scholarly journals ‘Consciousnessoids’: clues and insights from human cerebral organoids for the study of consciousness

2021 ◽  
Vol 7 (2) ◽  
Author(s):  
Andrea Lavazza
Keyword(s):  
Neural Development ◽  
Ethical Issues ◽  
Three Dimensional ◽  
Three Dimensional Model ◽  
Fast Pace ◽  
Strict Regulation ◽  
Muscle Contract ◽  
Preterm Babies ◽  
Structure And Functions

Abstract Human cerebral organoids (HCOs) are an in vitro three-dimensional model of early neural development, aimed at modelling and understanding brain development and neurological disorders. In just a few years, there has been a rapid and considerable progress in the attempt to create a brain model capable of showcasing the structure and functions of the human brain. There are still strong limitations to address, including the absence of vascularization that makes it difficult to feed the central layers of organoids. Nevertheless, some important features of the nervous system have recently been observed: HCOs manifest electrical activity, are sensitive to light stimulation and are able to connect to a spinal cord by sending impulses that make a muscle contract. Recent data show that cortical organoid network development at 10 months resembles some preterm babies’ electroencephalography (EEG) patterns. In the light of the fast pace of research in this field, one might consider the hypothesis that HCOs might become a living laboratory for studying the emergence of consciousness and investigating its mechanisms and neural correlates. HCOs could be also a benchmark for different neuroscientific theories of consciousness. In this paper, I propose some potential lines of research and offer some clues and insights so as to use HCOs in trying to unveil some puzzles concerning our conscious states. Finally, I consider some relevant ethical issues regarding this specific experimentation on HCOs and conclude that some of them could require strict regulation in this field.

scholarly journals Human cerebral organoids and consciousness: a double-edged sword

2020 ◽  
Vol 38 (2) ◽  
pp. 105-128 ◽  
Author(s):  
Andrea Lavazza
Keyword(s):  
Moral Status ◽  
Ethical Issues ◽  
Developmental Process ◽  
Three Dimensional ◽  
Human Consciousness ◽  
Preterm Babies ◽  
Test Treatments ◽  
In Vitro Cell Cultures ◽  
Further Development

AbstractHuman cerebral organoids (HCOs) are three-dimensional in vitro cell cultures that mimic the developmental process and organization of the developing human brain. In just a few years this technique has produced brain models that are already being used to study diseases of the nervous system and to test treatments and drugs. Currently, HCOs consist of tens of millions of cells and have a size of a few millimeters. The greatest limitation to further development is due to their lack of vascularization. However, recent research has shown that human cerebral organoids can manifest the same electrical activity and connections between brain neurons and EEG patterns as those recorded in preterm babies. All this suggests that, in the future, HCOs may manifest an ability to experience basic sensations such as pain, therefore manifesting sentience, or even rudimentary forms of consciousness. This calls for consideration of whether cerebral organoids should be given a moral status and what limitations should be introduced to regulate research. In this article I focus particularly on the study of the emergence and mechanisms of human consciousness, i.e. one of the most complex scientific problems there are, by means of experiments on HCOs. This type of experiment raises relevant ethical issues and, as I will argue, should probably not be considered morally acceptable.

Inhibitory effect of resveratrol on the growth and angiogenesis of human endometrial tissue in an In Vitro three-dimensional model of endometriosis

2020 ◽  
Vol 20 (4) ◽  
pp. 484-490
Author(s):  
Mohammad Rasool Khazaei ◽  
Zahra Rashidi ◽  
Farzaneh Chobsaz ◽  
Elham Niromand ◽  
Mozafar Khazaei
Keyword(s):  
Three Dimensional ◽  
Inhibitory Effect ◽  
Endometrial Tissue ◽  
Dimensional Model ◽  
Three Dimensional Model

scholarly journals Apicomplexan co-infections impair with phagocytic activity in avian macrophages

2020 ◽  
Vol 119 (12) ◽  
pp. 4159-4168
Author(s):  
Runhui Zhang ◽  
Wanpeng Zheng ◽  
Arwid Daugschies ◽  
Berit Bangoura
Keyword(s):  
Laser Scanning ◽  
Three Dimensional ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Three Dimensional Model ◽  
Host Interactions ◽  
Macrophage Phagocytosis ◽  
High Doses ◽  
Free Ranging

AbstractMixed infections of Toxoplasma gondii and Eimeria tenella are likely to occur frequently due to the high prevalence of both pathogens in free-ranging chickens. In this study, we investigated the co-occurrence of the two parasites in the same immune-competent host cell towards altered patterns of parasite-host interactions. Chicken blood monocyte–derived macrophages were co-infected with T. gondii RH tachyzoites and E. tenella Houghton sporozoites in vitro for 24 h. Through monitoring the uptake of pH-sensitive pHrodo™ Zymosan BioParticles (“Zymosan”) by macrophages, we created a three-dimensional model and to analyze quantitatively phagocytosis using confocal laser scanning microscopy. Assessments of parasite populations were performed by qPCR at 2, 6, 12, and 24 h post-infection (hpi). At 6 hpi, phagocytosis was inhibited in the E. tenella–infected cultures while no inhibition of phagocytosis was observed due to T. gondii. Phagocytosis activity revealed more complex interactions during co-infection. At 12 and 24 hpi, phagocytosis response to “Zymosan” was distinctly weaker in co-infected cells than in all other groups except for cells mono-infected with high doses of E. tenella at 24 hpi. By qPCR, significantly reduced numbers of both intracellular parasites were recorded (10-fold) in all infected groups at 2 hpi. At 12 hpi, the T. gondii population reached lowest values but dramatically increased by 24 hpi. Our data confirm that macrophage phagocytosis is involved in the control of invasion by apicomplexan parasites in chicken which particularly applies to E. tenella infection and it was able to be altered by the co-existing parasites.

scholarly journals Identification of Novel Recognition Motifs and Regulatory Targets for the Yeast Actin-regulating Kinase Prk1p

2003 ◽  
Vol 14 (12) ◽  
pp. 4871-4884 ◽  
Author(s):  
Bo Huang ◽  
Guisheng Zeng ◽  
Alvin Y.J. Ng ◽  
Mingjie Cai
Keyword(s):  
Actin Cytoskeleton ◽  
Phosphorylation Site ◽  
Three Dimensional ◽  
Kinase Domain ◽  
Yeast Genome ◽  
Three Dimensional Model ◽  
Recognition Sequence ◽  
Yeast Saccharomyces Cerevisiae

Prk1p is a serine/threonine kinase involved in the regulation of the actin cytoskeleton organization in the yeast Saccharomyces cerevisiae. Previously, we have identified LxxQxTG as the phosphorylation site of Prk1p. In this report, the recognition sequence for Prk1p is investigated more thoroughly. It is found that the presence of a hydrophobic residue at the position of P-5 is necessary for Prk1p phosphorylation and L, I, V, and M are all able to confer the phosphorylation at various efficiencies. The residue flexibility at P-2 has also been identified to include Q, N, T, and S. A homology-based three-dimensional model of the kinase domain of Prk1p provided some structural interpretations for these substrate specificities. The characterization of the [L/I/V/M]xx[Q/N/T/S]xTG motif led to the identification of a spectrum of potential targets for Prk1p from yeast genome. One of them, Scd5p, which contains three LxxTxTG motifs and is previously known to be important for endocytosis and actin organization, has been chosen to demonstrate its relationship with Prk1p. Phosphorylation of Scd5p by Prk1p at the three LxxTxTG motifs could be detected in vitro and in vivo, and deletion of PRK1 suppressed the defects in actin cytoskeleton and endocytosis in one of the scd5 mutants. These results allowed us to conclude that Scd5p is likely another regulatory target of Prk1p.

scholarly journals Cleavage targets and the D-arginine-based inhibitors of the West Nile virus NS3 processing proteinase

2005 ◽  
Vol 393 (2) ◽  
pp. 503-511 ◽  
Author(s):  
Sergey A. Shiryaev ◽  
Boris I. Ratnikov ◽  
Alexei V. Chekanov ◽  
Sergey Sikora ◽  
Dmitri V. Rozanov ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Protein A ◽  
Three Dimensional ◽  
Proteolytic Processing ◽  
Three Dimensional Model ◽  
West Nile ◽  
Highly Active ◽  
Polyprotein Precursor ◽  
Global Threat

Mosquito-borne WNV (West Nile virus) is an emerging global threat. The NS3 proteinase, which is essential for the proteolytic processing of the viral polyprotein precursor, is a promising drug target. We have isolated and biochemically characterized the recombinant, highly active NS3 proteinase. We have determined that the NS3 proteinase functions in a manner that is distantly similar to furin in cleaving the peptide and protein substrates. We determined that aprotinin and D-arginine-based 9–12-mer peptides are potent inhibitors of WNV NS3 with Ki values of 26 nM and 1 nM respectively. Consistent with the essential role of NS3 activity in the life cycle of WNV and with the sensitivity of NS3 activity to the D-arginine-based peptides, we showed that nona-D-Arg-NH2 reduced WNV infection in primary neurons. We have also shown that myelin basic protein, a deficiency of which is linked to neurological abnormalities of the brain, is sensitive to NS3 proteolysis in vitro and therefore this protein represents a convenient test substrate for the studies of NS3. A three-dimensional model of WNV NS3 that we created may provide a structural guidance and a rationale for the subsequent design of fine-tuned inhibitors. Overall, our findings represent a foundation for in-depth mechanistic and structural studies as well as for the design of novel and efficient inhibitors of WNV NS3.

scholarly journals Mutagenesis and Molecular Modeling Reveal Three Key Extracellular Loops of the Membrane Receptor HasR That Are Involved in Hemophore HasA Binding

2007 ◽  
Vol 189 (14) ◽  
pp. 5379-5382 ◽  
Author(s):  
Clément Barjon ◽  
Karine Wecker ◽  
Nadia Izadi-Pruneyre ◽  
Philippe Delepelaire
Keyword(s):  
Molecular Modeling ◽  
Outer Membrane ◽  
Three Dimensional ◽  
Membrane Receptor ◽  
Dimensional Model ◽  
Outer Membrane Receptor ◽  
Three Dimensional Model ◽  
Extracellular Loops

ABSTRACT On the basis of the three-dimensional model of the heme/hemophore TonB-dependent outer membrane receptor HasR, mutants with six-residue deletions in the 11 putative extracellular loops were generated. Although all mutants continued to be active TonB-dependent heme transporters, mutations in three loops abolished hemophore HasA binding both in vivo and in vitro.

scholarly journals A three-dimensional model of the human blood-brain barrier to analyse the transport of nanoparticles and astrocyte/endothelial interactions

F1000Research ◽  
2016 ◽  
Vol 4 ◽  
pp. 1279 ◽  
Author(s):  
Peddagangannagari Sreekanthreddy ◽  
Radka Gromnicova ◽  
Heather Davies ◽  
James Phillips ◽  
Ignacio A. Romero ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Human Blood ◽  
Three Dimensional ◽  
Collagen Gel ◽  
Cell Types ◽  
Brain Barrier ◽  
Two Dimensional ◽  
Three Dimensional Model ◽  
Blood Brain

The aim of this study was to develop a three-dimensional (3D) model of the human blood-brain barrier in vitro, which mimics the cellular architecture of the CNS and could be used to analyse the delivery of nanoparticles to cells of the CNS. The model includes human astrocytes set in a collagen gel, which is overlaid by a monolayer of human brain endothelium (hCMEC/D3 cell line). The model was characterised by transmission electron microscopy (TEM), immunofluorescence microscopy and flow cytometry. A collagenase digestion method could recover the two cell types separately at 92-96% purity.  Astrocytes grown in the gel matrix do not divide and they have reduced expression of aquaporin-4 and the endothelin receptor, type B compared to two-dimensional cultures, but maintain their expression of glial fibrillary acidic protein. The effects of conditioned media from these astrocytes on the barrier phenotype of the endothelium was compared with media from astrocytes grown conventionally on a two-dimensional (2D) substratum. Both induce the expression of tight junction proteins zonula occludens-1 and claudin-5 in hCMEC/D3 cells, but there was no difference between the induced expression levels by the two media. The model has been used to assess the transport of glucose-coated 4nm gold nanoparticles and for leukocyte migration. TEM was used to trace and quantitate the movement of the nanoparticles across the endothelium and into the astrocytes. This blood-brain barrier model is very suitable for assessing delivery of nanoparticles and larger biomolecules to cells of the CNS, following transport across the endothelium.

scholarly journals Comparative analysis of stress distribution in one-piece and two-piece implants with narrow and extra-narrow diameters: A finite element study

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0245800
Author(s):  
Fabricia Teixeira Barbosa ◽  
Luiz Carlos Silveira Zanatta ◽  
Edélcio de Souza Rendohl ◽  
Sergio Alexandre Gehrke
Keyword(s):  
Finite Element ◽  
Stress Distribution ◽  
Three Dimensional ◽  
In Vitro Study ◽  
Von Mises Stress ◽  
Axial Loads ◽  
Three Dimensional Model ◽  
The One ◽  
Von Mises

Objectives The aim of this in vitro study was to evaluate the stress distribution on three implant models with narrow and extra-narrow diameters using the finite element method (FEA). Materials and methods Dental implants of extra-narrow diameter of 2.5 mm for a one-piece implant (group G1), a narrow diameter of 3.0 mm for a one-piece implant (group G2) and a narrow diameter of 3.5 mm for a two-piece implant with a Morse taper connection (group G3). A three-dimensional model was designed with cortical and cancellous bone, a crown and an implant/abutment set of each group. Axial and angled (30°) loads of 150 N was applied. The equivalent von Mises stress was used for the implants and peri-implant bone plus the Mohr-Coulomb analysis to confirm the data of the peri-implant bone. Results In the axial load, the maximum stress value of the cortical bone for the group G1 was 22.35% higher than that the group G2 and 321.23% than the group G3. Whereas in angled load, the groups G1 and G2 showing a similar value (# 3.5%) and a highest difference for the group G3 (391.8%). In the implant structure, the group G1 showed a value of 2188MPa, 93.6% higher than the limit. Conclusions The results of this study show that the extra-narrow one-piece implant should be used with great caution, especially in areas of non-axial loads, whereas the one- and two-piece narrow-diameter implants show adequate behavior in both directions of the applied load.

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