scholarly journals Deregulated cellular circuits driving immunoglobulins and complement consumption associate with the severity of COVID‐19 patients

2020 ◽  
Author(s):  
Ana Marcos‐Jiménez ◽  
Santiago Sánchez‐Alonso ◽  
Ana Alcaraz‐Serna ◽  
Laura Esparcia ◽  
Celia López‐Sanz ◽  
...  
Keyword(s):  
Cellular Circuits

scholarly journals 2D printed multicellular devices performing digital and analogue computation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sira Mogas-Díez ◽  
Eva Gonzalez-Flo ◽  
Javier Macía
Keyword(s):  
Experimental Validation ◽  
Spatial Arrangement ◽  
End User ◽  
Paper Surface ◽  
Final Output ◽  
Analogue Circuits ◽  
Analogue Computation ◽  
Cellular Circuits ◽  
Working Out ◽  
Digital Or

AbstractMuch effort has been expended on building cellular computational devices for different applications. Despite the significant advances, there are still several addressable restraints to achieve the necessary technological transference. These improvements will ease the development of end-user applications working out of the lab. In this study, we propose a methodology for the construction of printable cellular devices, digital or analogue, for different purposes. These printable devices are designed to work in a 2D surface, in which the circuit information is encoded in the concentration of a biological signal, the so-called carrying signal. This signal diffuses through the 2D surface and thereby interacts with different device components. These components are distributed in a specific spatial arrangement and perform the computation by modulating the level of the carrying signal in response to external inputs, determining the final output. For experimental validation, 2D cellular circuits are printed on a paper surface by using a set of cellular inks. As a proof-of-principle, we have printed and analysed both digital and analogue circuits using the same set of cellular inks but with different spatial topologies. The proposed methodology can open the door to a feasible and reliable industrial production of cellular circuits for multiple applications.

scholarly journals Redox, amino acid, and fatty acid metabolism intersect with bacterial virulence in the gut

2018 ◽  
Vol 115 (45) ◽  
pp. E10712-E10719 ◽  
Author(s):  
Reed Pifer ◽  
Regan M. Russell ◽  
Aman Kumar ◽  
Meredith M. Curtis ◽  
Vanessa Sperandio
Keyword(s):  
Fatty Acid ◽  
High Throughput ◽  
Fatty Acid Metabolism ◽  
Metabolic Pathways ◽  
Virulence Genes ◽  
Acid Metabolism ◽  
Feedback Mechanism ◽  
Regulatory Pathways ◽  
Successful Infection ◽  
Cellular Circuits

The gut metabolic landscape is complex and is influenced by the microbiota, host physiology, and enteric pathogens. Pathogens have to exquisitely monitor the biogeography of the gastrointestinal tract to find a suitable niche for colonization. To dissect the important metabolic pathways that influence virulence of enterohemorrhagicEscherichia coli(EHEC), we conducted a high-throughput screen. We generated a dataset of regulatory pathways that control EHEC virulence expression under anaerobic conditions. This unraveled that the cysteine-responsive regulator, CutR, converges with the YhaO serine import pump and the fatty acid metabolism regulator FadR to optimally control virulence expression in EHEC. CutR activates expression of YhaO to increase activity of the YhaJ transcription factor that has been previously shown to directly activate the EHEC virulence genes. CutR enhances FadL, which is a pump for fatty acids that represses inhibition of virulence expression by FadR, unmasking a feedback mechanism responsive to metabolite fluctuations. Moreover, CutR and FadR also augment murine infection byCitrobacter rodentium, which is a murine pathogen extensively employed as a surrogate animal model for EHEC. This high-throughput approach proved to be a powerful tool to map the web of cellular circuits that allows an enteric pathogen to monitor the gut environment and adjust the levels of expression of its virulence repertoire toward successful infection of the host.

scholarly journals Landauer in the age of synthetic biology: energy consumption and information processing in biochemical networks

2015 ◽  
Author(s):  
Pankaj Mehta ◽  
Alex H Lang ◽  
David J Schwab
Keyword(s):  
Information Processing ◽  
Energy Consumption ◽  
Synthetic Biology ◽  
Protein Modification ◽  
Theoretical Work ◽  
Biochemical Networks ◽  
Fundamental Physics ◽  
Recent Theoretical Work ◽  
Cellular Circuits ◽  
Molecular Components

A central goal of synthetic biology is to design sophisticated synthetic cellular circuits that can perform complex computations and information processing tasks in response to specific inputs. The tremendous advances in our ability to understand and manipulate cellular information processing networks raises several fundamental physics questions: How do the molecular components of cellu- lar circuits exploit energy consumption to improve information processing? Can one utilize ideas from thermodynamics to improve the design of synthetic cellular circuits and modules? Here, we summarize recent theoretical work addressing these questions. Energy consumption in cellular cir- cuits serves five basic purposes: (1) increasing specificity, (2) manipulating dynamics, (3) reducing variability, (4) amplifying signal, and (5) erasing memory. We demonstrate these ideas using several simple examples and discuss the implications of these theoretical ideas for the emerging field of synthetic biology. We conclude by discussing how it may be possible to overcome these limitations using “post-translational” synthetic biology that exploits reversible protein modification.

scholarly journals Probabilistic adaptation in changing microbial environments

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2716 ◽  
Author(s):  
Yarden Katz ◽  
Michael Springer
Keyword(s):  
Real Time ◽  
Particle Filtering ◽  
Microbial Growth ◽  
Internal State ◽  
Probabilistic Inference ◽  
Growth Strategy ◽  
Changing Environments ◽  
Fitness Advantage ◽  
Heuristic Strategies ◽  
Cellular Circuits

Microbes growing in animal host environments face fluctuations that have elements of both randomness and predictability. In the mammalian gut, fluctuations in nutrient levels and other physiological parameters are structured by the host’s behavior, diet, health and microbiota composition. Microbial cells that can anticipate environmental fluctuations by exploiting this structure would likely gain a fitness advantage (by adapting their internal state in advance). We propose that the problem of adaptive growth in structured changing environments, such as the gut, can be viewed as probabilistic inference. We analyze environments that are “meta-changing”: where there are changes in the way the environment fluctuates, governed by a mechanism unobservable to cells. We develop a dynamic Bayesian model of these environments and show that a real-time inference algorithm (particle filtering) for this model can be used as a microbial growth strategy implementable in molecular circuits. The growth strategy suggested by our model outperforms heuristic strategies, and points to a class of algorithms that could support real-time probabilistic inference in natural or synthetic cellular circuits.

scholarly journals Cellular Circuits in the Brain and Their Modulation in Acute and Chronic Pain

2021 ◽  
Vol 101 (1) ◽  
pp. 213-258 ◽  
Author(s):  
Rohini Kuner ◽  
Thomas Kuner
Keyword(s):  
Chronic Pain ◽  
Neural Circuits ◽  
Cell Types ◽  
Mammalian Brain ◽  
Specific Cell ◽  
Dynamic Regulation ◽  
Maladaptive Plasticity ◽  
Pathological Pain ◽  
Dimensions Of Pain ◽  
Cellular Circuits

Chronic, pathological pain remains a global health problem and a challenge to basic and clinical sciences. A major obstacle to preventing, treating, or reverting chronic pain has been that the nature of neural circuits underlying the diverse components of the complex, multidimensional experience of pain is not well understood. Moreover, chronic pain involves diverse maladaptive plasticity processes, which have not been decoded mechanistically in terms of involvement of specific circuits and cause-effect relationships. This review aims to discuss recent advances in our understanding of circuit connectivity in the mammalian brain at the level of regional contributions and specific cell types in acute and chronic pain. A major focus is placed on functional dissection of sub-neocortical brain circuits using optogenetics, chemogenetics, and imaging technological tools in rodent models with a view towards decoding sensory, affective, and motivational-cognitive dimensions of pain. The review summarizes recent breakthroughs and insights on structure-function properties in nociceptive circuits and higher order sub-neocortical modulatory circuits involved in aversion, learning, reward, and mood and their modulation by endogenous GABAergic inhibition, noradrenergic, cholinergic, dopaminergic, serotonergic, and peptidergic pathways. The knowledge of neural circuits and their dynamic regulation via functional and structural plasticity will be beneficial towards designing and improving targeted therapies.

scholarly journals Improving electrocorticograms of awake and anaesthetized mice using wavelet denoising

2018 ◽  
Vol 4 (1) ◽  
pp. 469-472 ◽  
Author(s):  
Michael Schweigmann ◽  
Klaus Peter Koch ◽  
Fabian Auler ◽  
Frank Kirchhoff
Keyword(s):  
Signal To Noise Ratio ◽  
Wavelet Denoising ◽  
Functional Evaluation ◽  
Electrode Impedance ◽  
Electrode Arrays ◽  
Brain Surface ◽  
Micro Electrode Arrays ◽  
Cellular Circuits ◽  
Noise Models

AbstractThe quality of bioelectrical signals is essential for functional evaluation of cellular circuits. The electrical activity recorded from the cortical brain surface represents the average of many individual synaptic processes. By downsizing micro-electrode arrays, the spatial resolution of electrocortico-grams (ECoGs) can be increased. But, upon increasing electrode impedance, recorded noise from the electrode-tissue interface and the surroundings will become more prominent. Frequently, signal interpretation is improved by post-processing using filtering or pattern recognition. For a variety of applications, wavelet denoising has become an accepted tool. Here, we present how wavelet denoising affects the signal-to-noise ratio of ECoGs. The recording qualities from awake and anesthetized mice was artificially reduced by adding two noise models prior to filtering. Raw and filtered signals were compared by calculating the linear correlation coefficient.

scholarly journals A Synthetic Microbial Operational Amplifier

2017 ◽  
Author(s):  
Ji Zeng ◽  
Jaewook Kim ◽  
Areen Banerjee ◽  
Rahul Sarpeshkar
Keyword(s):  
Transcription Factor ◽  
Synthetic Biology ◽  
Operational Amplifier ◽  
Biological Systems ◽  
Logic Gates ◽  
Living Cells ◽  
Output Stage ◽  
Cellular Circuits ◽  
Differential Transcription ◽  
Insight Into

AbstractSynthetic biology has created oscillators, latches, logic gates, logarithmically linear circuits, and load drivers that have electronic analogs in living cells. The ubiquitous operational amplifier, which allows circuits to operate robustly and precisely has not been built with bio-molecular parts. As in electronics, a biological operational-amplifier could greatly improve the predictability of circuits despite noise and variability, a problem that all cellular circuits face. Here, we show how to create a synthetic 3-stage inducer-input operational amplifier with a differential transcription-factor stage, a CRISPR-based push-pull stage, and an enzymatic output stage with just 5 proteins including dCas9. Our ‘Bio-OpAmp’ expands the toolkit of fundamental circuits available to bioengineers or biologists, and may shed insight into biological systems that require robust and precise molecular homeostasis and regulation.One Sentence SummaryA synthetic bio-molecular operational amplifier that can enable robust, precise, and programmable homeostasis and regulation in living cells with just 5 protein parts is described.

scholarly journals Poised cell circuits in human skin are activated in disease

2020 ◽  
Author(s):  
Gary Reynolds ◽  
Peter Vegh ◽  
James Fletcher ◽  
Elizabeth F.M. Poyner ◽  
Emily Stephenson ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Human Skin ◽  
Immune Cell ◽  
Vascular Endothelial Cells ◽  
Single Cells ◽  
Lymphoid Cells ◽  
Keratinocyte Differentiation ◽  
Cell Trafficking ◽  
Immunological Protection ◽  
Cellular Circuits

AbstractThe human skin confers biophysical and immunological protection through a complex cellular network that is established early in development. We profiled ~500,000 single cells using RNA-sequencing from healthy adult and developing skin, and skin from patients with atopic dermatitis and psoriasis. Our findings reveal a predominance of innate lymphoid cells and macrophages in developing skin in contrast to T cells and migratory dendritic cells in adult skin. We demonstrate dual keratinocyte differentiation trajectories and activated cellular circuits comprising vascular endothelial cells mediating immune cell trafficking, disease-specific clonally expanded IL13/IL22 and IL17A/F-expressing lymphocytes, epidermal IL23-expressing dendritic cells and inflammatory keratinocytes in disease. Our findings provide key insights into the dynamic cellular landscape of human skin in health and disease.One Sentence SummarySingle cell atlas of human skin reveals cell circuits which are quantitatively and qualitatively reconfigured in inflammatory skin disease.

scholarly journals A Toolkit for Rapid Modular Construction of Biological Circuits in Mammalian Cells

2018 ◽  
Author(s):  
João Pedro Fonseca ◽  
Alain R. Bonny ◽  
G. Renuka Kumar ◽  
Andrew H. Ng ◽  
Jason Town ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Ebola Virus ◽  
Transcriptional Unit ◽  
Biological Research ◽  
Modular Construction ◽  
Complex Circuits ◽  
Dna Vectors ◽  
Cellular Circuits ◽  
Biological Circuits ◽  
Different Characteristics

AbstractThe ability to rapidly assemble and prototype cellular circuits is vital for biological research and its applications in biotechnology and medicine. Current methods that permit the assembly of DNA circuits in mammalian cells are laborious, slow, expensive and mostly not permissive of rapid prototyping of constructs. Here we present the Mammalian ToolKit (MTK), a Golden Gate-based cloning toolkit for fast, reproducible and versatile assembly of large DNA vectors and their implementation in mammalian models. The MTK consists of a curated library of characterized, modular parts that can be easily mixed and matched to combinatorially assemble one transcriptional unit with different characteristics, or a hierarchy of transcriptional units weaved into complex circuits. MTK renders many cell engineering operations facile, as showcased by our ability to use the toolkit to generate single-integration landing pads, to create and deliver libraries of protein variants and sgRNAs, and to iterate through Cas9-based prototype circuits. As a biological proof of concept, we used the MTK to successfully design and rapidly construct in mammalian cells a challenging multicistronic circuit encoding the Ebola virus (EBOV) replication complex. This construct provides a non-infectious biosafety level 2 (BSL2) cellular assay for exploring the transcription and replication steps of the EBOV viral life cycle in its host. Its construction also demonstrates how the MTK can enable important and time sensitive applications such as the rapid testing of pharmacological inhibitors of emerging BSL4 viruses that pose a major threat to human health.

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