by Keyword: science

F Amil A, Rubio Ballester B, Maier M, FMJ Verschure P, (2022). Chronic use of cannabis might impair sensory error processing in the cerebellum through endocannabinoid dysregulation Addictive Behaviors 131, 107297

Chronic use of cannabis leads to both motor deficits and the downregulation of CB1 receptors (CB1R) in the cerebellum. In turn, cerebellar damage is often related to impairments in motor learning and control. Further, a recent motor learning task that measures cerebellar-dependent adaptation has been shown to distinguish well between healthy subjects and chronic cannabis users. Thus, the deteriorating effects of chronic cannabis use in motor performance point to cerebellar adaptation as a key process to explain such deficits. We review the literature relating chronic cannabis use, the endocannabinoid system in the cerebellum, and different forms of cerebellar-dependent motor learning, to suggest that CB1R downregulation leads to a generalized underestimation and misprocessing of the sensory errors driving synaptic updates in the cerebellar cortex. Further, we test our hypothesis with a computational model performing a motor adaptation task and reproduce the behavioral effect of decreased implicit adaptation that appears to be a sign of chronic cannabis use. Finally, we discuss the potential of our hypothesis to explain similar phenomena related to motor impairments following chronic alcohol dependency. © 2022

JTD Keywords: adaptation, addiction, alcohol-abuse, cerebellum, cognition, deficits, endocannabinoid system, error processing, explicit, modulation, motor learning, release, synaptic plasticity, Adaptation, Adaptation, physiological, Alcoholism, Article, Behavioral science, Cannabinoid 1 receptor, Cannabis, Cannabis addiction, Cerebellum, Cerebellum cortex, Cerebellum disease, Chronic cannabis use, Computer model, Down regulation, Endocannabinoid, Endocannabinoid system, Endocannabinoids, Error processing, Hallucinogens, Human, Humans, Motor dysfunction, Motor learning, Nerve cell plasticity, Nonhuman, Physiology, Psychedelic agent, Purkinje-cells, Regulatory mechanism, Sensation, Sensory dysfunction, Sensory error processing impairment, Synaptic transmission, Task performance

González-Piñero M, Páez-Avilés C, Juanola-Feliu E, Samitier J, (2021). Cross-fertilization of knowledge and technologies in collaborative research projects Journal Of Knowledge Management 25, 34-59

Purpose: This paper aims to explore how the cross-fertilization of knowledge and technologies in EU-funded research projects, including serious games and gamification, is influenced by the following variables: multidisciplinarity, knowledge base and organizations (number and diversity). The interrelation of actors and projects form a network of innovation. The largest contribution to cross-fertilization comes from the multidisciplinary nature of projects and the previous knowledge and technology of actors. The analysis draws on the understanding of how consortia perform as an innovation network, what their outcomes are and what capabilities are needed to reap value. Design/methodology/approach: All the research projects including serious games and/or gamification, funded by the EU-Horizon 2020 work programme, have been analyzed to test the hypotheses in this paper. The study sample covers the period between 2014 and 2016 (June), selecting the 87 research projects that comprised 519 organizations as coordinators and participants, and 597 observations – because more organizations participate in more than one project. The data were complemented by documentary and external database analysis. Findings: To create cross-fertilization of knowledge and technologies, the following emphasis should be placed on projects: partners concern various disciplines; partners have an extensive knowledge base for generating novel combinations and added-value technologies; there is a diverse typology of partners with unique knowledge and skills; and there is a limited number of organizations not too closely connected to provide cross-fertilization. Research limitations/implications: First, the database sample covers a period of 30 months. The authors’ attention was focused on this period because H2020 prioritized for the first time the serious games and gamification with two specific calls (ICT-21–14 and ICT-24–16) and, second, for the explosion of projects including these technologies in the past years (Adkins, 2017). These facts can be understood as a way to push the research to higher technology readiness levels (TRLs) and introducing the end-user in the co-creation and co-development along the value chain. Second, an additional limitation makes reference to the European focus of the projects, missing strong regional initiatives not identified and studied. Originality/value: This paper has attempted to explore and define theoretically and empirically the characteristics found in the cross-fertilization of collaborative research projects, emphasizing which variables, and how, need to be stimulated to benefit more multidisciplinary consortia and accelerate the process of innovation. © 2021, Manel González-Piñero, Cristina Páez-Avilés, Esteve Juanola-Feliu and Josep Samitier.

JTD Keywords: absorptive-capacity, business model, cross-fertilization of knowledge, diversity, front-end, impact, innovation systems, knowledge management, management research, science, social networks, team, technology, Cross-fertilization of knowledge, Innovation, Knowledge management, Management research, Research-and-development, Technology

Santos-Pata D, Amil AF, Raikov IG, Rennó-Costa C, Mura A, Soltesz I, Verschure PFMJ, (2021). Entorhinal mismatch: A model of self-supervised learning in the hippocampus Iscience 24,

The hippocampal formation displays a wide range of physiological responses to different spatial manipulations of the environment. However, very few attempts have been made to identify core computational principles underlying those hippocampal responses. Here, we capitalize on the observation that the entorhinal-hippocampal complex (EHC) forms a closed loop and projects inhibitory signals “countercurrent” to the trisynaptic pathway to build a self-supervised model that learns to reconstruct its own inputs by error backpropagation. The EHC is then abstracted as an autoencoder, with the hidden layers acting as an information bottleneck. With the inputs mimicking the firing activity of lateral and medial entorhinal cells, our model is shown to generate place cells and to respond to environmental manipulations as observed in rodent experiments. Altogether, we propose that the hippocampus builds conjunctive compressed representations of the environment by learning to reconstruct its own entorhinal inputs via gradient descent.

JTD Keywords: cognitive neuroscience, grid cells, long-term, networks, neural networks, novelty, oscillations, pattern separation, region, representation, working-memory, Cognitive neuroscience, Neural networks, Rat dentate gyrus, Systems neuroscience

Lerche, Martina, Elosegui-Artola, Alberto, Kechagia, Jenny Z., Guzmán, Camilo, Georgiadou, Maria, Andreu, Ion, Gullberg, Donald, Roca-Cusachs, Pere, Peuhu, Emilia, Ivaska, Johanna, (2020). Integrin binding dynamics modulate ligand-specific mechanosensing in mammary gland fibroblasts iScience 23, (3), 100907

The link between integrin activity regulation and cellular mechanosensing of tissue rigidity, especially on different extracellular matrix ligands, remains poorly understood. Here, we find that primary mouse mammary gland stromal fibroblasts (MSFs) are able to spread efficiently, generate high forces, and display nuclear YAP on soft collagen-coated substrates, resembling the soft mammary gland tissue. We describe that loss of the integrin inhibitor, SHARPIN, impedes MSF spreading specifically on soft type I collagen but not on fibronectin. Through quantitative experiments and computational modeling, we find that SHARPIN-deficient MSFs display faster force-induced unbinding of adhesions from collagen-coated beads. Faster unbinding, in turn, impairs force transmission in these cells, particularly, at the stiffness optimum observed for wild-type cells. Mechanistically, we link the impaired mechanotransduction of SHARPIN-deficient cells on collagen to reduced levels of collagen-binding integrin α11β1. Thus integrin activity regulation and α11β1 play a role in collagen-specific mechanosensing in MSFs.

JTD Keywords: Biological Sciences, Cell Biology, Functional Aspects of Cell Biology

Palmisano, I., Danzi, M. C., Hutson, T. H., Zhou, L., McLachlan, E., Serger, E., Shkura, K., Srivastava, P. K., Hervera, A., Neill, N. O., Liu, T., Dhrif, H., Wang, Z., Kubat, M., Wuchty, S., Merkenschlager, M., Levi, L., Elliott, E., Bixby, J. L., Lemmon, V. P., Di Giovanni, S., (2019). Epigenomic signatures underpin the axonal regenerative ability of dorsal root ganglia sensory neurons Nature Neuroscience 22, (11), 1913-1924

Axonal injury results in regenerative success or failure, depending on whether the axon lies in the peripheral or the CNS, respectively. The present study addresses whether epigenetic signatures in dorsal root ganglia discriminate between regenerative and non-regenerative axonal injury. Chromatin immunoprecipitation for the histone 3 (H3) post-translational modifications H3K9ac, H3K27ac and H3K27me3; an assay for transposase-accessible chromatin; and RNA sequencing were performed in dorsal root ganglia after sciatic nerve or dorsal column axotomy. Distinct histone acetylation and chromatin accessibility signatures correlated with gene expression after peripheral, but not central, axonal injury. DNA-footprinting analyses revealed new transcriptional regulators associated with regenerative ability. Machine-learning algorithms inferred the direction of most of the gene expression changes. Neuronal conditional deletion of the chromatin remodeler CCCTC-binding factor impaired nerve regeneration, implicating chromatin organization in the regenerative competence. Altogether, the present study offers the first epigenomic map providing insight into the transcriptional response to injury and the differential regenerative ability of sensory neurons.

JTD Keywords: Cell biology, Computational biology and bioinformatics, Molecular biology, Neuroscience

Infante, Elvira, Stannard, Andrew, Board, Stephanie J., Rico-Lastres, Palma, Rostkova, Elena, Beedle, Amy E. M., Lezamiz, Ainhoa, Wang, Yong Jian, Gulaidi Breen, Samuel, Panagaki, Fani, Sundar Rajan, Vinoth, Shanahan, Catherine, Roca-Cusachs, Pere, Garcia-Manyes, Sergi, (2019). The mechanical stability of proteins regulates their translocation rate into the cell nucleus Nature Physics 15, 973-981

A cell’s ability to react to mechanical stimuli is known to be affected by the transport of transcription factors, the proteins responsible for regulating transcription of DNA into RNA, across the membrane enveloping its nucleus. Yet the molecular mechanisms by which mechanical cues control this process remain unclear. Here we show that one such protein, myocardin-related transcription factor A (MRTFA), is imported into the nucleus at a rate that is inversely correlated with its nanomechanical stability, but independent of its thermodynamic stability. Attaching mechanically stable proteins to MRTFA results in reduced gene expression and the subsequent slowing down of cell migration. We conclude that the mechanical unfolding of proteins regulates their nuclear translocation rate, and highlight the role of the nuclear pore complex as a selective mechanosensor that is capable of detecting forces as low as 10 pN. The modulation of the mechanical stability of transcription factors may represent a general strategy for the control of gene expression.

JTD Keywords: Biological physics, Biophysics, Chemistry, Nanoscience and technology

Gil, V., Del Río, J. A., (2019). Generation of 3-d collagen-based hydrogels to analyze axonal growth and behavior during nervous system development Journal of Visualized Experiments , (148), e59481

This protocol uses natural type I collagen to generate three-dimensional (3-D) hydrogel for monitoring and analyzing the axonal growth. The protocol is centered on culturing small pieces of embryonic or early postnatal rodent brains inside a 3-D hydrogel formed by the rat tail tendon-derived type I collagen with specific porosity. Tissue pieces are cultured inside the hydrogel and confronted to specific brain fragments or genetically-modified cell aggregates to produce and secrete molecules suitable for creating a gradient inside the porous matrix. The steps of this protocol are simple and reproducible but include critical steps to be considered carefully during its development. Moreover, the behavior of growing axons can be monitored and analyzed directly using a phase-contrast microscope or mono/multiphoton fluorescence microscope after fixation by immunocytochemical methods.

JTD Keywords: 3-D hydrogel cultures, Axonal growth, Cell transfection, Chemoattraction, Chemorepulsion, Embryonic nervous system, Issue 148, Neuroscience, Tissue explants

Arsiwalla, Xerxes D., Verschure, Paul, (2018). Measuring the complexity of consciousness Frontiers in Neuroscience 12, (424), Article 424

The grand quest for a scientific understanding of consciousness has given rise to many new theoretical and empirical paradigms for investigating the phenomenology of consciousness as well as clinical disorders associated to it. A major challenge in this field is to formalize computational measures that can reliably quantify global brain states from data. In particular, information-theoretic complexity measures such as integrated information have been proposed as measures of conscious awareness. This suggests a new framework to quantitatively classify states of consciousness. However, it has proven increasingly difficult to apply these complexity measures to realistic brain networks. In part, this is due to high computational costs incurred when implementing these measures on realistically large network dimensions. Nonetheless, complexity measures for quantifying states of consciousness are important for assisting clinical diagnosis and therapy. This article is meant to serve as a lookup table of measures of consciousness, with particular emphasis on clinical applicability. We consider both, principle-based complexity measures as well as empirical measures tested on patients. We address challenges facing these measures with regard to realistic brain networks, and where necessary, suggest possible resolutions. We address challenges facing these measures with regard to realistic brain networks, and where necessary, suggest possible resolutions.

JTD Keywords: Consciousness in the Clinic, Computational neuroscience, Complexity measures, Clinical Neuroscience, Measures of consciousness

Arsiwalla, X. D., Pacheco, D., Principe, A., Rocamora, R., Verschure, P., (2018). A temporal estimate of integrated information for intracranial functional connectivity Artificial Neural Networks and Machine Learning (Lecture Notes in Computer Science) 27th International Conference on Artificial Neural Networks (ICANN 2018) , Springer, Cham (Rhodes, Greece) 11140, 403-412

A major challenge in computational and systems neuroscience concerns the quantification of information processing at various scales of the brain’s anatomy. In particular, using human intracranial recordings, the question we ask in this paper is: How can we estimate the informational complexity of the brain given the complex temporal nature of its dynamics? To address this we work with a recent formulation of network integrated information that is based on the Kullback-Leibler divergence between the multivariate distribution on the set of network states versus the corresponding factorized distribution over its parts. In this work, we extend this formulation for temporal networks and then apply it to human brain data obtained from intracranial recordings in epilepsy patients. Our findings show that compared to random re-wirings of the data, functional connectivity networks, constructed from human brain data, score consistently higher in the above measure of integrated information. This work suggests that temporal integrated information may indeed be a good starting point as a future measure of cognitive complexity.

JTD Keywords: Brain networks, Complexity measures, Computational neuroscience, Functional connectivity

Verschure, P., Prescott, T. J., (2018). A living machines approach to the sciences of mind and brain Living Machines: A Handbook of Research in Biomimetic and Biohybrid Systems (ed. Prescott, T. J., Lepora, Nathan, Verschure, P.), Oxford Scholarship (Oxford, UK) , 15-25

How do the sciences of mind and brain—neuroscience, psychology, cognitive science, and artificial intelligence (AI)—stand in relation to each other in the 21st century? This chapter proposes that despite our knowledge expanding at ever-accelerating rates, our understanding of the relationship between mind and brain is, in some important sense, becoming less and less. An increasing explanatory gap can only be bridged by a multi-tiered and integrated theoretical framework that recognizes the value of developing explanations at different levels, combining these into cross-level integrated theories, and directly contributing to new technologies that improve the human condition. Development of technologies that instantiate principles gleaned from the study of the mind and brain, or biomimetic technologies, is a key part of the validation process for scientific theories of mind and brain. We call this strategy for the integration of science and engineering a Living Machines approach. Following this path can lead not only to better science, and useful engineering, but also a richer view of human experience and of relationships between science, engineering, and art.

JTD Keywords: Convergent validation, Multi-tiered theories, Paradigms in cognitive science, Philosophy of science, Physical models, Reductionism

Fernandez, L., Martin-Gomez, A., Mar Contreras, M., Padilla, M., Marco, S., Arce, L., (2017). Ham quality evaluation assisted by gas chromatography ion mobility spectrometry IEEE Conference Publications ISOCS/IEEE International Symposium on Olfaction and Electronic Nose (ISOEN) , IEEE (Montreal, Canada) , 1-3

In recent years, Gas Chromatography-Ion Mobility Spectrometry (GC-IMS) has been successfully employed in food science as a control technique for the prevention of fraud according to food and labeling regulations. In this work, we propose the use of GC-IMS technique to assess the quality of Iberian ham with regard to the Iberian Pig's diet (either nourished with feed or with acorns). For this purpose, we have acquired a dataset composed of 53 samples of Iberian ham from different food providers using a commercial GC-IMS (FlavourSpec, from G.A.S. Dortmund, Germany). Intensive signal pre-processing for GC-IMS was applied to the raw data. This dataset was employed to create four Partial Least Squares Discriminant Analysis (PLSDA) models corresponding to different train/test partitions of the dataset. Nearly perfect classification rates (above 91 %) were obtained for each partition of the dataset, denoting the high power of GC-IMS to characterize food samples.

JTD Keywords: Classification, Food Science, GC-IMS, Ham quality, PLSDA

Marco, S., Gutiérrez-Gálvez, A., Lansner, A., Martinez, D., Rospars, J. P., Beccherelli, R., Perera, A., Pearce, T., Vershure, P., Persaud, K., (2013). Biologically inspired large scale chemical sensor arrays and embedded data processing Proceedings of SPIE - The International Society for Optical Engineering Smart Sensors, Actuators, and MEMS VI , SPIE Digital Library (Grenoble, France) 8763, 1-15

Biological olfaction outperforms chemical instrumentation in specificity, response time, detection limit, coding capacity, time stability, robustness, size, power consumption, and portability. This biological function provides outstanding performance due, to a large extent, to the unique architecture of the olfactory pathway, which combines a high degree of redundancy, an efficient combinatorial coding along with unmatched chemical information processing mechanisms. The last decade has witnessed important advances in the understanding of the computational primitives underlying the functioning of the olfactory system. EU Funded Project NEUROCHEM (Bio-ICT-FET- 216916) has developed novel computing paradigms and biologically motivated artefacts for chemical sensing taking inspiration from the biological olfactory pathway. To demonstrate this approach, a biomimetic demonstrator has been built featuring a large scale sensor array (65K elements) in conducting polymer technology mimicking the olfactory receptor neuron layer, and abstracted biomimetic algorithms have been implemented in an embedded system that interfaces the chemical sensors. The embedded system integrates computational models of the main anatomic building blocks in the olfactory pathway: The olfactory bulb, and olfactory cortex in vertebrates (alternatively, antennal lobe and mushroom bodies in the insect). For implementation in the embedded processor an abstraction phase has been carried out in which their processing capabilities are captured by algorithmic solutions. Finally, the algorithmic models are tested with an odour robot with navigation capabilities in mixed chemical plumes.

JTD Keywords: Antennal lobes, Artificial olfaction, Computational neuroscience, Olfactory bulbs, Plume tracking, Abstracting, Actuators, Algorithms, Biomimetic processes, Chemical sensors, Conducting polymers, Data processing, Flavors, Odors, Robots, Smart sensors, Embedded systems

Gil, V., Del Río, J. A., (2012). Analysis of axonal growth and cell migration in 3D hydrogel cultures of embryonic mouse CNS tissue Nature Protocols 7, (2), 268-280

This protocol uses rat tail-derived type I collagen hydrogels to analyze key processes in developmental neurobiology, such as chemorepulsion and chemoattraction. The method is based on culturing small pieces of brain tissue from embryonic or early perinatal mice inside a 3D hydrogel formed by rat tail-derived type I collagen or, alternatively, by commercial Matrigel. The neural tissue is placed in the hydrogel with other brain tissue pieces or cell aggregates genetically modified to secrete a particular molecule that can generate a gradient inside the hydrogel. The present method is uncomplicated and generally reproducible, and only a few specific details need to be considered during its preparation. Moreover, the degree and behavior of axonal growth or neural migration can be observed directly using phase-contrast, fluorescence microscopy or immunocytochemical methods. This protocol can be carried out in 4 weeks.

JTD Keywords: Cell biology, Cell culture, Developmental biology, Imaging, Model organisms, Neuroscience, Tissue culture

Altankov, George, Groth, Thomas, Engel, Elisabeth, Gustavsson, Jonas, Pegueroles, Marta, Aparicio, Conrado, Gil, Francesc J., Ginebra, Maria-Pau, Planell, Josep A., (2010). Development of provisional extracellular matrix on biomaterials interface: Lessons from in vitro cell culture NATO Science for Peace and Security Series A: Chemistry and Biology Advances in Regenerative Medicine: Role of Nanotechnology, and Engineering Principles (ed. Shastri, P., Altankov, G., Lendlein, A.), Springer Netherlands (Dortrecht, The Netherlands) , 19-43

The initial cellular events that take place at the biomaterials interface mimic to a certain extent the natural interaction of cells with the extracellular matrix (ECM). The cells adhering to the adsorbed soluble matrix proteins, such as fibronectin (FN) and fibrinogen (FNG) tend to re-arrange them in fibril-like pattern. Using model surfaces we have demonstrated that this cellular activity is abundantly dependent on the surface properties of materials, such as wettability, surface chemistry, charge and topography. This raises the possibility that tissue compatibility of materials is connected with the allowance of cells to remodel substratum associated proteins presumably to form provisional ECM. We have further shown that antibodies which bind β1 and αv integrins (subunits of the FN and FNG receptors respectively) may induce their linear rearrangement on the dorsal surface of living cells – a phenomenon presumably related to the same early molecular events of fibrillar matrix assembly. Because the quantitative measurements revealed that this receptor dynamics is strongly altered on the low compatible (hydrophobic) substrata we hypothesized that in order to be biocompatible, materials need to adsorb matrix proteins loosely, i.e. in such a way that the cells can easily remove and organize them in matrix-like fibrils via coordinated functioning of integrins. More recent studies on the fate of FN on some real biomaterial surfaces, including different rough titanium (Ti) and hydroxyapatite (HA) cements and the surface of biosensors confirmed this point of view. They also show that quantitative measurements of adsorbed matrix proteins and their dynamic rearrangement at cell-material interface might provide insight to the biocompatibility of given material and even predict its tissue integration.

JTD Keywords: Materials Science

Planell, Josep A., Navarro, Melba, Altankov, George, Aparicio, Conrado, Engel, Elisabeth, Gil, Javier, Ginebra, Maria Pau, Lacroix, Damien, (2010). Materials surface effects on biological interactions NATO Science for Peace and Security Series A: Chemistry and Biology Advances in Regenerative Medicine: Role of Nanotechnology, and Engineering Principles (ed. Shastri, P., Altankov, G., Lendlein, A.), Springer Netherlands (Dortrecht, The Netherlands) , 233-252

At present it is well accepted that different surface properties play a strong role in the interaction between synthetic materials and biological entities. Surface properties such as surface energy, topography, surface chemistry and crystallinity affect the protein adsorption mechanisms as well as cell behaviour in terms of attachment, proliferation and differentiation. The aim of this chapter is to show the most relevant processes and interactions that take place during the first stages of contact between the material and the physiological environment. Some examples show that the modification of different biomaterials surfaces affects both protein adsorption and cell behaviour.

JTD Keywords: Materials Science