scholarly journals Neuronal Network Topology Indicates Distinct Recovery Processes after Stroke

2020 ◽  
Vol 30 (12) ◽  
pp. 6363-6375
Author(s):  
Shahrzad Latifi ◽  
Simon Mitchell ◽  
Rouhollah Habibey ◽  
Fouzhan Hosseini ◽  
Elissa Donzis ◽  
...  
Keyword(s):  
Network Topology ◽  
Premotor Cortex ◽  
Length Distribution ◽  
Cell Types ◽  
Functional Connections ◽  
Recovery Processes ◽  
Connection Length ◽  
In Vivo Calcium Imaging ◽  
The Impact

Abstract Despite substantial recent progress in network neuroscience, the impact of stroke on the distinct features of reorganizing neuronal networks during recovery has not been defined. Using a functional connections-based approach through 2-photon in vivo calcium imaging at the level of single neurons, we demonstrate for the first time the functional connectivity maps during motion and nonmotion states, connection length distribution in functional connectome maps and a pattern of high clustering in motor and premotor cortical networks that is disturbed in stroke and reconstitutes partially in recovery. Stroke disrupts the network topology of connected inhibitory and excitatory neurons with distinct patterns in these 2 cell types and in different cortical areas. These data indicate that premotor cortex displays a distinguished neuron-specific recovery profile after stroke.

scholarly journals The impact of D-cycloserine and sarcosine on in vivo frontal neural activity in a schizophrenia-like model

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Lulu Yao ◽  
Zongliang Wang ◽  
Di Deng ◽  
Rongzhen Yan ◽  
Jun Ju ◽  
...  
Keyword(s):  
Neural Activity ◽  
Brain Activity ◽  
Brain Slices ◽  
Unit Recording ◽  
Glycine Transporter 1 ◽  
Glycine Transporter ◽  
Neural Spiking ◽  
In Vivo Calcium Imaging ◽  
The Impact

Abstract Background N-methyl-D-aspartate receptor (NMDAR) hypofunction has been proposed to underlie the pathogenesis of schizophrenia. Specifically, reduced function of NMDARs leads to altered balance between excitation and inhibition which further drives neural network malfunctions. Clinical studies suggested that NMDAR modulators (glycine, D-serine, D-cycloserine and glycine transporter inhibitors) may be beneficial in treating schizophrenia patients. Preclinical evidence also suggested that these NMDAR modulators may enhance synaptic NMDAR function and synaptic plasticity in brain slices. However, an important issue that has not been addressed is whether these NMDAR modulators modulate neural activity/spiking in vivo. Methods By using in vivo calcium imaging and single unit recording, we tested the effect of D-cycloserine, sarcosine (glycine transporter 1 inhibitor) and glycine, on schizophrenia-like model mice. Results In vivo neural activity is significantly higher in the schizophrenia-like model mice, compared to control mice. D-cycloserine and sarcosine showed no significant effect on neural activity in the schizophrenia-like model mice. Glycine induced a large reduction in movement in home cage and reduced in vivo brain activity in control mice which prevented further analysis of its effect in schizophrenia-like model mice. Conclusions We conclude that there is no significant impact of the tested NMDAR modulators on neural spiking in the schizophrenia-like model mice.

scholarly journals Molecular Mechanisms of Topography Sensing by Osteoblasts: An Update

2021 ◽  
Vol 11 (4) ◽  
pp. 1791
Author(s):  
Pablo Rougerie ◽  
Rafaela Silva dos Santos ◽  
Marcos Farina ◽  
Karine Anselme
Keyword(s):  
Cell Biology ◽  
Bone Repair ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Flat Surfaces ◽  
Total Potential ◽  
Gene Expression Matrix ◽  
Specialized Tissue ◽  
The Impact

Bone is a specialized tissue formed by different cell types and a multiscale, complex mineralized matrix. The architecture and the surface chemistry of this microenvironment can be factors of considerable influence on cell biology, and can affect cell proliferation, commitment to differentiation, gene expression, matrix production and/or composition. It has been shown that osteoblasts encounter natural motifs in vivo, with various topographies (shapes, sizes, organization), and that cell cultures on flat surfaces do not reflect the total potential of the tissue. Therefore, studies investigating the role of topographies on cell behavior are important in order to better understand the interaction between cells and surfaces, to improve osseointegration processes in vivo between tissues and biomaterials, and to find a better topographic surface to enhance bone repair. In this review, we evaluate the main available data about surface topographies, techniques for topographies’ production, mechanical signal transduction from surfaces to cells and the impact of cell–surface interactions on osteoblasts or preosteoblasts’ behavior.

Flexible-substratum technique for viewing cells from the side: some in vivo properties of primary (9+0) cilia in cultured kidney epithelia

1988 ◽  
Vol 89 (4) ◽  
pp. 457-466 ◽  
Author(s):  
K.E. Roth ◽  
C.L. Rieder ◽  
S.S. Bowser
Keyword(s):  
Epithelial Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Kidney Cell ◽  
Primary Cilia ◽  
Length Distribution ◽  
Cell Types ◽  
Phenotypic Marker ◽  
Kidney Epithelial Cell

Cells cultured on thin plastic (e.g. Formvar, Teflon, polycarbonate) membranes can be clearly imaged from the side in vivo by video microscopy. We have used this flexible-substratum technique to examine the behaviour and properties of primary cilia in confluent cultures of the kidney epithelial cell lines PtK1, PtK2, LLC-PK1, MDCK and BSC-40. In these cells primary cilia appear as rigid rods, up to 55 micron long, which project at various angles from the dorsal cell surface. The length distribution of primary cilia in confluent cultures is a distinct characteristic of each established kidney cell line examined, with LLC-PK1 exhibiting three distinct length populations. Primary cilia of kidney cell lines bend passively in response to flow but do not display propagated bending or vortical motions. Up to 26% of the cilia in the cell types examined possess one or more conspicuous swellings along the ciliary shaft. Treatment with 0.05% trypsin, which is sufficient to cause cell rounding, does not induce the resorption or shedding of the cilium. These direct observations demonstrate that kidney epithelial-cell primary cilia are non-motile and longer than previously thought, and suggest that their length represents a phenotypic marker for each cell line.

scholarly journals CurvChip - chip platform for investigating cell responses to curved surface features

2018 ◽  
Vol 4 (1) ◽  
pp. 453-456
Author(s):  
Ralf Kemkemer ◽  
Kerstin Frey ◽  
Alena Fischer ◽  
Rumen Krastev
Keyword(s):  
Low Cost ◽  
Cell Types ◽  
Cell Responses ◽  
Surface Topographies ◽  
Sharp Edges ◽  
Pdms Molding ◽  
The Impact ◽  
Thermal Reflow

AbstractSurface topographies are often discussed as an important parameter influencing basic cell behavior. Whereas most in-vitro studies deal with microstructures with sharp edges, smooth, curved microscale topographies might be more relevant concerning in-vivo situations. Addressing the lack of highly defined surfaces with varying curvature, we present a topography chip system with 3D curved features of varying spacing, curvature radii as well as varying overall dimensions of curved surfaces. The CurvChip is produced by low-cost photolithography with thermal reflow, subsequent (repetitive) PDMS molding and hot embossing. The platform facilitates the systematic invitro investigation of the impact of substrate curvature on cell types like epithelial, endothelial, smooth muscle cells, or stem cells. Such investigations will not only help to further understand the mechanism of curvature sensation but may also contribute to optimize cellmaterial interactions in the field of regenerative medicine.

scholarly journals Genetic Screen in Adult Drosophila Reveals That dCBP Depletion in Glial Cells Mitigates Huntington Disease Pathology through a Foxo-Dependent Pathway

2021 ◽  
Vol 22 (8) ◽  
pp. 3884
Author(s):  
Elodie Martin ◽  
Raheleh Heidari ◽  
Véronique Monnier ◽  
Hervé Tricoire
Keyword(s):  
Glial Cells ◽  
Cell Types ◽  
Cag Repeat ◽  
Mutant Huntingtin ◽  
Tissue Targeting ◽  
Specific Tissue ◽  
In Vivo Screen ◽  
The Impact ◽  
Dependent Pathway

Huntington’s disease (HD) is a progressive and fatal autosomal dominant neurodegenerative disease caused by a CAG repeat expansion in the first exon of the huntingtin gene (HTT). In spite of considerable efforts, there is currently no treatment to stop or delay the disease. Although HTT is expressed ubiquitously, most of our knowledge has been obtained on neurons. More recently, the impact of mutant huntingtin (mHTT) on other cell types, including glial cells, has received growing interest. It is currently unclear whether new pathological pathways could be identified in these cells compared to neurons. To address this question, we performed an in vivo screen for modifiers of mutant huntingtin (HTT-548-128Q) induced pathology in Drosophila adult glial cells and identified several putative therapeutic targets. Among them, we discovered that partial nej/dCBP depletion in these cells was protective, as revealed by strongly increased lifespan and restored locomotor activity. Thus, dCBP promotes the HD pathology in glial cells, in contrast to previous opposite findings in neurons. Further investigations implicated the transcriptional activator Foxo as a critical downstream player in this glial protective pathway. Our data suggest that combinatorial approaches combined to specific tissue targeting may be required to uncover efficient therapies in HD.

Photopatterned Membranes and Chemical Gradients Enable Scalable Phenotypic Organization of Primary Human Colon Epithelial Models

2019 ◽  
Author(s):  
Sam Hinman ◽  
Yuli Wang ◽  
Nancy Allbritton
Keyword(s):  
Human Colon ◽  
Cell Types ◽  
Self Renewal ◽  
Chemical Gradients ◽  
Plate Spacing ◽  
Wide Range ◽  
Cell Compartmentalization ◽  
The Impact

Biochemical gradients across the intestinal epithelium play a major role in governing intestinal stem cell compartmentalization, differentiation dynamics, and organ-level self-renewal. Advances in primary cell-derived <i>in vitro</i> models, in which a full suite of stem and differentiated cell types are present, have vastly accelerated our understanding of intestinal homeostasis and disease. However, scalable platforms that recapitulate the architecture and gradients present <i>in vivo</i> are absent. We present a platform in which individually addressable arrays of chemical gradients along the crypt long axis can be generated, enabling scalable culture of <i>in vitro</i> colonic epithelial replicas. The platform utilizes standardized well plate spacing, maintains access to basal and luminal compartments, and relies on a photopatterned porous membrane to act as diffusion windows while supporting the<i> in vitro </i>crypts. Simultaneous fabrication of 3,875 crypts over a single membrane was developed. Growth factor gradients were modelled and then experimentally optimized to promote long-term health and self-renewal of the crypts which were assayed <i>in situ</i> by confocal fluorescence microscopy. The cultured <i>in vitro</i> crypt arrays successfully recapitulated the architecture, stem/proliferative and differentiated cell compartmentalization, and luminal-to-basal polarity observed <i>in vivo</i>. Furthermore, known signaling regulators produced measurable and predictable effects on the proliferative and differentiated cell compartments. This platform is readily adaptable to the screening of tissue from individual patients to assay the impact of food and bacterial metabolites and/or drugs on colonic crypt dynamics. Importantly, the cassette is compatible with a wide range of sensing/detection modalities, and the developed fabrication methods should find applications for other cell and tissue types.

scholarly journals Biodistribution, Uptake and Effects Caused by Cancer-Derived Extracellular Vesicles

2015 ◽  
Vol 4 (1) ◽  
Author(s):  
Lilite Sadovska ◽  
Cristina Bajo Santos ◽  
Zane Kalniņa ◽  
Aija Linē
Keyword(s):  
Extracellular Vesicles ◽  
Cell Types ◽  
Cell Phenotype ◽  
Chromosomal Dna ◽  
Metastatic Niche ◽  
Paracrine Signalling ◽  
Cancerous Cell ◽  
The Impact

Extracellular vesicles (EVs) have recently emerged as important mediators of intercellular communication. They are released in the extracellular space by a variety of normal and cancerous cell types and have been found in all human body fluids. Cancer-derived EVs have been shown to carry lipids, proteins, mRNAs, non-coding and structural RNAs and even extra-chromosomal DNA, which can be taken up by recipient cells and trigger diverse physiological and pathological responses. An increasing body of evidence suggests that cancer-derived EVs mediate paracrine signalling between cancer cells. This leads to the increased invasiveness, proliferation rate and chemoresistance, as well as the acquisition of the cancer stem cell phenotype. This stimulates angiogenesis and the reprogramming of normal stromal cells into cancer-promoting cell types. Furthermore, cancer-derived EVs contribute to the formation of the pre-metastatic niche and modulation of anti-tumour immune response. However, as most of these data are obtained by in vitro studies, it is not entirely clear which of these effects are recapitulated in vivo. In the current review, we summarize studies that assess the tissue distribution, trafficking, clearance and uptake of cancer-derived EVs in vivo and discuss the impact they have, both locally and systemically.

scholarly journals Simultaneous quantification of protein-DNA contacts and transcriptomes in single cells

2019 ◽  
Author(s):  
Koos Rooijers ◽  
Corina M. Markodimitraki ◽  
Franka J. Rang ◽  
Sandra S. de Vries ◽  
Alex Chialastri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mammalian Cells ◽  
Single Cells ◽  
Critical Role ◽  
Nuclear Lamina ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Expression Variability ◽  
The Impact

AbstractThe epigenome plays a critical role in regulating gene expression in mammalian cells. However, understanding how cell-to-cell heterogeneity in the epigenome influences gene expression variability remains a major challenge. Here we report a novel method for simultaneous single-cell quantification of protein-DNA contacts with DamID and transcriptomics (scDamID&T). This method enables quantifying the impact of protein-DNA contacts on gene expression from the same cell. By profiling lamina-associated domains (LADs) in human cells, we reveal different dependencies between genome-nuclear lamina (NL) association and gene expression in single cells. In addition, we introduce the E. coli methyltransferase, Dam, as an in vivo marker of chromatin accessibility in single cells and show that scDamID&T can be utilized as a general technology to identify cell types in silico while simultaneously determining the underlying gene-regulatory landscape. With this strategy the effect of chromatin states, transcription factor binding, and genome organization on the acquisition of cell-type specific transcriptional programs can be quantified.

Photopatterned Membranes and Chemical Gradients Enable Scalable Phenotypic Organization of Primary Human Colon Epithelial Models

2019 ◽  
Author(s):  
Sam Hinman ◽  
Yuli Wang ◽  
Nancy Allbritton
Keyword(s):  
Human Colon ◽  
Cell Types ◽  
Self Renewal ◽  
Chemical Gradients ◽  
Plate Spacing ◽  
Wide Range ◽  
Cell Compartmentalization ◽  
The Impact

Biochemical gradients across the intestinal epithelium play a major role in governing intestinal stem cell compartmentalization, differentiation dynamics, and organ-level self-renewal. Advances in primary cell-derived <i>in vitro</i> models, in which a full suite of stem and differentiated cell types are present, have vastly accelerated our understanding of intestinal homeostasis and disease. However, scalable platforms that recapitulate the architecture and gradients present <i>in vivo</i> are absent. We present a platform in which individually addressable arrays of chemical gradients along the crypt long axis can be generated, enabling scalable culture of <i>in vitro</i> colonic epithelial replicas. The platform utilizes standardized well plate spacing, maintains access to basal and luminal compartments, and relies on a photopatterned porous membrane to act as diffusion windows while supporting the<i> in vitro </i>crypts. Simultaneous fabrication of 3,875 crypts over a single membrane was developed. Growth factor gradients were modelled and then experimentally optimized to promote long-term health and self-renewal of the crypts which were assayed <i>in situ</i> by confocal fluorescence microscopy. The cultured <i>in vitro</i> crypt arrays successfully recapitulated the architecture, stem/proliferative and differentiated cell compartmentalization, and luminal-to-basal polarity observed <i>in vivo</i>. Furthermore, known signaling regulators produced measurable and predictable effects on the proliferative and differentiated cell compartments. This platform is readily adaptable to the screening of tissue from individual patients to assay the impact of food and bacterial metabolites and/or drugs on colonic crypt dynamics. Importantly, the cassette is compatible with a wide range of sensing/detection modalities, and the developed fabrication methods should find applications for other cell and tissue types.

scholarly journals CARD9 in Neutrophils Protects from Colitis and Controls Mitochondrial Metabolism and Cell Survival

2022 ◽  
Author(s):  
Camille Danne ◽  
Chloe Michaudel ◽  
Jurate Skerniskyte ◽  
Julien Planchais ◽  
Aurelie Magniez ◽  
...  
Keyword(s):  
Fungal Infection ◽  
Intestinal Inflammation ◽  
Profile Analysis ◽  
Premature Death ◽  
Cell Types ◽  
Protective Role ◽  
In Vivo Model ◽  
Knock Out ◽  
The Impact

Objectives: Inflammatory bowel disease (IBD) results from a combination of genetic predisposition, dysbiosis of the gut microbiota and environmental factors, leading to alterations in the gastrointestinal immune response and chronic inflammation. Caspase recruitment domain 9 (Card9), one of the IBD susceptibility genes, has been shown to protect against intestinal inflammation and fungal infection. However, the cell types and mechanisms involved in the CARD9 protective role against inflammation remain unknown. Design: We used dextran sulfate sodium (DSS)-induced and adoptive transfer colitis models in total and conditional CARD9 knock-out mice to uncover which cell types play a role in the CARD9 protective phenotype. The impact of Card9 deletion on neutrophil function was assessed by an in vivo model of fungal infection and various functional assays, including endpoint dilution assay, apoptosis assay by flow cytometry, proteomics and real time bioenergetic profile analysis (Seahorse). Results: Lymphocytes are not intrinsically involved in the CARD9 protective role against colitis. CARD9 expression in neutrophils, but not in epithelial or CD11c+ cells, protects against DSS-induced colitis. In the absence of CARD9, mitochondrial dysfunction in neutrophils leads to their premature death through apoptosis, especially in oxidative environment. The decrease of fonctional neutrophils in tissues could explain the impaired containment of fungi and increased susceptibility to intestinal inflammation. Conclusion: These results provide new insight into the role of CARD9 in neutrophil mitochondrial function and its involvement in intestinal inflammation, paving the way for new therapeutic strategies targeting neutrophils.

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