scholarly journals Beading of injured axons driven by tension- and adhesion-regulated membrane shape instability

2020 ◽  
Vol 17 (168) ◽  
pp. 20200331
Author(s):  
Xueying Shao ◽  
Maja Højvang Sørensen ◽  
Xingyu Xia ◽  
Chao Fang ◽  
Tsz Hin Hui ◽  
...  
Keyword(s):  
Average Distance ◽  
Membrane Surface ◽  
Treatment Strategies ◽  
Key Factors ◽  
Neuron Death ◽  
Atomic Force ◽  
System Degeneration ◽  
Underlying Mechanisms ◽  
Work Done ◽  
Membrane Shape

The formation of multiple beads along an injured axon will lead to blockage of axonal transport and eventually neuron death, and this has been widely recognized as a hallmark of nervous system degeneration. Nevertheless, the underlying mechanisms remain poorly understood. Here, we report a combined experimental and theoretical study to reveal key factors governing axon beading. Specifically, by transecting well-developed axons with a sharp atomic force microscope probe, significant beading of the axons was triggered. We showed that adhesion was not required for beading to occur, although when present strong axon–substrate attachments seemed to set the locations for bead formation. In addition, the beading wavelength, representing the average distance between beads, was found to correlate with the size and cytoskeleton integrity of axon, with a thinner axon or a disrupted actin cytoskeleton both leading to a shorter beading wavelength. A model was also developed to explain these observations which suggest that axon beading originates from the shape instability of the membrane and is driven by the release of work done by axonal tension as well as the reduction of membrane surface energy. The beading wavelength predicted from this theory was in good agreement with our experiments under various conditions. By elucidating the essential physics behind axon beading, the current study could enhance our understanding of how axonal injury and neurodegeneration progress as well as provide insights for the development of possible treatment strategies.

Targeting Tumour Metastasis: The Emerging Role of Nanotechnology

2020 ◽  
Vol 27 (8) ◽  
pp. 1367-1381 ◽  
Author(s):  
Sarah Visentin ◽  
Mirela Sedić ◽  
Sandra Kraljević Pavelić ◽  
Krešimir Pavelić
Keyword(s):  
Cancer Progression ◽  
Metastatic Cancer ◽  
Treatment Strategies ◽  
Metastatic Progression ◽  
Therapeutic Concept ◽  
Molecular Alterations ◽  
Tumour Metastasis ◽  
Metastatic Cells ◽  
Metastatic Process ◽  
Underlying Mechanisms

The metastatic process has still not been completely elucidated, probably due to insufficient knowledge of the underlying mechanisms. Here, we provide an overview of the current findings that shed light on specific molecular alterations associated with metastasis and present novel concepts in the treatment of the metastatic process. In particular, we discuss novel pharmacological approaches in the clinical setting that target metastatic progression. New insights into the process of metastasis allow optimisation and design of new treatment strategies, especially in view of the fact that metastatic cells share common features with stem cells. Nano- and micro-technologies are herein elaborated in details as a promising therapeutic concept in targeted drug delivery for metastatic cancer. Progression in the field could provide a more efficient way to tackle metastasis and thus bring about advancements in the treatment and management of patients with advanced cancer.

Does Vitamin K Intake Influence High Phosphate Induced Vascular Pseudo-ossification: An Underappreciated Therapeutic Prospect in General Population?

2019 ◽  
Vol 20 (4) ◽  
pp. 421-430
Author(s):  
Zar Chi Thent ◽  
Gabriele R.A. Froemming ◽  
Suhaila Abd Muid
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vascular Calcification ◽  
Vitamin K ◽  
Prolonged Exposure ◽  
Vascular Complication ◽  
Key Factors ◽  
The Matrix ◽  
Underlying Mechanisms ◽  
High Phosphate

Increasing interest in vascular pseudo-ossification has alarmed the modern atherosclerotic society. High phosphate is one of the key factors in vascular pseudo ossification, also known as vascular calcification. The active process of deposition of the phosphate crystals in vascular tissues results in arterial stiffness. High phosphate condition is mainly observed in chronic kidney disease patients. However, prolonged exposure with high phosphate enriched foods such as canned drinks, dietary foods, etc. can be considered as modifiable risk factors for vascular complication in a population regardless of chronic kidney disease. High intake of vitamin K regulates the vascular calcification by exerting its anti-calcification effect. The changes in serum phosphate and vitamin K levels in a normal individual with high phosphate intake are not well investigated. This review summarised the underlying mechanisms of high phosphate induced vascular pseudo ossification such as vascular transdifferentiation, vascular apoptosis and phosphate uptake by sodium-dependent co-transporters. Pubmed, Science Direct, Scopus, ISI Web of Knowledge and Google Scholar were searched using the terms ‘vitamin K’, ‘vascular calcification, ‘phosphate’, ‘transdifferentiation’ and ‘vascular pseudoossification’. Vitamin K certainly activates the matrix GIA protein and inhibits vascular transition and apoptosis in vascular pseudo-ossification. The present view highlighted the possible therapeutic linkage between vitamin K and the disease. Understanding the role of vitamin K will be considered as potent prophylaxis agent against the vascular disease in near future.

Huntington Disease

2019 ◽  
pp. 644-678
Author(s):  
Jane S. Paulsen
Keyword(s):  
Huntington Disease ◽  
Trinucleotide Repeat ◽  
Behavioral Control ◽  
Time Estimation ◽  
Brain Dysfunction ◽  
Medium Spiny Neuron ◽  
Loss Of Function ◽  
Neuron Death ◽  
Gene Therapies ◽  
Underlying Mechanisms

Huntington disease (HD) is a autosomal dominant neurodegenerative disease caused by expansion of a trinucleotide repeat (cytosine, adenine, and guanine [CAG]) on the short arm of chromosome four. Average age of motor diagnosis is 39 years, and age at diagnosis is associated with the length of the CAG mutation. The prodrome of HD can be recognized 15 years prior to motor diagnosis and is characterized by subtle impairments in emotional recognition, smell identification, speed of processing, time estimation and production, and psychiatric abnormalities. HD shows particular vulnerability of the medium spiny neuron in the basal ganglia. Progressive brain dysfunction and neuron death lead to insidious loss of function in motor, cognitive, and behavioral control over 34 years (17 prodromal and 17 post-diagnosis). Treatment plans rely on genetic counseling, psychiatric symptom treatment as needed, physical therapy, and environmental modifications. There are two treatments for the reduction of chorea, but there are no disease-modifying therapies. Experimental therapeutics are rapidly emerging with multiple and various targets, however, and gene therapies to silence the mutant HD gene are currently ongoing. This chapter reviews clinical and neuropathological descriptions of HD and discusses potential underlying mechanisms and animal models, diagnostic and clinical assessments used to characterize and track the disease, treatment planning, and challenges for research to advance care.

Mechanical Properties of Membrane Surface of Cultured Astrocyte Revealed by Atomic Force Microscopy

2000 ◽  
Vol 39 (Part 1, No. 6B) ◽  
pp. 3711-3716 ◽  
Author(s):  
Hatsuki Shiga ◽  
Yukako Yamane ◽  
Etsuro Ito ◽  
Kazuhiro Abe ◽  
Kazushige Kawabata ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Atomic Force Microscopy ◽  
Membrane Surface ◽  
Force Microscopy ◽  
Atomic Force

scholarly journals From Stress to Shape: Equilibrium of Cloister and Cross Vaults

2021 ◽  
Vol 11 (9) ◽  
pp. 3846
Author(s):  
Andrea Montanino ◽  
Carlo Olivieri ◽  
Giulio Zuccaro ◽  
Maurizio Angelillo
Keyword(s):  
Error Function ◽  
Membrane Surface ◽  
Equilibrium Analysis ◽  
Test Cases ◽  
Order Partial Differential Equation ◽  
Negative Semidefinite ◽  
Historical Heritage ◽  
Masonry Vaults ◽  
Membrane Shape ◽  
The Given

The assessment of the equilibrium and the safety of masonry vaults is of high relevance for the conservation and restoration of historical heritage. In the literature many approaches have been proposed for this tasks, starting from the 17th century. In this work we focus on the Membrane Equilibrium Analysis, developed under the Heyman’s theory of Limit Analysis. Within this theory, the equilibrium of a vault is assessed if it is possible to find at least one membrane surface, between the volume of the vaults, being in equilibrium under the given loads through a purely compressive stress field. The equilibrium of membranes is described by a second order partial differential equation, which is definitely elliptic only when a negative semidefinite stress is assigned, and the shape is the unknown of the problem. The proposed algorithm aims at finding membrane shapes, entirely comprised between the geometry of the vault, in equilibrium with admissible stress fields, through the minimization of an error function with respect to shape parameters of the stress potential, and then, with respect to the boundary values of the membrane shape. The application to two test cases shows the viability of this tool for the assessment of the equilibrium of existing masonry vaults.

Image enhancement of polyethersulfone ultrafiltration membrane surface structure for atomic force microscopy

1992 ◽  
Vol 46 (1) ◽  
pp. 167-178 ◽  
Author(s):  
A. K. Fritzsche ◽  
A. R. Arevalo ◽  
M. D. Moore ◽  
C. J. Weber ◽  
V. B. Elings ◽  
...  
Keyword(s):  
Atomic Force Microscopy ◽  
Surface Structure ◽  
Image Enhancement ◽  
Membrane Surface ◽  
Ultrafiltration Membrane ◽  
Force Microscopy ◽  
Atomic Force

scholarly journals A Systematic Study of Ammonia Recovery from Anaerobic Digestate Using Membrane-Based Separation

Membranes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 19
Author(s):  
Fanny Rivera ◽  
Raúl Muñoz ◽  
Pedro Prádanos ◽  
Antonio Hernández ◽  
Laura Palacio
Keyword(s):  
Flow Rate ◽  
Membrane Surface ◽  
H2so4 Solution ◽  
Membrane Area ◽  
Recirculation Flow ◽  
Force Microscopy ◽  
Reservoir Volume ◽  
Atomic Force ◽  
Flat Sheet ◽  
Ammonia Recovery

Ammonia recovery from synthetic and real anaerobic digestates was accomplished using hydrophobic flat sheet membranes operated with H2SO4 solutions to convert ammonia into ammonium sulphate. The influence of the membrane material, flow rate (0.007, 0.015, 0.030 and 0.045 m3 h−1) and pH (7.6, 8.9, 10 and 11) of the digestate on ammonia recovery was investigated. The process was carried out with a flat sheet configuration at a temperature of 35 °C and with a 1 M, or 0.005 M, H2SO4 solution on the other side of the membrane. Polytetrafluoroethylene membranes with a nominal pore radius of 0.22 µm provided ammonia recoveries from synthetic and real digestates of 84.6% ± 1.0% and 71.6% ± 0.3%, respectively, for a membrane area of 8.6 × 10−4 m2 and a reservoir volume of 0.5 L, in 3.5 h with a 1 M H2SO4 solution and a recirculation flow on the feed side of the membrane of 0.030 m3 h−1. NH3 recovery followed first order kinetics and was faster at higher pHs of the H2SO4 solution and recirculation flow rate on the membrane feed side. Fouling resulted in changes in membrane surface morphology and pore size, which were confirmed by Atomic Force Microscopy and Air Displacement Porometry.

scholarly journals Key Factors Contributing to Quality of Life for Breast Cancer Patients in Latvia: Supplementing Quantitative Surveys with Qualitative Interviews

2012 ◽  
Vol 12 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Agnese Dzērvīte ◽  
Maruta Pranka ◽  
Tana Lace ◽  
Ritma Rungule ◽  
Edvins Miklasevics ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Cancer Patients ◽  
Qualitative Interviews ◽  
Treatment Strategies ◽  
Well Being ◽  
University Hospital ◽  
Breast Cancer Patients ◽  
Key Factors

Summary Introduction. Health related quality of life is a much debated topic in medicine with much quantitative and qualitative research contributing to the understanding of how to improve the lives of patients, yet little has been published in relation to the quality of life of Latvian breast cancer patients. Aim of the Study. To gather base measurements of subjective and objective quality of life factors for breast cancer patients in Latvia and discover which key factors contribute most to quality of life of Latvian breast cancer patients at the start of treatment. Materials and Methods. This paper presents data collected from April 2010 to June 2011 at the Pauls Stradins Clinical University hospital on key factors influencing quality of life for breast cancer patients: health and physical well-being; state of surroundings and environment; social support and functionality; financial state, employment and leisure. Quantitative survey material has been supplemented with insight from qualitative in-depth interviews to better explain the objective and subjective implications for breast cancer patients’ quality of life. Results. Interviewed breast cancer patients rated their quality of life as being average or good at the beginning of treatment. Negative factors contributing to lowered quality of life were mainly linked to patient financial, social and emotional state at the first weeks of treatment and correspond to previous research done in Latvia on quality of life issues. Conclusions. Further follow-up surveys will contribute to the evaluation of breast cancer patients’ needs while undergoing treatment to further improve treatment strategies, especially if validated quality of life measurement surveys were to be implemented in Latvian hospitals.

scholarly journals Experimental and computational analyses reveal dynamics of tumor vessel cooption and optimal treatment strategies

2019 ◽  
Vol 116 (7) ◽  
pp. 2662-2671 ◽  
Author(s):  
Chrysovalantis Voutouri ◽  
Nathaniel D. Kirkpatrick ◽  
Euiheon Chung ◽  
Fotios Mpekris ◽  
James W. Baish ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Antiangiogenic Therapy ◽  
Treatment Strategies ◽  
Tumor Evolution ◽  
Combination Therapies ◽  
Tumor Vessel ◽  
Antiangiogenic Treatment ◽  
Antiangiogenic Drugs ◽  
Underlying Mechanisms ◽  
Computational Analyses

Cooption of the host vasculature is a strategy that some cancers use to sustain tumor progression without—or before—angiogenesis or in response to antiangiogenic therapy. Facilitated by certain growth factors, cooption can mediate tumor infiltration and confer resistance to antiangiogenic drugs. Unfortunately, this mode of tumor progression is difficult to target because the underlying mechanisms are not fully understood. Here, we analyzed the dynamics of vessel cooption during tumor progression and in response to antiangiogenic treatment in gliomas and brain metastases. We followed tumor evolution during escape from antiangiogenic treatment as cancer cells coopted, and apparently mechanically compressed, host vessels. To gain deeper understanding, we developed a mathematical model, which incorporated compression of coopted vessels, resulting in hypoxia and formation of new vessels by angiogenesis. Even if antiangiogenic therapy can block such secondary angiogenesis, the tumor can sustain itself by coopting existing vessels. Hence, tumor progression can only be stopped by combination therapies that judiciously block both angiogenesis and cooption. Furthermore, the model suggests that sequential blockade is likely to be more beneficial than simultaneous blockade.

scholarly journals Current and Future Treatments in Alzheimer Disease: An Update

2020 ◽  
Vol 12 ◽  
pp. 117957352090739 ◽  
Author(s):  
Konstantina G Yiannopoulou ◽  
Sokratis G Papageorgiou
Keyword(s):  
Alzheimer Disease ◽  
Clinical Symptoms ◽  
Neurofibrillary Tangle ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Amyloid Β ◽  
Cell Therapies ◽  
Novel Biomarkers ◽  
Disease Modifying ◽  
Underlying Mechanisms

Disease-modifying treatment strategies for Alzheimer disease (AD) are still under extensive research. Nowadays, only symptomatic treatments exist for this disease, all trying to counterbalance the neurotransmitter disturbance: 3 cholinesterase inhibitors and memantine. To block the progression of the disease, therapeutic agents are supposed to interfere with the pathogenic steps responsible for the clinical symptoms, classically including the deposition of extracellular amyloid β plaques and intracellular neurofibrillary tangle formation. Other underlying mechanisms are targeted by neuroprotective, anti-inflammatory, growth factor promotive, metabolic efficacious agents and stem cell therapies. Recent therapies have integrated multiple new features such as novel biomarkers, new neuropsychological outcomes, enrollment of earlier populations in the course of the disease, and innovative trial designs. In the near future different specific agents for every patient might be used in a “precision medicine” context, where aberrant biomarkers accompanied with a particular pattern of neuropsychological and neuroimaging findings could determine a specific treatment regimen within a customized therapeutic framework. In this review, we discuss potential disease-modifying therapies that are currently being studied and potential individualized therapeutic frameworks that can be proved beneficial for patients with AD.

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