scholarly journals Polyamine catabolism and disease

2009 ◽  
Vol 421 (3) ◽  
pp. 323-338 ◽  
Author(s):  
Robert A. Casero ◽  
Anthony E. Pegg
Keyword(s):  
Dominant Role ◽  
Therapeutic Benefit ◽  
Spermine Oxidase ◽  
Polyamine Catabolism ◽  
Disease States ◽  
Disease Aetiology ◽  
Multiple Cell ◽  
Druggable Targets ◽  
Acetylpolyamine Oxidase ◽  
Insight Into

In addition to polyamine homoeostasis, it has become increasingly clear that polyamine catabolism can play a dominant role in drug response, apoptosis and the response to stressful stimuli, and contribute to the aetiology of several pathological states, including cancer. The highly inducible enzymes SSAT (spermidine/spermine N1-acetyltransferase) and SMO (spermine oxidase) and the generally constitutively expressed APAO (N1-acetylpolyamine oxidase) appear to play critical roles in many normal and disease processes. The dysregulation of polyamine catabolism frequently accompanies several disease states and suggests that such dysregulation may both provide useful insight into disease mechanism and provide unique druggable targets that can be exploited for therapeutic benefit. Each of these enzymes has the potential to alter polyamine homoeostasis in response to multiple cell signals and the two oxidases produce the reactive oxygen species H2O2 and aldehydes, each with the potential to produce pathological states. The activity of SSAT provides substrates for APAO or substrates for the polyamine exporter, thus reducing the intracellular polyamine concentration, the net effect of which depends on the magnitude and rate of any increase in SSAT. SSAT may also influence cellular metabolism via interaction with other proteins and by perturbing the content of acetyl-CoA and ATP. The goal of the present review is to cover those aspects of polyamine catabolism that have an impact on disease aetiology or treatment and to provide a solid background in this ever more exciting aspect of polyamine biology.

scholarly journals Quantifying exosome secretion from single cells reveals a modulatory role for GPCR signaling

2018 ◽  
Vol 217 (3) ◽  
pp. 1129-1142 ◽  
Author(s):  
Frederik Johannes Verweij ◽  
Maarten P. Bebelman ◽  
Connie R. Jimenez ◽  
Juan J. Garcia-Vallejo ◽  
Hans Janssen ◽  
...  
Keyword(s):  
Total Internal Reflection ◽  
Single Cells ◽  
Cell Communication ◽  
Exosome Biogenesis ◽  
Real Time Visualization ◽  
Target Membrane ◽  
Syntaxin 4 ◽  
Optical Reporters ◽  
Druggable Targets ◽  
Insight Into

Exosomes are small endosome-derived extracellular vesicles implicated in cell–cell communication and are secreted by living cells when multivesicular bodies (MVBs) fuse with the plasma membrane (PM). Current techniques to study exosome physiology are based on isolation procedures after secretion, precluding direct and dynamic insight into the mechanics of exosome biogenesis and the regulation of their release. In this study, we propose real-time visualization of MVB–PM fusion to overcome these limitations. We designed tetraspanin-based pH-sensitive optical reporters that detect MVB–PM fusion using live total internal reflection fluorescence and dynamic correlative light–electron microscopy. Quantitative analysis demonstrates that MVB–PM fusion frequency is reduced by depleting the target membrane SNAREs SNAP23 and syntaxin-4 but also can be induced in single cells by stimulation of the histamine H1 receptor (H1HR). Interestingly, activation of H1R1 in HeLa cells increases Ser110 phosphorylation of SNAP23, promoting MVB–PM fusion and the release of CD63-enriched exosomes. Using this single-cell resolution approach, we highlight the modulatory dynamics of MVB exocytosis that will help to increase our understanding of exosome physiology and identify druggable targets in exosome-associated pathologies.

Clinical Analysis of Laryngeal Trauma Secondary to Intubation

1983 ◽  
Vol 76 (11) ◽  
pp. 928-932 ◽  
Author(s):  
M J Gleeson ◽  
A J Fourcin
Keyword(s):  
Frequency Distribution ◽  
Vocal Fold ◽  
Clinical Analysis ◽  
Short Term ◽  
Frequency Distributions ◽  
Laryngeal Trauma ◽  
Disease States ◽  
Objective Evidence ◽  
The Voice ◽  
Insight Into

A study was undertaken to analyse the effect of short-term intubation on the voice. Children were examined laryngographically both pre- and postoperatively. Changes in larynx frequency distribution following intubation were documented using the technique of electrolaryngography; the resolution of these changes was similarly recorded. The results, in comparison with the frequency distributions associated with other disease states, give insight into the nature of the damage and its effect on vocal fold vibratory patterns. The technique therefore enables objective evidence of minor degrees of laryngeal trauma to be demonstrated and differentiated.

scholarly journals Dual inhibitors of LSD1 and spermine oxidase

MedChemComm ◽  
2019 ◽  
Vol 10 (5) ◽  
pp. 778-790 ◽  
Author(s):  
Steven Holshouser ◽  
Matthew Dunworth ◽  
Tracy Murray-Stewart ◽  
Yuri K. Peterson ◽  
Pieter Burger ◽  
...  
Keyword(s):  
Spermine Oxidase ◽  
Dual Inhibitors ◽  
Acetylpolyamine Oxidase

Dual inhibitors of LSD1 and SMOX, with no activity against N1-acetylpolyamine oxidase (PAOX).

scholarly journals Galvanic vestibular stimulation modulates the electrophysiological response during face processing

2012 ◽  
Vol 29 (4-5) ◽  
pp. 255-262 ◽  
Author(s):  
DAVID WILKINSON ◽  
HEATHER J. FERGUSON ◽  
ALAN WORLEY
Keyword(s):  
Face Processing ◽  
Power Spectra ◽  
Vestibular Stimulation ◽  
Therapeutic Benefit ◽  
Galvanic Vestibular Stimulation ◽  
Event Related Potential ◽  
Electrophysiological Response ◽  
Disease States ◽  
Vestibular Information ◽  
Theta Frequency

AbstractAlthough galvanic vestibular stimulation (GVS) is known to affect the speed and accuracy of visual judgments, the underlying electrophysiological response has not been explored. In the present study, we therefore investigated the effect of GVS on the N170 event-related potential, a marker commonly associated with early visual structural encoding. To elicit the waveform, participants distinguished famous from nonfamous faces that were presented in either upright or inverted orientation. Relative to a sham, stimulation increased the amplitude of the N170 and also elevated power spectra within the delta and theta frequency bands, components that have likewise been associated with face processing. This study constitutes the first attempt to model the effects of GVS on the electrophysiological response and, more specifically, indicates that unisensory visual processes linked to object construction are influenced by vestibular information. Given that reductions in the magnitude of both the N170 event-related potential and delta/theta activity accompany certain disease states, GVS may provide hitherto unreported therapeutic benefit.

Dynamic Crushing of All-Metallic Corrugated Panels Filled With Close-Celled Aluminum Foams

2015 ◽  
Vol 82 (1) ◽  
Author(s):  
B. Yu ◽  
B. Han ◽  
C. Y. Ni ◽  
Q. C. Zhang ◽  
C. Q. Chen ◽  
...  
Keyword(s):  
Aluminum Foam ◽  
Sandwich Panel ◽  
Dominant Role ◽  
Sandwich Panels ◽  
Rate Sensitivity ◽  
Aluminum Foams ◽  
Foam Filling ◽  
Plastic Hardening ◽  
Insight Into

Under quasi-static uniaxial compression, inserting aluminum foams into the interstices of a metallic sandwich panel with corrugated core increased significantly both its peak crushing strength and energy absorption per unit mass. This beneficial effect diminished however if the foam relative density was relatively low or the compression velocity became sufficiently high. To provide insight into the varying role of aluminum foam filler with increasing compression velocity, the crushing response and collapse modes of all metallic corrugate-cored sandwich panels filled with close-celled aluminum foams were studied using the method of finite elements (FEs). The constraint that sandwich panels with and without foam filling had the same total weight was enforced. The effects of plastic hardening and strain rate sensitivity of the strut material as well as foam/strut interfacial debonding were quantified. Three collapse modes (quasi-static, transition, and shock modes) were identified, corresponding to different ranges of compression velocity. Strengthening due to foam insertion and inertial stabilization both acted to provide support for the struts against buckling. At relatively low compression velocities, the struts were mainly strengthened by the surrounding foam; at high compression velocities, inertia stabilization played a more dominant role than foam filling.

Mucin mRNA Expression in Normal and Vasomotor Inferior Turbinates

1997 ◽  
Vol 11 (4) ◽  
pp. 293-302 ◽  
Author(s):  
Michelle R. Aust ◽  
Cathy S. Madsen ◽  
Anita Jennings ◽  
Jan L. Kasperbauer ◽  
Sandra J. Gendler
Keyword(s):  
Respiratory Tract ◽  
Expression Patterns ◽  
Inferior Turbinate ◽  
Cell Types ◽  
Upper Respiratory Tract ◽  
Vasomotor Rhinitis ◽  
Disease States ◽  
Multiple Cell ◽  
Nasal Secretions

Mucins are the major glycoprotein component of respiratory tract secretions. Little is known about their expression in the upper respiratory tract. In order to define this expression, in situ hybridization was performed on 19 normal and 4 vasomotor rhinitis (VMR) inferior turbinates to identify mucin mRNA. MUC1, MUC2, MUC4, MUC5AC, MUC5B, and MUC7 were expressed in both the normal and VMR turbinates. MUC 4 and MUC5AC were the most highly expressed mucins. MUC1, MUC2, MUC4, and MUC5AC were expressed mainly by the epithelial border, whereas MUC5B and MUC7 were expressed by the submucosal glands. MUC1 and MUC4 exhibited a diffuse expression by multiple cell types along the mucosal border, whereas MUC2 and MUC5AC expression appeared to be limited to a subpopulation of epithelial cells, most likely goblet cells. Although MUC1, MUC4, and MUC5AC showed sporadic submucosal glandular expression, MUC5B and MUC7 appeared to be the predominant submucosal gland mucins in the inferior turbinates. MUC3 and MUC6 expression, which have been found primarily in the gastric mucosa, were not seen in any of the inferior turbinate samples examined. The only difference seen between normal and VMR turbinates was a slight decrease in MUC1 expression in the VMR group. The variety of mucins expressed and the diversity of their expression patterns may have significance in terms of the rheologic and particle clearance properties of nasal secretions. Understanding the expression patterns in normal turbinates will serve as the foundation for further study of these mucins in disease states.

scholarly journals The magneto-Rayleigh–Taylor instability in dynamic z pinches

2001 ◽  
Vol 19 (4) ◽  
pp. 527-540 ◽  
Author(s):  
M.R. DOUGLAS ◽  
J.S. DE GROOT ◽  
R.B. SPIELMAN
Keyword(s):  
Peak Plasma ◽  
Dominant Role ◽  
Three Dimensional ◽  
Vacuum Field ◽  
Nonlinear Growth ◽  
Spatial Uniformity ◽  
Rayleigh Taylor Instability ◽  
Magnetohydrodynamic Simulations ◽  
Insight Into ◽  
Initial Seeding

The magneto-Rayleigh–Taylor (MRT) instability limits the performance of dynamic z pinches. This instability develops at the plasma-vacuum/field interface, growing in amplitude throughout the implosion, thereby reducing the peak plasma velocity and spatial uniformity at stagnation. MRT instabilities are believed to play a dominant role in the case of high wire number arrays, gas puffs and foils. In this article, the MRT instability is discussed in terms of initial seeding, linear and nonlinear growth, experimental evidence, radiation magnetohydrodynamic simulations, and mitigating schemes. A number of experimental results are presented, where the mitigating schemes have been realized. In general, the problem is inherently three dimensional, but two-dimensional simulations together with theory and experiment enhance our physical understanding and provide insight into future load design.

scholarly journals Searching for new therapy options – the microbiome in the spotlight of stroke research

2017 ◽  
Vol 39 (2) ◽  
pp. 18-21
Author(s):  
Andreas Meisel ◽  
Katarzyna Winek
Keyword(s):  
Neurological Disorders ◽  
Proper Function ◽  
Disease States ◽  
Stroke Research ◽  
Trace Back ◽  
Microbiome Research ◽  
The Central Nervous System ◽  
Basic Ideas ◽  
And Function ◽  
Insight Into

Commensal microorganisms are indispensable for the proper function of the central nervous system, and alterations in the composition and function of the microbiome are linked to different disease states. In this feature, we provide insight into microbiome research from a neuroscientific perspective and trace back basic ideas concerning the contribution of the microbiome to the pathophysiological processes in stroke – one of the most important neurological disorders.

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