scholarly journals Active perception during angiogenesis: filopodia speed up Notch selection of tip cells in silico and in vivo

2021 ◽  
Vol 376 (1821) ◽  
pp. 20190753 ◽  
Author(s):  
Bahti Zakirov ◽  
Georgios Charalambous ◽  
Raphael Thuret ◽  
Irene M. Aspalter ◽  
Kelvin Van-Vuuren ◽  
...  
Keyword(s):  
In Silico ◽  
Selection Process ◽  
Cellular Level ◽  
Cell Selection ◽  
Active Perception ◽  
Conceptual Approach ◽  
Bistable Switch ◽  
Cell Behaviour ◽  
Tip Cell

How do cells make efficient collective decisions during tissue morphogenesis? Humans and other organisms use feedback between movement and sensing known as ‘sensorimotor coordination’ or ‘active perception’ to inform behaviour, but active perception has not before been investigated at a cellular level within organs. Here we provide the first proof of concept in silico / in vivo study demonstrating that filopodia (actin-rich, dynamic, finger-like cell membrane protrusions) play an unexpected role in speeding up collective endothelial decisions during the time-constrained process of ‘tip cell’ selection during blood vessel formation (angiogenesis). We first validate simulation predictions in vivo with live imaging of zebrafish intersegmental vessel growth. Further simulation studies then indicate the effect is due to the coupled positive feedback between movement and sensing on filopodia conferring a bistable switch-like property to Notch lateral inhibition, ensuring tip selection is a rapid and robust process. We then employ measures from computational neuroscience to assess whether filopodia function as a primitive (basal) form of active perception and find evidence in support. By viewing cell behaviour through the ‘basal cognitive lens' we acquire a fresh perspective on the tip cell selection process, revealing a hidden, yet vital time-keeping role for filopodia. Finally, we discuss a myriad of new and exciting research directions stemming from our conceptual approach to interpreting cell behaviour. This article is part of the theme issue ‘Basal cognition: multicellularity, neurons and the cognitive lens’.

scholarly journals Active Perception during Angiogenesis: Filopodia speed up Notch selection of tip cells in silico and in vivo

2020 ◽  
Author(s):  
Bahti Zakirov ◽  
Georgios Charalambous ◽  
Irene M. Aspalter ◽  
Kelvin Van-Vuuren ◽  
Thomas Mead ◽  
...  
Keyword(s):  
In Silico ◽  
Selection Process ◽  
Cellular Level ◽  
Cell Selection ◽  
Active Perception ◽  
Bistable Switch ◽  
Cell Behaviour ◽  
Tip Cell ◽  
Vessel Growth

AbstractHow do cells make efficient collective decisions during tissue morphogenesis? Humans and other organisms utilize feedback between movement and sensing known as ‘sensorimotor coordination’ or ‘active perception’ to inform behaviour, but active perception has not before been investigated at a cellular level within organs. Here we provide the first proof of concept in silico/in vivo study demonstrating that filopodia (actin-rich, dynamic, finger like cell-membrane protrusions) play an unexpected role in speeding up collective endothelial decisions during the time-constrained process of ‘tip cell’ selection during blood vessel formation (angiogenesis).We first validate simulation predictions in vivo with live imaging of zebrafish intersegmental vessel growth. Further simulation studies then indicate the effect is due to the coupled positive feedback between movement and sensing on filopodia conferring a bistable switch-like property to Notch lateral inhibition, ensuring tip selection is a rapid and robust process. We then employ measures from computational neuroscience to assess whether filopodia function as a primitive (‘basal’) form of active perception and find evidence in support. By viewing cell behaviour in tissues through the ‘basal cognitive lens’ we acquire a fresh perspective on not only the well-studied tip cell selection process, revealing a hidden, yet vital, time-keeping role for filopodia, but on how to interpret and understand cell behaviour in general, opening up a myriad of new and exciting research directions.

An in Silico, Biomarker-Based Method for the Evaluation of Virtual Neuropsychiatric Drug Effects

2017 ◽  
Vol 29 (4) ◽  
pp. 1021-1052 ◽  
Author(s):  
Peter J. Siekmeier
Keyword(s):  
In Silico ◽  
Fragile X ◽  
Drug Effects ◽  
Cellular Level ◽  
Model Parameters ◽  
Virtual Agents ◽  
In Vitro Test ◽  
Pharmacologic Treatments

The recent explosion in neuroscience research has markedly increased our understanding of the neurobiological correlates of many psychiatric illnesses, but this has unfortunately not translated into more effective pharmacologic treatments for these conditions. At the same time, researchers have increasingly sought out biological markers, or biomarkers, as a way to categorize psychiatric illness, as these are felt to be closer to underlying genetic and neurobiological vulnerabilities. While biomarker-based drug discovery approaches have tended to employ in vivo (e.g., rodent) or in vitro test systems, relatively little attention has been paid to the potential of computational, or in silico, methodologies. Here we describe such a methodology, using as an example a biophysically detailed computational model of hippocampus that is made to generate putative schizophrenia biomarkers by the inclusion of a number of neuropathological changes that have been associated with the illness (NMDA system deficit, decreased neural connectivity, hyperdopaminergia). We use the specific inability to attune to gamma band (40 Hz) auditory stimulus as our illness biomarker. We expose this system to a large number of virtual medications, defined by systematic variation of model parameters corresponding to five cellular-level effects. The potential efficacy of virtual medications is determined by a wellness metric (WM) that we have developed. We identify a number of virtual agents that consist of combinations of mechanisms, which are not simply reversals of the causative lesions. The manner in which this methodology could be extended to other neuropsychiatric conditions, such as Alzheimer’s disease, autism, and fragile X syndrome, is discussed.

scholarly journals Temporal modulation of collective cell behavior controls vascular network topology

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Esther Kur ◽  
Jiha Kim ◽  
Aleksandra Tata ◽  
Cesar H Comin ◽  
Kyle I Harrington ◽  
...  
Keyword(s):  
Feedback Loop ◽  
Network Formation ◽  
Vascular Network ◽  
General Mechanism ◽  
Network Density ◽  
Vascular Density ◽  
Cell Selection ◽  
Temporal Regulation ◽  
Tip Cell

Vascular network density determines the amount of oxygen and nutrients delivered to host tissues, but how the vast diversity of densities is generated is unknown. Reiterations of endothelial-tip-cell selection, sprout extension and anastomosis are the basis for vascular network generation, a process governed by the VEGF/Notch feedback loop. Here, we find that temporal regulation of this feedback loop, a previously unexplored dimension, is the key mechanism to determine vascular density. Iterating between computational modeling and in vivo live imaging, we demonstrate that the rate of tip-cell selection determines the length of linear sprout extension at the expense of branching, dictating network density. We provide the first example of a host tissue-derived signal (Semaphorin3E-Plexin-D1) that accelerates tip cell selection rate, yielding a dense network. We propose that temporal regulation of this critical, iterative aspect of network formation could be a general mechanism, and additional temporal regulators may exist to sculpt vascular topology.

scholarly journals Generation of anisotropic strain dysregulates wild-type cell division at the interface between host and oncogenic tissue

2019 ◽  
Author(s):  
Megan Moruzzi ◽  
Alexander Nestor-Bergmann ◽  
Georgina K. Goddard ◽  
Keith Brennan ◽  
Sarah Woolner
Keyword(s):  
Cell Division ◽  
Cellular Level ◽  
Host Tissue ◽  
Host Cells ◽  
Cell Stiffness ◽  
Cell Behaviour ◽  
Oncogenic Ras ◽  
Anisotropic Strain ◽  
Highly Sensitive

SUMMARYEpithelial tissues are highly sensitive to anisotropies in mechanical force, with cells altering fundamental behaviours such as cell adhesion, migration and cell division [1-5]. It is well known that in the later stages of carcinoma (epithelial cancer), the presence of tumours alters the mechanical properties of a host tissue and that these changes contribute to disease progression [6-9]. However, in the earliest stages of carcinoma, when a clonal cluster of oncogene-expressing cells first establishes in the epithelium, the extent to which mechanical changes alter cell behaviour in the tissue as a whole remains unclear. This is despite knowledge that many common oncogenes, such as oncogenic Ras, alter cell stiffness and contractility [10-13]. Here, we investigate how mechanical changes at the cellular level of an oncogenic cluster can translate into the generation of anisotropic strain across an epithelium, altering cell behaviour in neighbouring host tissue. We generated clusters of oncogene-expressing cells within otherwise normal in vivo epithelium, using Xenopus laevis embryos. We find that cells in kRasV12, but not cMYC, clusters have increased contractility, which introduces radial stress in the tissue and deforms surrounding host cells. The strain imposed by kRasV12 clusters leads to increased cell division and altered division orientation in the neighbouring host tissue, effects that can be rescued by reducing actomyosin contractility specifically in the kRasV12 cells. Our findings indicate that some oncogenes can alter the mechanical and proliferative properties of host tissue from the very earliest stages of cancer development, changes which have the potential to contribute to tumorigenesis.

scholarly journals In-silico amplification of randomly selected male - specific region – Y (MSY) genes as candidate genes for the selection of fertile indigenous bulls for artificial insemination

2020 ◽  
Vol 46 (5) ◽  
Author(s):  
A. B. Sikiru ◽  
S. S. A. Egena ◽  
O. M. Akinsola ◽  
I. C. Alemede ◽  
J. O. Makinde ◽  
...  
Keyword(s):  
In Silico ◽  
Selection Process ◽  
Polymerase Chain Reaction Amplification ◽  
Specific Region ◽  
Breeding Programmes ◽  
Reaction Amplification ◽  
Male Specific ◽  
Genome Assemblies ◽  
Selection Of

Molecular markers-based selection is a novel tool for unbundling complexities associated with the selection of animals for breeding improvement programmes because these markers could contribute to full exploitation of animal potential prior to enrollment for improvement programmes. This study examined in-silico polymerase chain reaction amplification of some selected Male Specific region Y (MSY) genes in genome assemblies including Bos_taurus_UMD_3.1.1/bosTau8 and ARS-UCD1.2/bosTau9;BaylorBtau_4.6.1/bosTau7, Bos_taurus_UMD_3.1/bosTau6, and Baylor4.0/bosTau4. The results of the amplification showed that 12 out of the selected 30 genes were expressed at an average primer melting temperature of 61.78 oC; while salt and annealing oligo concentrations were 50 mM and 50 nM per reaction, respectively. Out of expressed genes; 6, 5 and 1 genes were expressed in genome assemblies Bos_taurus_UMD_3.1.1/bosTau8, ARS-UCD1.2/bosTau9, and BaylorBtau_4.6. 1/bosTau7, respectively. The study concluded that the expressed genes are potential markers for selection of fertile bulls and the primers used are suitable for in-vivo annotation of the genes in the prospective bull selection process for breeding programmes.

Biomedical applications: Pitfalls in the practice

1994 ◽  
Vol 52 ◽  
pp. 378-379
Author(s):  
J. D. Shelburne ◽  
Peter Ingram ◽  
Victor L. Roggli ◽  
Ann LeFurgey
Keyword(s):  
Operating Room ◽  
Liquid Nitrogen ◽  
Lung Tissue ◽  
Biomedical Applications ◽  
Microprobe Analysis ◽  
Tissue Sample ◽  
Cellular Level ◽  
Tissue Samples ◽  
Asbestos Fibers

At present most medical microprobe analysis is conducted on insoluble particulates such as asbestos fibers in lung tissue. Cryotechniques are not necessary for this type of specimen. Insoluble particulates can be processed conventionally. Nevertheless, it is important to emphasize that conventional processing is unacceptable for specimens in which electrolyte distributions in tissues are sought. It is necessary to flash-freeze in order to preserve the integrity of electrolyte distributions at the subcellular and cellular level. Ideally, biopsies should be flash-frozen in the operating room rather than being frozen several minutes later in a histology laboratory. Electrolytes will move during such a long delay. While flammable cryogens such as propane obviously cannot be used in an operating room, liquid nitrogen-cooled slam-freezing devices or guns may be permitted, and are the best way to achieve an artifact-free, accurate tissue sample which truly reflects the in vivo state. Unfortunately, the importance of cryofixation is often not understood. Investigators bring tissue samples fixed in glutaraldehyde to a microprobe laboratory with a request for microprobe analysis for electrolytes.

Mechanisms of action of antihyperglycemic mexicanolides isolated from Swietenia humillis: in vivo and in silico approaches

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381 ◽  
Author(s):  
B Ovalle-Magallanes ◽  
A Madariaga-Mazón ◽  
A Navarrete ◽  
R Mata
Keyword(s):  
In Silico ◽  
Mechanisms Of Action

Ruthenium Complexes for 1- and 2-Photon Photodynamic Therapy: From In Silico Prediction to In Vivo Applications

2020 ◽  
Author(s):  
Johannes Karges ◽  
Shi Kuang ◽  
Federica Maschietto ◽  
Olivier Blacque ◽  
Ilaria Ciofini ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
In Silico ◽  
Aqueous Solubility ◽  
The Body ◽  
Photon Absorption ◽  
Multicellular Tumor Spheroids ◽  
Spectral Window ◽  
Photon Excitation ◽  
Polypyridine Complexes

<div>The use of photodynamic therapy (PDT) against cancer has received increasing attention overthe recent years. However, the application of the currently approved photosensitizers (PSs) is somehow limited by their poor aqueous solubility, aggregation, photobleaching and slow clearance from the body. To overcome these limitations, there is a need for the development of new classes of PSs with ruthenium(II) polypyridine complexes currently gaining momentum. However, these compounds generally lack significant absorption in the biological spectral window, limiting their application to treat deep-seated or large tumors. To overcome this drawback, ruthenium(II) polypyridine complexes designed in silico with (E,E’)-4,4´-bisstyryl 2,2´-bipyridine ligands showed impressive 1- and 2-Photon absorption up to a magnitude higher than the ones published so far. While non-toxic in the dark, these compounds were found phototoxic in various 2D monolayer cells, 3D multicellular tumor spheroids and be able to eradicate a multiresistant tumor inside a mouse model upon clinically relevant 1-Photon and 2 Photon excitation.</div>

Exploiting Anti-Inflammation Effects of Flavonoids in Chronic Inflammatory Diseases

2020 ◽  
Vol 26 (22) ◽  
pp. 2610-2619 ◽  
Author(s):  
Tarique Hussain ◽  
Ghulam Murtaza ◽  
Huansheng Yang ◽  
Muhammad S. Kalhoro ◽  
Dildar H. Kalhoro
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Inflammatory Diseases ◽  
Therapeutic Option ◽  
Cellular Level ◽  
Antiinflammatory Drugs ◽  
Suitable Alternative ◽  
Chronic Inflammatory Diseases

Background: Inflammation is a complex response of the host defense system to different internal and external stimuli. It is believed that persistent inflammation may lead to chronic inflammatory diseases such as, inflammatory bowel disease, neurological and cardiovascular diseases. Oxidative stress is the main factor responsible for the augmentation of inflammation via various molecular pathways. Therefore, alleviating oxidative stress is effective a therapeutic option against chronic inflammatory diseases. Methods: This review article extends the knowledge of the regulatory mechanisms of flavonoids targeting inflammatory pathways in chronic diseases, which would be the best approach for the development of suitable therapeutic agents against chronic diseases. Results: Since the inflammatory response is initiated by numerous signaling molecules like NF-κB, MAPK, and Arachidonic acid pathways, their encountering function can be evaluated with the activation of Nrf2 pathway, a promising approach to inhibit/prevent chronic inflammatory diseases by flavonoids. Over the last few decades, flavonoids drew much attention as a potent alternative therapeutic agent. Recent clinical evidence has shown significant impacts of flavonoids on chronic diseases in different in-vivo and in-vitro models. Conclusion: Flavonoid compounds can interact with chronic inflammatory diseases at the cellular level and modulate the response of protein pathways. A promising approach is needed to overlook suitable alternative compounds providing more therapeutic efficacy and exerting fewer side effects than commercially available antiinflammatory drugs.

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