, while 157 were protective.

Comparison between an exact and a heuristic neural mass model with second-order synapses.

Neural mass models (NMMs) are designed to reproduce the collective dynamics of neuronal populations. A common framework for NMMs assumes heuristically that the output firing rate of a neural population can be described by a static nonlinear transfer function (NMM1). However, a recent exact mean-field theory for quadratic integrate-and-fire (QIF) neurons challenges this view by showing that the mean firing rate is not a static function of the neuronal state but follows two coupled nonlinear differential equations (NMM2).

Periodic spatial patterning with a single morphogen.

During multicellular development, periodic spatial patterning systems generate repetitive structures, such as digits, vertebrae, and teeth. Turing patterning provides a foundational paradigm for understanding such systems. The simplest Turing systems are believed to require at least two morphogens to generate periodic patterns.

Differential regulation of insulin signalling by monomeric and oligomeric amyloid beta-peptide.

Alzheimer's disease and Type 2 diabetes are pathological processes associated to ageing. Moreover, there are evidences supporting a mechanistic link between Alzheimer's disease and insulin resistance (one of the first hallmarks of Type 2 diabetes). Regarding Alzheimer's disease, amyloid β-peptide aggregation into β-sheets is the main hallmark of Alzheimer's disease.

Proteomic signatures of synergistic interactions in antimicrobials.

Mounting evidence has shown that antimicrobial agents can interfere synergistically with bacterial viability and proliferation when acting together at both the planktonic and biofilm levels without clear underlying molecular mechanisms. Here, multiplexed proteomics by iTRAQ was used to study the interplay between two biocides, the isothiazolone 1,2-benzisothiazolin-3-one (BIT) and the chelating agent disodium ethylenediaminetetraacetic acid (EDTA-2Na), employing the Citrobacter werkmanii as a model system. We first confirmed that these two biocides act synergistically on this bacterial species and then extracted the proteomic profiles of C.

Electrochemical potential enables dormant spores to integrate environmental signals.

The dormant state of bacterial spores is generally thought to be devoid of biological activity. We show that despite continued dormancy, spores can integrate environmental signals over time through a preexisting electrochemical potential. Specifically, we studied thousands of individual spores that remain dormant when exposed to transient nutrient pulses.

Signaling oscillations: Molecular mechanisms and functional roles.

Mounting evidence shows that oscillatory activity is widespread in cell signaling. Here, we review some of this recent evidence, focusing on both the molecular mechanisms that potentially underlie such dynamical behavior, and the potential advantages that signaling oscillations might have in cell function. The biological processes considered include cellular differentiation and tissue maintenance, intermittent responses in pluripotent stem cells, and collective cell migration during wound healing.

Blood Neutrophil Counts Define Specific Clusters of Bronchiectasis Patients: A Hint to Differential Clinical Phenotypes.

We sought to investigate differential phenotypic characteristics according to neutrophil counts, using a biostatistics approach in a large-cohort study from the Spanish Online Bronchiectasis Registry (RIBRON). The 1034 patients who met the inclusion criteria were clustered into two groups on the basis of their blood neutrophil levels. Using the Mann-Whitney U test to explore potential differences according to FACED and EFACED scores between the two groups, a neutrophil count of 4990 cells/µL yielded the most balanced cluster sizes: (1) above-threshold ( = 337) and (2) below-threshold ( = 697) groups.

Localized electrical stimulation triggers cell-type-specific proliferation in biofilms.

Biological systems ranging from bacteria to mammals utilize electrochemical signaling. Although artificial electrochemical signals have been utilized to characterize neural tissue responses, the effects of such stimuli on non-neural systems remain unclear. To pursue this question, we developed an experimental platform that combines a microfluidic chip with a multielectrode array (MiCMA) to enable localized electrochemical stimulation of bacterial biofilms.