scholarly journals In Vivo Protein Complementation Demonstrates Presynaptic α-Synuclein Oligomerization and Age-Dependent Accumulation of 8–16-mer Oligomer Species

Cell Reports ◽  
2019 ◽  
Vol 29 (9) ◽  
pp. 2862-2874.e9 ◽  
Author(s):  
Martin Kiechle ◽  
Bjoern von Einem ◽  
Lennart Höfs ◽  
Patrizia Voehringer ◽  
Veselin Grozdanov ◽  
...  
Keyword(s):  
Age Dependent ◽  
Protein Complementation

Capturing Age-Dependent Properties of Human Skin Using Magnetorheological Elastomers

2018 ◽  
Author(s):  
Kyle Weaver ◽  
Jeong-Hoi Koo ◽  
Tae-Heon Yang ◽  
Young-Min Kim
Keyword(s):  
Mechanical Properties ◽  
Human Skin ◽  
Skin Testing ◽  
Filler Particle ◽  
Variable Stiffness ◽  
Particle Volume ◽  
Magnetorheological Elastomers ◽  
Age Dependent ◽  
Skin Samples

Artificial and synthetic skins are widely used in the medical field; used in applications ranging from skin grafts to suture training pads. There is a growing need for artificial skins with tunable properties. However, current artificial skins do not take into account the variability of mechanical properties between individual humans as well as the age-dependent properties of human skin. Furthermore, there has been little development in artificial skins based on these properties. Thus, the primary purpose of this research is to develop variable stiffness artificial skin samples using magnetorheological elastomers (MREs) whose properties that can be controlled using external magnetic fields. In this study, multiple MRE skin samples were fabricated with varying filler particle volume contents. Using a precision dynamic mechanical analyzer, a series of indenting experiments were performed on the samples to characterize their mechanical properties. The samples were tested using a spherical indenter that indented a total depth of 1 mm with a speed of 0.01 mm/s and unloaded at the same rate. The results show that the modulus or stiffness increases significantly as the iron percent (w/w) in the sample increases. Additionally, the stiffness of the sample increases proportional to the intensity of the applied external magnetic field. To assess the MRE samples’ variability of properties, the testing results were compared with in vivo human skin testing data. The results show the MRE samples are feasible to represent the age-dependent stiffness demonstrated in in vivo human skin testing. The MRE materials studied will be further studied as a variable-stiffness skin model in medical devices, such as radial pulse simulators.

367. Assessing the age-dependent profile of healthy normal controls using in vivo 31P MRS

2000 ◽  
Vol 47 (8) ◽  
pp. S111
Author(s):  
J.A. Stanley ◽  
N.J. Minshew ◽  
M.S. Keshavan ◽  
K. Panchalingam ◽  
R.J. McClure ◽  
...  
Keyword(s):  
31P Mrs ◽  
Age Dependent ◽  
Normal Controls

scholarly journals Age-dependent changes in electrophysiology and calcium handling – implications for pediatric cardiac research

2019 ◽  
Author(s):  
Luther M. Swift ◽  
Morgan Burke ◽  
Devon Guerrelli ◽  
Manelle Ramadan ◽  
Marissa Reilly ◽  
...  
Keyword(s):  
Postnatal Development ◽  
Cardiac Electrophysiology ◽  
Calcium Handling ◽  
Cell Coupling ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Age Dependent ◽  
Genes Encoding ◽  
Cardiac Maturation

ABSTRACTRationaleThe heart continues to develop and mature after birth and into adolescence. Accordingly, cardiac maturation is likely to include a progressive refinement in both organ morphology and function during the postnatal period. Yet, age-dependent changes in cardiac electrophysiology and calcium handling have not yet been fully characterized.ObjectiveThe objective of this study, was to examine the relationship between cardiac maturation, electrophysiology, and calcium handling throughout postnatal development in a rat model.MethodsPostnatal rat cardiac maturation was determined by measuring the expression of genes involved in cell-cell coupling, electrophysiology, and calcium handling. In vivo electrocardiograms were recorded from neonatal, juvenile, and adult animals. Simultaneous dual optical mapping of transmembrane voltage and calcium transients was performed on isolated, Langendorff-perfused rat hearts (postnatal day 0–3, 4-7, 8-14, adult).ResultsYounger, immature hearts displayed slowed electrical conduction, prolonged action potential duration and increased ventricular refractoriness. Slowed calcium handling in the immature heart increased the propensity for calcium transient alternans which corresponded to alterations in the expression of genes encoding calcium handling proteins. Developmental changes in cardiac electrophysiology were associated with the altered expression of genes encoding potassium channels and intercalated disc proteins.ConclusionUsing an intact whole heart model, this study highlights chronological changes in cardiac electrophysiology and calcium handling throughout postnatal development. Results of this study can serve as a comprehensive baseline for future studies focused on pediatric cardiac research, safety assessment and/or preclinical testing using rodent models.

scholarly journals Interindividual variability and lateralization of µ-opioid receptors in the human brain

2019 ◽  
Author(s):  
Tatu Kantonen ◽  
Tomi Karjalainen ◽  
Janne Isojärvi ◽  
Pirjo Nuutila ◽  
Jouni Tuisku ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Body Mass ◽  
Opioid Receptors ◽  
Hierarchical Modeling ◽  
Small Sample ◽  
Hemispheric Lateralization ◽  
Binding Potential ◽  
Neuropsychiatric Diseases ◽  
Age Dependent

AbstractThe brain’s µ-opioid receptors (MORs) are involved in analgesia, reward and mood regulation. Several neuropsychiatric diseases have been associated with dysfunctional MOR system, and there is also considerable variation in receptor density among healthy individuals. Sex, age, body mass and smoking have been proposed to influence the MOR system, but due to small sample sizes the magnitude of their influence remains inconclusive. Here we quantified in vivo MOR availability in the brains of 204 individuals with no neurologic or psychiatric disorders using positron emission tomography (PET) with tracer [11C]carfentanil. We then used Bayesian hierarchical modeling to estimate the effects of sex, age, body mass index (BMI) and smoking on [11C]carfentanil binding potential. We also examined hemispheric lateralization of MOR availability. Age had regionally specific effects on MOR availability, with age-dependent increase in frontotemporal areas but decrease in amygdala, thalamus, and nucleus accumbens. The age-dependent increase was stronger in males. MOR availability was globally lowered in smokers but independent of BMI. Finally, MOR availability was higher in the right versus the left hemisphere. The presently observed variation in MOR availability may explain why some individuals are prone to develop MOR-linked pathological states, such as chronic pain or psychiatric disorders.

scholarly journals Aging of Podospora anserina Leads to Alterations of OXPHOS and the Induction of Non-Mitochondrial Salvage Pathways

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3319
Author(s):  
Verena Warnsmann ◽  
Jana Meisterknecht ◽  
Ilka Wittig ◽  
Heinz D. Osiewacz
Keyword(s):  
Protein Complexes ◽  
Mitochondrial Protein ◽  
Podospora Anserina ◽  
Mitochondrial Morphology ◽  
Complex Iv ◽  
Protein Levels ◽  
Age Dependent ◽  
Functionally Impaired ◽  
Salvage Pathways

The accumulation of functionally impaired mitochondria is a key event in aging. Previous works with the fungal aging model Podospora anserina demonstrated pronounced age-dependent changes of mitochondrial morphology and ultrastructure, as well as alterations of transcript and protein levels, including individual proteins of the oxidative phosphorylation (OXPHOS). The identified protein changes do not reflect the level of the whole protein complexes as they function in-vivo. In the present study, we investigated in detail the age-dependent changes of assembled mitochondrial protein complexes, using complexome profiling. We observed pronounced age-depen-dent alterations of the OXPHOS complexes, including the loss of mitochondrial respiratory supercomplexes (mtRSCs) and a reduction in the abundance of complex I and complex IV. Additionally, we identified a switch from the standard complex IV-dependent respiration to an alternative respiration during the aging of the P. anserina wild type. Interestingly, we identified proteasome components, as well as endoplasmic reticulum (ER) proteins, for which the recruitment to mitochondria appeared to be increased in the mitochondria of older cultures. Overall, our data demonstrate pronounced age-dependent alterations of the protein complexes involved in energy transduction and suggest the induction of different non-mitochondrial salvage pathways, to counteract the age-dependent mitochondrial impairments which occur during aging.

Abstract 1421: In Vivo Measurement of Flow-Mediated Vasodilation in Living Rats using High Resolution Ultrasound: Age-Dependent Endothelial Dysfunction

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Christian Heiss ◽  
Richard E Sievers ◽  
Nicolas Amabile ◽  
Tony Y Momma ◽  
Shobha Natarajan ◽  
...  
Keyword(s):  
High Resolution ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Femoral Artery ◽  
Reactive Hyperemia ◽  
Surrogate Marker ◽  
Flow Measurements ◽  
Age Related ◽  
Age Dependent

In humans, endothelial function serves as a surrogate marker for cardiovascular health and is measured as changes in arterial diameter after temporary ischemia (flow-mediated dilation; FMD). We developed an FMD-related approach to study conduit artery vasodilation in living rats, and demonstrate a reduction in FMD in older versus younger animals consistent with age-related endothelial dysfunction. Diameter and Doppler-flow measurements were obtained from the femoral artery using high-resolution ultrasound (35 MHz). We observed dose-dependent vasodilation using both endothelium-dependent and endothelium-independent pharmacologic vasodilators (acetylcholine and nitroglycerine). Flow-dependent vasodilation was observed in response to flow increase induced both by adenosine and local saline infusion. Transient hindlimb ischemia led to reactive hyperemia with sequential flow velocity increase and femoral artery dilation, the latter of which was completely abolished by NO-synthase (NOS) inhibition with L-NMMA. To demonstrate its applicability in a model of endothelial dysfunction, we show that FMD is significantly reduced in older versus younger animals. While FMD was completely NOS-dependent in younger animals, NOS-dependent mechanisms accounted for only half of the FMD in older animals, with the remainder being blocked by charybdotoxin (CTx) and apamin suggesting contribution of endothelium-derived-hyperpolarizing-factor. Using this new integrative physiologic model to reproducibly study FMD in living rats, we show that age-dependent endothelial dysfunction is accompanied by a shift in mechanisms underlying vasodilatory endothelial function.

scholarly journals Age-dependent emergence of neurophysiological and behavioral abnormalities in progranulin-deficient mice

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Dávid Nagy ◽  
Lauren Herl Martens ◽  
Liza Leventhal ◽  
Angela Chen ◽  
Craig Kelley ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Neurodegenerative Disorder ◽  
Neuronal Loss ◽  
Loss Of Function ◽  
Behavioral Alterations ◽  
Response Latencies ◽  
Reward Seeking ◽  
Behavioral Abnormalities ◽  
Age Dependent

Abstract Background Loss-of-function mutations in the progranulin gene cause frontotemporal dementia, a genetic, heterogeneous neurodegenerative disorder. Progranulin deficiency leads to extensive neuronal loss in the frontal and temporal lobes, altered synaptic connectivity, and behavioral alterations. Methods The chronological emergence of neurophysiological and behavioral phenotypes of Grn heterozygous and homozygous mice in the dorsomedial thalamic—medial prefrontal cortical pathway were evaluated by in vivo electrophysiology and reward-seeking/processing behavior, tested between ages 3 and 12.5 months. Results Electrophysiological recordings identified a clear age-dependent deficit in the thalamocortical circuit. Both heterozygous and homozygous mice exhibited impaired input-output relationships and paired-pulse depression, but evoked response latencies were only prolonged in heterozygotes. Furthermore, we demonstrate firstly an abnormal reward-seeking/processing behavior in the homozygous mice which correlates with previously reported neuroinflammation. Conclusion Our findings indicate that murine progranulin deficiency causes age-dependent neurophysiological and behavioral abnormalities thereby indicating their validity in modeling aspects of human frontotemporal dementia.

scholarly journals Cav2.3 channels contribute to dopaminergic neuron loss in a model of Parkinson’s disease

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Julia Benkert ◽  
Simon Hess ◽  
Shoumik Roy ◽  
Dayne Beccano-Kelly ◽  
Nicole Wiederspohn ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Neuronal Viability ◽  
Age Dependent ◽  
Human Ipsc ◽  
Reduced Activity ◽  
Dopaminergic Neuron Loss ◽  
Full Protection

Abstract Degeneration of dopaminergic neurons in the substantia nigra causes the motor symptoms of Parkinson’s disease. The mechanisms underlying this age-dependent and region-selective neurodegeneration remain unclear. Here we identify Cav2.3 channels as regulators of nigral neuronal viability. Cav2.3 transcripts were more abundant than other voltage-gated Ca2+ channels in mouse nigral neurons and upregulated during aging. Plasmalemmal Cav2.3 protein was higher than in dopaminergic neurons of the ventral tegmental area, which do not degenerate in Parkinson’s disease. Cav2.3 knockout reduced activity-associated nigral somatic Ca2+ signals and Ca2+-dependent after-hyperpolarizations, and afforded full protection from degeneration in vivo in a neurotoxin Parkinson’s mouse model. Cav2.3 deficiency upregulated transcripts for NCS-1, a Ca2+-binding protein implicated in neuroprotection. Conversely, NCS-1 knockout exacerbated nigral neurodegeneration and downregulated Cav2.3. Moreover, NCS-1 levels were reduced in a human iPSC-model of familial Parkinson’s. Thus, Cav2.3 and NCS-1 may constitute potential therapeutic targets for combatting Ca2+-dependent neurodegeneration in Parkinson’s disease.

Age-dependent calibration factors for in-vivo monitoring of 131I in thyroid using Monte Carlo simulations

2019 ◽  
Vol 125 ◽  
pp. 96-105 ◽  
Author(s):  
J.M. Gómez-Ros ◽  
M. Moraleda ◽  
P. Teles ◽  
K. Tymińska ◽  
M.A. Saizu ◽  
...  
Keyword(s):  
Monte Carlo ◽  
Monte Carlo Simulations ◽  
In Vivo Monitoring ◽  
Age Dependent
Sign in / Sign up

Export Citation Format

Share Document