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© 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles. The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

The emergence of publications on extracellular RNA (exRNA) and extracellular vesicles (EV) has highlighted the potential of these molecules and vehicles as biomarkers of disease and therapeutic targets. These findings have created a paradigm shift, most prominently in the field of oncology, prompting expanded interest in the field and dedication of funds for EV research. At the same time, understanding of EV subtypes, biogenesis, cargo and mechanisms of shuttling remains incomplete. The techniques that can be harnessed to address the many gaps in our current knowledge were the subject of a special workshop of the International Society for Extracellular Vesicles (ISEV) in New York City in October 2012. As part of the “ISEV Research Seminar: Analysis and Function of RNA in Extracellular Vesicles (evRNA)”, 6 round-table discussions were held to provide an evidence-based framework for isolation and analysis of EV, purification and analysis of associated RNA molecules, and molecular engineering of EV for therapeutic intervention. This article arises from the discussion of EV isolation and analysis at that meeting. The conclusions of the round table are supplemented with a review of published materials and our experience. Controversies and outstanding questions are identified that may inform future research and funding priorities. While we emphasize the need for standardization of specimen handling, appropriate normative controls, and isolation and analysis techniques to facilitate comparison of results, we also recognize that continual development and evaluation of techniques will be necessary as new knowledge is amassed. On many points, consensus has not yet been achieved and must be built through the reporting of well-controlled experiments. Keywords: extracellular vesicle; exosome; microvesicle; standardization; isolation (Published: 27 May 2013) Citation: Journal of Extracellular Vesicles 2013, 2 : 20360 - http://dx.doi.org/10.3402/jev.v2i0.20360

El artículo incluye más de 400 autores The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

The release of RNA-containing extracellular vesicles (EV) into the extracellular milieu has been demonstrated in a multitude of different in vitro cell systems and in a variety of body fluids. RNA-containing EV are in the limelight for their capacity to communicate genetically encoded messages to other cells, their suitability as candidate biomarkers for diseases, and their use as therapeutic agents. Although EV-RNA has attracted enormous interest from basic researchers, clinicians, and industry, we currently have limited knowledge on which mechanisms drive and regulate RNA incorporation into EV and on how RNA-encoded messages affect signalling processes in EV-targeted cells. Moreover, EV-RNA research faces various technical challenges, such as standardisation of EV isolation methods, optimisation of methodologies to isolate and characterise minute quantities of RNA found in EV, and development of approaches to demonstrate functional transfer of EV-RNA in vivo. These topics were discussed at the 2015 EV-RNA workshop of the International Society for Extracellular Vesicles. This position paper was written by the participants of the workshop not only to give an overview of the current state of knowledge in the field, but also to clarify that our incomplete knowledge – of the nature of EV(-RNA)s and of how to effectively and reliably study them – currently prohibits the implementation of gold standards in EV-RNA research. In addition, this paper creates awareness of possibilities and limitations of currently used strategies to investigate EV-RNA and calls for caution in interpretation of the obtained data.

The release of RNA-containing extracellular vesicles (EV) into the extracellular milieu has been demonstrated in a multitude of different in vitro cell systems and in a variety of body fluids. RNA-containing EV are in the limelight for their capacity to communicate genetically encoded messages to other cells, their suitability as candidate biomarkers for diseases, and their use as therapeutic agents. Although EV-RNA has attracted enormous interest from basic researchers, clinicians, and industry, we currently have limited knowledge on which mechanisms drive and regulate RNA incorporation into EV and on how RNA-encoded messages affect signalling processes in EV-targeted cells. Moreover, EV-RNA research faces various technical challenges, such as standardisation of EV isolation methods, optimisation of methodologies to isolate and characterise minute quantities of RNA found in EV, and development of approaches to demonstrate functional transfer of EV-RNA in vivo. These topics were discussed at the 2015 EV-RNA workshop of the International Society for Extracellular Vesicles. This position paper was written by the participants of the workshop not only to give an overview of the current state of knowledge in the field, but also to clarify that our incomplete knowledge – of the nature of EV(-RNA)s and of how to effectively and reliably study them – currently prohibits the implementation of gold standards in EV-RNA research. In addition, this paper creates awareness of possibilities and limitations of currently used strategies to investigate EV-RNA and calls for caution in interpretation of the obtained data., Journal of Extracellular Vesicles, 6 (1), ISSN:2001-3078

La régression linéaire est pénalisée par l'usage de variables explicatives corrélées, situation fréquente pour les bases de données d'origine industrielleò u les corrélations sont nombreuses et enen a des estimateurs de forte variance. Lemo ele proposé ex-plicite les corrélations présentes sous la forme d'une famille de régressions linéaires en-tre covariables, permettant d'obtenir par marginalisation unmo ele de régression parci-monieux libéré des corrélations, facilement interprétable et consistant en une présélection de variables. La structure de corrélations est estiméè a l'aide d'un algorithme MCMC qui repose sur unmo ele génératif complet. Le package CorReg (sur le CRAN) permet la mise en oeuvre en R de cette méthode qui sera illustrée sur données simulées et sur données réelles issues de l'industrie sidérurgique. Linear regression is generally penalized by correlated covariates, frequent situation for industrial datasets, in particular impacting the variance of the estimators. The proposed generative model consists in modeling explicitly the correlations with a family of linear regressions between the covariates permitting to obtain by marginalization a parsimonious correlation-free regression model, easily understandable and that can be seen as a variable preselection. The structure of correlations is found with an MCMC algorithm. An R package (CorReg) available on the CRAN implements this new method which will be illustrated on both simulated datasets and real-life datasets from steel industry.

Inside APCs, MHC class II molecules associate with antigenic peptides before reaching the cell surface. This association takes place in compartments of the endocytic pathway, more related to endosomes or lysosomes depending on the cell type. Here, we compared MHC class II transport from endosomal vs lysosomal compartments to the plasma membrane. We show that transport of MHC class II molecules to the cell surface does not depend on the cytosolic domains of the α- and β-chains. In contrast, the stability of the αβ-peptide complexes determined the efficiency of transport to the cell surface from lysosomal, but not from endosomal, compartments. In murine B lymphoma cells, SDS-unstable and -stable complexes were transported to the cell surface at almost similar rates, whereas after lysosomal relocalization or in a cell line in which MHC class II molecules normally accumulate in lysosomal compartments, stable complexes were preferentially addressed to the cell surface. Our results suggest that when peptide loading occurs in lysosomal compartments, selective retention and lysosomal degradation of unstable dimers result in the expression of highly stable MHC class II-peptide complexes at the APC surface.

It is with much sadness that the Executive Board of ISEV announces the death of one of its members, Dr. Melissa “Missy” Piper, aged 45, who succumbed to complications of colon cancer on Wednesday, 11 December 2013. She is survived by her husband, Joseph Klusacek; daughter, Megan Hunter; son, Matthew Hunter; step-daughter, Allison Klusacek; step-son, Adam Klusacek; and her parents, Victor S. Piper Sr. and Helen Piper, and brother, Victor S. Piper Jr.(Published: 3 February 2014)Citation: Journal of Extracellular Vesicles 2014, 3: 23842 - http://dx.doi.org/10.3402/jev.v3.23842

First described in 1937, giant cell aortitis (aortitis associated with giant cell arteritis) occurs in 20 to 40% of patients with giant cell arteritis and is often clinically silent. Temporal involvement usually precedes aortic involvement. The process may involve the entire aorta, but complications are usually related to thoracic involvement. Patients with giant cell aortitis may be asymptomatic, or present with aortic arch syndrome, dilation of the aorta, aortic aneurysm, aortic dissection, sudden rupture of the aorta, or aortic valve incompetence. Thoracic aneurysms are usually fusiform and can be complicated by dissection in up to 50% of patients. Aortic involvement may be the presenting feature of giant cell arteritis: it may also occur in patients with preexisting temporal arteritis, often when corticosteroid therapy is reduced or discontinued. Aortic rupture complicating aortitis may be the cause of death in 3-12% of patients with giant cell arteritis. Clinical follow-up with assessment of disease activity by chest X-ray and biological markers of inflammation should be performed yearly in giant cell arteritis. Aortic involvement should be suspected if cardiac or vascular echo-Doppler shows evidence of an aortic arch syndrome, aortic dilation, aneurysm, or of aortic valve incompetence. Corticosteroid therapy, beginning with a dose of 1 mg/kg/day remains the key point of therapy. The dose is subsequently adjusted based on the clinical course and the results of ancillary tests. This treatment might prevent fatal outcome with aortic rupture. Long-term follow-up of all patients with giant cell arteritis or polymyalgia rheumatica is essential, as complications may develop late in the course of the disease.

Airborne in situ measurements of NO, NO2, NOy, CO, CO2, O3, J(NO2), and CN were performed in European thunderstorms during the field experiment EULINOX in July 1998. The measurements in the upper troposphere show enhanced NOx (= NO + NO2) concentrations within thunderstorms and their outflow at horizontal scales from 300 m to several 100 km. The maximum NO mixing ratio measured inside a thundercloud close to lightning (the aircraft was also hit by a small lightning strike) was 25 ppbv. A regional NOx enhancement of 0.5 ppbv over central Europe could be traced back to a thunderstorm event starting ∼24 hours earlier over Spain. The fractions of NOx in thunderclouds which are produced by lightning and convectively transported from the polluted boundary layer are determined by using CO2 and CO as tracers for boundary layer air. The analyses show that on average about 70% of the NOx increase measured in the anvil region was found to result from production by lightning and about 30% from NOx in the boundary layer. Thunderstorms are also strong sources of small particles. The peak CN concentrations measured within thunderstorm outflows (>30,000 particles STP cm-3) were distinctly higher than in the polluted boundary layer. The amount of NOx produced per thunderstorm and NO produced per lightning flash was estimated. The results imply that the annual mean NOx budget in the upper troposphere over Europe is dominated by aircraft emissions (0.1 TgN yr-1) in comparison to lightning production (∼0.03 TgN yr-1). On the global scale, NOx produced by lightning (mean 3 TgN yr-1) prevails over aircraft-produced NOx (0.6 TgN yr-1).