scholarly journals Thinking Quantitatively of RNA-Based Information Transfer via Extracellular Vesicles: Lessons to Learn for the Design of RNA-Loaded EVs

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1931
Author(s):  
Max Piffoux ◽  
Jeanne Volatron ◽  
Amanda Silva ◽  
Florence Gazeau
Keyword(s):  
Extracellular Vesicles ◽  
Information Transfer ◽  
Point Of View ◽  
The Body ◽  
Endosomal Escape ◽  
Cell Type ◽  
Long Distance ◽  
Transfer Of Information ◽  
Transfer Mechanisms ◽  
Delivery Efficiency

Extracellular vesicles (EVs) are 50–1000 nm vesicles secreted by virtually any cell type in the body. They are expected to transfer information from one cell or tissue to another in a short- or long-distance way. RNA-based transfer of information via EVs at long distances is an interesting well-worn hypothesis which is ~15 years old. We review from a quantitative point of view the different facets of this hypothesis, ranging from natural RNA loading in EVs, EV pharmacokinetic modeling, EV targeting, endosomal escape and RNA delivery efficiency. Despite the unique intracellular delivery properties endowed by EVs, we show that the transfer of RNA naturally present in EVs might be limited in a physiological context and discuss the lessons we can learn from this example to design efficient RNA-loaded engineered EVs for biotherapies. We also discuss other potential EV mediated information transfer mechanisms, among which are ligand–receptor mechanisms.

scholarly journals Horizontal Transmission of Cytosolic Sup35 Prions by Extracellular Vesicles

mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
Shu Liu ◽  
André Hossinger ◽  
Julia P. Hofmann ◽  
Philip Denner ◽  
Ina M. Vorberg
Keyword(s):  
Extracellular Vesicles ◽  
Mammalian Cells ◽  
Information Transfer ◽  
Quaternary Structure ◽  
Horizontal Transmission ◽  
Biologically Active ◽  
Host Cells ◽  
Transmissible Spongiform Encephalopathies ◽  
Yeast Prion ◽  
Long Distance

ABSTRACT Prions are infectious protein particles that replicate by templating their aggregated state onto soluble protein of the same type. Originally identified as the causative agent of transmissible spongiform encephalopathies, prions in yeast ( Saccharomyces cerevisiae ) are epigenetic elements of inheritance that induce phenotypic changes of their host cells. The prototype yeast prion is the translation termination factor Sup35. Prions composed of Sup35 or its modular prion domain NM are heritable and are transmitted vertically to progeny or horizontally during mating. Interestingly, in mammalian cells, protein aggregates derived from yeast Sup35 NM behave as true infectious entities that employ dissemination strategies similar to those of mammalian prions. While transmission is most efficient when cells are in direct contact, we demonstrate here that cytosolic Sup35 NM prions are also released into the extracellular space in association with nanometer-sized membrane vesicles. Importantly, extracellular vesicles are biologically active and are taken up by recipient cells, where they induce self-sustained Sup35 NM protein aggregation. Thus, in mammalian cells, extracellular vesicles can serve as dissemination vehicles for protein-based epigenetic information transfer. IMPORTANCE Prions are proteinaceous infectious particles that propagate by templating their quaternary structure onto nascent proteins of the same kind. Prions in yeast act as heritable epigenetic elements that can alter the phenotype when transmitted to daughter cells or during mating. Prion activity is conferred by so-called prion domains often enriched in glutamine and asparagine residues. Interestingly, many mammalian proteins also contain domains with compositional similarity to yeast prion domains. We have recently provided a proof-of-principle demonstration that a yeast prion domain also retains its prion activity in mammalian cells. We demonstrate here that cytosolic prions composed of a yeast prion domain are also packaged into extracellular vesicles that transmit the prion phenotype to bystander cells. Thus, proteins with prion-like domains can behave as proteinaceous information molecules that exploit the cellular vesicle trafficking machinery for intercellular long-distance dissemination.

Integrating Focusing and Differentiation: A Therapeutic Path for Couples in Intimate Relationships

2018 ◽  
Vol 3 ◽  
Author(s):  
Evi Zohar
Keyword(s):  
Couples Therapy ◽  
Therapeutic Potential ◽  
Well Being ◽  
Point Of View ◽  
The Body ◽  
Self Awareness ◽  
Emotional Healing ◽  
Felt Sense ◽  
Inner World

Continuing the workshop I've given in the WPC Paris (2017), this article elaborates my discussion of the way I interlace Focusing with Differentiation Based Couples Therapy (Megged, 2017) under the systemic view, in order to facilitate processes of change and healing in working with intimate couples. This article presents the theory and rationale of integrating Differentiation (Bowen, 1978; Schnarch, 2009; Megged, 2017) and Focusing (Gendlin, 1981) approaches, and its therapeutic potential in couple's therapy. It is written from the point of view of a practicing professional in order to illustrate the experiential nature and dynamics of the suggested therapeutic path. Differentiation is a key to mutuality. It offers a solution to the central struggle of any long term intimate relationship: balancing two basic life forces - the drive for individuality and the drive for togetherness (Schnarch, 2009). Focusing is a body-oriented process of self-awareness and emotional healing, in which one learns to pay attention to the body and the ‘Felt Sense’, in order to unfold the implicit, keep it in motion at the precise pace it needs for carrying the next step forward (Gendlin, 1996). Combining Focusing and Differentiation perspectives can cultivate the kind of relationship where a conflict can be constructively and successfully held in the inner world of each partner, while taking into consideration the others' well-being. This creates the possibility for two people to build a mutual emotional field, open to changes, permeable and resilient.

Presentation

2014 ◽  
Vol 2 (3) ◽  
Author(s):  
Redacción CEIICH
Keyword(s):  
Cultural History ◽  
Social Reality ◽  
Point Of View ◽  
The Body ◽  
Literary Studies ◽  
The Third ◽  
The Social ◽  
Feminist Theories ◽  
History Of

<p class="p1">The third number of <span class="s1"><strong>INTER</strong></span><span class="s2"><strong>disciplina </strong></span>underscores this generic reference of <em>Bodies </em>as an approach to a key issue in the understanding of social reality from a humanistic perspective, and to understand, from the social point of view, the contributions of the research in philosophy of the body, cultural history of the anatomy, as well as the approximations queer, feminist theories and the psychoanalytical, and literary studies.</p>

scholarly journals Transition from Emotional to Rational Advertising for Food Products on the Romanian Market

2017 ◽  
Vol 50 (1) ◽  
pp. 101-108
Author(s):  
A.F. Jităreanu ◽  
Elena Leonte ◽  
A. Chiran ◽  
Benedicta Drobotă
Keyword(s):  
Urban Areas ◽  
Eating Habits ◽  
Well Being ◽  
Point Of View ◽  
The Body ◽  
Positive Effects ◽  
New Methods ◽  
Brand Advertising ◽  
Tangible Evidence ◽  
Health And Well Being

Abstract Advertising helps to establish a set of assumptions that the consumer will bring to all other aspects of their engagement with a given brand. Advertising provides tangible evidence of the financial credibility and competitive presence of an organization. Persuasion is becoming more important in advertising. In marketing, persuasive advertising acts to establish wants/motivations and beliefs/attitudes by helping to formulate a conception of the brand as being one which people like those in the target audience would or should prefer. Considering the changes in lifestyle and eating habits of a significant part of the population in urban areas in Romania, the paper aims to analyse how brands manage to differentiate themselves from competitors, to reposition themselves on the market and influence consumers, meeting their increasingly varied needs. Food brands on the Romanian market are trying, lately, to identify new methods of differentiation and new benefits for their buyers. Given that more and more consumers are becoming increasingly concerned about what they eat and the products’ health effects, brands struggle to highlight the fact that their products offer real benefits for the body. The advertisements have become more diversified and underline the positive effects, from the health and well - being point of view, that those foods offer (no additives and preservatives, use of natural ingredients, various vitamins and minerals or the fact that they are dietary). Advertising messages’ diversification is obvious on the Romanian market, in the context of an increasing concern of the population for the growing level of information of some major consumer segments.

scholarly journals Extracellular Vesicles of Mesenchymal Stem Cells: Therapeutic Properties Discovered with Extraordinary SuccessOK

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 667
Author(s):  
Gabriella Racchetti ◽  
Jacopo Meldolesi
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Responses ◽  
Extracellular Vesicles ◽  
Immune Regulation ◽  
Great Increase ◽  
The Body ◽  
Cell Aging ◽  
Therapeutic Effects ◽  
Therapeutic Properties

Mesenchymal stem cells (MSCs), the cells distributed in the stromas of the body, are known for various properties including replication, the potential of various differentiations, the immune-related processes including inflammation. About two decades ago, these cells were shown to play relevant roles in the therapy of numerous diseases, dependent on their immune regulation and their release of cytokines and growth factors, with ensuing activation of favorable enzymes and processes. Such discovery induced great increase of their investigation. Soon thereafter, however, it became clear that therapeutic actions of MSCs are risky, accompanied by serious drawbacks and defects. MSC therapy has been therefore reduced to a few diseases, replaced for the others by their extracellular vesicles, the MSC-EVs. The latter vesicles recapitulate most therapeutic actions of MSCs, with equal or even better efficacies and without the serious drawbacks of the parent cells. In addition, MSC-EVs are characterized by many advantages, among which are their heterogeneities dependent on the stromas of origin, the alleviation of cell aging, the regulation of immune responses and inflammation. Here we illustrate the MSC-EV therapeutic effects, largely mediated by specific miRNAs, covering various diseases and pathological processes occurring in the bones, heart and vessels, kidney, and brain. MSC-EVs operate also on the development of cancers and on COVID-19, where they alleviate the organ lesions induced by the virus. Therapy by MSC-EVs can be improved by combination of their innate potential to engineering processes inducing precise targeting and transfer of drugs. The unique properties of MSC-EVs explain their intense studies, carried out with extraordinary success. Although not yet developed to clinical practice, the perspectives for proximal future are encouraging.

scholarly journals 695 Oral delivery of a microbial extracellular vesicle induces potent anti-tumor immunity in mice

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A737-A737
Author(s):  
Loise Francisco-Anderson ◽  
Loise Francisco-Anderson ◽  
Mary Abdou ◽  
Michael Goldberg ◽  
Erin Troy ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Extracellular Vesicles ◽  
Tumor Immunity ◽  
Extracellular Vesicle ◽  
The Body ◽  
Checkpoint Inhibition ◽  
Small Intestinal ◽  
The Impact

BackgroundThe small intestinal axis (SINTAX) is a network of anatomic and functional connections between the small intestine and the rest of the body. It acts as an immunosurveillance system, integrating signals from the environment that affect physiological processes throughout the body. The impact of events in the gut in the control of tumor immunity is beginning to be appreciated. We have previously shown that an orally delivered single strain of commensal bacteria induces anti-tumor immunity preclinically via pattern recognition receptor-mediated activation of innate and adaptive immunity. Some bacteria produce extracellular vesicles (EVs) that share molecular content with the parent bacterium in a particle that is roughly 1/1000th the volume in a non-replicating form. We report here an orally-delivered and gut-restricted bacterial EV which potently attenuates tumor growth to a greater extent than whole bacteria or checkpoint inhibition.MethodsEDP1908 is a preparation of extracellular vesicles produced by a gram-stain negative strain of bacterium of the Oscillospiraceae family isolated from a human donor. EDP1908 was selected for its immunostimulatory profile in a screen of EVs from a range of distinct microbial strains. Its mechanism of action was determined by ex vivo analysis of the tumor microenvironment (TME) and by in vitro functional studies with murine and human cells.ResultsOral treatment of tumor-bearing mice with EDP1908 shows superior control of tumor growth compared to checkpoint inhibition (anti-PD-1) or an intact microbe. EDP1908 significantly increased the percentage of IFNγ and TNF producing CD8+ CTLs, NK cells, NKT cells and CD4+ cells in the tumor microenvironment (TME). EDP1908 also increased tumor-infiltrating dendritic cells (DC1 and DC2). Analysis of cytokines in the TME showed significant increases in IP-10 and IFNg production in mice treated with EDP1908, creating an environment conducive to the recruitment and activation of anti-tumor lymphocytes.ConclusionsThis is the first report of striking anti-tumor effects of an orally delivered microbial extracellular vesicle. These data point to oral EVs as a new class of immunotherapeutic drugs. They are particularly effective at harnessing the biology of the small intestinal axis, acting locally on host cells in the gut to control distal immune responses within the TME. EDP1908 is in preclinical development for the treatment of cancer.Ethics ApprovalPreclinical murine studies were conducted under the approval of the Avastus Preclinical Services’ Ethics Board. Human in vitro samples were attained by approval of the IntegReview Ethics Board; informed consent was obtained from all subjects.

scholarly journals Analysis of the Impact of a Multi-Strain Probiotic on Body Composition and Cardiorespiratory Fitness in Long-Distance Runners

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3758
Author(s):  
Joanna Smarkusz-Zarzecka ◽  
Lucyna Ostrowska ◽  
Joanna Leszczyńska ◽  
Karolina Orywal ◽  
Urszula Cwalina ◽  
...  
Keyword(s):  
Body Composition ◽  
Cardiorespiratory Fitness ◽  
The Body ◽  
Double Blind Study ◽  
Distance Runners ◽  
Long Distance ◽  
Double Blind ◽  
Necrosis Factor Alpha ◽  
Total Body ◽  
The Impact

Use of probiotic supplements, the benefits of which have not been proven in sportspeople, is becoming more widespread among runners. The aim of this study was to evaluate the effect of a multi-strain probiotic on body composition, cardiorespiratory fitness and inflammation in the body. The randomised, double-blind study included 66 long-distance runners. The intervention factor was a multi-strain probiotic or placebo. At the initial and final stages of the study, evaluation of body composition and cardiorespiratory fitness was performed and the presence of inflammation determined. In the group of men using the probiotic, an increase in lean body mass (p = 0.019) and skeletal muscle mass (p = 0.022) was demonstrated, while in the group of women taking the probiotic, a decrease in the content of total body fat (p = 0.600) and visceral fat (p = 0.247) was observed. Maximum oxygen consumption (VO2max) increased in women (p = 0.140) and men (p = 0.017) using the probiotic. Concentration of tumour necrosis factor-alpha decreased in women (p = 0.003) and men (p = 0.001) using the probiotic and in women (p = 0.074) and men (p = 0.016) using the placebo. Probiotic therapy had a positive effect on selected parameters of body composition and cardiorespiratory fitness of study participants and showed a tendency to reduce inflammation.

scholarly journals Cardiovascular risks awareness in coaches and amateur athletes

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
A Markovich ◽  
O Mironova
Keyword(s):  
Physical Activity ◽  
Cardiovascular Diseases ◽  
Heart Attack ◽  
Conflicts Of Interest ◽  
The Body ◽  
Treadmill Test ◽  
Cardiovascular Risks ◽  
Sports Cardiology ◽  
Long Distance ◽  
Endurance Sport

Abstract Funding Acknowledgements Type of funding sources: None. Background Regular physical activity is an important component of therapy for most сardiovascular diseases and is associated with reduced cardiovascular and all-cause mortality. The promotion of the physical activity and regular exercise is an important preventive measure that affects the prognosis. Purpose To assess the awareness of the prevalence of cardiovascular disease in exercising population and its influence on the safety of the patients and healthy adults among coaches and people actively engaged in sports activities. Methods An open non-randomized observation was conducted. The questionnaire created by our team included 45 questions about cardiovascular diseases and sport. 111 athletes and coaches aged from 19 to 46 were enrolled in the study. 61,5% (68) are men and 38,5% (42) of the respondents are women. 30,3% (33) of the respondents are coaches. 45,5% (15) of them have over 5 years of coaching experience. 44% (48) of all respondents prefer endurance sport, 25,7% (28) train strength exercise. 63,6% (70) train 3-8 hours per week, 12,7% (14 [7 women and 7 men]) train more than 8 hours each week. Results 18,5% (20 [6 women and 14 men]) think that ECG is enough for screening for cardiovascular diseases. 20% (4) of them are coaches. Only 69,5% (77) of all respondents know about treadmill test. And 41,6% (32/77) of them know about the necessary screening for arrhythmogenic condition. 13% (10/77) of them train more than 8 hours per week. And only 27,3% (21/77) of people who know about treadmill test, passed it themselves. Also 21,6% (24) of all respondents think that any episode of arrhythmia is the  contraindication for any sport. But 96,4% (107) of the respondents know that it is necessary to regularly screen the cardiovascular system, even in the absence of complaints. 9% (10) of the interviewed think that diet is not important for people with cardiovascular diseases. And 18,9% (21) of the respondents don’t know about the effect of electrolytes on the body and the work of the heart muscle. Only 53,2% (59 [21 women and 38 men]) of the respondents trust the doctors more than coaches or themselves. And this is one of the reasons why it is necessary to talk about the basic principles of sports cardiology not only to doctors. 8,1% (9) of the respondents have never heard about any cases of sudden death of an athlete during training or at competitions due to «heart problems». 63,6% (21) of the coaches would not train a person who has suffered a heart attack. 71,8% (56) of the sportsmen would like to return to training after a heart attack. Conclusions Despite the fact that most people prefer a sedentary lifestyle, high-intensity fitness and long-distance endurance sport is getting more popular. Our survey proves the relatively low level of education about the underlying health conditions and possible risks associated with sports not only among  athletes but  professional coaches as well. There are no conflicts of interest to declare.

scholarly journals The wave pattern of a doublet in a stream

1928 ◽  
Vol 121 (788) ◽  
pp. 515-523 ◽  
Keyword(s):  
Surface Effect ◽  
Ideal Point ◽  
Finite Size ◽  
Wave Pattern ◽  
Wave Resistance ◽  
Point Of View ◽  
The Body ◽  
Surface Elevation ◽  
More Care ◽  
Forced Waves

The following paper is a study of the surface waves caused by a doublet in a uniform stream, and in particular the variation in the pattern with the velocity of the stream or the depth of the doublet. In most recent work on this subject attention has been directed more to the wave resistance, which can be evaluated with less difficulty than is involved in a detailed study of the waves; in fact, it would seem that it is not necessary for that purpose to know the surface elevation completely, but only certain significant terms at large distances from the disturbance. Recent experimental work has shown con­siderable agreement between theoretical expressions for wave resistance and results for ship models of simple form, and attempts have been made at a similar comparison for the surface elevation in the neighbourhood of the ship. In the latter respect it may be necessary to examine expressions for the surface elevation with more care, as they are not quite determinate; any suitable free disturbance may be superposed upon the forced waves. For instance, it is well known that in a frictionless liquid a possible solution is one which gives waves in advance as well as in the rear of the ship, and the practical solution is obtained by superposing free waves which annul those in advance, or by some equivalent artifice. This process is simple and definite for an ideal point disturbance, but for a body of finite size or a distributed disturbance the complete surface elevation in the neighbourhood of the body requires more careful specification as regards the local part due to each element. It had been intended to consider some expressions specially from this point of view, but as the matter stands at present it would entail a very great amount of numerical calculation, and the present paper is limited to a much simpler problem although also involving considerable computation. A horizontal doublet of given moment is at a depth f below the surface of a stream of velocity c ; the surface effect may be described as a local disturbance symmetrical fore and aft of the doublet together with waves to the rear. Two points are made in the following work.

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