In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.

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Biological properties of extracellular vesicles and their physiological functions

Carcinoma of the prostate gland is peculiarly favorable for endocrine investigation since frequent serial observations of the activity of phosphatases in serum were found to provide objective indices of activity of the neo/~i~m when the enzymes were increased in amount above normal. In the present paper data are given for the values of serum phosphatases in carcinoma of the prostate and in normal men. We shall demonstrate that the acid phosphatase of serum is reduced in metastatic carcinoma of the prostate by decreasing the activity of androgens through castration or estrogenic injections and that this enzyme is increased by injecting androgens. We have been unable to find previous observations indicating any relationship of hormones to carcinoma of the prostate gland. An enzyme capable of hydrolyzing phosphoric esters was discovered by Grosser and Husler (4) in intestinal mucosa and kidney. Robison (16) found that this enzyme was particularly high in activity in growing bone and cartilage and that its activity was greatest at pH 9 to 9.5. This ~alkaline phosphatase," was found by Kay (9) to be increased in the serum in certain bone diseases including metastasis of neoplasms to bone and later work has shown that among these conditions is carcinoma of the prostate. Davies (3) and Bamann and Riedel (1) discovered that there occurs in the spleen and kidney of swine and cattle, in addition to the alkaline phosphatase, a phosphatase with an activity maximum at pH 4.8. An enzyme believed to be identical with this "acid phosphatase" was found by Kutscher and Wolbergs (11) to be present in very large amount in the human prostate gland. This finding of great activity of acid phosphatase in the prostate gland was confirmed and extended to include prostatic cancer by Gutman, Sproul, and Gutman (7). The serum of certain patients with disseminated prostatic carcinoma was found by Gutman and Gutman (6) and Barringer and Woodard (2) to exhibit increased acid phosphatase activity. Robinson, Gutman, and Gutman'~I5) summarized the acid phosphatase activity levels of 44 patients with carcinoma of the prostate. They concluded that a marked rise in acid phosphatase in serum is associated with the appearance or spread of roentgenologically demonstrable skeletal metastases and implies dissemination of the primary tumor and thus is of unfavorable prognostic significance. METttODS AND MATERIALS

Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate

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The colorimetric determination of phosphorus.

1. From Type III pneumococci a biologically active fraction has been isolated in highly purified form which in exceedingly minute amounts is capable under appropriate cultural conditions of inducing the transformation of unencapsulated R variants of Pneumococcus Type II into fully encapsulated cells of the same specific type as that of the heat-killed microorganisms from which the inducing material was recovered. 2. Methods for the isolation and purification of the active transforming material are described. 3. The data obtained by chemical, enzymatic, and serological analyses together with the results of preliminary studies by electrophoresis, ultracentrifugation, and ultraviolet spectroscopy indicate that, within the limits of the methods, the active fraction contains no demonstrable protein, unbound lipid, or serologically reactive polysaccharide and consists principally, if not solely, of a highly polymerized, viscous form of desoxyribonucleic acid. 4. Evidence is presented that the chemically induced alterations in cellular structure and function are predictable, type-specific, and transmissible in series. The various hypotheses that have been advanced concerning the nature of these changes are reviewed.

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Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III

Publisher Summary This chapter discusses the chemical analysis of microbial cells. The preparation of material for analysis is discussed, because changes in the chemical composition of cells may occur as a result of the washing and storage conditions used. Wet- and dry-weight determinations of bacterial samples and assay of total cell numbers are described, because analytical results must refer to one or other of these values. Selection of an analytical procedure is a subjective process, because the number of suitable methods is large and each will have different merits and defects. Primary considerations are sensitivity, specificity, reproducibility, and absolute accuracy. Automatic methods for performing biochemical analyses, already widely accepted in hospitals and in industry, are beginning to make their way into the research laboratory. All automatic analyzers developed so far may be classified as either “continuous-flow” or “discrete” types. All of them use colorimetric methods exclusively and contain some form of automatic colorimeter for final read-out. The first and best-known is the Technicon “AutoAnalyzer,” which is of the continuous-flow type.

Chapter III Chemical Analysis of Microbial Cells

Robert Robison (Fig. 1) was born in 1883 in Newark-on-Trent. He attended the University College. Nottingham. He began his career in research before he obtained his initial degree. Having obtained a scholarship, Robison was able to study for two years in Leipzig in the kdbordtories of Professor Hantz

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The Possible Significance of Hexosephosphoric Esters in Ossification.

/pdf/the-growth-development-and-phosphatase-activity-of-embryonic-19tg2x3xwo.pdf

The growth, development and phosphatase activity of embryonic avian femora and limb-buds cultivated in vitro.

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The Possible Significance of Hexosephosphoric Esters in Ossification: Part II. The Phosphoric Esterase of Ossifying Cartilage.

The Possible Significance of Hexosephosphoric Esters in Ossification

THE explanation of the process of calcification suggested in the first of these papers requires that a suitable phosphoric ester shall be supplied to those regions of bone and cartilage where ossification is taking place. It has been shown that one of the acid-soluble phosphoric esters occurring in blood fulfils the conditions of suitability in that it yields a soluble calcium salt and is hydrolysed by aqueous extracts of the bone enzyme,'but the fact that these esters are almost entirely confined to the corpuscles' makes it necessary to enquire further into the possibility of this compound passing into the fluids bathing the cartilage cells. This possibility would not -be excluded even if the ester were normally absent from blood-plasma, for a varying permeability of cell membranes must be assumed to explain many of the facts of physiology. The amounts of organic acid-soluble P found by previous workers in normal plasma or serum are set out in Table I.

Robert Robison

Papers

The Possible Significance of Hexosephosphoric Esters in Ossification.

The growth, development and phosphatase activity of embryonic avian femora and limb-buds cultivated in vitro.

The Possible Significance of Hexosephosphoric Esters in Ossification: Part II. The Phosphoric Esterase of Ossifying Cartilage.

The Possible Significance of Hexosephosphoric Esters in Ossification

Possible Significance of Hexosephosphoric Esters in Ossification: Part VI. Phosphoric Esters in Blood-Plasma.