Structural changes in rat bone subjected to long-term, in vivo mechanical loading

Abstract Background A major challenge for any glaucoma implant is their ability to provide long-term intraocular pressure lowering efficacy. The formation of a low-permeability fibrous capsule around the device often leads to obstructed drainage channels, which may impair the drainage function of devices. These foreign body-related limitations point to the need to develop biologically inert biomaterials to improve performance in reaching long-term intraocular pressure reduction. The aim of this study was to evaluate in vivo (in rabbits) the ocular biocompatibility and tissue integration of a novel suprachoroidal microinvasive glaucoma implant, MINIject™ (iSTAR Medical, Wavre, Belgium). Results In two rabbit studies, no biocompatibility issue was induced by the suprachoroidal, ab-externo implantation of the MINIject™ device. Clinical evaluation throughout the 6 post-operative months between the sham and test groups were similar, suggesting most reactions were related to the ab-externo surgical technique used for rabbits, rather than the implant material itself. Histological analysis of ocular tissues at post-operative months 1, 3 and 6 revealed that the implant was well-tolerated and induced only minimal fibroplasia and thus minimal encapsulation around the implant. The microporous structure of the device became rapidly colonized by cells, mostly by macrophages through cell migration, which do not, by their nature, impede the flow of aqueous humor through the device. Time-course analysis showed that once established, pore colonization was stable over time. No fibrosis nor dense connective tissue development were observed within any implant at any time point. The presence of pore colonization may be the process by which encapsulation around the implant is minimized, thus preserving the permeability of the surrounding tissues. No degradation nor structural changes of the implant occurred during the course of both studies. Conclusions The novel MINIject™ microinvasive glaucoma implant was well-tolerated in ocular tissues of rabbits, with observance of biointegration, and no biocompatibility issues. Minimal fibrous encapsulation and stable cellular pore colonization provided evidence of preserved drainage properties over time, suggesting that the implant may produce a long-term ability to enhance aqueous outflow.

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Beneficial effect of voluntary physical exercise in Plakophilin2 transgenic mice

PLoS ONE ◽

10.1371/journal.pone.0252649 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0252649

Author(s):

Karin P. Hammer ◽

Julian Mustroph ◽

Teresa Stauber ◽

Walter Birchmeier ◽

Stefan Wagner ◽

...

Keyword(s):

Beneficial Effect ◽

Structural Changes ◽

Arrhythmogenic Right Ventricular Cardiomyopathy ◽

Voluntary Exercise ◽

Loss Of Function ◽

Functional Development ◽

Increased Risk ◽

Exercise Induced

Arrhythmogenic right ventricular cardiomyopathy is a hereditary, rare disease with an increased risk for sudden cardiac death. The disease-causing mutations are located within the desmosomal complex and the highest incidence is found in plakophilin2. However, there are other factors playing a role for the disease progression unrelated to the genotype such as inflammation or exercise. Competitive sports have been identified as risk factor, but the type and extend of physical activity as cofactor for arrhythmogenesis remains under debate. We thus studied the effect of light voluntary exercise on cardiac health in a mouse model. Mice with a heterozygous PKP2 loss-of-function mutation were given the option to exercise in a running wheel which was monitored 24 h/d. We analyzed structural and functional development in vivo by echocardiography which revealed that neither the genotype nor the exercise caused any significant structural changes. Ejection fraction and fractional shortening were not influenced by the genotype itself, but exercise did cause a drop in both parameters after 8 weeks, which returned to normal after 16 weeks of training. The electrophysiological analysis revealed that the arrhythmogenic potential was slightly higher in heterozygous animals (50% vs 18% in wt littermates) and that an additional stressor (isoprenaline) did not lead to an increase of arrhythmogenic events pre run or after 8 weeks of running but the vulnerability was increased after 16 weeks. Exercise-induced alterations in Ca handling and contractility of isolated myocytes were mostly abolished in heterozygous animals. No fibrofatty replacements or rearrangement of gap junctions could be observed. Taken together we could show that light voluntary exercise can cause a transient aggravation of the mutation-induced phenotype which is abolished after long term exercise indicating a beneficial effect of long term light exercise.

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Long-term Mechanical Loading is Required for the Formation of 3D Bioprinted Functional Osteocyte Bone Organoids using Human Mesenchymal Stem Cells

10.21203/rs.3.rs-1194277/v1 ◽

2021 ◽

Author(s):

Jianhua Zhang ◽

Julia Griesbach ◽

Marsel Ganeyev ◽

Anna-Katharina Zehnder ◽

Peng Zeng ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Mechanical Loading ◽

Network Formation ◽

Human Mesenchymal Stem Cells ◽

Animal Testing ◽

Mineral Density

Abstract Mechanical loading has been shown to influence various osteogenic responses of bone-derived cells and bone formation in vivo. However, the influence of mechanical stimulation on the formation of bone organoid in vitro is not clearly understood. Here, 3D bioprinted human mesenchymal stem cells (hMSCs)-laden graphene oxide composite scaffolds were cultured in cyclic-loading bioreactors for up to 56 days. Our results showed that mechanical loading from day 1 (ML01) significantly increased organoid mineral density, organoid stiffness, and osteoblast differentiation compared with non-loading and mechanical loading from day 21. Importantly, ML01 stimulated collagen I maturation, osteocyte differentiation, lacunar-canalicular network formation and YAP expression on day 56. These finding are the first to reveal that long-term mechanical loading is required for the formation of 3D bioprinted functional osteocyte bone organoids. Such 3D bone organoids may serve as a human-specific alternative to animal testing for the study of bone pathophysiology and drug screening.

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Changes of Synaptic Structures Associated with Learning, Memory and Diseases

Brain Science Advances ◽

10.26599/bsa.2018.2018.9050012 ◽

2018 ◽

Vol 4 (2) ◽

pp. 99-117 ◽

Cited By ~ 3

Author(s):

Yang Yang ◽

Ju Lu ◽

Yi Zuo

Keyword(s):

Synaptic Plasticity ◽

Laser Scanning ◽

Structural Changes ◽

Laser Scanning Microscopy ◽

Two Photon ◽

Sensory Experiences ◽

Synaptic Boutons ◽

Synaptic Structures

Synaptic plasticity is widely believed to be the cellular basis of learning and memory. It is influenced by various factors including development, sensory experiences, and brain disorders. Long-term synaptic plasticity is accompanied by protein synthesis and trafficking, leading to structural changes of the synapse. In this review, we focus on the synaptic structural plasticity, which has mainly been studied with in vivo two-photon laser scanning microscopy. We also discuss how a special type of synapses, the multi-contact synapses (including those formed by multi-synaptic boutons and multi-synaptic spines), are associated with experience and learning.

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Ultrastructural Evidence for a Role of Astrocytes and Glycogen-Derived Lactate in Learning-Dependent Synaptic Stabilization

Cerebral Cortex ◽

10.1093/cercor/bhz226 ◽

2019 ◽

Vol 30 (4) ◽

pp. 2114-2127 ◽

Cited By ~ 7

Author(s):

E Vezzoli ◽

C Calì ◽

M De Roo ◽

L Ponzoni ◽

E Sogne ◽

...

Keyword(s):

Structural Changes ◽

Glycogen Metabolism ◽

Selective Inhibition ◽

Long Term Potentiation ◽

Learning Task ◽

Long Term Memory ◽

Spine Density ◽

Synaptic Changes

Abstract Long-term memory formation (LTM) is a process accompanied by energy-demanding structural changes at synapses and increased spine density. Concomitant increases in both spine volume and postsynaptic density (PSD) surface area have been suggested but never quantified in vivo by clear-cut experimental evidence. Using novel object recognition in mice as a learning task followed by 3D electron microscopy analysis, we demonstrate that LTM induced all aforementioned synaptic changes, together with an increase in the size of astrocytic glycogen granules, which are a source of lactate for neurons. The selective inhibition of glycogen metabolism in astrocytes impaired learning, affecting all the related synaptic changes. Intrahippocampal administration of l-lactate rescued the behavioral phenotype, along with spine density within 24 hours. Spine dynamics in hippocampal organotypic slices undergoing theta burst-induced long-term potentiation was similarly affected by inhibition of glycogen metabolism and rescued by l-lactate. These results suggest that learning primes astrocytic energy stores and signaling to sustain synaptic plasticity via l-lactate.

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Towards elucidation of dynamic structural changes of plant thylakoid architecture

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2012.0373 ◽

2012 ◽

Vol 367 (1608) ◽

pp. 3515-3524 ◽

Cited By ~ 49

Author(s):

Jan M. Anderson ◽

Peter Horton ◽

Eun-Ha Kim ◽

Wah Soon Chow

Keyword(s):

Thylakoid Membrane ◽

Structural Organization ◽

Structural Changes ◽

Ultrastructural Changes ◽

Light Harvesting Complex ◽

Dynamic Architecture ◽

Fluctuating Irradiance ◽

Differential Phosphorylation

Long-term acclimation of shade versus sun plants modulates the composition, function and structural organization of the architecture of the thylakoid membrane network. Significantly, these changes in the macroscopic structural organization of shade and sun plant chloroplasts during long-term acclimation are also mimicked following rapid transitions in irradiance: reversible ultrastructural changes in the entire thylakoid membrane network increase the number of grana per chloroplast, but decrease the number of stacked thylakoids per granum in seconds to minutes in leaves. It is proposed that these dynamic changes depend on reversible macro-reorganization of some light-harvesting complex IIb and photosystem II supracomplexes within the plant thylakoid network owing to differential phosphorylation cycles and other biochemical changes known to ensure flexibility in photosynthetic function in vivo. Some lingering grana enigmas remain: elucidation of the mechanisms involved in the dynamic architecture of the thylakoid membrane network under fluctuating irradiance and its implications for function merit extensive further studies.

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Assembly and regulation of the yeast vacuolar H(+)-ATPase

Journal of Experimental Biology ◽

10.1242/jeb.203.1.81 ◽

2000 ◽

Vol 203 (1) ◽

pp. 81-87 ◽

Cited By ~ 5

Author(s):

P.M. Kane ◽

K.J. Parra

Keyword(s):

Carbon Source ◽

Structural Changes ◽

Growth Conditions ◽

Yeast Cells ◽

Yeast Saccharomyces Cerevisiae ◽

Term Basis ◽

Membrane Bound ◽

Dynamic Structures

The yeast vacuolar H(+)-ATPase (V-ATPase) consists of a complex of peripheral subunits containing the ATP binding sites, termed the V(1) sector, attached to a complex of membrane subunits containing the proton pore, termed the V(o) sector. Interaction between the V(1) and V(o) sectors is essential for ATP-driven proton transport, and this interaction is manipulated in vivo as a means of regulating V-ATPase activity. When yeast (Saccharomyces cerevisiae) cells are deprived of glucose for as little as 5 min, up to 75% of the assembled V-ATPase complexes are disassembled into cytoplasmic V(1) sectors and membrane-bound V(o) sectors. Remarkably, this disassembly is completely reversible. Restoration of glucose to the growth medium results in quantitative reassembly of the disassembled complexes in as little as 5 min, even in the absence of any new protein synthesis. Cells also appear to regulate the extent of V(1)V(o) assembly on a long-term basis. Yeast cells grown for extended periods in a poor carbon source contain a high proportion of free V(1) and V(o) sectors, and these sectors remain poised for reassembly when growth conditions improve. Parallel experiments on the Manduca sexta V-ATPase suggest that reversible disassembly may be a general regulatory mechanism for V-ATPases. These results imply that V-ATPases are surprisingly dynamic structures, and their unique ‘regulated instability’ raises a number of interesting physiological and structural questions. How are extracellular conditions such as carbon source communicated to V-ATPase complexes present on intracellular membranes? How are such major structural changes in the V-ATPase generated and how are V(1) sectors ‘silenced’ in vivo to prevent unproductive hydrolysis of cytoplasmic ATP by the dissociated enzyme? We are addressing these questions using a combination of genetic and biochemical approaches.

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