Soluble State Research Articles

Liquid–Liquid Equilibrium, Solubility, and Critical States in an Acetic Acid–n-Butyl Alcohol–n-Butyl Acetate–Water System at 328.15 K and 101.3 kPa: Topology of Phase Diagrams and NRTL Modeling

Compositions of coexisting phases (liquid–liquid equilibrium), solubility, and critical states for the quaternary acetic acid–n-butyl alcohol–n-butyl acetate–water system were carried out at 328.15...

Multiscale Modeling Reveals Physical Interactions that Influence the Mechanical Behaviour of Polysaccharide-Surfactant Hydrogels

Chitosan is a gel-forming polysaccharide biopolymer. The amine groups on chitosan monomers ionize with a pKa ∼6.5 which facilitates pH-responsive transition from an insoluble physically crosslinked hydrogel at basic pH, to a soluble polycationic state at acidic pH. However, addition of anionic surfactants such as sodium dodecyl sulfate (SDS) to cationic chitosan allows the formation of electrostatically linked hydrogels. In contrast to the elastic nature of chitosan gels at basic pH, these acid-stable SDS:chitosan gels have been shown to display viscoelasticity and self-healing properties. This tunable nature of chitosan makes it an attractive biomaterial for bioelectronics fabrication, and other biomedical applications. Here, we use a multiscale molecular modeling approach to identify the molecular interactions responsible for the orthogonal dependence of mechanical properties on pH and SDS concentration. We use coarse-grained molecular dynamics to self-assemble large, space-spanning SDS:chitosan networks. We then back-map these networks to atomistic resolution to further investigate the finer differences between their interaction profiles. Our findings show that water mediated contacts are the predominant crosslinking interaction at basic pH, but not at acidic pH. Instead, SDS-chitosan salt bridges and hydrogen bonds are the dominating crosslinks at acidic pH. Furthermore, direct chitosan-chitosan hydrogen-bonds appear to have a much smaller role in hydrogel structure than previously thought. These findings offer valuable insights into the fine molecular interactions that stabilize these polysaccharide-surfactant hydrogels. Taken together with the known mechanical behaviours of these hydrogels, our results offer directions for the rational design of chitosan materials from the bottom up.

Форми знаходження радіонуклідів у донних відкладеннях приміщення 012/7 об’єкта «Укриття»

After installation of the Arch of New Safe Confinement (NSC) into design position, precipitations intake in the underroof space of the Shelter object ceased, and water evaporation began from the unorganized accumulations of radioactively contaminated water. As a result of physical and chemical processes of coagulation and deposition of sparingly soluble salts, bottom sediments, containing uranium and radionuclides, formed. The aim of the work is to determine speciation forms of uranium and radionuclides in the bottom sediments, which formed due to the drying out of unorganized accumulations of radioactively contaminated water in room 012/7 of the NSC – Shelter object. Results of the experimental determination of speciation forms of uranium and radionuclides 90Sr, 137Cs, 154Eu, 238Pu, 239+240Pu, 241Am and 244Cm in the bottom sediments of room 012/7 of the NSC – Shelter object are presented. An amount of water-soluble, exchangeable and acid-soluble uranium forms, fission products and transuranium elements in the bottom sediments of room 012/7 of the NSC – Shelter object was determined by the method of consecutive extractions. Content of uranium, 90Sr, 238Pu, 239+240Pu, 241Am and 244Cm in the leaching solutions and insoluble residue was determined by the ion-exchange method. 90Sr activity was determined by beta-radiometric measurements. Activity of 234,235,236,238U, 238Pu, 239+240Pu, 241Am and 244Cm was determined by alpha-spectrometric measurements of uranium, plutonium and americium sources. The concentration of uranium in the bottom sediments of room 012/7 was 1.02 ± 0.26 mg/g. Abundance content of uranium isotopes is 234U – 0.0159, 235U – 1.09, 236U – 0.192 and 238U – 98.71%. Isotope content of uranium in the bottom sediments, on the whole, corresponds to the isotope content of uranium in the irradiated fuel of the Chornobyl NPP 4th unit with an average burnup. The specific activity of 90Sr and 137Cs in the bottom sediments of room 012/7 is in the range of 6∙108−1∙109 Bq/kg. 239+240Pu and 241Am specific activity in the bottom sediments is in the range of 6∙105 – 8∙106 Bq/kg. 90Sr, 137Cs, 154Eu, 238Pu, 239+240Pu, 241Am and 244Сm radionuclides in the bottom sediments are in different physical and chemical forms, which determine their potential mobility. Mainly uranium and 137Cs in the bottom sediments of room 012/7 are in the exchangeable forms. An amount of water-soluble forms of uranium and 137Cs is about 1.5 – 3%. The main amount of 90Sr, more than 60% is in the carbonate forms, which are very soluble in weak acid medium, when pH is 4.8. More than 65% of 238Pu and 239+240Pu in the bottom sediments of room 012/7 are in the acid-soluble forms. Potential mobility of 241Am in the bottom sediments is notably higher than of plutonium in the soluble state, when pH 4.8, transfer more than 40% of 241Am. Relations of activities of radionuclides 137Cs/90Sr, 90Sr/239+240Pu, 241Am/239+240Pu and 44Cm/239+240Pu in the bottom sediments of room 012/7 differ significantly from the similar relations in the fuel containing materials of the Shelter object.

Improving the quality of secondary fiber raw materials studying a process.

The article presents the results of improving the quality of waste paper by converting the printing ink in the MS-3 waste paper mass into a soluble state. The necessary conditions for the solubility of printing ink in the waste paper mass have been recommended.

Going full circle: Determining the structures of complement component 9.

Pore forming proteins (PFPs) undergo dramatic conformational changes to punch holes in the target membrane. These PFPs have the ability to self-assemble, by way of oligomerization, and have the capacity to transform from a water soluble state (commonly referred to as fluid phase) to a membrane adhered form. Accordingly, PFPs are metastable, that is they are inert until the right conditions cause the release of potential energy stored in the conformational fold leading to a vast structural rearrangement into a membrane-inserted oligomeric form. However, the metastable state of PFPs poses a problem of leading to aggregation and precipitation in conditions typically required for structural biology techniques. Here, we discuss the protein chemistry of the MACPF protein complement component 9 (C9). C9 is part of a larger complex assembly known as the membrane attack complex (MAC) that has been studied extensively for its ability to form pores in bacteria. An unusual artifact of human C9 is the ability to form a soluble oligomeric state of the channel portion of the MAC, called polyC9. PolyC9 formation does not require the presence of membranes or other complement factors. It is only in recent years that structural studies of the MAC have become successful owing to improved recombinant DNA expression systems and the improvement of high-resolution techniques (both X-ray crystallography and single particle cryo-EM). We discuss the expression and purification of recombinant C9, crystallization of the soluble monomeric form of C9 and the preparation of the oligomeric polyC9.

Proton-transfer and charge-transfer interactions between the antibiotic trimethoprim and several σ− and π−acceptors: A spectroscopic study

The σ−acceptor iodine and π−acceptors chloranil (CHL), chloranilic acid (CLA), and picric acid (PA) were complexed with the antibiotic trimethoprim (TMP) as the donor through transfer-type reactions. The spectroscopic properties and structural morphology of the resultant complexes were investigated in both their soluble and solid states; CHN elemental analysis, 1H NMR, 13C NMR, FT−IR, Raman, UV-visible spectroscopies, TEM, and SEM-EDX were used to determine these properties. This work highlights that TMP reacted with iodine and CHL via a CT interaction and with CLA and PA via a PT interaction to form stable solid complexes that ranged in color from yellow (TMP-PA), to violet (TMP-CLA), brown (TMP-CHL), and black (TMP-iodine). The 1:2 stoichiometry between TMP and iodine and 1:1 stoichiometry with the other acceptors was verified by elemental analysis and the spectrophotometric titration method. TEM revealed that the structural morphologies of the TMP complexes were markedly different ranging from spherical particles with the CHL and CLA acceptors to short rods with iodine acceptor to long tubes with the PA acceptor.

(Invited) Understanding the Structure and Interfacial Chemistry of High Temperature Molten Salts

There has been a renewed interest over the past decade in the use of molten salts as coolants and fuels in next-generation nuclear reactors that are used for electricity generation and to supply high-temperature, low-pressure heat. For solid-fuel salt-cooled reactors, molten salts are used as the coolant for solid-fueled reactors that operate at high temperatures (>500 °C) while for liquid salt fueled reactors, fissile, fertile, and fission products are dissolved in a homogeneous molten salt which serves as both the fuel matrix and the primary coolant. Two key challenges with a liquid salt fueled reactor is to manage the solubility and oxidation state of the materials dissolved in the molten salt and to manage the interfacial interactions of the molten salt with the reactor materials to limit corrosion. To understand how the structure and dynamics of molten salts impact their physical and chemical properties, such as viscosity, solubility, and thermal conductivity, as well as chemical reactivity, it is necessary to determine the structure and speciation of the molten salt at the atomic/molecular scale. The Molten Salts in Extreme Environments (MSEE) Energy Frontier Research Center is addressing these challenges through a coordinated experimental and theoretical effort to elucidate the atomic and molecular basis of molten salt behavior, including interactions with solutes and interfaces and under coupled extremes of temperature and radiation. The structure of bulk salt mixtures, such as MgCl2/KCl, and solute speciation in molten salts has been studied to better understand behavior in these complex environments using combined X-ray scattering and spectroscopy, neutron scattering, optical spectroscopy and computational modeling. The chemical and morphological evolution of metal/molten salt interfaces has been examined using X-ray tomography and electron microscopy to better understand corrosion processes in molten salt systems. This presentation will discuss the challenges in molten salt chemistry for nuclear energy applications and highlight recent results in understanding the structure, properties and reactivity of high temperature molten salts.

Comparison of the In Vitro and Ex Vivo Permeation of Existing Topical Formulations Used in the Treatment of Facial Angiofibroma and Characterization of the Variations Observed.

Rapamycin has been used topically to treat facial angiofibromas associated with tuberous sclerosis for more than a decade. In the absence of a commercial form, a large number of formulations have been clinically tested. However, given the great heterogeneity of these studies, particularly with regard to the response criteria, it was difficult to know the impact and thus to compare the relevance of the formulations used. The objective of this work was therefore to evaluate the link between the diffusion of rapamycin and the physico-chemical characteristics of these different formulations on Strat-M® membranes as well as on human skin using Franz cells. Our results underline the importance of the type of vehicle used (hydrogel > cream > lipophilic ointment), the soluble state of rapamycin and its concentration close to saturation to ensure maximum thermodynamic activity. Thus, this is the first time that a comparative study of the different rapamycin formulations identified in the literature for the management of facial angiofibromas has been carried out using a pharmaceutical and biopharmaceutical approach. It highlights the important parameters to be considered in the development and optimization of topical rapamycin formulations with regard to cutaneous absorption for clinical efficacy.

Small-molecule sequestration of amyloid-β as a drug discovery strategy for Alzheimer's disease.

Disordered proteins are challenging therapeutic targets, and no drug is currently in clinical use that modifies the properties of their monomeric states. Here, we identify a small molecule (10074-G5) capable of binding and sequestering the intrinsically disordered amyloid-β (Aβ) peptide in its monomeric, soluble state. Our analysis reveals that this compound interacts with Aβ and inhibits both the primary and secondary nucleation pathways in its aggregation process. We characterize this interaction using biophysical experiments and integrative structural ensemble determination methods. We observe that this molecule increases the conformational entropy of monomeric Aβ while decreasing its hydrophobic surface area. We also show that it rescues a Caenorhabditis elegans model of Aβ-associated toxicity, consistent with the mechanism of action identified from the in silico and in vitro studies. These results illustrate the strategy of stabilizing the monomeric states of disordered proteins with small molecules to alter their behavior for therapeutic purposes.

RETURNABLE BAKING WASTE — A NEW TYPE OF RAW MATERIALS FOR DISTILLATES PRODUCTION (PART II. STAGE OF RAW MATERIALS PREPARATION FOR DISTILLATION)

The processes that take place upon saccharified wort obtaining from the returnable baking waste and its fermentation was the research subject of this work. The development of operational parameters at the stage of returnable baking waste preparation for distillation, which provides a high-quality product is the purpose of the work. The samples of saccharified and fermented wort obtained from various bread and bakery products types produced by large enterprises in Moscow were the objects of the study. To characterize the composition of saccharified and fermented wort, the indicators to assess the quality of the wort from grain raw materials were used. The mass concentration of individual sugars in the wort was determined using high performance liquid chromatography on an Agilent Technologies 1200 Series device. The qualitative composition and volatile components concentration in the fermented wort was determined using gas chromatography on a Thermo Trace GC Ultra device. It was established that the percentage of solids transition to a soluble state does not depend on a returnable waste type and is in the range from 87.6% to 90.7%, and the starch transition to a soluble state, on the contrary, is determined by the processed raw materials type. It is shown that the use of rye-wheat bread after its preliminary enzymatic treatment with thinning and cytolytic drugs in a mixture with wheat bread in a ratio of 1÷1 to 1÷2 can improve the wort rheological characteristics and transfer from 98.1% to 99.3% starch of raw materials in a soluble state. It has been shown that for the efficient process of saccharified wort fermentation from returnable baking waste, the Fermiol and Turbo‑24 alcohol yeast races are most suitable, which ensure a high yield of ethanol and an optimal composition of volatile components in the fermented wort.

Iron Speciation in PM2.5 From Urban, Agriculture, and Mixed Environments in Colorado, USA

AbstractAtmospheric iron solubility varies depending on whether the particles are collected in rural or urban areas, with urban areas showing increased iron solubility. In this study, we investigate if the iron species present in different environments affects its ultimate solubility. Field data are presented from the Platte River Air Pollution and Photochemistry Experiment (PRAPPE), aimed at understanding the interactions between organic carbon and trace elements in atmospheric particulate matter (PM). 24‐hr PM2.5 samples were collected during the summer and winter (2016–2017), at three different sites on the Eastern Colorado plains: an urban, agricultural, and a mixed site. Downtown Denver had an average total and water‐soluble iron air concentration of 181.2 and 7.7 ng m−3, respectively. Platteville, the mixed site, had an average of total iron of 76.1 ng m−3, with average water‐soluble iron concentration of 9.1 ng m−3. Jackson State Park (rural/agricultural) had the lowest total iron average of 31.5 ng m−3 and the lowest water‐soluble iron average, 1.3 ng m−3. The iron oxidation state and chemical speciation of 97 samples across all sites and seasons was probed by X‐ray absorption near edge structure (XANES) spectroscopy. The most common iron phases observed were almandine (Fe₃Al₂Si₃O₁₂) (Denver 21%, Platteville 16%, Jackson 24%), magnetite (Fe3O4) (Denver 9%, Platteville 4%, Jackson 5%) and Fe (III)dextran (Denver 5%, Platteville 13%, Jackson 5%), a surrogate for Fe‐organic complexes. Additionally, native iron [Fe(0)] was found in significant amounts at all sites. No correlation was observed between iron solubility and iron oxidation state or chemical speciation.

Enzymatic degradation of RNA causes widespread protein aggregation in cell and tissue lysates.

Most proteins in cell and tissue lysates are soluble. We show here that in lysate from human neurons, more than 1,300 proteins are maintained in a soluble and functional state by association with endogenous RNA, as degradation of RNA invariably leads to protein aggregation. The majority of these proteins lack conventional RNA‐binding domains. Using synthetic oligonucleotides, we identify the importance of nucleic acid structure, with single‐stranded pyrimidine‐rich bulges or loops surrounded by double‐stranded regions being particularly efficient in the maintenance of protein solubility. These experiments also identify an apparent one‐to‐one protein‐nucleic acid stoichiometry. Furthermore, we show that protein aggregates isolated from brain tissue from Amyotrophic Lateral Sclerosis patients can be rendered soluble after refolding by both RNA and synthetic oligonucleotides. Together, these findings open new avenues for understanding the mechanism behind protein aggregation and shed light on how certain proteins remain soluble.

Quantitative analysis of weakly bound insulin oligomers in solution using polarized multidimensional fluorescence spectroscopy

Being able to measure the size and distribution of oligomers in solution is a critical issue in the manufacture and stability of insulin and other protein formulations. Measuring oligomers reliably can however be complicated, due to their fragile self-assembled structures, which are held together by weak forces. This can cause issues in chromatographic based methods, where dissociation or re-equilibration of oligomer populations can occur e.g. upon dilution in a different eluting buffer, but also for light scattering based methods like dynamic light scattering (DLS) where the size difference involved (often less than a factor 3) does not allow mixtures of oligomers to be resolved. Intrinsic fluorescence offers an attractive alternative as it is non-invasive, sensitive but also because it contains scattered light when implemented via excitation emission matrix (EEM) measurements, that is sensitive to changes in particle size.Here, using insulin at formulation level concentrations, we show for the first time how EEM can both discriminate and quantify the proportion of oligomeric states in solution. This was achieved by using the Rayleigh scatter (RS) band and the fluorescence signal contained in EEM. After validating size changes with DLS, we show in particular how the volume under the RS band correlated linearly with protein/oligomer molecular weight, in agreement with the Debye-Zimm relationship. This was true for the RS data from both EEM and polarized EEM (pEEM) measurements, the latter providing a stronger scatter signal, more sensitive to particle size changes.The fluorescence signal was then used with multivariate curve resolution (MCR) to quantify more precisely the soluble oligomer composition of insulin solutions. In conditions that promoted the formation of mainly one type of oligomer (monomer, dimer, or hexamer), pEEM-MCR helped identify the presence of small amounts of other oligomeric forms, while in conditions that were previously said to favour the insulin tetramer, we show that in the presence of zinc, these insulin samples were instead a heterogenous mixture composed of mostly dimers and hexamers. These MCR results correlated in all cases with the observed discrimination by principal component analysis (PCA), and deviations observed in the RS data. In conclusion, using pEEM scatter and emission components with chemometric data analysis provides a unique analytical method for characterising and monitoring changes in the soluble oligomeric state of proteins.

The cocrystal of 3-((4-(3-isocyanobenzyl) piperazine-1-yl) methyl) benzonitrile with 5-hydroxy isophthalic acid prevents protofibril formation of serum albumin

The formation of amyloid-like fibrils is a central problem in biophysical chemistry and medicine. Fibril formation and their deposition in various tissues and organs are associated with many human diseases. Searching for molecules able to prevent the formation of fibrils is, therefore, necessary. In this work, we examined the potential of a cocrystal (SS3) of 3-((4-(3-isocyanobenzyl) piperazine-1-yl) methy) benzonitrile with 5-hydroxy isophthalic acid, to prevent fibrillation of human serum albumin. We found that the cocrystal strongly bound to human serum albumin (HSA) with association constant (K a) of 5.8 ± 0.7 × 105 M−1. The SS3 binding was found to cause small alterations in both secondary and tertiary structure of the protein. Transmission electron microscopy showed that the cocrystal completely prevented the formation of worm-like protofibrils by HSA at SS3/HSA molar ratio of 1:1. The molecule was found to prevent the aggregation in a concentration dependent manner. It was also observed that most of protein in the presence of SS3 remained in soluble state and the secondary structure contained native-like α-helical structure. Therefore, we conclude that the cocrystal effectively prevented conversion of HSA into worm-like protofibril. These finding suggest that combination of molecules in the form of cocrystal or other stable combination could pave a way for the development of drugs against amyloidosis. Communicated by Ramaswamy H. Sarma

Conformational States of the Cytoprotective Protein Bcl-xL

Bcl-xL is a major inhibitor of apoptosis, a fundamental homeostatic process of programmed cell death that is highly conserved across evolution. Because it plays prominent roles in cancer, Bcl-xL is a major target for anticancer therapy and for studies aimed at understanding its structure and activity. Although Bcl-xL is active primarily at intracellular membranes, most studies have focused on soluble forms of the protein lacking both the membrane-anchoring C-terminal tail and the intrinsically disordered loop, and this has resulted in a fragmented view of the protein’s biological activity. Here, we describe the conformation of full-length Bcl-xL. Using NMR spectroscopy, molecular dynamics simulations, and isothermal titration calorimetry, we show how the three structural elements affect the protein’s structure, dynamics, and ligand-binding activity in both its soluble and membrane-anchored states. The combined data provide information about the molecular basis for the protein’s functionality and a view of its complex molecular mechanisms.

Improvement of In Vitro Dissolution of the Poor Water-Soluble Amlodipine Drug by Solid Dispersion with Irradiated Polyvinylpyrrolidone.

The aim of this study was to increase both the rates of dissolution and bioavailability of the amlodipine (Amlo) drug. Due to the low cost, high solubility, and amorphous state, polyvinylpyrrolidone (PVP) has been used as a drug carrier in the solid dispersion process. Through applying an irradiation technique, powder of (PVP) is irradiated with six 0–50 kGy irradiation doses. The six irradiated (PVP) samples were characterized using gel permeation chromatography, electron spin resonance, and Fourier transform infrared (FT-IR) spectroscopy. The formulation of six (PVP/Amlo) samples at a ratio of 2:1 wt/wt were characterized using FT-IR spectroscopy and X-ray powder diffraction. In vitro dissolution of (Amlo) drug was assessed in a water solvent at pH 1.2 and pH 7. Results demonstrated that there is a change in the physicochemical properties of irradiated (PVP). FT-IR confirmed that there is an intermolecular H bond between the (Amlo) drug and (PVP) polymer. XRD confirmed that (PVP) changes the crystalline (Amlo) to amorphous amlodipine. Irradiated (PVP) at a dose of 20 kGy released approximately 89% from 40 mg of (Amlo) in 60 s. The in vitro rate of amlodipine dissolution depends on the drug–polymer intermolecular H bond. The rate of (Amlo) dissolution is increased due to the drug–drug intramolecular hydrogen bonding replaced with the drug–polymer intermolecular hydrogen bonding, which reduces the crystal packing. Irradiated (PVP) improved the rate of (Amlo) dissolution compared to unirradiated (PVP).

Liquid-liquid equilibria, solubility and critical states in the system propionic acid – 1-propanol – n-propyl propionate – water at 303.15 K

New experimental data on liquid-liquid equilibria (LLE), solubility and critical states in quaternary system propionic acid – 1-propanol – n-propyl propionate – water at 303.15 K and atmospheric pressure are presented. LLE was studied by Gas Chromatography (GC). Solubility and critical (plait) points were investigated by “cloud-point technique” method. Binodal curves and surfaces are presented in concentration tetrahedron. The critical curve is presented in 3d concentration space. A comparative analysis of the results obtained in the work with literature data is carried out. The experimental data are correlated by NRTL model. Standart deviation σ for quaternary mixture does not exceed 0.344%.

Daily Cycles of Reversible Protein Condensation in Cyanobacteria

An emerging principle of cell biology is the regulated conversion of macromolecules between soluble and condensed states. To screen for such regulation of the cyanobacterial proteome, we use quantitative mass spectrometry to identify proteins that change solubility during the day-night cycle. We find a set of night-insoluble proteins that includes many enzymes in essential metabolic pathways. Using time-lapse microscopy and isotope labeling, we show that these proteins reversibly transition between punctate structures at night and a soluble state during the day without substantial degradation. We find that the cyanobacterial circadian clock regulates the kinetics of puncta formation during the night and that the appearance of puncta indicates the metabolic status of the cell. Reversible condensation of specific enzymes is thus a regulated response to the day-night cycle and may reflect a general bacterial strategy used in fluctuating growth conditions.

Preparation of SiC ceramic fiber from a photosensitive polycarbosilane

Curing treatment is essential for ceramic precursors to maintain their shape during pyrolysis. In this study, a photosensitive SiC ceramic precursor was synthesized by chlorinating partial Si–H groups of polycarbosilane (PCS) with Cl2 followed by reacting with hydroxyethyl acrylate. According to 1H NMR and element analysis, about 10% structural unit of PCS was grafted with the acrylate group. After mixing with photo-initiator, the acrylate-grafted PCS transformed from soluble and fusible state to insoluble and non-fusible state under UV light. Its curing rate with related ceramic yield and oxygen content were compared with PCSs cured by the traditional air oxidation and electronic radiation. By electrospinning synchronized with UV illumination and pyrolyzing the acrylate-grafted PCS, one-dimensional continuous SiC fibers were prepared. The effects of pyrolysis temperature on the morphology, crystallographic structure and elemental composition were also characterized and discussed.

Hiding in plain sight: vesicle-mediated export and transmission of prion-like proteins.

Infectious proteins or prions are non-native conformations of proteins that are the causative agents of devastating neurodegenerative diseases in humans and heritable traits in filamentous fungi and yeasts. Prion proteins form highly ordered self-perpetuating fibrillar aggregates that traffic vertically and horizontally from cell to cell. The spreading of these infectious entities relies on different mechanisms, among which the extracellular vesicles (EV)-mediated traffic. The prion form of the yeast Saccharomyces cerevisiae Sup35p translation terminator causes the [PSI+] nonsense suppression phenotype. This fascinating biological model helped us shape our understanding of the mechanisms of formation, propagation and elimination of infectious protein aggregates. We discovered that Sup35p is exported via EV, both in its soluble and aggregated infectious states. We recently reported that high amounts of Sup35p prion particles are exported to the yeast periplasm via periplasmic vesicles (PV) in glucose-starved cells. EV and PV are different in terms of size and protein content, and their export is inversely regulated by glucose availability in the growth medium. We believe these are important observations that should make us revise our current view on the way yeast prions propagate. Hence, I propose several hypotheses as to the significance of these observations for the transmission of yeast prions. I also discuss how yeast could be used as a powerful tractable biological model to investigate the molecular mechanisms of vesicle-mediated export of pathological protein aggregates implicated in neurodegenerative diseases.