Faculty Opinions recommendation of Loss of spatial organization and destruction of the pericellular matrix in early osteoarthritis in vivo and in a novel in vitro methodology.

2016 ◽  
Author(s):  
Yefu Li ◽  
Lin Xu
Keyword(s):  
Spatial Organization ◽  
Pericellular Matrix ◽  
Early Osteoarthritis

scholarly journals Loss of spatial organization and destruction of the pericellular matrix in early osteoarthritis in vivo and in a novel in vitro methodology

2016 ◽  
Vol 24 (7) ◽  
pp. 1200-1209 ◽  
Author(s):  
T. Felka ◽  
M. Rothdiener ◽  
S. Bast ◽  
T. Uynuk-Ool ◽  
S. Zouhair ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Pericellular Matrix ◽  
Early Osteoarthritis

scholarly journals Simple biophysics underpins collective conformations of the intrinsically disordered proteins of the Nuclear Pore Complex

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Andrei Vovk ◽  
Chad Gu ◽  
Michael G Opferman ◽  
Larisa E Kapinos ◽  
Roderick YH Lim ◽  
...  
Keyword(s):  
Spatial Organization ◽  
Intrinsically Disordered Proteins ◽  
Nucleocytoplasmic Transport ◽  
Transport Proteins ◽  
Disordered Proteins ◽  
Biophysical Model ◽  
Nuclear Pore ◽  
Intrinsically Disordered

Nuclear Pore Complexes (NPCs) are key cellular transporter that control nucleocytoplasmic transport in eukaryotic cells, but its transport mechanism is still not understood. The centerpiece of NPC transport is the assembly of intrinsically disordered polypeptides, known as FG nucleoporins, lining its passageway. Their conformations and collective dynamics during transport are difficult to assess in vivo. In vitro investigations provide partially conflicting results, lending support to different models of transport, which invoke various conformational transitions of the FG nucleoporins induced by the cargo-carrying transport proteins. We show that the spatial organization of FG nucleoporin assemblies with the transport proteins can be understood within a first principles biophysical model with a minimal number of key physical variables, such as the average protein interaction strengths and spatial densities. These results address some of the outstanding controversies and suggest how molecularly divergent NPCs in different species can perform essentially the same function.

scholarly journals Mapping the structure and biological functions within mesenchymal bodies using microfluidics

2020 ◽  
Vol 6 (10) ◽  
pp. eaaw7853 ◽  
Author(s):  
Sébastien Sart ◽  
Raphaël F.-X. Tomasi ◽  
Antoine Barizien ◽  
Gabriel Amselem ◽  
Ana Cumano ◽  
...  
Keyword(s):  
Cell Fate ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Actin Polymerization ◽  
Bone Repair ◽  
Spatial Organization ◽  
Molecular Signaling ◽  
Correlative Analysis

Organoids that recapitulate the functional hallmarks of anatomic structures comprise cell populations able to self-organize cohesively in 3D. However, the rules underlying organoid formation in vitro remain poorly understood because a correlative analysis of individual cell fate and spatial organization has been challenging. Here, we use a novel microfluidics platform to investigate the mechanisms determining the formation of organoids by human mesenchymal stromal cells that recapitulate the early steps of condensation initiating bone repair in vivo. We find that heterogeneous mesenchymal stromal cells self-organize in 3D in a developmentally hierarchical manner. We demonstrate a link between structural organization and local regulation of specific molecular signaling pathways such as NF-κB and actin polymerization, which modulate osteo-endocrine functions. This study emphasizes the importance of resolving spatial heterogeneities within cellular aggregates to link organization and functional properties, enabling a better understanding of the mechanisms controlling organoid formation, relevant to organogenesis and tissue repair.

scholarly journals Cross-Epithelial Hydrogen Transfer from the Midgut Compartment Drives Methanogenesis in the Hindgut of Cockroaches

2001 ◽  
Vol 67 (10) ◽  
pp. 4657-4661 ◽  
Author(s):  
Thorsten Lemke ◽  
Theo van Alen ◽  
Johannes H. P. Hackstein ◽  
Andreas Brune
Keyword(s):  
Intestinal Tract ◽  
Spatial Organization ◽  
Hydrogen Transfer ◽  
Microbial Populations ◽  
Concentration Gradients ◽  
Sources And Sinks ◽  
Partial Pressures ◽  
Fermenting Bacteria

ABSTRACT In the intestinal tracts of animals, methanogenesis from CO2 and other C1 compounds strictly depends on the supply of electron donors by fermenting bacteria, but sources and sinks of reducing equivalents may be spatially separated. Microsensor measurements in the intestinal tract of the omnivorous cockroachBlaberus sp. showed that molecular hydrogen strongly accumulated in the midgut (H2 partial pressures of 3 to 26 kPa), whereas it was not detectable (<0.1 kPa) in the posterior hindgut. Moreover, living cockroaches emitted large quantities of CH4 [105 ± 49 nmol (g of cockroach)−1h−1] but only traces of H2. In vitro incubation of isolated gut compartments, however, revealed that the midguts produced considerable amounts of H2, whereas hindguts emitted only CH4 [106 ± 58 and 71 ± 50 nmol (g of cockroach)−1 h−1, respectively]. When ligated midgut and hindgut segments were incubated in the same vials, methane emission increased by 28% over that of isolated hindguts, whereas only traces of H2 accumulated in the headspace. Radial hydrogen profiles obtained under air enriched with H2 (20 kPa) identified the hindgut as an efficient sink for externally supplied H2. A cross-epithelial transfer of hydrogen from the midgut to the hindgut compartment was clearly evidenced by the steep H2 concentration gradients which developed when ligated fragments of midgut and hindgut were placed on top of each other—a configuration that simulates the situation in vivo. These findings emphasize that it is essential to analyze the compartmentalization of the gut and the spatial organization of its microbiota in order to understand the functional interactions among different microbial populations during digestion.

scholarly journals Functional insight into the role of Orc6 in septin complex filament formation in Drosophila

2015 ◽  
Vol 26 (1) ◽  
pp. 15-28 ◽  
Author(s):  
Katarina Akhmetova ◽  
Maxim Balasov ◽  
Richard P. H. Huijbregts ◽  
Igor Chesnokov
Keyword(s):  
Origin Recognition Complex ◽  
Spatial Organization ◽  
Cell Cortex ◽  
Filament Formation ◽  
Gtp Binding ◽  
Complex Functions ◽  
Septin Filament

Septins belong to a family of polymerizing GTP-binding proteins that are important for cytokinesis and other processes that involve spatial organization of the cell cortex. We reconstituted a recombinant Drosophila septin complex and compared activities of the wild-type and several mutant septin complex variants both in vitro and in vivo. We show that Drosophila septin complex functions depend on the intact GTP-binding and/or hydrolysis domains of Pnut, Sep1, and Sep2. The presence of the functional C-terminal domain of septins is required for the integrity of the complex. Drosophila Orc6 protein, the smallest subunit of the origin recognition complex (ORC), directly binds to septin complex and facilitates septin filament formation. Orc6 forms dimers through the interactions of its N-terminal, TFIIB-like domains. This ability of the protein suggests a direct bridging role for Orc6 in stimulating septin polymerization in Drosophila. Studies reported here provide a functional dissection of a Drosophila septin complex and highlight the basic conserved and divergent features among metazoan septin complexes.

scholarly journals Mapping Structure and Biological Functions within Mesenchymal Bodies using Microfluidics

2019 ◽  
Author(s):  
Sébastien Sart ◽  
Raphaël F.-X. Tomasi ◽  
Antoine Barizien ◽  
Gabriel Amselem ◽  
Ana Cumano ◽  
...  
Keyword(s):  
Cell Fate ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Actin Polymerization ◽  
Bone Repair ◽  
Spatial Organization ◽  
Molecular Signaling ◽  
Correlative Analysis

AbstractOrganoids that recapitulate the functional hallmarks of anatomic structures comprise cell populations able to self-organize cohesively in 3D. However, the rules underlying organoid formation in vitro remain poorly understood because a correlative analysis of individual cell fate and spatial organization has been challenging. Here, we use a novel microfluidics platform to investigate the mechanisms determining the formation of organoids by human mesenchymal stromal cells that recapitulate the early steps of condensation initiating bone repair in vivo. We find that heterogeneous mesenchymal stromal cells self-organize in 3D in a developmentally hierarchical manner. We demonstrate a link between structural organization and local regulation of specific molecular signaling pathways such as NF-κB and actin polymerization, which modulate osteo-endocrine functions. This study emphasizes the importance of resolving spatial heterogeneities within cellular aggregates to link organization and functional properties, enabling a better understanding of the mechanisms controlling organoid formation, relevant to organogenesis and tissue repair.

scholarly journals In vivo engineered extracellular matrix scaffolds with instructive niches for oriented tissue regeneration

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Meifeng Zhu ◽  
Wen Li ◽  
Xianhao Dong ◽  
Xingyu Yuan ◽  
Adam C. Midgley ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Tissue Regeneration ◽  
Spatial Organization ◽  
Cultured Cells ◽  
Functional Integration ◽  
Host Cells ◽  
Hierarchical Porous ◽  
Parallel Microchannels

Abstract Implanted scaffolds with inductive niches can facilitate the recruitment and differentiation of host cells, thereby enhancing endogenous tissue regeneration. Extracellular matrix (ECM) scaffolds derived from cultured cells or natural tissues exhibit superior biocompatibility and trigger favourable immune responses. However, the lack of hierarchical porous structure fails to provide cells with guidance cues for directional migration and spatial organization, and consequently limit the morpho-functional integration for oriented tissues. Here, we engineer ECM scaffolds with parallel microchannels (ECM-C) by subcutaneous implantation of sacrificial templates, followed by template removal and decellularization. The advantages of such ECM-C scaffolds are evidenced by close regulation of in vitro cell activities, and enhanced cell infiltration and vascularization upon in vivo implantation. We demonstrate the versatility and flexibility of these scaffolds by regenerating vascularized and innervated neo-muscle, vascularized neo-nerve and pulsatile neo-artery with functional integration. This strategy has potential to yield inducible biomaterials with applications across tissue engineering and regenerative medicine.

The Abundance and Organization of Salmonella Extracellular Polymeric Substances in Gallbladder-Mimicking Environments and In Vivo

2021 ◽  
Author(s):  
Mark M. Hahn ◽  
Juan F. González ◽  
Regan Hitt ◽  
Lauren Tucker ◽  
John S. Gunn
Keyword(s):  
Spatial Organization ◽  
Extracellular Polymeric Substances ◽  
Wild Type ◽  
Chronic Infections ◽  
Human Bile ◽  
Cholesterol Gallstones ◽  
Coated Surfaces ◽  
Biofilm Development

Salmonella enterica serovar Typhi ( S. Typhi ) causes chronic infections by establishing biofilms on cholesterol gallstones. Production of extracellular polymeric substances (EPSs) is key to biofilm development and biofilm architecture depends on which EPSs are made. The presence and spatial distribution of Salmonella EPSs produced in vitro and in vivo were investigated in S. Typhi murium and S. Typhi biofilms by confocal microscopy. Comparisons between serovars and EPS-mutant bacteria were examined by growth on cholesterol-coated surfaces, with human gallstones in ox or human bile, and in mice with gallstones. On cholesterol-coated surfaces, major differences in EPS biomass were not found between serovars. Co-culture biofilms containing wild-type (WT) and EPS-mutant bacteria demonstrated WT compensation for EPS mutations. Biofilm EPS analysis from gallbladder-mimicking conditions found that culture in human bile more consistently replicated the relative abundance and spatial organization of each EPS on gallstones from the chronic mouse model than culture in ox bile. S. Typhi murium biofilms cultured in vitro on gallstones in ox bile exhibited co-localized pairings of curli fimbriae/lipopolysaccharide and O antigen capsule/cellulose while these associations were not present in S. Typhi biofilms or in mouse gallstone biofilms. In general, inclusion of human bile with gallstones in vitro replicated biofilm development on gallstones in vivo , demonstrating its strength as a model for studying biofilm parameters or EPS-directed therapeutic treatments.

scholarly journals Structure of hibernating ribosomes studied by cryoelectron tomography in vitro and in situ

2010 ◽  
Vol 190 (4) ◽  
pp. 613-621 ◽  
Author(s):  
Julio O. Ortiz ◽  
Florian Brandt ◽  
Valério R.F. Matias ◽  
Lau Sennels ◽  
Juri Rappsilber ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Stress Response ◽  
Spatial Organization ◽  
Three Dimensional ◽  
E Coli ◽  
Escherichia Coli Cells ◽  
Three Dimensional Configuration

Ribosomes arranged in pairs (100S) have been related with nutritional stress response and are believed to represent a “hibernation state.” Several proteins have been identified that are associated with 100S ribosomes but their spatial organization has hitherto not been characterized. We have used cryoelectron tomography to reveal the three-dimensional configuration of 100S ribosomes isolated from starved Escherichia coli cells and we have described their mode of interaction. In situ studies with intact E. coli cells allowed us to demonstrate that 100S ribosomes do exist in vivo and represent an easily reversible state of quiescence; they readily vanish when the growth medium is replenished.

scholarly journals Small organelle, big responsibility: the role of centrosomes in development and disease

2014 ◽  
Vol 369 (1650) ◽  
pp. 20130468 ◽  
Author(s):  
Pavithra L. Chavali ◽  
Monika Pütz ◽  
Fanni Gergely
Keyword(s):  
Developmental Disorders ◽  
Primary Cilia ◽  
Spatial Organization ◽  
Growth Failure ◽  
Cell Types ◽  
Model Systems ◽  
And Migration ◽  
Division Cell

The centrosome, a key microtubule organizing centre, is composed of centrioles, embedded in a protein-rich matrix. Centrosomes control the internal spatial organization of somatic cells, and as such contribute to cell division, cell polarity and migration. Upon exiting the cell cycle, most cell types in the human body convert their centrioles into basal bodies, which drive the assembly of primary cilia, involved in sensing and signal transduction at the cell surface. Centrosomal genes are targeted by mutations in numerous human developmental disorders, ranging from diseases exclusively affecting brain development, through global growth failure syndromes to diverse pathologies associated with ciliary malfunction. Despite our much-improved understanding of centrosome function in cellular processes, we know remarkably little of its role in the organismal context, especially in mammals. In this review, we examine how centrosome dysfunction impacts on complex physiological processes and speculate on the challenges we face when applying knowledge generated from in vitro and in vivo model systems to human development.

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